# ent

id: cord-288558-rthnj6wd
type: WORK_OF_ART
entity:
  Nasopharynx Is Associated with Diarrhea in Patients with Severe Acute Respiratory Syndrome date 2004


id: cord-278816-l92lkj69
type: CHEMICAL
entity:
  otite moyenne aiguë une laryngite une bronchiolite une pneumopathie Chez les sujets hospitalisés la fièvre


id: cord-304899-vruq4r7z
type: CHEMICAL
entity:
  plusieurs aspects D abord sur le plan médical l identification d un nouveau virus pathogène pour l homme


id: cord-291210-ghjseynl
type: WORK_OF_ART
entity:
  A Highly Unusual Palindromic Transmembrane Helical Hairpin Formed by SARS Coronavirus E Protein date 2004


id: cord-284372-v95fzp8n
type: CELL_LINE
entity:
  RSVA 2C GAT GTT ACG GTG GGG AGT CT 2 334 RSVA 2D GTA CAC TGT AGT TAA TCA CA RSVB 2C AAT GCT AAG ATG GGG AGTTC 2 183 RSVB 2D GAA ATT GAG TTA ATG ACA GC ADV 2A 2 GCCGCAGTGGTCTTACATGCACATC Hexon 1 301 ADV 2B 2


id: cord-284372-v95fzp8n
type: TAXON
entity:
  A respiratory syncytial virus type B adenovirus coronavirus 229E parainfluenza virus type 1 parainfluenza virus type 2 parainfluenza virus type 3 human rhinovirus


id: cord-284372-v95fzp8n
type: DISEASE
entity:
  influenza A virus FLA influenza B virus FLB respiratory syncytial virus RSV parainfluenza virus type 1 PF1 parainfluenza virus type 2 PF2 parainfluenza virus type 3


id: cord-284372-v95fzp8n
type: CHEMICAL
entity:
  virus 4 influenza B virus 2 human rhinovirus 39 adenovirus 22 parainfluenza virus type 2 1 parainfluenza virus type 3 10 respiratory syncytial virus type A 2 respiratory syncytial virus type B 2 No parainfluenza virus type 1 coronavirus 229E


id: cord-284372-v95fzp8n
type: DISEASE
entity:
  influenza A influenza B respiratory syncytial virus adenovirus parainfluenza type 1 parainfluenza type 2 and parainfluenza type 3


id: cord-284372-v95fzp8n
type: DISEASE
entity:
  influenza B respiratory syncytial virus type A respiratory syncytial virus type B adenovirus coronavirus 229E parainfluenza virus type 1 parainfluenza virus type 2 parainfluenza virus type 3 human rhinovirus and human metapneumovirus The final


id: cord-264848-wl29jk16
type: PROTEIN
entity:
  primary antibodies rat anti BrdU 1 200 Accurate Chemical and Scientific Corporation mouse anti APC CC1 1 20 Oncogene Research Products San


id: cord-274112-6t0wpiqy
type: DNA
entity:
  primer sets 1 Bm HA 1 5Ј TATTCGTCTCAGGGAGCAA AAGCAGGGG 3Ј and 739 R 5Ј TAATCGTC TCGTTTCAATTTGAGGGCTATTTCTGAGCC 3Ј and 2 739 F 5Ј TAATCGTCTCTGAAA CTAGAGGATTATTTGGAGCTATAGC 3Ј


id: cord-254107-02bik024
type: PROTEIN
entity:
  epidermal growth factor receptor tyrosine kinase protein 35 36 Bruton s tyrosine kinase 37 Janus kinase 3 38


id: cord-290133-4ou7ubb4
type: ORG
entity:
  Board on Health Promotion and Disease Prevention Institute of Medicine Review of the Centers for Disease Control and Prevention


id: cord-298312-tvc39eg7
type: ORG
entity:
  Beijing China Statistical Publishing House Beijing China Statistical Publishing House Beijing China Statistical Publishing House Beijing China Statistical Publishing House Beijing China Statistical Publishing House State Power Cooperation


id: cord-267564-ulavigi7
type: EVENT
entity:
  CPMP CPMP Note for Guidance on Virus Validation Studies the Design Contribution and Interpretation of Studies Validating the Inactivation and Removal of Viruses Transfusion


id: cord-312848-vbadg8ki
type: DNA
entity:
  follows 1st upstream primer 5 ATGTTTTTGATACTTTTAATTTCC 3 1 24 1st downstream primer 5 ACACCAGTAGATGGTGCTAT 3 901 920 2nd upstream primer 5


id: cord-312848-vbadg8ki
type: ORG
entity:
  the Technology Development Program for Agriculture and Forestry Ministry of Agriculture and Forestry Republic


id: cord-322834-rl6yum7n
type: DISEASE
entity:
  human sexual network formation Maximum likelihood from incomplete data via the EM algorithm This article


id: cord-262776-6k7tcgfs
type: ORG
entity:
  Animal Health Report of the Federation of European Laboratory Animal Science Associations FELASA Working Group


id: cord-010203-dt9m596i
type: DNA
entity:
  P1 or PI Substituents X ray Crystal Structure Assisted Design Computer assisted molecular modelling was used to design derivatives of the lead inhibitor L 685 434 14


id: cord-010203-dt9m596i
type: EVENT
entity:
  A Series of Potent HIV 1 Protease Inhibitors Containing a Hydroxyethyl Secondary Amine Transition State


id: cord-010203-dt9m596i
type: ORG
entity:
  Antiviral and Pharmokinetic Properties of C 2 Symmetric Inhibitors of the Human Immunodeficiency Virus Type 1 Protease


id: cord-010203-dt9m596i
type: WORK_OF_ART
entity:
  Crystallographic Structure of a Complex Between a Synthetic Protease of Human Immunodeficiency Virus 1


id: cord-293403-o1i999hy
type: ORG
entity:
  OECD Forum Taiwan Council of Economic Planning and Development Taiwan Statistical Data Book World Development Indicators


id: cord-327819-7p05jk1h
type: DISEASE
entity:
  influenza A H5N1 Thailand World Health Organization International Avian Influenza Investigative Team Avian influenza A H5N1


id: cord-275993-isff6lp2
type: DNA
entity:
  antisense primer 5V AAT GAA GCG GAT CCCGGG TTA GTG ATG GTG GTG ATG ATG TTG CTC ATA TTT TCC CAA 3V Base pairing region nts 3553 3570


id: cord-307968-sqe7h05t
type: TAXON
entity:
  Salmonella spp Shigella spp Campylobacter spp Yersinia spp Mycobacterium spp Escherichia coli O157 H7 enteroviruses Hepatitis A virus


id: cord-307968-sqe7h05t
type: TAXON
entity:
  Herpesvirus Cytomegalovirus Coronavirus Astrovirus Rotavirus Norovirus Adenovirus HIV Clostridium difficile toxin enterotoxin


id: cord-307968-sqe7h05t
type: ORG
entity:
  the Public Health Regional Surveillance Team Office of Public Health Preparedness and Response Division of Public Health North Carolina


id: cord-307968-sqe7h05t
type: DISEASE
entity:
  enteroviruses Hepatitis A virus HAV Herpesvirus Cytomegalovirus Coronavirus Astrovirus Rotavirus Norovirus Adenovirus HIV Clostridium difficile


id: cord-255201-shrmdkco
type: ORG
entity:
  medidas de salud pública como el lavado de manos los procedimientos de control de las infecciones el aislamiento de los casos


id: cord-286825-bu7j7kdr
type: PROTEIN
entity:
  Angiotensin converting enzyme ACE dipeptidyl carboxypeptidase I DCP I peptidase P carboxycathepsin peptidyl dipeptidase A


id: cord-286825-bu7j7kdr
type: PROTEIN
entity:
  Drosophila melanogaster Peptidyl dipeptidase A Angiotensin Iconverting enzyme Angiotensinconverting enzyme 2


id: cord-286825-bu7j7kdr
type: GGP
entity:
  Angiotensin converting enzyme ACE dipeptidyl carboxypeptidase I DCP I peptidase P carboxycathepsin peptidyl dipeptidase A peptidyl dipeptidase I kininase II EC 3 4 15 1


id: cord-006544-yr4u61qv
type: WORK_OF_ART
entity:
  Subcommittee on Lupus Anticoagulant Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH Lupus


id: cord-319792-16upcncw
type: CHEMICAL
entity:
  S gene amino acids 1149 1192 Cloned constructs were verified by direct DNA sequencing Protein expression and purification All the relevant positive expression vectors 30a HR1 GST HR2 38 and GST HR2


id: cord-308833-ei1faruy
type: LAW
entity:
  Standard Test Method for Resistance of Materials Used in Protective Clothing to Penetration by Blood


id: cord-312865-nno2yjae
type: GGP
entity:
  Antigens DOI 10 1111 j 0001 2815 2004 00221 x sha cc42fc360f1a18e72a2db1517715b48cbe4d069d doc_id 312865 cord_uid nno2yjae Abstract


id: cord-004608-3u00cpsc
type: PROTEIN
entity:
  Virusnachweis durch Anzucht nicht mehr möglich jedoch bleibt die PCR für einige weitere Tage positiv Der Nachweis von spezifischem IgM bzw ein mindestens


id: cord-004608-3u00cpsc
type: PROTEIN
entity:
  Zulassung von Arzneimitteln Abwehr von Arzneimittelrisiken Anordnung des Ausschlusses von Blutspendern zur Verhinderung einer möglichen


id: cord-004608-3u00cpsc
type: CHEMICAL
entity:
  sich teilweise mit Malariaendemiegebieten Daher werden durch den Ausschluss von Reisenden in Malariaendemiegebiete auch Infektionen mit Arboviren erfasst


id: cord-321691-46la29tm
type: ORG
entity:
  the Departments of Laboratory Medicine and Internal Medicine National Taiwan University Hospital National Taiwan University College of Medicine


id: cord-008523-avkgldnp
type: PROTEIN
entity:
  B10 A 18R mice even though the background of this strain may be favorable for the selection of CTL escape mutants 6 MHV JHM


id: cord-008480-p41oae8e
type: PROTEIN
entity:
  detergent concentration Proteins markers alcohol deshydrogenase 7 4S Boehringer catalase 11 3S Boehringer and fl galactosidase 16S Sigma


id: cord-312899-ot5pvtbl
type: CHEMICAL
entity:
  acyclovir ganciclovir cidofovir foscarnet interferon alpha 2a interferon alpha 2b amantadine zidovudine stavudine nevirapine abacavir


id: cord-260503-yq4dtf8n
type: ORG
entity:
  Hygiene Task Force Society for Healthcare Epidemiology of America Association for Professionals in Infection Control Infectious Diseases Society of America Hospital


id: cord-266018-8bhnlsgy
type: DNA
entity:
  APCconjugated rat anti mouse CD8 PERCP conjugated rat anti mouse CD4 Pharmingen San Diego CA PE conjugated D b S510 518 MHC class I tetramer Beckman Coulter San Diego CA


id: cord-266018-8bhnlsgy
type: GGP
entity:
  Th2 associated cytokine IL 10 Table 1 Therefore the data indicate that cytokine production rather than the type of CD11c cell


id: cord-021554-uxxrpfl0
type: GGP
entity:
  enterotoxigenic Escherichia coli V cholerae clostridial and staphylococcal food poisoning rotavirus Norwalk virus agent Giardia lamblia


id: cord-258778-er0ug8w4
type: WORK_OF_ART
entity:
  Necrotizing Enterocolitis in Full Term Infants Case Control Study and Review of the Literature date 2004


id: cord-258778-er0ug8w4
type: DISEASE
entity:
  intrauterine growth retardation IUGR birth asphyxia congenital heart disease gastroschisis polycythemia hypoglycemia sepsis


id: cord-270788-w0pewq52
type: PROTEIN
entity:
  N terminal amino acid residues 270 510 Babcock et al 2004 303 537 Xiao et al 2003 and 318 510 Wong et al 2004 In


id: cord-312797-hohzjx74
type: CELL_LINE
entity:
  Madin Darby canine kidney Vero African green monkey kidney human laryngeal carcinoma HEp 2 human foreskin fibroblast human rhabdomyosarcoma transformed human kidney 293 human lung adenocarcinoma A 549 and human colon adenocarcinoma HT 29 4 7


id: cord-312797-hohzjx74
type: PROTEIN
entity:
  nucleoprotein N phosphoprotein P matrix M protein fusion F protein transcription elongation factor RNA


id: cord-334366-gl5eqlkh
type: CHEMICAL
entity:
  Cette étude bien que rétrospective donc imparfaite sur le plan méthodologique mais reprenant les résultats de deux études


id: cord-333405-ji58jbct
type: WORK_OF_ART
entity:
  The Restless Tide The Persistent Challenge of the Microbial World National Foundation for Infectious Diseases Committee on Emerging Microbial Threats to Health Emerging Infections Microbial Threats to Health


id: cord-333405-ji58jbct
type: ORG
entity:
  World Health Organization Consensus Document on the Epidemiology of Severe Acute Respiratory Syndrome SARS


id: cord-333405-ji58jbct
type: DISEASE
entity:
  influenza and respiratory syncytial virus in the United States The Chilling True Story of the Largest Covert Biological Weapons


id: cord-332522-adul9nzf
type: PROTEIN
entity:
  Taq DNA polymerase Promega 0 1 mM dNTPs 10 mM Tris HCl pH 8 3 50 mM KCl 1 25 mM MgCl 2 and 1 25 l of SYBR Green I or 0 5 l of Taqman probe 5 M


id: cord-354130-mi7saerx
type: ORG
entity:
  American Conference of Governmental Industrial Hygienists Threshold Limit Values for Chemical Substances


id: cord-339976-tg2jkss7
type: ORG
entity:
  the Plasma and Peripheral Blood Lymphocytes of Patients with Severe Acute Respiratory Syndrome date 2004


id: cord-354209-g1zynbul
type: ORG
entity:
  Stigma and Global Health Developing a Research Agenda Centers for Disease Control and Prevention Use


id: cord-021087-n4epxwn9
type: PROTEIN
entity:
  X ray mammograms K Murase 1 N Tanki 1 M Iinuma 1 H Kubota 1 M Nagao 2 1 Osaka JP 2 Matsuyama JP Purpose


id: cord-021087-n4epxwn9
type: CELL_TYPE
entity:
  gastric varices T Ninoi 1 K Nakamura 1 N Nishida 1 Y Sakai 1 T Kitayama 1 M Hamuro 1 R Yamada 1 Y Inoue 1 T Kaminou 2 1 Osaka JP 2 Yonago JP Purpose


id: cord-021087-n4epxwn9
type: PROTEIN
entity:
  T2FSE 18 33 p 0 002 and PD T2 11 33 p 0 000 Reduced hippocampal size 28 33 atrophy of hippocampus 22 33


id: cord-021087-n4epxwn9
type: DNA
entity:
  X ray imaging P Monnin 1 R Meuli 1 J Hoszowska 2 J F Valley 1 F R Verdun 1 1 Lausanne CH 2 Grenoble FR Purpose


id: cord-021087-n4epxwn9
type: GGP
entity:
  K S Cho Y Jung S Kim J Kim Seoul KR Learning Objectives To discuss the role and findings of US CT and MRI


id: cord-021087-n4epxwn9
type: GGP
entity:
  K Steinke 1 K S Haghighi 2 K K Hazratwala 2 D L Morris 2 1 Basle CH 2 Sydney AU Purpose To evaluate the effect of vessel size on radiofrequency lesion creation in the lung with respect to potential for perfusion mediated heat sink effect and for vascular and bronchial injury Methodology Radiofrequency lesions targeted to tissue encompassing a variety of vessels were created in vivo in the lung of 10 cross bred sheep The access was either open after thoracotomy along the 5 th intercostal space


id: cord-021087-n4epxwn9
type: GGP
entity:
  Hashimoto 1 T Kaminou 1 P Haage 2 Y Ohuchi 1 K Nakamura 1 K Sugiura 1 Y Noishiki 3 R W Günther 2 T Ogawa 1 1


id: cord-021087-n4epxwn9
type: GGP
entity:
  serum ICAM 1 p 0 0001 and p 0 0001 respectively and VCAM 1 p 0 0001 and p 0 0001 respectively levels IMT


id: cord-021087-n4epxwn9
type: FAC
entity:
  A Miquel 1 E Dion 2 C Graef 2 Y Menu 1 P Grenier 2 J D Laredo 2 1 Le Kremlin Bicêtre FR 2 Paris FR Learning Objectives


id: cord-021087-n4epxwn9
type: ORG
entity:
  Conventional Radiography Digital Subtraction Angiography Computed Tomography Ultrasound Magnetic Resonance Imaging


id: cord-021087-n4epxwn9
type: PRODUCT
entity:
  G S Karlsdottir T Aspelund S Sigurdsson G Eiriksdottir L Launer T Harris V Gudnason R Detrano Kopavogur


id: cord-021087-n4epxwn9
type: DISEASE
entity:
  cystic echinococcosis CE W P Hosch G W Kauffmann T Junghanss Heidelberg DE Learning Objects The new WHO classification provides for the first time a standardized sonomorphological staging of echinococcal cysts


id: cord-021087-n4epxwn9
type: DISEASE
entity:
  KS 6 cervical cancers 8 leukaemias 3 testicular 2 larynx 3 lung 2 breast 2 esophagus 2 stomach 3 liver 4 kidney and 4 adrenal carcinomas


id: cord-021087-n4epxwn9
type: DISEASE
entity:
  paraganglioma epidermoid cyst cystic teratoma tailgut cyst mucocele of appendix perianal mucinous adenocarcinoma cystic change


id: cord-021087-n4epxwn9
type: DISEASE
entity:
  abnormal chest X rays and this influenced change in clinical management In the group where chest signs symptoms


id: cord-021087-n4epxwn9
type: DISEASE
entity:
  airway and lung diseases A L Brun C Beigelman Aubry Y Badachi P A Grenier Paris FR Learning Objectives


id: cord-021087-n4epxwn9
type: DISEASE
entity:
  lymphatic obstruction pulmonary manifestations lymphangitic carcinomatosis pulmonary metastases endobronchial metastases neoplastic


id: cord-021087-n4epxwn9
type: DISEASE
entity:
  metastases in the extrahepatic abdominal solid organs bone central nervous system and abdominal wall


id: cord-021087-n4epxwn9
type: DISEASE
entity:
  temporomandibular joint effusion F Tognini 1 D Manfredini 1 V Zampa 1 G Tognini 2 M Bosco 1 1 Pisa IT 2 Parma IT


id: cord-021087-n4epxwn9
type: CHEMICAL
entity:
  L E Bacigalupo 2 R Podestà 2 G Succio 2 F Pugliese 2 S Bianchi 3 C Martinoli 2 1 Siena IT 2 Genoa IT 3 Geneva CH Learning


id: cord-021087-n4epxwn9
type: DISEASE
entity:
  breast and penile prostheses ventriculo peritoneal shunts intra ocular lens cardiac pacemakers and valves will


id: cord-021087-n4epxwn9
type: DISEASE
entity:
  bone lesions 1 cervical adenopathy 2 abdominal involvement 2 abdominal and lung 1 pituitary gland 1 middle ears 1


id: cord-021087-n4epxwn9
type: DISEASE
entity:
  inherited neurometabolic disorders A pictorial review S P Prabhu S A Barnard N Stoodley S A Renowden Bristol UK Learning Objectives


id: cord-021087-n4epxwn9
type: DISEASE
entity:
  arachnoid cyst colloid cyst epidermoid cyst dermoid cyst pineal cyst Rathke cleft cyst choroid plexus cyst


id: cord-021087-n4epxwn9
type: DISEASE
entity:
  skeletal dysplasias achondroplasia thanatophoric dwarfism chondrodysplasia punctata spondyloepiphyseal dysplasia


id: cord-021087-n4epxwn9
type: DISEASE
entity:
  Meckel s diverticulum n 9 small bowel tumour n 2 duplication enteric cyst n 1 postoperative n 6 and bowel wall hemorrhage


id: cord-021087-n4epxwn9
type: CHEMICAL
entity:
  Özsarlak O D Archambeau F Delrue P M Parizel Antwerp BE Learning Objectives Thoracic outlet syndrome PAT


id: cord-021087-n4epxwn9
type: DISEASE
entity:
  inferior mesenteric renal intercostal lumbar right and left hepatic and anterior and posterior pancreaticoduodenal arteries


# bib

id: cord-004608-3u00cpsc
author: nan
date: 2004
txt: ./txt/cord-004608-3u00cpsc.txt
cache: ./cache/cord-004608-3u00cpsc.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080098/
doi: 10.1007/s00103-004-0890-8
abstract: nan
summary:
  Unter dem Oberbegriff Arboviren (arthropod-borne viruses) werden diejenigen Viren zusammengefasst, die sich sowohl in Arthropoden wie Mücken oder Zecken als auch in Vertebraten (Vögeln, Säugetieren) vermeh-ren. Hantaviren, die zum Genus Hantavirus der Bunyaviridae gehören, werden dagegen nicht von Arthropoden auf den Menschen übertragen, sondern durch dessen Kontakt mit Ausscheidungen der natürlichen Wirte, Mäuse und Ratten. In Deutschland spielt nach dem heutigen Wissensstand nur das Virus der Frühsommermeningoenzephalitis (FSME), das durch Zecken (Ixodes ricinus) übertragen wird, epidemiologisch eine wesentliche Rolle. Für einige Viren, wie etwa West-Nil-Virus (WNV) und St.-Louis-Enzephalitis-Virus (SLEV), wurde nachgewiesen, dass die Virusvermehrung in den Mücken abhängig ist von der durchschnittlichen Umgebungstemperatur. Für verschiedene Erreger wurde gezeigt, dass einerseits infizierte Mücken überwintern können; annahme an Krankheitsfällen bei Menschen in den USA Das Verhältnis von Infektionen zu Erkrankungen wird dabei je nach Erreger und untersuchtem Kollektiv mit 20:1 bis 1.000:1 angegeben.

title:
  Arboviren—durch Arthropoden übertragbare Viren: Stellungnahmen des Arbeitskreises Blut des Bundesministeriums für Gesundheit und Soziale Sicherung


id: cord-005606-c8c2rfzi
title: Clinical identification of cognitive impairment in ICU survivors: insights for intensivists
author: Gordon, Sharon M.
date: 2004-10-02
txt: ./txt/cord-005606-c8c2rfzi.txt
cache: ./cache/cord-005606-c8c2rfzi.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094980/
doi: 10.1007/s00134-004-2418-y
summary:
  -Personality changes -Increased apathy -Loss of social inhibitions, display of socially inappropriate behavior with staff -Increased irritability or suspiciousness toward family, visitors, or medical team -Outbursts of inappropriate or unprovoked anger -Memory complaints -Difficulty learning new facts and information about one''s medical condition -Persistent word finding problems -Inability to recall conversations with medical staff and recent events in the hospital such as visits by staff, family, or friends -Inability to remember having eaten or what was eaten at meal time -Executive dysfunction -Difficulty following nurses'', physicians'', or therapists'' directions -Problems with planning and decision making related to such things as discharge planning -Confusion when trying to perform multiple tasks -Functional deficits -Difficulty looking up telephone numbers or using the telephone or other equipment such as the television and hospital bed -Decline in self-care not attributable to physical problems or limitations -Inability to find one''s room -Inability to follow a conversation -Difficulty following through with tasks Caution should be exercised when drawing conclusions about cognitive functioning based on in-hospital assessments as performance may be adversely affected by factors such as fatigue and residual effects of sedative and narcotic medications.

abstract:
  BACKGROUND: A growing body of research has demonstrated the presence of ongoing cognitive impairment in large numbers of ICU survivors. OBJECTIVE: This review offers a practical framework for practicing intensivists and those following patients after their ICU stay for the identification of cognitive impairment in ICU survivors. CONCLUSIONS: Early detection of cognitive impairment in critically ill patients is an important and achievable goal, but overt cognitive impairment remains unrecognized in most cases. However, it can be identified by objective (test scores) or subjective evidence (clinical judgment, patient observation, family interaction).


id: cord-006544-yr4u61qv
author: Miesbach, W.
date: 2004-03-20
txt: ./txt/cord-006544-yr4u61qv.txt
cache: ./cache/cord-006544-yr4u61qv.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102000/
doi: 10.1007/s10067-004-0864-0
summary:
  title: Recurrent life-threatening thromboembolism and catastrophic antiphospholipid syndrome in a patient despite sufficient oral anticoagulation Over the preceding 3 years the patient had presented a wide spectrum of manifestations of APS, including recurrent venous and arterial thromboses, cardiac, gynecological (HELLP syndrome), neurological involvements, livedo reticularis, a mild thrombocytopenia and the most feared manifestation of the catastrophic antiphospholipid syndrome (CAPS). The antiphospholipid syndrome (APS) is one of the most common causes of acquired thrombophilia and is characterized by arterial and/or venous thrombosis, recurrent pregnancy losses, and the laboratory evidence of antibodies against phospholipids or phospholipidbinding protein cofactors [1] . Retrospective studies suggest that patients with APS have an increased risk of recurrent thromboembolism [4, 5, 6] , and for this reason it is recommended that they receive oral vitamin K antagonists, such as warfarin, in order to achieve an international normalized ratio (INR) range within a therapeutic level (INR fi 3).

title:
  Recurrent life-threatening thromboembolism and catastrophic antiphospholipid syndrome in a patient despite sufficient oral anticoagulation

abstract:
  We report on a 32-year old female patient with primary antiphospholipid syndrome (PAPS) and several thromboembolic events despite stable doses of oral anticoagulation, good patient compliance and maintained INR values of >3. Over the preceding 3 years the patient had presented a wide spectrum of manifestations of APS, including recurrent venous and arterial thromboses, cardiac, gynecological (HELLP syndrome), neurological involvements, livedo reticularis, a mild thrombocytopenia and the most feared manifestation of the catastrophic antiphospholipid syndrome (CAPS). Life-threatening bilateral subdural bleeding occurred while she was anticoagulated. The clinical features appeared to be refractory to oral anticoagulation with phenprocoumon. They were life threatening on each occasion and she developed repetitive episodes of organ damage with cardiac insufficiency (NYHA III), pulmonary hypertension and other residual defects. Even during heparinization recurrent thromboembolism supervened as well as livedo reticularis of the extremities. Lupus anticoagulants (LAC), anticardiolipin (aCL) antibodies and anti-β(2)-glycoprotein-1 (β(2)GPI) titers were all markedly elevated. This case report shows that recurrent episodes of thrombosis can occur despite seemingly adequate anticoagulation in patients with CAPS.


id: cord-007049-02p8ug67
author: McGeer, Allison
date: 2004-07-15
txt: ./txt/cord-007049-02p8ug67.txt
cache: ./cache/cord-007049-02p8ug67.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7107923/
doi: 10.1086/421784
abstract: nan
summary:
  In June 2003, the Centers for Disease Control and Prevention (CDC) surveyed members of the Infectious Disease Society of America Emerging Infections Network (EIN) about SARS preparedness in their hospitals. Of the 456 EIN members responding to the survey in this issue of Clinical Infectious Diseases [2] , 381 (83%) reported that patients with respiratory symptoms in their emergency department (ED) would be screened for a travel history. A careful assessment of exposures in SARS outbreaks, particularly those due to superspreading events and transmission despite compliance with isolation precautions, is needed to determine whether airborne spread occurs [10, [13] [14] [15] . At least 2 analyses of risks associated with health care worker infection despite the use of precautions now identify that 12 h of infection-control training and confidence that precautions would be protective are associated with substantial reductions in the risk of infection (Toronto SARS hospital investigation, unpublished data; Lau et al. Hospital preparedness for severe acute respiratory syndrome in the United States: views from a national survey of infectious diseases consultants

title:
  Let Him Who Desires Peace Prepare for War: United States Hospitals and Severe Acute Respiratory Syndrome Preparedness


id: cord-007838-lvw31h1w
title: Career options in aerospace and aviation medicine()
author: Atzema, Clare
date: 2004-04-16
txt: ./txt/cord-007838-lvw31h1w.txt
cache: ./cache/cord-007838-lvw31h1w.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124312/
doi: 10.1016/j.annemergmed.2004.02.015
abstract: nan
summary:
  2, 3 In general, physicians trained in aerospace medicine practice health care in populations exposed to flight and space, consult on the physical and engineering aspects of the flight environment, and manage public safety issues at a variety of regulatory agencies. They might work for the National Aeronautics and Space Administration, the Federal Aviation Administration, a commercial or corporate airline, the Department of Transportation, an aerospace manufacturer, the Occupational Safety and Health Administration, the Centers for Disease Control and Prevention, or in private practice. 10, 11 In addition, teamwork is ubiquitous in aerospace medicine: one is likely to take part in several committees, and if one is a flight physician, one works in a confined environment with a medical team (ie, a respiratory therapist, a nurse, paramedics), often for many hours at a time. Some aerospace medicine physicians will maintain a part-time position in an emergency department or another ambulatory setting, 9 providing both variety and the opportunity to maintain clinical skills.


id: cord-007923-j3jpqd7k
title: Cats
author: O''Brien, Stephen J.
date: 2004-12-14
txt: ./txt/cord-007923-j3jpqd7k.txt
cache: ./cache/cord-007923-j3jpqd7k.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127084/
doi: 10.1016/j.cub.2004.11.017
abstract: nan
summary:
  Wild cats dominate their habitat but require vast expanses to survive, which explains the tragic depredation such that every species of Felidae, except the domestic cat, is considered either endangered or threatened in the wild today by CITES, IUCN Red Book and other monitors of the world''s most endangered species. Domestic cats and dogs enjoy more medical scrutiny than any species except humans. The cat offers the promise of a second carnivore species (in addition to the dog, which shares a common ancestor with cats dating back to approximately 60 million years ago) to improve human genome annotation, as well as to complement the biomedical and genomic discoveries that make the feline genome attractive. The conserved genome of the cat is retained in the other 36 Felidae species, as well as most of the 246 species of the Carnivora order, the only reshuffled exceptions occuring in the dog and bear families.


id: cord-008480-p41oae8e
title: Characterization of aminopeptidase N from Torpedo marmorata kidney
author: O''Callaghan, Barbara
date: 2004-11-12
txt: ./txt/cord-008480-p41oae8e.txt
cache: ./cache/cord-008480-p41oae8e.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131328/
doi: 10.1016/s0248-4900(94)80003-0
summary:
  Depending on solubilization conditions, both the antigen and peptidase activity were recovered either as a broad peak with a sedimentation coefficient of 18S (2% CHAPS) or as a single peak of 7.8S (1% CHAPS plus 0.2 % C(12)E(9)), showing that Torpedo aminopeptidase N behaves as an oligomer stabilized by hydrophobic interactions, easily converted into a 160 kDa monomer. The antigen is highly concentrated in the apical membrane of proximal tubule epithelial cells (600 gold particles/μm(2) of brush border membrane) whereas no labeling could be detected in other cell types or in other membranes of the same cells (basolatéral membranes, vacuoles or vesicles). Hybrids were selected in hypoxanthine, aminopterin and thymidine medium and superuatants from the culture wefts containing hybrid cells were tested for the presence of antibodies binding to the apical membrane of tubular epithelial cells on Torpedo kidney frozen sections.

abstract:
  A major antigen of the brush border membrane of Torpedo marmorata kidney was identified and purified by immunoprecipitation. The sequence of its 18 N terminal amino acids was determined and found to be very similar to that of mammalian aminopeptidase N (EC 3.4.11.2). Indeed aminopeptidase N activity was efficiently immunoprecipitated by monoclonal antibody 180K1. The purified antigen gives a broad band at 180 kDa after SDS-gel electrophoresis, which, after treatment by endoglycosidase F, is converted to a thinner band at 140 kDa. This antigen is therefore heavily glycosylated. Depending on solubilization conditions, both the antigen and peptidase activity were recovered either as a broad peak with a sedimentation coefficient of 18S (2% CHAPS) or as a single peak of 7.8S (1% CHAPS plus 0.2 % C(12)E(9)), showing that Torpedo aminopeptidase N behaves as an oligomer stabilized by hydrophobic interactions, easily converted into a 160 kDa monomer. The antigen is highly concentrated in the apical membrane of proximal tubule epithelial cells (600 gold particles/μm(2) of brush border membrane) whereas no labeling could be detected in other cell types or in other membranes of the same cells (basolatéral membranes, vacuoles or vesicles). Monoclonal antibodies prepared here will be useful tools for further functional and structural studies of Torpedo kidney aminopeptidase N.


id: cord-008523-avkgldnp
title: Selection of and evasion from cytotoxic T cell responses in the central nervous system
author: Perlman, Stanley
date: 2004-01-07
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131566/
doi: 10.1016/s0065-3527(01)56029-7
abstract:
  Cytotoxic CD8 T lymphocytes (CTLs) are critical for the clearance of noncytopathic viruses from infected cells. This chapter discusses one mechanism used by viruses to persist—namely, the selection of a variant virus in which changes in the sequence of a CTL epitope abrogate recognition. The unique features of cytotoxic CD8 T cell function in the central nervous system (CNS) are discussed. The role of CTL escape mutants in the viral evasion of the immune system and subsequent disease progression in non-CNS infections are summarized. The immune response in the CNS is similar to the response in extraneural tissue, but several aspects of the activation of the immune response, cellular trafficking, and antigen presentation are unique to the CNS. Although the CNS has classically been considered a site of immune privilege, surveillance of the normal CNS by circulating, activated lymphocytes occurs, with a limited number of lymphocytes being present in the normal CNS at any given time. In mice infected with mouse hepatitis virus and in some humans persistently infected with human immunodeficiency virus type1, hepatitis B virus or hepatitis C virus, CTL escape mutants play an important role in virus amplification and disease progression.


id: cord-009153-zxx4m1kz
author: Heymann, David L
date: 2004-05-15
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135754/
doi: 10.1016/s0140-6736(04)16234-x
abstract: nan
title:
  Dangerous pathogens in the laboratory: from smallpox to today's SARS setbacks and tomorrow's polio-free world


id: cord-009558-xw1nz6g5
title: Epidemiology of encephalitis in children: A 20‐Year survey
author: Koskiniemi, Marjaleena
date: 2004-10-08
txt: ./txt/cord-009558-xw1nz6g5.txt
cache: ./cache/cord-009558-xw1nz6g5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159592/
doi: 10.1002/ana.410290508
summary:
  In infants younger than 1 year of age, the major agents were enteroviruses, herpes simplex virus, and the group of "others," whereas in older children, respiratory viruses and Mycoplasma Pneumoniae as well as varicella‐zoster virus, dominated. In the 1to 1 1-month age group, the major role was played by enteroviruses and HSV, followed by the group of "others" (this group includes CMV, EBV, rotavirus and reovirus, multiple etiologies, and bacterial and vaccination-associated encephalitides) (see Fig 2) . The high level of unknown causes in the youngest children aged 1 to 11 months (see Table) may reflect underdiagnosis of respiratory virus infections (see Fig 3) . VZV causes a severe disease in children younger than 1 year old f131; our series included only one such patient, and the child made a good recovery.

abstract:
  Four hundred five children from the Helsinki area who were 1 month to 16 years old were treated for acute encephalitis at the Children's Hospital, University of Helsinki, from January 1968 through December 1987. Encephalitis occurred most commonly in children 1 to 1.9 years of age, among whom the incidence was 16.7 per 100,000 child‐years. The incidence remained quite high until the age of 10 years, and then gradually declined to 1.0 per 100,000 child‐years at the age of 15 years. Since 1983, when mumps, measles, and rubella vaccination eradicated the encephalitides associated with these microbes, the major associated agents have been varicella‐zoster, Mycoplasma pneumoniae, and respiratory and enteroviruses. In infants younger than 1 year of age, the major agents were enteroviruses, herpes simplex virus, and the group of “others,” whereas in older children, respiratory viruses and Mycoplasma Pneumoniae as well as varicella‐zoster virus, dominated. In children aged 1 to 11 months, the causal agent could not be identified in one‐half of all cases, whereas in children who were at least 10 years old, the etiology remained unknown in only one‐fourth of cases. Male dominance was most evident in the 4‐ to 9‐year age group. The difference in etiology between males and females was significant (p = 0.02); mumps and varicella were more common in boys, and adenovirus and Mycoplasma pneumoniae were more common in girls. The overall male‐to‐female ratio was 1.4:1. Characteristic seasonal variation occurred in encephalitides associated with mumps, measles, and entero‐ and respiratory viruses. In the whole series, some accumulation appeared in February and March. Less than one‐half of this number appeared in July and August.


id: cord-010188-884d196k
title: Alphaviruses — vectors for the expression of heterologous genes
author: Schlesinger, Sondra
date: 2004-08-26
txt: ./txt/cord-010188-884d196k.txt
cache: ./cache/cord-010188-884d196k.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172487/
doi: 10.1016/0167-7799(93)90070-p
summary:
  Sindbis virus and Semliki Forest vires are best known as valuable models for molecular and cell biology, and it is these two viruses that are presently being developed as vectors for the expression of heterologous genes. The basic strategy for using alphaviruses as vectors for the expression of heterologous genes has been to construct cDNAs of the alphavirus genome, in which the heterologous gene is placed downstream from the promoter used to transcribe a subgenomic RNA 13 (Fig. 2a) . A second potential problem is recombination between the packaging helper virus RNA and vector RNAs. The two Sindbis RNAs can undergo recombination to produce a single molecule of RNA containing the genes that encode both the nonstructural and structural proteins m. The initial studies with Sindbis and Semliki Forest virus suggest that both viruses are promising as vectors for heterologous gene expression.

abstract:
  DNA viruses and retroviruses are well established as vectors for the expression of heterologous genes, but there is increasing interest in the possibilities of using RNA viruses, which do not replicate through a DNA intermediate, for this purpose. This article summarizes some of the general properties of RNA viruses and concentrates on one class of RNA viruses — the alphaviruses — and their potential as expression vectors.


id: cord-010203-dt9m596i
title: Viral proteases as targets for chemotherapeutic intervention
author: Hellen, Christopher U.T.
date: 2004-08-26
txt: ./txt/cord-010203-dt9m596i.txt
cache: ./cache/cord-010203-dt9m596i.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172713/
doi: 10.1016/0958-1669(92)90010-g
summary:
  Many human and animal viruses encode proteinases that play important roles at different stages in the infection cycle, including separation of functionally different domains from a precursor polyprotein (enabling cleavage products to be transported to different cellular compartments) and regulation of a variety of events in viral replication, such as uncoating, activation of replicative enzymes and morphogenesis [1] . Statine-based (I), reduced amide (II) and phosphinate (III) transition state analogues exhibited modest potency, but placement of Phe-Gly hydroxyethylene dipeptide isosteres (IV) into the consensus template yielded compounds that inhibited HIV PR at nanomolar concentrations in vitro and prevented polyprotein processing, virion maturation and viral spread at 25-100btM in cell culture. Truncation and extensive structure-activity analysis at the P1, PI" and P2'' positions led to the identification of highly potent (subnanomolar) PR inhibitors based on dihydroxyethylene (V) [12-] and hydroxyethylene (IV) [13"] isostere transition state analogues.

abstract:
  Many viruses encode proteinases that are essential for infectivity, and are consequently attractive chemotherapeutic targets. The biochemistry and structure of the human immunodeficiency virus proteinase have been characterized extensively, and potent peptide-mimetic inhibitors have been developed. Techniques and strategies used to improve the efficiency of these compounds are likely to be applicable to other viral proteinases.


id: cord-014435-45zzj4ts
title: Ethics and Epidemics
author: Baker, Robert
date: 2004-09-17
txt: ./txt/cord-014435-45zzj4ts.txt
cache: ./cache/cord-014435-45zzj4ts.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320297/
doi: 10.3201/eid1009.040407
abstract: nan
summary:
  The U.S. Centers for Disease Control and Prevention has quarantine responsibilities at national ports of entry or departure; this agency may also become involved when a disease is spreading across state borders or even within a state (when invited by the governor of the state or ordered by the U.S. Secretary of Health and Human Services or the U.S. President). European public health officials have forged some bilateral cooperative agreements and are discussing establishing a regional disease control center for EU nations. He further stated that policies on epidemic control that involve consistent, open, and truthful communication with the public-like those used in New York and Toronto during the recent SARS outbreak-create cooperative environments that minimize conflicts between freedom and safety and limit the effects of isolation and quarantine. The result of the debate was that 21st century methods need to be developed to control infectious disease epidemics that reconcile the need to protect public health and respect human rights.


id: cord-020769-elzkwyz0
title: The new normal: lessons learned from SARS for corporations operating in emerging markets
author: Day, Brennan
date: 2004-07-01
txt: ./txt/cord-020769-elzkwyz0.txt
cache: ./cache/cord-020769-elzkwyz0.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147509/
doi: 10.1108/00251740410542357
summary:
  This paper uses the recent SARS epidemic as a background to highlight the importance of crisis planning, particularly in emerging economies, and suggests how organizations can address these concerns. This paper will start by presenting background information on the SARS epidemic and the impact on organizations, especially those operating in emerging markets. Since emerging markets are increasingly important to the world economy and are at the same time susceptible to outbreaks of infectious diseases, we need to understand how we are linked together on an interdependent global level. If just three of the Asian emerging economies -China, India, and Indonesia -are able to maintain this growth rate of 6 percent per year, the Organisation for Economic Co-operation and Development (OECD) has estimated that by 2010 approximately 700 million people in those countries will have an average income equivalent to that of Spain today.

abstract:
  The modern industrialized world was completely caught off guard by the recent SARS outbreak. Fortunately, for most organizations, the impact has been short lived, but management has been provided with a reminder of the impact of the external environment in a world of ever increasing globalization. As seen with the SARS outbreak, a lack of preparedness can have devastating effects on business and warrant inclusion in a business definition of a crisis. This paper uses the recent SARS epidemic as a background to highlight the importance of crisis planning, particularly in emerging economies, and suggests how organizations can address these concerns.


id: cord-021079-m6nbs2c0
title: Major histocompatibility complex molecules on glial cells
author: Yong, Voon Wee
date: 2004-11-23
txt: ./txt/cord-021079-m6nbs2c0.txt
cache: ./cache/cord-021079-m6nbs2c0.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148993/
doi: 10.1016/1044-5765(92)90006-n
summary:
  While glial cells of the central nervous system do not constitutively express class I or II major histocompatibility complex (MHC) molecules, astrocytes and microglial cells can be induced by a variety of factors to express these antigens. 17 The majority of rat CNS cells newly induced to express MHC class II following 3 days of continuous intravenous administration of gamma-interferon, which is a potent inducer of class II antigens on astrocytes in vitro (see below), were found to be microglia and not astrocytes . There does not appear to be changes in MHC expression due to age factors, from the limited number of studies currently available, 23 , 48, 49 Significance of MHC expression by glial cells Antigen presentation Neonatal murine astrocytes and microglia, especially after gamma-interferon treatment, can present antigen, e .g. myelin basic protein, to previously sensitized CD4+ T cell lines in an MHC class IIrestricted manner .

abstract:
  While glial cells of the central nervous system do not constitutively express class I or II major histocompatibility complex (MHC) molecules, astrocytes and microglial cells can be induced by a variety of factors to express these antigens. Oligodendrocytes have inducible class I but not class II elements. There are considerable differences in regulation of MHC antigen expression between glial cells from rodent and human brains, both in situ and in vitro. The consequence of glial cell MHC expression for immune interactions in the CNS is discussed in the context of glial cell antigen presentation capacity and neural cell susceptibility to cell-mediated immune effector mechanisms.


id: cord-021087-n4epxwn9
title: ECR – Final Programme: Scientific and Educational Exhibits
author: nan
date: 2004
txt: ./txt/cord-021087-n4epxwn9.txt
cache: ./cache/cord-021087-n4epxwn9.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149010/
doi: 10.1007/s10406-005-0142-5
abstract: nan
summary:
  Conclusions: MRI is useful to identify tumor response to Imatinib Mesylate in advanced GIST as from the early months of therapy with the following indicators of treatment activity: A) Size of lesions; B) signal intensity; C) vascularization; D) amount of degenerative tissue or necrosis; E) presence of peritoneal fluid. Materials and Methods: 34 patients (13 female, 21 male) from two centres with proven myocardial infarction by ECG, clinical and echo criteria underwent stress/ rest Tc99 sestamibi Gated SPECT scanning with a dual headed gamma camera and late contract enhanced MRI on identical 1.5 Tesla scanners in each centre using a protocol which imaged 15 minutes after injection of 0.1 mmol/kg IV gadolinium. These preliminary results illustrate the ability of MRI to assess the integrity of the TFCC and suggests its use as the first imaging method following plain radiography in the evaluation of patients with chronic posttraumatic pain on the ulnar side of the wrist.


id: cord-021116-rh0e4n2w
title: Viral Contagion and Anti-Terrorism: Notes on Medical Emergency, Legality and Diplomacy
author: Lippens, Ronnie
date: 2004
txt: ./txt/cord-021116-rh0e4n2w.txt
cache: ./cache/cord-021116-rh0e4n2w.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149041/
doi: 10.1023/b:sela.0000033617.97749.13
summary:
  This paper traces the main outlines of this emerging imaginary that has left notions of Empire as spheres of integrative production firmly behind, and is now geared towards imagining Empire as a complete, organic body of free-but-organic-and-therefore-orderly flows that however needs to be kept intact by means of epidemiological interventions aimed at excluding or neutralizing viral entities. Law and diplomacy were important technologies (however repressive at times) by which nation-states as well as Empires were held together, or indeed, by which they were produced or maintained, and by which they were made to be productive. There is no need for the productive negotiations of a ''cosmopolitan globalism'' either (to use Mikkel Rasmussen''s words 30 ), nor for reconciliatory efforts (one does not reconcile with viruses): the sanitary exclusion of viral contagion will suffice to keep the body of today''s imperial new world order healthy.

abstract:
  The dominant imagery in current international relations seems to betray the emergence of an imperialist imaginary that differs markedly from an earlier one. This paper traces the main outlines of this emerging imaginary that has left notions of Empire as spheres of integrative production firmly behind, and is now geared towards imagining Empire as a complete, organic body of free-but-organic-and-therefore-orderly flows that however needs to be kept intact by means of epidemiological interventions aimed at excluding or neutralizing viral entities. Dealing with terrorism, or invading states that allegedly breed them, in this imaginary, is first and foremost a matter of medical necessity and urgency. The legal and diplomatic 'logic' of UN resolutions (Resolution 1441 for example), in this imaginary space, can only be imagined as being of secondary importance. Cooperation and `cosmopolitan' negotiation, as alternatives, disappear in this imaginary that projects an imperialist globalism of epidemiological purity.


id: cord-021554-uxxrpfl0
title: Diarrhea, Infectious
author: Resta-Lenert, Silvia
date: 2004-06-17
txt: ./txt/cord-021554-uxxrpfl0.txt
cache: ./cache/cord-021554-uxxrpfl0.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150217/
doi: 10.1016/b0-12-386860-2/00180-5
abstract: nan
summary:
  Diarrheal diseases are a major cause of morbidity and mortality around the world, especially in developing countries where children suffer the greatest brunt of infectious diarrhea, malnutrition, and death. In developing countries, inadequate water supply, inef®cient or nonexistent sewage removal systems, chronic malnutrition, and lack of access to oral rehydration are responsible for the high incidence of infectious diarrheal diseases. In the industrialized world, acute diarrhea is still one of the most frequent diagnoses in general practice and children, elderly, and immunocompromised patients are the most vulnerable individuals and account for the majority of these cases. Approximately 100 million episodes of acute diarrhea occur in the United States yearly, with an incidence of 1.2 to 1.5 diarrheal episodes per person-year. These patients are more likely to develop persistent or chronic diarrhea after an acute episode because of their impaired immunity, with a signi®cant increase in morbidity and mortality.


id: cord-022499-7d58f1k3
title: Transmembrane α helices
author: Mall, Sanjay
date: 2004-01-07
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157917/
doi: 10.1016/s1063-5823(02)52014-7
abstract:
  This chapter discusses effects of intrinsic membrane proteins on lipid bilayers and model transmembrane α helices. Incorporation of a protein into a lipid bilayer has significant effects on the properties of the bilayer. The rough surface presented by a protein to the surrounding lipid bilayer tends to produce poor packing unless the lipid fatty acyl chains distort to match the surface of the protein. In a liquid crystalline bilayer the lipid fatty acyl chains are disordered, because the chains undergo extensive wobbling fluctuations. The presence of a rigid protein surface reduces the extent of these motional fluctuations. However, the chains tilt and become conformationally disordered to maximize contact with the rough surface of the protein. The net result is that the presence of a protein leads to decreased order for the chains, with a wide range of chain orientations relative to the bilayer normal, but with reduced extent and rate of motion. Because of the reduced motion, lipids adjacent to membrane proteins are often referred to as being motionally restricted. It is clear that the reasons for the disorder of the bulk lipids and the disorder of the lipids adjacent to the protein are different; for the bulk phospholipids, the disorder is dynamic, whereas, for the boundary lipids the disorder is static.


id: cord-023610-zj13gy7z
title: Seasonal variation in the culture rate of M. tuberculosis in children
author: Schaaf, H.S.
date: 2004-04-02
txt: ./txt/cord-023610-zj13gy7z.txt
cache: ./cache/cord-023610-zj13gy7z.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172750/
doi: 10.1016/0962-8479(94)90829-x
abstract: nan
summary:
  This provides us the opportunity to use it in EIA test system for specific antibodies detection in lung tuberculosis patient''s sera. No more than 10 % false-positive results were obtained while testing 1:200 diluted sera from non-tuberculosis lung patients. The method described is used to confirm the diagnosis of tuberculosis in clinical practice as well as for high risk groups detection in mass surveys at epidemic centres. The results of this study revealed that on admission, mean ADA level 37.07 k 2.49 U/L was significantly higher than the control group 15.88 & 0.97 U/L. The value of ADA on admission was significantly higher than at one and two months after treatment. Serum IgG to A60 presented significantly higher values after 2 months of treatment than its level on admission. When a cutoff value of 200 units was chosen, 36.6 % of patients were found to be positive for A60 IgG on admission, while the figure increased to 68.2 % after 2 months of treatment.


id: cord-103536-etin5i7y
author: Timmins, Joanna
date: 2004-04-15
txt: ./txt/cord-103536-etin5i7y.txt
cache: ./cache/cord-103536-etin5i7y.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0378109704001739
doi: 10.1016/j.femsle.2004.03.002
summary:
  Although in some cases matrix protein expression in eukaryotic cells is sufficient to induce virus-like particles (VLPs) [3] [4] [5] , the structural requirements for such ordered membrane-associated polymerisation reactions are not well understood and often depend on other viral components such as the glycoprotein [2] . Like the matrix protein from negative strand RNA viruses MA is associated with the viral membrane and thus performs essentially the same structural function [6] . The first evidence for the involvement of specific Gag domains in viral budding came from the work of G€ ottlinger and colleagues who reported that a deletion of the C-terminal region of HIV Gag (p6 protein) caused a significant defect in virus particle release [8] . A minimal structural conservation is the presence of late domain sequences that mediate interaction with the class E Vps machinery for budding, although this still has to be shown in case of influenza virus M1.

title:
  Structural studies on the Ebola virus matrix protein VP40 indicate that matrix proteins of enveloped RNA viruses are analogues but not homologues

abstract:
  Abstract Matrix proteins are the driving force of assembly of enveloped viruses. Their main function is to interact with and polymerize at cellular membranes and link other viral components to the matrix–membrane complex resulting in individual particle shapes and ensuring the integrity of the viral particle. Although matrix proteins of different virus families show functional analogy, they share no sequence or structural homology. Their diversity is also evident in that they use a variety of late domain motifs to commit the cellular vacuolar protein sorting machinery to virus budding. Here, we discuss the structural and functional aspects of the filovirus matrix protein VP40 and compare them to other known matrix protein structures from vesicular stomatitis virus, influenza virus and retroviral matrix proteins.


id: cord-252103-lsaa1nx0
title: Coronavirus outbreak in cheetahs: Lessons for SARS
author: Pearks Wilkerson, Alison J
date: 2004-03-23
txt: ./txt/cord-252103-lsaa1nx0.txt
cache: ./cache/cord-252103-lsaa1nx0.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0960982204001435
doi: 10.1016/j.cub.2004.02.051
abstract: nan
summary:
  To characterize the genomic disposition of the cheetahs'' Aju-CoV strain, PCR primers based on alignment of seven coronavirus gene segments (pol1a, pol1b, S, M, N, 7a/7b, and 3′ ′UTR), were used to amplify cDNA from archived cheetah liver and kidney tissues collected during the Winston outbreak. The phylogenetic analyses indicate a close similarity of the Aju-CoV and the FCoV strains, suggesting the cheetah virus is closely related to, if not indistinguishable from, domestic cat isolates. Fourth, while mortality among humans with SARS symptoms and house cats with FCoV is low, around 5-10%, cheetahs with Aju-CoV exhibited the opposite extreme, showing 90% morbidity and over 60% mortality. If this hypothesis is correct, the greater genetic diversity of domestic cats and humans may reduce the severity of the epidemic, and also contribute to the occurrence of rare genetically determined SARS-CoV super-spreaders who can infect with high virulence.


id: cord-254107-02bik024
title: Utility of homology models in the drug discovery process
author: Hillisch, Alexander
date: 2004-08-31
txt: ./txt/cord-254107-02bik024.txt
cache: ./cache/cord-254107-02bik024.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1359644604031964
doi: 10.1016/s1359-6446(04)03196-4
summary:
  The quality of these homology models, and thus their applicability to, for example, drug discovery, predominantly depends on the sequence similarity between the protein of known structure (template) and the protein to be modeled (target). In conjunction with homology models, Cengent Therapeutics (http://www.cengent.com) offers dynamic structural information generated from molecular dynamics simulations for 5500 human drug target proteins. If sequence identity is greater than ~50%, the resulting models are frequently of sufficient quality to be used in the prediction of detailed protein-ligand interactions, such as structure-based drug design and prediction of the preferred sites of metabolism of small molecules ( Figure 2 ). It has recently been shown that it is possible to design small molecules based on homology models and then to use these compounds as tools to study the physiological role of the respective target protein of that particular drug [31] .

abstract:
  Abstract Advances in bioinformatics and protein modeling algorithms, in addition to the enormous increase in experimental protein structure information, have aided in the generation of databases that comprise homology models of a significant portion of known genomic protein sequences. Currently, 3D structure information can be generated for up to 56% of all known proteins. However, there is considerable controversy concerning the real value of homology models for drug design. This review provides an overview of the latest developments in this area and includes selected examples of successful applications of the homology modeling technique to pharmaceutically relevant questions. In addition, the strengths and limitations of the application of homology models during all phases of the drug discovery process are discussed.


id: cord-255201-shrmdkco
title: Las enseñanzas del síndrome respiratorio agudo grave
author: Vaqué, Josep
date: 2004-12-31
txt: ./txt/cord-255201-shrmdkco.txt
cache: ./cache/cord-255201-shrmdkco.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0213911104718270
doi: 10.1016/s0213-9111(04)71827-0
abstract: nan
summary:
  E ntre noviembre de 2002 y julio de 2003, merced a los medios de comunicación, la red de Internet y las publicaciones médicas, hemos podido seguir de cerca la eclosión, la amplia diseminación y el posterior declive de una enfermedad transmisible emergente, el síndrome respiratorio agudo grave (SRAG), causada por un coronavirus desconocido hasta hace poco (SARS-CoV) que, a través una propagación de persona a persona y un fuerte tropismo pulmonar, mostró una notable capacidad patogénica y letalidad. En este sentido, en el informe sobre la nueva epidemia elaborado por el gobierno de Canadá, se expone: «El SRAG ha sido contenido, al menos temporalmente, no mediante la revolución genómica ni con avanzados productos farmacéuticos, sino con el uso de anticuadas medidas de salud pública, como el lavado de manos, los procedimientos de control de las infecciones, el aislamiento de los casos y el seguimiento y la cuarentena de los contactos» 2 .


id: cord-256109-dkp0fwe3
title: Severe Acute Respiratory Syndrome–associated Coronavirus in Lung Tissue
author: Mazzulli, Tony
date: 2004-01-17
txt: ./txt/cord-256109-dkp0fwe3.txt
cache: ./cache/cord-256109-dkp0fwe3.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15078592/
doi: 10.3201/eid1001.030404
summary:
  Efforts to contain severe acute respiratory syndrome (SARS) have been limited by the lack of a standardized, sensitive, and specific test for SARS-associated coronavirus (CoV). Efforts to contain severe acute respiratory syndrome (SARS) have been limited by the lack of a standardized, sensitive, and specific test for SARS-associated coronavirus (CoV). All patients who met the current World Health Organization case definition of probable SARS and who underwent a postmortem examination in Canada during the March-April 2003 outbreak were included in this study. The clinical description and RT-PCR results for the 11 patients with probable SARS from whom postmortem lung tissue samples were examined are summarized in Table 1 . By using a standardized RT-PCR assay, SARS-CoV has been unequivocally identified in the lung tissue of all patients who died with probable SARS but not in any of the controls.

abstract:
  Efforts to contain severe acute respiratory syndrome (SARS) have been limited by the lack of a standardized, sensitive, and specific test for SARS-associated coronavirus (CoV). We used a standardized reverse transcription-polymerase chain reaction assay to detect SARS-CoV in lung samples obtained from well-characterized patients who died of SARS and from those who died of other reasons. SARS-CoV was detected in all 22 postmortem lung tissues (to 10(9) viral copies/g) from 11 patients with probable SARS but was not detected in any of the 23 lung control samples (sample analysis was blinded). The sensitivity and specificity (95% confidence interval) were 100% (84.6% to 100%) and 100% (85.1% to 100%), respectively. Viral loads were significantly associated with a shorter course of illness but not with the use of ribavirin or steroids. CoV was consistently identified in the lungs of all patients who died of SARS but not in control patients, supporting a primary role for CoV in deaths.


id: cord-256808-lxlerb13
author: Lim, W.S
date: 2004-06-02
txt: ./txt/cord-256808-lxlerb13.txt
cache: ./cache/cord-256808-lxlerb13.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0163445304000830
doi: 10.1016/j.jinf.2004.04.001
summary:
  Severe Acute Respiratory Syndrome (SARS) is a potentially severe and highly infectious disease to which healthcare workers involved in the management of cases are particularly vulnerable. These guidelines briefly summarise optimal and safe practice for clinicians involved in the emergency care of patients with probable or confirmed SARS. During 2003 Severe Acute Respiratory Syndrome caused by a novel coronavirus (SARS-CoV) emerged as an infectious disease with a significant inhospital mortality and posed a considerable occupational risk for healthcare workers. Please discuss the classification of SARS patients with the Health Protection Agency''s Communicable Disease Surveillance Centre (CDSC) Duty doctor (Tel.: 0208-200-6868) and complete a standard SARS report form and fax to your local Consultant in Communicable Disease Control (CCDC) and CDSC (details at: http://www.hpa.org.uk/infections/ topics_az/SARS/forms.htm). Inform the local Health Protection Team/CCDC regarding the hospital discharge of patients to ensure follow-up in the community. Severe acute respiratory syndrome (SARS): infection control

title:
  Hospital management of adults with severe acute respiratory syndrome (SARS) if SARS re-emerges—updated 10 February 2004

abstract:
  Severe Acute Respiratory Syndrome (SARS) is a potentially severe and highly infectious disease to which healthcare workers involved in the management of cases are particularly vulnerable. These guidelines briefly summarise optimal and safe practice for clinicians involved in the emergency care of patients with probable or confirmed SARS.


id: cord-258778-er0ug8w4
title: Necrotizing Enterocolitis in Full-Term Infants: Case–Control Study and Review of the Literature
author: Maayan-Metzger, Ayala
date: 2004-07-01
url: https://www.ncbi.nlm.nih.gov/pubmed/15229620/
doi: 10.1038/sj.jp.7211135
abstract:
  OBJECTIVE: To examine the increasing number of full-term infants at our hospital exhibiting necrotizing enterocolitis (NEC) in order to characterize these cases and to discover common risk factors. METHODS: Medical charts were reviewed for all full-term infants (gestational age > 36 weeks) that were born in our institution during a 5-year period (from January 1, 1998 to December 31, 2002) and that developed definite NEC. Data regarding the rate of Cesarean section (CS) in our institution over the study period and five years prior to the study was also recorded. RESULTS: During the 5 years of the study, 14 full-term infants were found to have NEC. The incidence of NEC in full-term infants increased from 0.16 to 0.71 per 1000 live births in the 5-year period. Mean birth weight was 2829 g. All the NEC infants except one were delivered by CS, and all of them were fed either with a mixture of breast milk and formula or entirely by formula. Seven of the infants (50%) had no major known risk factors predisposing them for NEC. Mean age of disease onset was very early (4.1 days) in most of the infants (12 infants), and the colon was the main NEC site. The short-term outcome was favorable in all but one case, which required explorative laparotomy for intestinal perforation. The number of infants born by CS has been steadily increasing, and was almost three times greater during the study period in comparison to the preceding years. CONCLUSIONS: The etiology of NEC in the full-term population seems to differ from the etiology for the preterm group in its intestinal location and in the timing of its onset. The increase in the rate of CS over the years might be related to the concurrent increase in NEC, and this relationship should be further investigated.


id: cord-259627-8stewshp
title: Inactivation of dengue virus by methylene blue/narrow bandwidth light system
author: Huang, Qing
date: 2004-12-02
txt: ./txt/cord-259627-8stewshp.txt
cache: ./cache/cord-259627-8stewshp.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S1011134404001186
doi: 10.1016/j.jphotobiol.2004.08.005
summary:
  Because photodynamic virus inactivation with methylene blue (MB)/light system has proven effective in blood banking, MB was selected as a photosensitizing agent, dengue virus as a model virus for enveloped RNA viruses, and an in-house fabricated narrow bandwidth light system overlapping the absorption spectrum of MB as the light source. Results showed that the concentration of MB working solution, illumination intensity of light source, illumination distance and time were four key factors affecting efficiency of virus inactivation using the MB/narrow bandwidth light system. The results indicate that MB concentration, illumination time and distance are three key factors affecting efficiency of virus inactivation when the illumination intensity of the light source was held constant. MB working concentration and illumination intensity, time and distance are the four key factors affecting the inactivation efficiency of the MB/narrow bandwidth light system.

abstract:
  Abstract Peracetic acid was one of the most commonly used disinfectants on solid surfaces in hospitals or public places. However, peracetic acid is an environmental toxin. Therefore, safer, alternative disinfectants or disinfectant systems should be developed. Because photodynamic virus inactivation with methylene blue (MB)/light system has proven effective in blood banking, MB was selected as a photosensitizing agent, dengue virus as a model virus for enveloped RNA viruses, and an in-house fabricated narrow bandwidth light system overlapping the absorption spectrum of MB as the light source. Dengue virus was mixed with different concentrations of MB, and illuminated by the narrow bandwidth light system under different illumination distances and times. The amount of dengue virus remaining was evaluated by plaque forming assays. Results showed that the concentration of MB working solution, illumination intensity of light source, illumination distance and time were four key factors affecting efficiency of virus inactivation using the MB/narrow bandwidth light system. Dengue virus could be completely inactivated at 2.5 m in 5 min when MB⩾1.0 μg/ml. However, when the distance reached 3.0 m, only greater concentrations of MB (2.0 μg/ml) could completely inactivate virus in a reasonably short time (20 min), and smaller concentrations of MB (1.0 μg/ml) could only completely inactivate virus using longer times (25 min). The results of this virus inactivation model indicate that our MB/narrow bandwidth light system provides a powerful, easy way to inactivate dengue viruses.


id: cord-260238-2p209g2p
title: Severe acute respiratory syndrome
author: Peiris, J S M
date: 2004-11-30
url: https://www.ncbi.nlm.nih.gov/pubmed/15577937/
doi: 10.1038/nm1143
abstract:
  Severe acute respiratory syndrome (SARS) was caused by a previously unrecognized animal coronavirus that exploited opportunities provided by 'wet markets' in southern China to adapt to become a virus readily transmissible between humans. Hospitals and international travel proved to be 'amplifiers' that permitted a local outbreak to achieve global dimensions. In this review we will discuss the substantial scientific progress that has been made towards understanding the virus—SARS coronavirus (SARS-CoV)—and the disease. We will also highlight the progress that has been made towards developing vaccines and therapies The concerted and coordinated response that contained SARS is a triumph for global public health and provides a new paradigm for the detection and control of future emerging infectious disease threats.


id: cord-260376-29ih5c9v
title: SARS corona virus peptides recognized by antibodies in the sera of convalescent cases
author: Guo, Jian-Ping
date: 2004-07-01
txt: ./txt/cord-260376-29ih5c9v.txt
cache: ./cache/cord-260376-29ih5c9v.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15207612/
doi: 10.1016/j.virol.2004.04.017
summary:
  title: SARS corona virus peptides recognized by antibodies in the sera of convalescent cases We synthesized on cellulose membranes 4942 ten-amino-acid peptides which included all of the sequences predicted for the severe acute respiratory syndrome (SARS) corona virus. Peptides incorporating all of the sequences predicted in the open reading frames of the SARS-CoV genome were prepared on derivatized cellulose membranes using a robotic peptide synthesizer (Autospot ASP 222, Intavis Bioanalytical Instruments, Lagenfeld, Germany). These data indicate that the four recovered cases developed antibodies with viral neutralizing potency between the time of acute and convalescent serum sampling. Therefore, those peptides strongly recognized on membranes probed with convalescent sera, but not with acute or control sera, should be the most immunodominant and may include SARS-CoV epitopes that are vulnerable to neutralization by antibody. Shown in Table 2 are the 24 overlapping membrane peptides that were recognized exclusively, or much more strongly, in multiple pairs of convalescent compared with the respective acute sera.

abstract:
  We synthesized on cellulose membranes 4942 ten-amino-acid peptides which included all of the sequences predicted for the severe acute respiratory syndrome (SARS) corona virus. We probed these membranes with four pairs of acute and convalescent sera from recovered SARS cases. We correlated positively reacting peptides with the in vitro SARS-CoV neutralizing activity of the samples. We found that convalescent sera with high neutralizing activity recognized exclusively only a limited number of peptides on the membranes. This suggests that antibodies against the epitopes represented by these peptides could be responsible for much of the SARS-CoV neutralizing activity. The findings have implications for monitoring humoral responses to SARS-CoV as well as for developing a successful SARS vaccine.


id: cord-260407-jf1dnllj
author: Tang, Catherine So-kum
date: 2004-06-11
txt: ./txt/cord-260407-jf1dnllj.txt
cache: ./cache/cord-260407-jf1dnllj.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15539054/
doi: 10.1016/j.ypmed.2004.04.032
summary:
  This study aimed to determine factors associating with individuals'' practice of the target SARS preventive behavior (facemask wearing). Three of the five components of the Health Belief Model, namely, perceived susceptibility, cues to action, and perceived benefits, were significant predictors of facemask-wearing even after considering effects of demographic characteristics. Overall, perceived benefits, perceived barriers, and perceived susceptibility are the three most powerful components of the Health Belief Model in influencing whether individuals practice different preventive behaviors [21, 29, 30] . A logistic regression with odds ratios was conducted to test the efficacy of the Health Belief Model in predicting the wearing of facemasks to prevent SARS. Similar to previous research [15 -26] , this study found the Health Belief Model useful in identifying major determinants of the wearing of facemasks to prevent contracting and spreading SARS. The remaining two components of the Health Belief Model, perceived severity and perceived barriers, were found to be nonsignificant determinants of the target SARS preventive behavior in this study.

title:
  Factors influencing the wearing of facemasks to prevent the severe acute respiratory syndrome among adult Chinese in Hong Kong

abstract:
  Background. The global outbreak of the severe acute respiratory syndrome (SARS) in 2003 has been an international public health threat. Quick diagnostic tests and specific treatments for SARS are not yet available; thus, prevention is of paramount importance to contain its global spread. This study aimed to determine factors associating with individuals' practice of the target SARS preventive behavior (facemask wearing). Methods. A total of 1329 adult Chinese residing in Hong Kong were surveyed. The survey instrument included demographic data, measures on the five components of the Health Belief Model, and the practice of the target SARS preventive behavior. Logistic regression analyses were conducted to determine rates and predictors of facemask wearing. Results. Overall, 61.2% of the respondents reported consistent use of facemasks to prevent SARS. Women, the 50–59 age group, and married respondents were more likely to wear facemasks. Three of the five components of the Health Belief Model, namely, perceived susceptibility, cues to action, and perceived benefits, were significant predictors of facemask-wearing even after considering effects of demographic characteristics. Conclusions. The Health Belief Model is useful in identifying determinants of facemask wearing. Findings have significant implications in enhancing the effectiveness of SARS prevention programs.


id: cord-260503-yq4dtf8n
title: Severe acute respiratory syndrome and dentistry A retrospective view
author: SAMARANAYAKE, LAKSHMAN P.
date: 2004-09-30
url: https://www.ncbi.nlm.nih.gov/pubmed/15493394/
doi: 10.14219/jada.archive.2004.0405
abstract:
  ABSTRACT Background Severe acute respiratory syndrome, or SARS, which has created panic in Asia and in some parts of North America, is the first epidemic of the new century. Although it has been well-contained, sporadic cases continue to emerge. Objectives The authors trace the emergence of the SARS outbreak from southern China and its spread worldwide, discuss the viral etiology of the infection and its clinical features, and review the infection control guidelines issued during the outbreak by the health authorities in Hong Kong, the Centers for Disease Control and Prevention, the World Health Organization and the American Dental Association. They also review the prospects for a new outbreak and preventive measures. Overview The disease, which is caused by a novel coronavirus termed the “SARS coronavirus,” or SARS-CoV, essentially spreads through droplet infection and affects people of any age. It has a mortality rate ranging from 10 to 15 percent. A major hallmark of this disease has been the rate at which it has affected health care workers through nosocomial transmission; in some countries, up to one-fourth to one-third of those infected were in this category. However, no dental health care worker has been affected by SARS in a nosocomial or dental setting. Conclusions and Clinical Implications Researchers believe that a combination of factors, including the universal infection control measures that the dental community has implemented and/or the low degree of viral shedding in the prodromal phase of SARS, may have obviated the spread of the disease in dental settings. The dental community should reflect on this outbreak to reinforce the currently applied infection control measures.


id: cord-261011-bcyotwkf
title: Global health and moral values
author: Alkire, Sabina
date: 2004-09-17
txt: ./txt/cord-261011-bcyotwkf.txt
cache: ./cache/cord-261011-bcyotwkf.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0140673604170633
doi: 10.1016/s0140-6736(04)17063-3
abstract: nan
summary:
  To stimulate discussion, we have selected four major schools of moral values commonly used to justify global health initiatives: humanitarianism, utilitarianism, equity, and rights. At present, whether the 3 by 5 initiative was evaluated according to aggregate utility (increasing the utility of people with HIV/AIDS) or distributional equity (increasing the numbers of people in developing countries who are given antiretroviral treatment), human rights (for health care), or the need www.thelancet.com Vol 364 September 18, 2004 1071 De Cock 21 argued that a public health rather than a human rights approach should frame responses to HIV/AIDS in Africa, but again this analysis is based on a very narrow example of both ethical schools. A common usage of moral values is advocacy, often to rich and powerful leaders, institutions, and nation states with the goal of mobilising resources-finance, political will, human motivations-on behalf of particular health action.


id: cord-261287-l4649du3
author: Puoti, Massimo
date: 2004-05-06
txt: ./txt/cord-261287-l4649du3.txt
cache: ./cache/cord-261287-l4649du3.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15288482/
doi: 10.1016/j.jhep.2004.04.016
summary:
  However, a cumulative sustained virological response (SVR) was observed in only 22% (95% Confidence interval (CI), 14 -30%) of 111 patients enrolled in four pilot uncontrolled studies aiming to assess the efficacy and tolerability of ribavirin plus interferon alfa1 administered thrice weekly in HIV/HCV co-infected patients [4 -7] . In order to establish that the SVR in the triple therapy arm is at least three times higher than the 18% sustained response rate observed in HIV-co-infected patients treated with interferon and ribavirin in pilot studies [4] [5] [6] [7] , it was calculated that at least 64 patients should have been enrolled. In conclusion, intensification of interferon alpha schedule and amantadine addition do not appear to improve the limited efficacy of standard combination therapy including interferon thrice weekly plus ribavirin for the treatment of chronic hepatitis C in HIV-co-infected patients.

title:
  A randomized, controlled trial of triple antiviral therapy as initial treatment of chronic hepatitis C in HIV-infected patients()

abstract:
  BACKGROUND/AIMS: Interferon and ribavirin combination therapy for chronic hepatitis C induces a low response rate in human immunodeficiency virus (HIV) infected patients. To assess the impact of intensification of interferon administration and of the addition of amantadine on the efficacy and safety of standard anti-hepatitis C virus (HCV) treatment in HIV-infected patients. METHODS: Multicentre, prospective, open-label, randomized, phase III clinical trial. Eighty co-infected patients were randomized to receive ribavirin 800–1000 mg/day in combination with, group A: interferon alpha2a 3 MIU thrice weekly; group B: IFNα2a 3 MIU daily, plus amantadine 200 mg/day; treatment duration was 24–48 weeks according to HCV genotype. RESULTS: Forty-one patients were randomized in group A and 39 in group B. Intention-to-treat analysis showed a sustained virological response, defined as HCV-RNA negativization, 6 months after stopping treatment in 22% of patients from group A and 13% from group B (P>0.05). The lack of a 2-log drop in HCV-RNA levels after 12 weeks of treatment showed a 100% predictive value of lack of sustained response. CONCLUSIONS: Amantadine addition and interferon intensification do not improve the low efficacy of combination of interferon alfa plus ribavirin in HIV/HCV co-infected patients. Patients with no early virologic response did not have any probability of sustained response.


id: cord-262776-6k7tcgfs
title: Assessment of the viral safety of antivenoms fractionated from equine plasma
author: Burnouf, Thierry
date: 2004-09-30
url: https://www.sciencedirect.com/science/article/pii/S1045105604000223
doi: 10.1016/j.biologicals.2004.07.001
abstract:
  Abstract Antivenoms are preparations of intact or fragmented (F(ab′)2 or Fab) immunoglobulin G (IgG) used in human medicine to treat the severe envenomings resulting from the bites and stings of various animals, such as snakes, spiders, scorpions, or marine animals, or from the contact with poisonous plants. They are obtained by fractionating plasma collected from immunized horses or, less frequently, sheep. Manufacturing processes usually include pepsin digestion at acid pH, papain digestion, ammonium sulphate precipitation, caprylic acid precipitation, heat coagulation and/or chromatography. Most production processes do not have deliberately introduced viral inactivation or removal treatments, but antivenoms have never been found to transmit viruses to humans. Nevertheless, the recent examples of zoonotic diseases highlight the need to perform a careful assessment of the viral safety of antivenoms. This paper reviews the characteristics of equine viruses of antivenoms and discusses the potential of some manufacturing steps to avoid risks of viral contamination. Analysis of production parameters indicate that acid pH treatments and caprylic acid precipitations, which have been validated for the manufacture of some human IgG products, appear to provide the best potential for viral inactivation of antivenoms. As many manufacturers of antivenoms located in developing countries lack the resources to conduct formal viral validation studies, it is hoped that this review will help in the scientific understanding of the viral safety factors of antivenoms, in the controlled implementation of the manufacturing steps with expected impact on viral safety, and in the overall reinforcement of good manufacturing practices of these essential therapeutic products.


id: cord-264713-38dlh3wg
title: Molecular diagnostics in virology
author: Vernet, Guy
date: 2004-08-20
txt: ./txt/cord-264713-38dlh3wg.txt
cache: ./cache/cord-264713-38dlh3wg.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S1386653204001696
doi: 10.1016/j.jcv.2004.06.003
summary:
  Viral load and antiviral resistance or subtyping assays are now part of the biological monitoring of patients chronically infected by human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and CMV. The most striking illustration of the power of molecular techniques concerns blood transmitted viruses-human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) for which spectacular progresses in the detection and treatment of viral diseases have been made following the introduction of qualitative and quantitative nucleic acid tests (NAT). For example, we have observed, using a DNA-microarray assay (see below), that the analytical sensitivity of multiplex RT-PCR detection of six viruses, i.e. influenza A, influenza B, RSV A/B, parainfluenza 1, 2 and 3 is reduced by a factor of <1-2 logs compared to single detections, depending on the virus.

abstract:
  Molecular biology has significantly improved diagnosis in the field of clinical virology. Virus discovery and rapid implementation of diagnostic tests for newly discovered viruses has strongly beneficiated from the development of molecular techniques. Viral load and antiviral resistance or subtyping assays are now part of the biological monitoring of patients chronically infected by human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and CMV. It will be important to add to this panel assays for other viruses of the herpesviridae family. Qualitative assays for the detection of blood-borne viruses have increased safety of blood donation and organ transplantation. Screening of other blood-borne viruses (parvovirus B19, HAV), multiplexing of detection and test automation to improve practicability and reduce costs will be the next steps. A major evolution in the near future will be the generalization of NAT for the diagnosis of viral etiology in patients, mostly with respiratory, CNS or gastro-intestinal diseases. Major technical improvements have been made to avoid obstacles that still limit this generalization, i.e. genetic variability of viruses, multiplex detection, contamination risk. Commercial offers already exist but menus must be extended to limit the validation and documentation work associated with home-brew assays. Real-time amplification has allowed the development of new NAT platforms but automation and integration of all steps of the reaction are still required to reduce hands-on-time, time-to-result and costs, and to increase throughput.


id: cord-264848-wl29jk16
author: Totoiu, Minodora O.
date: 2004-03-21
txt: ./txt/cord-264848-wl29jk16.txt
cache: ./cache/cord-264848-wl29jk16.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S001448860400041X
doi: 10.1016/j.expneurol.2004.01.028
summary:
  Transplantation of glial-committed progenitor cells into the T8 spinal cord of MHV-infected mice demonstrating complete hindlimb paralysis resulted in migration of cells up to 12 mm from the implantation site and remyelination of up to 67% of axons. Counts of the total number of axons (normally myelinated, demyelinated, and remyelinated) within the region extending 8 mm cranial and 6 mm caudal to the transplantation site (the extent of spinal cord examined) suggest that transplanted animals had significantly more axons ( P < 0.01) within the ventral and lateral columns as compared to non-transplanted animals (Figs. Multipotential PSA-NCAM + neural precursors isolated from the postnatal rat brain have been shown to differentiate into oligodendrocytes, Schwann cells, and astrocytes following transplantation, to completely remyelinate regions of acute demyelination in the adult rat induced by ethidium bromide injection into x-irradiated dorsal column white matter .

title:
  Remyelination, axonal sparing, and locomotor recovery following transplantation of glial-committed progenitor cells into the MHV model of multiple sclerosis

abstract:
  The behavior and myelinogenic properties of glial cells have been well documented following transplantation into regions of focal experimental demyelination in animal models. However, the ability of glial cell preparations to remyelinate in such models does not necessarily indicate that their transplantation into demyelinated lesions in clinical disease will be successful. One of the precluding factors in this regard is a greater understanding of the environmental conditions that will support transplant-mediated remyelination. In this study, we determined whether the complex and reactive CNS environment of the mouse hepatitis virus (MHV) model of multiple sclerosis (MS) could support transplant-mediated remyelination. Striatal neural precursors derived from postnatal day 1 mice were committed to a glial cell lineage and labeled. Immunohistochemical staining indicated that this population generated >93% glial cells following differentiation in vitro. Transplantation of glial-committed progenitor cells into the T8 spinal cord of MHV-infected mice demonstrating complete hindlimb paralysis resulted in migration of cells up to 12 mm from the implantation site and remyelination of up to 67% of axons. Transplanted-remyelinated animals contained approximately 2× the number of axons within sampled regions of the ventral and lateral columns as compared to non-transplanted animals, suggesting that remyelination is associated with axonal sparing. Furthermore, transplantation resulted in behavioral improvement. This study demonstrates for the first time that transplant-mediated remyelination is possible in the pathogenic environment of the MHV demyelination model and that it is associated with locomotor improvement.


id: cord-264968-ctx39vhi
title: Relative rates of non-pneumonic SARS coronavirus infection and SARS coronavirus pneumonia
author: Woo, Patrick CY
date: 2004-03-13
txt: ./txt/cord-264968-ctx39vhi.txt
cache: ./cache/cord-264968-ctx39vhi.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0140673604157292
doi: 10.1016/s0140-6736(04)15729-2
summary:
  An ELISA based on recombinant nucleocapsid protein for IgG detection was tested with serum from 149 healthy blood donors who donated 3 years previously and with serum positive for antibodies against SARS-CoV (by indirect immunofluorescence assay) from 106 patients with SARS-CoV pneumonia. An ELISA based on recombinant nucleocapsid protein for IgG detection was tested with serum from 149 healthy blood donors who donated 3 years previously and with serum positive for antibodies against SARS-CoV (by indirect immunofluorescence assay) from 106 patients with SARS-CoV pneumonia. Assessment of recombinant nucleocapsid protein ELISA Serum samples from 149 healthy blood donors who donated blood 3 years previously (aged 18 years or older) and 106 patients with pneumonia positive for antibodies against SARS-CoV detected by our indirect immunofluorescence assay 1 were used for the assessment of the ELISA-based IgG antibody test.

abstract:
  BACKGROUND: Although the genome of severe acute respiratory syndrome coronavirus (SARS-CoV) has been sequenced and a possible animal reservoir identified, seroprevalence studies and mass screening for detection of subclinical and non-pneumonic infections are still lacking. METHODS: We cloned and purified the nucleocapsid protein and spike polypeptide of SARS-CoV and examined their immunogenicity with serum from patients with SARS-CoV pneumonia. An ELISA based on recombinant nucleocapsid protein for IgG detection was tested with serum from 149 healthy blood donors who donated 3 years previously and with serum positive for antibodies against SARS-CoV (by indirect immunofluorescence assay) from 106 patients with SARS-CoV pneumonia. The seroprevalence of SARS-CoV was studied with the ELISA in healthy blood donors who donated during the SARS outbreak in Hong Kong, non-pneumonic hospital inpatients, and symptom-free health-care workers. All positive samples were confirmed by two separate western-blot assays (with recombinant nucleocapsid protein and recombinant spike polypeptide). FINDINGS: Western-blot analysis showed that the nucleocapsid protein and spike polypeptide of SARS-CoV are highly immunogenic. The specificity of the IgG antibody test (ELISA with positive samples confirmed by the two western-blot assays) was 100%, and the sensitivity was 94·3%. Three of 400 healthy blood donors who donated during the SARS outbreak and one of 131 non-pneumonic paediatric inpatients were positive for IgG antibodies, confirmed by the two western-blot assays (total, 0·48% of our study population). INTERPRETATION: Our findings support the existence of subclinical or non-pneumonic SARS-CoV infections. Such infections are more common than SARS-CoV pneumonia in our locality.


id: cord-266018-8bhnlsgy
author: Trifilo, Matthew J.
date: 2004-09-15
txt: ./txt/cord-266018-8bhnlsgy.txt
cache: ./cache/cord-266018-8bhnlsgy.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S004268220400409X
doi: 10.1016/j.virol.2004.06.027
summary:
  The major findings of this study are (i) MHV infection of the CNS results in the appearance of two distinct populations of CD11c + cells each expressing markers characteristic of lymphoid (CD11c + CD11b À CD8a + DEC205 + ) and myeloid dendritic cells (CD11c + CD11b + CD8a À DEC205 À ), (ii) the accumulation of CD8a À DCs within the draining CLN is reduced in the absence of CCL3 signaling, (iii) expression of co-stimulatory molecules such as CD40 by CD8a À DCs within either the brain and CLN of MHV-infected CCL3 À/À mice is diminished suggesting that CCL3 signaling enhances expression of these molecules, and (iv) absence of CCL3 signaling results in the re-direction of the T cell response to viral antigens as determined by cytokine production. Our studies clearly indicate that CD8a À DCs isolated from the draining CLN of MHV-infected CCL3 +/+ mice secrete IL-12 suggesting that these cells help influence a protective Th1-mediated immune response characterized by the majority of antigen-specific T cells expressing IFN-g rather than IL-10 (Table 1 ).

title:
  The CC chemokine ligand 3 regulates CD11c(+)CD11b(+)CD8α(−) dendritic cell maturation and activation following viral infection of the central nervous system: implications for a role in T cell activation

abstract:
  The role of CC chemokine ligand 3 (CCL3) in activation of dendritic cells (DCs) following mouse hepatitis virus (MHV) infection of the central nervous system (CNS) was examined. The results indicate that CCL3 participates in an effective host response to MHV infection by contributing to CD11c(+)CD11b(+)CD8α(−) DC maturation, activation, and migration to cervical lymph nodes (CLN). Diminished CD8α(−) DC activation correlated with reduced IFN-γ expression by virus-specific T cells accompanied by increased IL-10 production suggesting that CCL3 contributes to an effective host response to viral infection by enhancing the T cell activation potential of DC.


id: cord-267564-ulavigi7
author: Remington, K. M.
date: 2004-07-16
txt: ./txt/cord-267564-ulavigi7.txt
cache: ./cache/cord-267564-ulavigi7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15260817/
doi: 10.1111/j.1423-0410.2004.00530.x
summary:
  Conclusions This study demonstrates that procedures used to inactivate enveloped viruses in manufacturing processes can achieve inactivation of West Nile virus and vaccinia virus. However, recent outbreaks of emergent viruses, such as West Nile virus ( WNV ), severe acute respiratory syndrome (SARS)-associated coronavirus and monkeypox, have indicated that potential threats to the blood supply exist and have resulted in a re-evaluation of the current pathogen safety strategy for plasma products. For VV-, WNV-or BVDV-inactivation studies, concentrated TNBP/ cholate from a stock solution was added to an aliquot of process intermediate to 0·3%/0·2% or to 0·15%/0·1% and then spiked to 10% (v/v) with virus. Table 3 Virus inactivation by tri-(n-butyl)-phosphate (TNBP)/Tween 80 in solutions of anti-haemophilic factor (AHF) or TNBP/cholate in intravenous immunoglobulin produced using the solvent/detergent process (IVIG-S/D) Incubation of WNV in an IVIG-S/D process intermediate solution, containing either 0·3% TNBP/0·2% cholate (manufacturing conditions) or 0·15% TNBP/0·1% cholate, resulted in complete inactivation of the virus within 30 min (Fig. 1c) .

title:
  Inactivation of West Nile virus, vaccinia virus and viral surrogates for relevant and emergent viral pathogens in plasma‐derived products

abstract:
  Background and Objectives Human plasma is the source of a wide variety of therapeutic proteins, yet it is also a potential source of viral contamination. Recent outbreaks of emergent viral pathogens, such as West Nile virus, and the use of live vaccinia virus as a vaccine have prompted a reassessment of the viral safety of plasma‐derived products. The purpose of this study was to evaluate the efficacy of current viral inactivation methods for West Nile and vaccinia viruses and to reassess the use of model viruses to predict inactivation of similar viral pathogens. Materials and Methods Virus‐spiked product intermediates were processed using a downscaled representation of various manufacturing procedures. Virus infectivity was measured before and after processing to determine virus inactivation. Results The results demonstrated effective inactivation of West Nile virus, vaccinia virus and a model virus, bovine viral diarrhoea virus, during pasteurization, solvent/detergent treatment and caprylate treatment. Caprylate provided rapid and effective inactivation of West Nile virus, vaccinia virus, duck hepatitis B virus and Sindbis virus. Inactivation of West Nile virus was similar to that of bovine viral diarrhoea virus. Conclusions This study demonstrates that procedures used to inactivate enveloped viruses in manufacturing processes can achieve inactivation of West Nile virus and vaccinia virus. In addition, the data support the use of model viruses to predict the inactivation of similar emergent viral pathogens.


id: cord-268238-ipfs7hcb
author: Mathieu, Patricia A.
date: 2004-07-17
txt: ./txt/cord-268238-ipfs7hcb.txt
cache: ./cache/cord-268238-ipfs7hcb.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0896841104000575
doi: 10.1016/j.jaut.2004.05.006
summary:
  The features of autoantibodies (autoAb) to liver fumarylacetoacetate hydrolase (FAH) elicited in mice infected with mouse hepatitis virus (MHV) were studied by ELISA and western-blot competition assays. ELISA and western-blot competition assays, as well as Ab reactivity with synthetic peptides from both FAH and viral proteins, indicated that the autoAb recognized a wide range of cryptic and conformational epitopes of the antigen and that the cross-reaction showed by the anti-MHV Ab could be different between individuals. Results obtained with sera from five BALB/c and three CBA/Ht mice showed that the enzyme did not compete for Ab binding to MHV neither in ELISA nor in western-blot competition assays, suggesting that the anti-MHV Ab did not recognize the native epitopes exposed in the soluble autoAg (see representative results in Fig. 2) .

title:
  Sequence similarity and structural homologies are involved in the autoimmune response elicited by mouse hepatitis virus A59

abstract:
  The features of autoantibodies (autoAb) to liver fumarylacetoacetate hydrolase (FAH) elicited in mice infected with mouse hepatitis virus (MHV) were studied by ELISA and western-blot competition assays. All sera tested contained Ab to cryptic FAH epitopes according with results from western-blot tests, whereas ELISA data indicated that some of these same sera did recognize native epitopes of the autoantigen (autoAg). Such differences were detected in individual sera from various mouse strains, and were ascribed to the fact that proteins insolubilized on solid supports expose a variety of conformational and cryptic antigenic determinants. On the other hand, whereas results from both experimental protocols showed that anti-MHV Ab did not cross-react with the soluble autoAg, the opposite situation did not show analogous results. Thus, binding of autoAb to insolubilized FAH could be inhibited by MHV depending on the mouse serum or the experimental protocol used. Additionally, a set of synthetic homologous peptides from mouse FAH and various viral proteins was employed to analyze the Ab repertoire of MHV-infected mice. Results indicated that two homologous peptides were recognized by most Ab: the N-terminal sequences (1–10) from FAH and the nucleocapside, both sharing 50% of identity, and sequence 2317–2326 of the RNA polymerase, a peptide showing 30% of identity with FAH 11–20. Results indicated that MHV-infection triggers at least three distinct Ab populations: anti-MHV, anti-FAH and cross-reacting Ab. This cross-reaction implies either sequential or conformational epitopes from both the viral proteins and the autoAg and may differ between individuals.


id: cord-269612-pmzdovna
title: Politics, media and microbiologists
author: Pennington, Hugh
date: 2004
txt: ./txt/cord-269612-pmzdovna.txt
cache: ./cache/cord-269612-pmzdovna.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15083161/
doi: 10.1038/nrmicro846
summary:
  Studies on the SARS outbreak in Hong Kong 1 -after the exclusion of two ''superspread'' events where special circumstances allowed index cases to infect many individuals (at the Prince of Wales Hospital and at the Amoy Gardens estate) -gave an estimated R 0 value of 2.7. From analyses of samples taken from Vietnam, Singapore and Hong Kong, laboratories in the network ruled out the possibility of infection by any of the known influenza virus strains or other established causes of pneumonia, and concluded that SARS was new. It meant that the Hong Kong Department of Health, Hospital Authority and laboratory surveillance facility 11 , and the WHO, were particularly well prepared to respond to the SARS outbreak. In March 1997, an outbreak of avian influenza caused by the A virus subtype H5N1 killed several thousand chickens in three rural Hong Kong chicken farms.

abstract:
  Severe acute respiratory syndrome (SARS) took everybody by surprise. Its emergence was one of the most significant microbiological events of 2003. It challenged microbiologists to identify the aetiological agent and satisfy Koch's postulates — in so far as they ever can be met for a virus — in real time. Not only were the patients' respiratory secretions and the agents grown in cultured cells put under the microscope, but so were the actions of politicians. What lessons can we learn from SARS?


id: cord-270788-w0pewq52
author: Chou, Chih-Fong
date: 2004-11-05
url: https://api.elsevier.com/content/article/pii/S0166093404002654
doi: 10.1016/j.jviromet.2004.09.008
title:
  A novel cell-based binding assay system reconstituting interaction between SARS-CoV S protein and its cellular receptor

abstract:
  Severe acute respiratory syndrome (SARS), a life-threatening disease, is caused by the newly identified virus SARS coronavirus (SARS-CoV). In order to study the spike (S) protein of this highly contagious virus, we established a clonal cell-line, CHO-SG, from the Chinese hamster ovary cells that stably expresses C-terminally EGFP-tagged SARS-CoV S protein (S-EGFP). The ectodomain of the S glycoprotein is localized on the surface of CHO-SG cells with N-acetyl-glucosamine-terminated carbohydrate structure. CHO-SG cells associated tightly with Vero E6 cells, a SARS-CoV receptor (ACE2) expressing cell-line, and the interaction remained stable under highly stringent condition (1 M NaCl). This interaction could be blocked by either the serum from a SARS convalescent patient or a goat anti-ACE2 antibody, indicating that the interaction is specific. A binding epitope with lesser degree of glycosylation and native conformation was localized by using rabbit anti-sera raised against five denatured recombinant S protein fragments expressed in Escherichia coli. One of the sera obtained from the fragment encompassing amino acids 48-358 significantly blocked the interaction between CHO-SG and Vero E6 cells. The region is useful for studying neutralizing antibodies in future vaccine development. This paper describes an easy and safe cell-based assay suitable for studying the binding between SARS-CoV S protein and its receptor.


id: cord-271445-eft2vwgb
title: Human metapneumovirus as a causative agent of acute bronchiolitis in infants
author: Xepapadaki, Paraskevi
date: 2004-05-06
txt: ./txt/cord-271445-eft2vwgb.txt
cache: ./cache/cord-271445-eft2vwgb.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15135747/
doi: 10.1016/j.jcv.2003.12.012
summary:
  Background: Human Metapneumovirus (hMPV), has been recently isolated from children with acute respiratory tract infections (RTIs), including bronchiolitis, and classified in the Pneumovirinae subfamily within the Paramyxoviridae family. Results and conclusions: PCR revealed the presence of hMPV in 16% of bronchiolitis cases, whereas respiratory syncytial virus (RSV; 67.9%) was the most frequently encountered viral pathogen. There were no differences in disease characteristics, either clinical or laboratory, between bronchiolitis cases where hMPV was present and those caused by RSV or other viral pathogens. A new respiratory virus, human metapneumovirus (hMPV), has been recently isolated from nasopharyngeal aspirates of young children in the Netherlands (van den Hoogen et al., 2001) . We have recently reported the results of virological evaluation of a well-characterized cohort of infants admitted to hospital with acute bronchiolitis, using reverse transcription polymerase chain reaction (PCR) for 11 respiratory pathogens (Papadopoulos et al., 2002) .

abstract:
  Background: Human Metapneumovirus (hMPV), has been recently isolated from children with acute respiratory tract infections (RTIs), including bronchiolitis, and classified in the Pneumovirinae subfamily within the Paramyxoviridae family. Objectives: Since most bronchiolitis studies fail to detect any viral pathogen in part of the samples, we sought for the presence of hMPV in a well characterized bronchiolitis cohort. Study design: Nasal washes were obtained from 56 children admitted to the hospital for acute bronchiolitis. RNA extraction and subsequent RT-PCR were used to detect hMPV, and correlated the presence of the virus with clinical characteristics of the disease. Results and conclusions: PCR revealed the presence of hMPV in 16% of bronchiolitis cases, whereas respiratory syncytial virus (RSV; 67.9%) was the most frequently encountered viral pathogen. hMPV was identified either as a unique viral pathogen or co-existed with RSV, with whom they shared a similar seasonal distribution. There were no differences in disease characteristics, either clinical or laboratory, between bronchiolitis cases where hMPV was present and those caused by RSV or other viral pathogens. These findings suggest that hMPV is a common and important causative agent in infants with bronchiolitis, with clinical characteristics similar to that of RSV.


id: cord-271919-pbs95hy0
title: Introduction of SARS in France, March–April, 2003
author: Desenclos, Jean-Claude
date: 2004-02-17
url: https://www.ncbi.nlm.nih.gov/pubmed/15030682/
doi: 10.3201/eid1002.030351
abstract:
  We describe severe acute respiratory syndrome (SARS) in France. Patients meeting the World Health Organization definition of a suspected case underwent a clinical, radiologic, and biologic assessment at the closest university-affiliated infectious disease ward. Suspected cases were immediately reported to the Institut de Veille Sanitaire. Probable case-patients were isolated, their contacts quarantined at home, and were followed for 10 days after exposure. Five probable cases occurred from March through April 2003; four were confirmed as SARS coronavirus by reverse transcription–polymerase chain reaction, serologic testing, or both. The index case-patient (patient A), who had worked in the French hospital of Hanoi, Vietnam, was the most probable source of transmission for the three other confirmed cases; two had been exposed to patient A while on the Hanoi-Paris flight of March 22–23. Timely detection, isolation of probable cases, and quarantine of their contacts appear to have been effective in preventing the secondary spread of SARS in France.


id: cord-272467-8heg5iql
title: Expression of coronavirus E1 and rotavirus VP10 membrane proteins from synthetic RNA
author: Armstrong, John
date: 2004-02-19
txt: ./txt/cord-272467-8heg5iql.txt
cache: ./cache/cord-272467-8heg5iql.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/2448319/
doi: 10.1002/jcb.240350206
summary:
  We have expressed the cloned cDNA for glycoproteins from two such viruses, the E1 protein of coronavirus, which buds in the Golgi region, and VP10 protein of rotavirus, which assembles in the endoplasmic reticulum. We are investigating two viral model proteins, one for the endoplasmic reticulum and one for the Golgi complex, with a view to determining the features of each molecule responsible for its correct localisation. RNAs prepared by this method for VPlO and E l were translated efficiencly in reticulocyte lysates, Xenopus oocytes, and cultured CVl cells (Figs. However, not all of the viral protein is restricted to the flattened cisternae of the Golgi complex; some at least is found in smooth membranes which are in the same region of the cell but are in fact continuous with the rough endoplasmic reticulum [ 12, 221 .

abstract:
  Some viruses acquire their envelopes by budding through internal membranes of their host cell. We have expressed the cloned cDNA for glycoproteins from two such viruses, the E1 protein of coronavirus, which buds in the Golgi region, and VP10 protein of rotavirus, which assembles in the endoplasmic reticulum. Messenger RNA was prepared from both cDNAs by using SP6 polymerase and either translated in vitro or injected into cultured CV1 cells or Xenopus oocytes. In CV1 cells, the El protein was localised to the Golgi region and VP10 protein to the endoplasmic reticulum. In Xenopus oocytes, the E1 protein acquired post‐translational modifications indistinguishable from the sialylated, O‐linked sugars found on viral protein, while the VP10 protein acquired endoglycosidase‐H‐sensitive N‐linked sugars, consistent with their localisation to the Golgi complex and endoplasmic reticulum, respectively. Thus the two proteins provide models with which to study targeting to each of these intracellular compartments. When the RNAs were expressed in matured, meiotic oocytes, the VP10 protein was modified as before, but the E1 protein was processed to a much lesser extent than in interphase oocytes, consistent with a cessation of vesicular transport during cell division.


id: cord-273479-kira7mz6
title: Mild acute inflammatory stimulation induces transient negative mood
author: Strike, Philip C.
date: 2004-10-02
txt: ./txt/cord-273479-kira7mz6.txt
cache: ./cache/cord-273479-kira7mz6.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0022399903005695
doi: 10.1016/s0022-3999(03)00569-5
summary:
  METHODS: Using a double blind study design, 26 healthy volunteers underwent baseline assessments of mood, financial strain and work stress and were randomised to injection of Salmonella typhi vaccine or placebo injection. Increases in anxiety and depressed mood were reported over the same time-scale in the endotoxin group, and the changes were correlated with the magnitude of cytokine responses. In the light of the kinetics of proinflammatory cytokine responses observed in earlier studies, we hypothesised that compared with placebo, vaccination would induce transient negative moods in the 1 -4 h following treatment, in the absence of rises in systemic body temperature or symptoms of illness. Changes in symptoms, body temperature, blood pressure and heart rate over the study were analysed with repeated measures analysis of variance with group (vaccine, placebo) as the between-subject factor, and time (base, 1, 2, 3, 4, 6 and 8 h) as the within-subject factor.

abstract:
  OBJECTIVE: This study aims to assess the mood changes induced by mild acute inflammatory stimulation (typhoid vaccination). METHODS: Using a double blind study design, 26 healthy volunteers underwent baseline assessments of mood, financial strain and work stress and were randomised to injection of Salmonella typhi vaccine or placebo injection. Mood, symptoms and body temperature was assessed by a modified version of the Profile of Mood States at 1, 2, 3, 4, 6 and 8 h post injection. RESULTS: Typhoid vaccination induces no increases in physical symptoms or temperature. Mood improved over the day in the placebo but not in the vaccine condition. Negative changes in mood following injection were correlated with chronic stress (financial strain) in the vaccination condition (r=−.65, P<.025). CONCLUSION: A mild acute inflammatory stimulus induces transient negative mood, and responses were modulated by chronic stress. Implications for depressed mood in physical illness are discussed.


id: cord-274112-6t0wpiqy
author: Webby, RJ
date: 2004-04-03
txt: ./txt/cord-274112-6t0wpiqy.txt
cache: ./cache/cord-274112-6t0wpiqy.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0140673604158923
doi: 10.1016/s0140-6736(04)15892-3
summary:
  INTERPRETATION: The ability to produce a candidate reference virus in such a short period of time sets a new standard for rapid response to emerging infectious disease threats and clearly shows the usefulness of reverse genetics for influenza vaccine development. The agent must be handled only under conditions of at least biosafety level 3 (BSL3), and it can kill fertilised chicken eggs, the standard medium for the reassortment and Responsiveness to a pandemic alert: use of reverse genetics for rapid development of influenza vaccines propagation of influenza virus before its inactivation and formulation for use in vaccines. The vaccine-candidate reference virus stock described in this report has been produced entirely on a cell substrate licensed for the manufacture of human vaccine, and as such, is-to our knowledge-the first reverse genetically derived influenza vaccine suitable for testing in clinical trials. Recombinant influenza A virus vaccines for the pathogenic human A/Hong Kong/97 (H5N1) viruses

title:
  Responsiveness to a pandemic alert: use of reverse genetics for rapid development of influenza vaccines

abstract:
  BACKGROUND: In response to the emergence of severe infection capable of rapid global spread, WHO will issue a pandemic alert. Such alerts are rare; however, on Feb 19, 2003, a pandemic alert was issued in response to human infections caused by an avian H5N1 influenza virus, A/Hong Kong/213/03. H5N1 had been noted once before in human beings in 1997 and killed a third (6/18) of infected people.1, 2 The 2003 variant seemed to have been transmitted directly from birds to human beings and caused fatal pneumonia in one of two infected individuals. Candidate vaccines were sought, but no avirulent viruses antigenically similar to the pathogen were available, and the isolate killed embryonated chicken eggs. Since traditional strategies of vaccine production were not viable, we sought to produce a candidate reference virus using reverse genetics. METHODS: We removed the polybasic aminoacids that are associated with high virulence from the haemagglutinin cleavage site of A/Hong Kong/213/03 using influenza reverse genetics techniques. A reference vaccine virus was then produced on an A/Puerto Rico/8/34 (PR8) backbone on WHO-approved Vero cells. We assessed this reference virus for pathogenicity in in-vivo and in-vitro assays. FINDINGS: A reference vaccine virus was produced in Good Manufacturing Practice (GMP)-grade facilities in less than 4 weeks from the time of virus isolation. This virus proved to be non-pathogenic in chickens and ferrets and was shown to be stable after multiple passages in embryonated chicken eggs. INTERPRETATION: The ability to produce a candidate reference virus in such a short period of time sets a new standard for rapid response to emerging infectious disease threats and clearly shows the usefulness of reverse genetics for influenza vaccine development. The same technologies and procedures are currently being used to create reference vaccine viruses against the 2004 H5N1 viruses circulating in Asia.


id: cord-275888-6u1o6414
title: N95 acne
author: Tan, Kian Teo
date: 2004-06-29
txt: ./txt/cord-275888-6u1o6414.txt
cache: ./cache/cord-275888-6u1o6414.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15230894/
doi: 10.1111/j.1365-4632.2004.02338.x
summary:
  1 The giant porokeratosis lesion on the left hand of our patient was totally excised and grafted. A diagnosis of sarcoidosis involving the central nervous system, lacrimal gland, nasal septum, vocal cord, lung and scalp was made, and the patient was treated with 20 mg of methylprednisone on alternate days with intralesional triamcinolone injection for skin lesions. Both were healthcare assistants working in the Singapore General Hospital throughout the severe acute respiratory syndrome (SARS) crisis, had worn N95 masks continuously for about 3 months whilst on the wards, and had suffered an outbreak of acne of the skin occluded by the mask. Both were healthcare assistants working in the Singapore General Hospital throughout the severe acute respiratory syndrome (SARS) crisis, had worn N95 masks continuously for about 3 months whilst on the wards, and had suffered an outbreak of acne of the skin occluded by the mask.

abstract:
  Two women, aged 27 and 45 years, presented to the Dermatology Outpatient Clinic with acne vulgaris. Both had nodular acne in a similar distribution over the cheeks, chin, and perioral areas (Fig. 1). Each had a history of acne vulgaris as a teenager. Both were healthcare assistants working in the Singapore General Hospital throughout the severe acute respiratory syndrome (SARS) crisis, had worn N95 masks continuously for about 3 months whilst on the wards, and had suffered an outbreak of acne of the skin occluded by the mask. They were treated with topical retinoid and systemic antimicrobials, and both responded well.


id: cord-275993-isff6lp2
title: Development of a safe neutralization assay for SARS-CoV and characterization of S-glycoprotein
author: Han, Dong P
date: 2004-08-15
txt: ./txt/cord-275993-isff6lp2.txt
cache: ./cache/cord-275993-isff6lp2.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15262502/
doi: 10.1016/j.virol.2004.05.017
summary:
  Similar to other coronaviruses, spike (S)-glycoprotein of the virus interacts with a cellular receptor and mediates membrane fusion to allow viral entry into susceptible target cells. S-protein of coronaviruses, which is thought to function as a trimer (Delmas and Laude, 1990) , is responsible for both binding to cellular receptors and inducing membrane fusion for virus entry into target cells (Collins et al., 1982; Godet et al., 1994; Kubo et al., 1994) . Despite difficulties in detecting S-protein directly by immunoassays, proteins expressed from both pcDNA-S and pHCMV-S constructs were able to pseudotype MuLV particles to produce SARS pseudoviruses that could readily infect Vero E6 cells (Fig. 3A) . To assess whether SARS pseudoviruses we generated could be used to quantify virus-neutralizing antibodies, we examined their susceptibility to convalescent sera from SARS-CoV-infected patients. Pseudotyping of murine leukemia virus with the envelope glycoproteins of HIV generates a retroviral vector with specificity of infection for CD4-expressing cells

abstract:
  The etiological agent of severe acute respiratory syndrome (SARS) has been identified as a novel coronavirus SARS-CoV. Similar to other coronaviruses, spike (S)-glycoprotein of the virus interacts with a cellular receptor and mediates membrane fusion to allow viral entry into susceptible target cells. Accordingly, S-protein plays an important role in virus infection cycle and is the primary target of neutralizing antibodies. To begin to understand its biochemical and immunological properties, we expressed both full-length and ectodomain of the protein in various primate cells. Our results show that the protein has an electrophoretic mobility of about 160–170 kDa. The protein is glycosylated with high mannose and/or hybrid oligosaccharides, which account for approximately 30 kDa of the apparent protein mass. The detection of S-protein by immunoassays was difficult using human convalescent sera, suggesting that the protein may not elicit strong humoral immune response in virus-infected patients. We were able to pseudotype murine leukemia virus particles with S-protein and produce SARS pseudoviruses. Pseudoviruses infected Vero E6 cells in a pH-independent manner and the infection could be specifically inhibited by convalescent sera. Consistent with low levels of antibodies against S-protein, neutralizing activity was weak with 50% neutralization titers ranging between 1:15 to 1:25. To facilitate quantifying pseudovirus-infected cells, which are stained blue with X-Gal, we devised an automated procedure using an ELISPOT analyzer. The high-throughput capacity of this procedure and the safety of using SARS pseudoviruses should make possible large-scale analyses of neutralizing antibody responses against SARS-CoV.


id: cord-276874-9rjbmsvb
title: Topographic Changes in SARS Coronavirus–infected Cells at Late Stages of Infection
author: Ng, M.L.
date: 2004-11-17
txt: ./txt/cord-276874-9rjbmsvb.txt
cache: ./cache/cord-276874-9rjbmsvb.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15550199/
doi: 10.3201/eid1011.040195
summary:
  Scanning electron and atomic force microscopy was used for the first time to view the maturation of the severe acute respiratory syndrome–associated coronavirus at the cell surface. Scanning electron and atomic force microscopy was used for the first time to view the maturation of the severe acute respiratory syndrome-associated coronavirus at the cell surface. High magnification of the maturing virus particles showed a rosette appearance with short knoblike spikes under both the scanning electron and atomic force microscopes. High magnification of the maturing virus particles showed a rosette appearance with short knoblike spikes under both the scanning electron and atomic force microscopes. The aim of this study was to use scanning electron and atomic force microscopes to investigate changes in the surface topography of SARS-CoV-infected cells at late infection. Scanning electron microscopy of Vero E6 cells infected with severe acute respiratory syndrome-associated coronavirus at 24 h after infection.

abstract:
  Scanning electron and atomic force microscopy was used for the first time to view the maturation of the severe acute respiratory syndrome–associated coronavirus at the cell surface. The surface form of the cells at advanced infection displayed prolific pseudopodia that, in addition to the rest of the plasma membrane, were also active sites of virus release. High magnification of the maturing virus particles showed a rosette appearance with short knoblike spikes under both the scanning electron and atomic force microscopes. The final expulsion step of the maturing virus particles seemed to result in some disruptions to the plasma membrane. The cytoskeletal network along the edge of the infected cells was enhanced and could be involved in transporting and expelling the progeny virus particles. Thickening of the actin filaments at the cell edge provided the bending force to extrude the virus particles.


id: cord-278816-l92lkj69
author: Brouard, J.
date: 2004-05-31
txt: ./txt/cord-278816-l92lkj69.txt
cache: ./cache/cord-278816-l92lkj69.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S1294550104942483
doi: 10.1016/s1294-5501(04)94248-3
summary:
  authors: Brouard, J.; Vabret, A.; Bach, N.; Toutain, F.; Duhamel, J. Freymuth Les adénovirus sont une cause commune d''atteinte respiratoire ; bien que dépendant du sérotype, ils peuvent également être la cause d''atteintes extrarespiratoires. Elle est par contre plus restreinte pour les enfants a priori sains : or chez eux des altérations bronchiolaires et bronchiques peuvent être à l''origine de lésions définitives parfois d''expression retardée. Les pneumopathies virales se définissent par l''existence d''une atteinte parenchymateuse : elles ne représentent qu''une faible part des infections respiratoires basses, environ 5 %. En dehors de ce contexte ces infections respiratoires sont le plus souvent bénignes, mais par-fois cette symptomatologie peut être marquée même chez l''enfant sain [18] . Les infections subaiguës des voies respiratoires par les AdV pourraient être impliquées dans la genèse de certaines formes de bronchopathies chroniques obstructives chez l''enfant et chez l''adulte. Les critères d''hospitalisation lors d''une pneumopathie supposée virale sont communs avec ceux des infections bactériennes.

title:
  Prise en charge des pathologies respiratoires à adénovirus chez l’enfant immunocompétent À propos d’une étude rétrospective de 116 enfants hospitalisés

abstract:
  Résumé Les adénovirus sont une cause commune d’atteinte respiratoire ; bien que dépendant du sérotype, ils peuvent également être la cause d’atteintes extrarespiratoires. Le diagnostic positif peut en être difficile. Les résultats cliniques chez 116 enfants hospitalisés en raison d’une infection adénovirale ont été repris rétrospectivement. Chez 71 enfants, le diagnostic virologique a été obtenu par immunofluorescence directe sur les aspirations nasales, 71 par culture virale de ces mêmes prélèvements. Le tableau clinique de l’infection adénovirale est caractérisé par une fièvre élevée (moyenne 39°1C) et prolongée (durée moyenne 4,3 jours). L’atteinte des voies aériennes supérieures (rhinopharyngite, angine, otite) et des voies aériennes inférieures (bronchite, bronchiolite, pneumopathie) sont les plus fréquentes. Douze enfants ont présenté des convulsions hyperpyrétiques, 6 avaient une méningite lymphocytaire. Les examens complémentaires ont objectivé des valeurs allant de la normalité à celles évocatrices d’infection bactérienne. Cinquante-neuf enfants furent adressés pour fièvre résistante à une antibiothérapie. Les symptômes de l’atteinte respiratoire dues aux infections adénovirales s’étendent de la rhinite à la pneumopathie et la bronchiolite. Les adénovirus peuvent entraîner des séquelles graves même chez l’enfant sain. Les recherches sur les mécanismes moléculaires de l’infection virale sur les voies aériennes amèneront d’importantes voies de réflexion sur la nature des processus inflammatoires participant à l’asthme et à la bronchite chronique obstructive. La plupart des infections sont modérées et ne nécessitent qu’un traitement symptomatique. Il n’existe pas actuellement de traitement antiviral efficace pour les infections adénovirales graves. Le diagnostic virologique rapide par l’étude des sécrétions nasopharyngées est d’une grande utilité clinique. Abstract Adenoviruses most commonly cause respiratory illness; however, depending on the infecting serotype, they may also cause various other diseases. Diagnosis may be difficult to achieve. The clinical findings for 116 children hospitalised with adenoviral infection were studied retrospectively. In 71 children, the diagnosis was based on detection of adenovirus antigen in the nasopharyngeal specimens and in 71 children on viral culture. The clinical picture of adenoviral infection was characterised by high-grade (mean 39°1C) and prolonged fever (mean duration 4,3 days). Upper respiratory and lower respiratory symptoms were the most common infections. Twelve had been admitted to the hospital due to febrile convulsions, 6 had meningitis. Laboratory findings varied from normal values to values seen in bacterial infections. Thus it was difficult to distinguish adenoviral disease from a bacterial disease. Fifty-nine children were referred to the hospital due to infection unresponsive to antimicrobial therapy. Symptoms of respiratory infection caused by adenovirus may range from the common cold syndrome to pneumonia, croup and bronchiolitis. Adenoviruses can be responsible for severe consequences, even in previously healthy children. Studies of the molecular mechanisms of viral infections of the airways could provide important insights into the nature of the inflammatory process involved in asthma and chronic obstructive pulmonary disease. Most infections are mild and require no therapy or only symptomatic treatment. There are at present time no recognised antiviral agents that are effective in treating serious adenovirus disease. The rapid detection of adenovirus antigen in nasopharygeal specimens proved to have a great clinical value in the diagnosis.


id: cord-281571-vob1bu9c
author: Tam, Theresa W.S
date: 2004-06-30
txt: ./txt/cord-281571-vob1bu9c.txt
cache: ./cache/cord-281571-vob1bu9c.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0531513104000391
doi: 10.1016/j.ics.2004.01.036
summary:
  The general concepts incorporated into the CPIP may be utilised in the contingency planning for a bioterrorism event or other communicable disease emergencies, including: a national, coordinated approach in planning; an emergency management structure to conduct the response; the use of common terminology to facilitate communication and response coordination, and the establishment of specific technical, communications and operational response groups and networks in advance. After the Hong Kong influenza A/H5N1 incident in 1997, the pandemic plan evolved to include a more comprehensive approach, incorporating the following key components: surveillance, vaccine programs, and use of antivirals, health services, emergency services, public health measures and communications. The general concepts incorporated into the CPIP that may be utilised in the contingency planning for other infectious disease emergencies include: a national, coordinated approach to planning; an emergency management structure to coordinate and conduct the response; the need for common terminology (e.g. using the same response phases), and the need to have specific technical, communications and operational response groups and networks formed in advance.

title:
  The Canadian Pandemic Influenza Plan: an evolution to the approach for national communicable disease emergencies

abstract:
  Abstract Advance planning for a large-scale and widespread health emergency is required to optimize health care delivery during an influenza pandemic. The Canadian Pandemic Influenza Plan (CPIP) is an example of a successful communicable disease emergency plan that ensures a national, coordinated approach to preparedness, response and recovery activities in the event of an influenza pandemic. The general concepts incorporated into the CPIP may be utilised in the contingency planning for a bioterrorism event or other communicable disease emergencies, including: a national, coordinated approach in planning; an emergency management structure to conduct the response; the use of common terminology to facilitate communication and response coordination, and the establishment of specific technical, communications and operational response groups and networks in advance. The multinational outbreak of Severe Acute Respiratory Syndrome (SARS) in 2003 offered the opportunity for the testing of these concepts. The experiences and lessons learnt during the SARS response may be utilised to strengthen communicable disease preparedness and response capacity.


id: cord-284028-l0r7f9sr
title: A loophole in international quarantine procedures disclosed during the SARS crisis
author: Lee, Chi-Wei
date: 2004-12-30
txt: ./txt/cord-284028-l0r7f9sr.txt
cache: ./cache/cord-284028-l0r7f9sr.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S1477893904001267
doi: 10.1016/j.tmaid.2004.10.002
summary:
  This phenomenon revealed a loophole in the control mechanisms of international quarantine procedures, letting travelers carrying a highly contagious virus slip by undetected and causing possible multi-country outbreaks of communicable diseases. Reasons for its rapid global spread were the highly contagious nature of the virus with its air-borne route of infection, the busy links between affected countries, and probably inadequacies in international quarantine procedures. As shown in Tables 1 and 2, although none of the six patients were eventually diagnosed wild SARS, this observed phenomenon disclosed a very important loophole in the control aspect of international quarantine procedures: the inability to prevent persons with a highly contagious virus from slipping past undetected and thus preventing the further spread of epidemics like SARS on international travel routes. In this study, we identified that there were loopholes in the international quarantine system for controlling the international spread of contagious disease like SARS, especially when travelers lack a strong motivation to cooperate with national health authorities.

abstract:
  This study describes a loophole in the international quarantine system during the recent Asian severe acute respiratory syndrome (SARS) outbreak. Specifically, that of travelers disguising symptoms of respiratory tract infection at international airports, in order to board aircraft to return to their home countries—notwithstanding the infection risks this involves to others. High medical fees for treatment to non-residents in epidemic areas were found to be the main cause for this behaviour. This phenomenon revealed a loophole in the control mechanisms of international quarantine procedures, letting travelers carrying a highly contagious virus slip by undetected and causing possible multi-country outbreaks of communicable diseases. Clinical evidence collected from medical records at medical centers can highlight this oversight.


id: cord-284372-v95fzp8n
author: Coyle, Peter V
date: 2004-10-25
txt: ./txt/cord-284372-v95fzp8n.txt
cache: ./cache/cord-284372-v95fzp8n.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15504232/
doi: 10.1186/1471-2180-4-41
summary:
  title: A touchdown nucleic acid amplification protocol as an alternative to culture backup for immunofluorescence in the routine diagnosis of acute viral respiratory tract infections To overcome this problem we developed a diagnostic molecular strip which combined a generic nested touchdown protocol with in-house primer master-mixes that could recognise 12 common respiratory viruses. CONCLUSIONS: The touchdown protocol with pre-dispensed primer master-mixes was suitable for replacing virus culture for the diagnosis of respiratory viruses which were negative by immunofluorescence. To test the feasibility of its routine use we needed to clinically validate its performance in a routine setting on specimens tested in parallel with our standard immunofluorescence protocol for the diagnosis of acute virus respiratory infections. In conclusion the use of the touchdown protocol with pre-dispensed and quality checked primer master-mixes was suitable for replacing virus culture for the diagnosis of respiratory viruses for immunofluorescence negative specimens.

title:
  A touchdown nucleic acid amplification protocol as an alternative to culture backup for immunofluorescence in the routine diagnosis of acute viral respiratory tract infections

abstract:
  BACKGROUND: Immunofluorescence and virus culture are the main methods used to diagnose acute respiratory virus infections. Diagnosing these infections using nucleic acid amplification presents technical challenges, one of which is facilitating the different optimal annealing temperatures needed for each virus. To overcome this problem we developed a diagnostic molecular strip which combined a generic nested touchdown protocol with in-house primer master-mixes that could recognise 12 common respiratory viruses. RESULTS: Over an 18 month period a total of 222 specimens were tested by both immunofluorescence and the molecular strip. The specimens came from 103 males (median age 3.5 y), 80 females (median age 9 y) and 5 quality assurance scheme specimens. Viruses were recovered from a number of specimen types including broncho-alveolar lavage, nasopharyngeal secretions, sputa, post-mortem lung tissue and combined throat and nasal swabs. Viral detection by IF was poor in sputa and respiratory swabs. A total of 99 viruses were detected in the study from 79 patients and 4 quality control specimens: 31 by immunofluorescence and 99 using the molecular strip. The strip consistently out-performed immunofluorescence with no loss of diagnostic specificity. CONCLUSIONS: The touchdown protocol with pre-dispensed primer master-mixes was suitable for replacing virus culture for the diagnosis of respiratory viruses which were negative by immunofluorescence. Results by immunofluorescence were available after an average of 4–12 hours while molecular strip results were available within 24 hours, considerably faster than viral culture. The combined strip and touchdown protocol proved to be a convenient and reliable method of testing for multiple viruses in a routine setting.


id: cord-284578-9opqbu7h
author: Leung, H.M.
date: 2004-05-10
txt: ./txt/cord-284578-9opqbu7h.txt
cache: ./cache/cord-284578-9opqbu7h.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0161893804000377
doi: 10.1016/j.jpolmod.2004.02.003
summary:
  If the NIE''s growth really were freak results from a lucky draw, then poor countries should forget about learning from the Asian examples, but instead try to improve their fortune through other means. The Asian NIE''s high degree of volatility was a consequence of their intensive investment policy (see Section 3); their luck and fortune are spin-offs from their toil and dexterity. Our recommendation to poor countries is to formulate good investment and growth policies now, as luck will take the side of those who strive. Second, for the four Asian NIEs, the relationship between growth rate and volatility is positive and statistically highly significant. The smaller the country, the higher the risk from investment indivisibility, and hence the more volatile is its economic growth. Small country-size and investment indivisibility led Asian NIEs to targeted investment policies, which brought fast growth as well as a high degree of fluctuations.

title:
  What has luck got to do with economic development? An interpretation of resurgent Asia’s growth experience

abstract:
  This paper critically reexamines the belief, currently gathering strength in the literature, that economic development depends on good luck rather than on good policy, and that Prometheus is “unchained by chance”. While it is impossible to disprove the role of luck in growth, we argue that luck is endogenous, and good luck is a function of good policy. Luck favours those who strive. Again contrary to common belief, we show that resurgent Asian economies have endured more, not less, than their fair share of economic volatility. They learned their lessons by success and failures, and luck is endogenous through learning-by-investing.


id: cord-286825-bu7j7kdr
author: Macours, Nathalie
date: 2004-10-04
txt: ./txt/cord-286825-bu7j7kdr.txt
cache: ./cache/cord-286825-bu7j7kdr.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15464852/
doi: 10.1016/s0074-7696(04)39002-9
summary:
  Because this peptide has been found to be an in vivo substrate specific for the N domain of sACE, it is suggested that ACE is implicated in the process of hematopoietic stem cell regulation by permanently degrading this natural circulating inhibitor (Azizi et al., 2001; Rousseau et al., 1995) . At present mammalian M13 family of zinc proteases consists of seven known members: neutral endopeptidase (NEP); the endothelin-converting enzymes ECE-1, ECE-2, and ECE-3; the Kell blood group antigen (Kell); the phosphate regulating gene (PEX); X-converting enzyme (XCE); and secreted endopeptidase (SEP). Sequencing, expression and biochemical characterization of the Porphyromonas gingivalis pepO gene encoding a protein homologous to human endothelin-converting enzyme Functional conservation of the active sites of human and Drosophila angiotensin I-converting enzyme Peptidyl dipeptidases (Ance and Acer) of Drosophila melanogaster: Major diVerences in the substrate specificity of two homologs of human angiotensin I-converting enzyme

title:
  Structure, Evolutionary Conservation, and Functions of Angiotensin- and Endothelin-Converting Enzymes

abstract:
  Angiotensin-converting enzyme, a member of the M2 metalloprotease family, and endothelin-converting enzyme, a member of the M13 family, are key components in the regulation of blood pressure and electrolyte balance in mammals. From this point of view, they serve as important drug targets. Recently, the involvement of these enzymes in the development of Alzheimer's disease was discovered. The existence of homologs of these enzymes in invertebrates indicates that these enzyme systems are highly conserved during evolution. Most invertebrates lack a closed circulatory system, which excludes the need for blood pressure regulators. Therefore, these organisms represent excellent targets for gaining new insights and revealing additional physiological roles of these important enzymes. This chapter reviews the structural and functional aspects of ACE and ECE and will particularly focus on these enzyme homologues in invertebrates.


id: cord-288558-rthnj6wd
author: Cheng, V. C. C.
date: 2004-02-15
txt: ./txt/cord-288558-rthnj6wd.txt
cache: ./cache/cord-288558-rthnj6wd.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/14765337/
doi: 10.1086/382681
summary:
  The role of severe acute respiratory syndrome (SARS) coronavirus as an enteric pathogen was investigated in a cohort of 142 patients with SARS who were treated with a standard treatment protocol. The role of severe acute respiratory syndrome (SARS) coronavirus as an enteric pathogen was investigated in a cohort of 142 patients with SARS who were treated with a standard treatment protocol. A higher mean virus load in nasopharyngeal specimens obtained on day 10 after the onset of symptoms was significantly associated with the occurrence of diarrhea (3.1 log 10 vs. A higher mean virus load in nasopharyngeal specimens obtained on day 10 after the onset of symptoms was significantly associated with the occurrence of diarrhea (3.1 log 10 vs. In this retrospective study, we attempt to correlate the virus load of SARS coronavirus shedding from the nasopharynx, the upper end of the aerodigestive tract, with the presence of diarrhea in a cohort of patients with SARS.

title:
  Viral Replication in the Nasopharynx Is Associated with Diarrhea in Patients with Severe Acute Respiratory Syndrome

abstract:
  The role of severe acute respiratory syndrome (SARS) coronavirus as an enteric pathogen was investigated in a cohort of 142 patients with SARS who were treated with a standard treatment protocol. Data from daily hematological, biochemical, radiological, and microbiological investigations were prospectively collected, and the correlation of these findings with diarrhea was retrospectively analyzed. Sixty-nine patients (48.6%) developed diarrhea at a mean (± standard deviation [SD]) of 7.6 ± 2.6 days after the onset of symptoms. The diarrhea was most severe at a mean (±SD) of 8.8 ± 2.4 days after onset, with a maximum frequency of 24 episodes per day (median, 5 episodes; range, 3–24 episodes). A higher mean virus load in nasopharyngeal specimens obtained on day 10 after the onset of symptoms was significantly associated with the occurrence of diarrhea (3.1 log(10) vs. 1.8 log(10) copies/mL; P = .01) and mortality (6.2 vs. 1.7 log(10) copies/mL; P < .01). However, diarrhea was not associated with mortality. The lung and the gastrointestinal tract may react differently to SARS coronavirus infection. Additional investigation of the role of SARS coronavirus in the pathogenesis of diarrhea in patients with SARS should be conducted.


id: cord-289332-hvakv08t
title: Pathogenic role of HMGB1 in SARS?
author: Chen, Guoqian
date: 2004-04-30
txt: ./txt/cord-289332-hvakv08t.txt
cache: ./cache/cord-289332-hvakv08t.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0306987704002208
doi: 10.1016/j.mehy.2004.01.037
summary:
  High mobility group box 1 protein (HMGB1) is released by necrotic cells or activated macrophages/monocytes, and functions as a late mediator of lethal systemic and local pulmonary inflammation. In light of observations that three Chinese herbal formulations recommended for treatment of severe acute respiratory syndrome (SARS) specifically inhibited the release of HMGB1 from innate immune cells, we hypothesize that HMGB1 might occupy a pathogenic role in SARS by mediating an injurious pulmonary inflammatory response. High mobility group box 1 protein (HMGB1, formerly known as HMG-1 or amphoterin) has recently been identified as a new proinflammatory cytokine and a late mediator of inflammation, sepsis, and acute lung injury. In light of observations that several Chinese herbal remedies recommended for treatment of SARS specifically inhibited the release of HMGB1 from activated innate immune cells, we hypothesize that HMGB1 might occupy a pathogenic role in SARS by mediating an injurious pulmonary inflammatory response.

abstract:
  High mobility group box 1 protein (HMGB1) is released by necrotic cells or activated macrophages/monocytes, and functions as a late mediator of lethal systemic and local pulmonary inflammation. Passive immunization with anti-HMGB1 antibodies confers significant protection against lethal endotoxemia, sepsis, and acute lung injury, even when antibodies are administered after the onset of these diseases. In light of observations that three Chinese herbal formulations recommended for treatment of severe acute respiratory syndrome (SARS) specifically inhibited the release of HMGB1 from innate immune cells, we hypothesize that HMGB1 might occupy a pathogenic role in SARS by mediating an injurious pulmonary inflammatory response.


id: cord-289605-gvc673ij
title: Considerations for Setting up a Small-Animal Imaging Facility
author: Klaunberg, Brenda A.
date: 2004
url: https://www.ncbi.nlm.nih.gov/pubmed/15235626/
doi: 10.1038/laban0304-28
abstract:
  Imaging techniques allow for the conduct of noninvasive, in vivo longitudinal small-animal studies, but also require access to expensive and complex equipment, and personnel who are properly trained in their use. The authors describe their planning and staffing of the NIH Mouse Imaging Facility, and highlight important issues to consider when designing a similar facility.


id: cord-290133-4ou7ubb4
title: Rethinking Smallpox
author: Weiss, Martin M.
date: 2004-12-01
txt: ./txt/cord-290133-4ou7ubb4.txt
cache: ./cache/cord-290133-4ou7ubb4.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15578369/
doi: 10.1086/425745
summary:
  The last recorded death due to smallpox, according to World Health Organization investigators, was likely associated with virus that had been transmitted by aerosol [16] . Such observations-along with the long incubation period of smallpox (mean, 12-14 days; range, 7-21 days)suggest that there would be adequate time to vaccinate the public and prevent a more widespread outbreak. Nonetheless, these masks, if distributed to the public, could prove to be critical for the control of a smallpox epidemic that was overwhelming our health care system, and they might also prove to be effective in limiting contagion of smaller viruses, such as influenza virus (either natural virus, as in 1918, or engineered virus [61] ). Because of the possibility of an attack involving bioengineered smallpox virus that is resistant to the current vaccine, methisazone should be reexamined, and research should be continued on other antiviral agents.

abstract:
  The potential consequences of a competently executed smallpox attack have not been adequately considered by policy makers. The possibility of release of an aerosolized and/or bioengineered virus must be anticipated and planned for. The transmission and infectivity of variola virus are examined. Arguments for and against pre-event vaccination are offered. The likely morbidity and mortality that would ensue from implementation of a mass pre-event vaccination program, within reasonable boundaries, are known. The extent of contagion that could result from an aerosolized release of virus is unknown and may have been underestimated. Pre-event vaccination of first responders is urged, and voluntary vaccination programs should be offered to the public. Two defenses against a vaccine-resistant, engineered variola virus are proposed for consideration. Methisazone, an overlooked drug, is reported to be effective for prophylaxis only. The extent of reduction in the incidence of smallpox with use of this agent is uncertain. It is useless for treatment of clinical smallpox. N-100 respirators (face masks) worn by uninfected members of the public may prevent transmission of the virus.


id: cord-290396-cy4y8vnt
author: Kumar, Matam Vijay
date: 2004-07-01
url: https://api.elsevier.com/content/article/pii/S0165572804001444
doi: 10.1016/j.jneuroim.2004.04.018
title:
  Innate immunity in the retina: Toll-like receptor (TLR) signaling in human retinal pigment epithelial cells

abstract:
  Toll-like receptors (TLRs) are crucial components of innate immunity that participate in host defense against microbial pathogens. We evaluated the expression and function of TLRs in human retinal pigment epithelial (RPE) cells. Real time PCR analysis revealed gene expression for TLRs 1–7, 9, and 10 in RPE cells. TLRs 1 and 3 were the most highly expressed TLRs. Protein expression for TLRs 2, 3, and 4 was observed on RPE cells and this expression was augmented by treatment with poly I:C or interferon-γ (IFN-γ). TLR 3 is the receptor for dsRNA, an intermediate of virus replication. Because RPE cells express TLR 3 and are frequently the site of virus replication within the retina, we evaluated TLR 3 signaling. RPE cells treated with poly I:C produced IFN-β but not IFN-α, and this was inhibited by the treatment of RPE cells with anti-TLR 3 antibody. Human recombinant IFN-β was shown to be biologically active on RPE cells by inhibiting viral replication. Poly I:C treatment of RPE resulted in an increase in the production of IL-6, IL-8, MCP-1, and sICAM-1. The presence of TLRs on RPE cells and the resultant TLR signaling in RPE cells suggest that these molecules may play an important role in innate and adaptive immune responses within the retina.


id: cord-291210-ghjseynl
title: A Highly Unusual Palindromic Transmembrane Helical Hairpin Formed by SARS Coronavirus E Protein
author: Arbely, Eyal
date: 2004-08-13
txt: ./txt/cord-291210-ghjseynl.txt
cache: ./cache/cord-291210-ghjseynl.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15288785/
doi: 10.1016/j.jmb.2004.06.044
summary:
  2, 3 In an effort to better understand the components contributing to the pathogenic mechanism of the virus, we have structurally analyzed the transmembrane domain of SCoV E protein using Fourier Transform Infrared (FTIR) spectroscopy, X-ray scattering, electron microscopy and global searching molecular dynamics simulations. In order to examine the secondary structure of the transmembrane domain (TMD) of SCoV E protein, peptides were made which encompassed the entire hydrophobic region of the protein (Glu7-Arg38), as depicted in Figure 1 . So far three lines of evidence were obtained characterizing the transmembrane domain of SCoV E protein: (i) it is highly helical, (ii) it is composed of 26 amino acid residues and (iii) the helical elements are oriented normal to the membrane plane. As shown in Figure 4 , the electron density of lipid vesicles containing iodinated and unlabeled SCoV E protein transmembrane domain exhibit normal density profiles.

abstract:
  Abstract The agent responsible for the recent severe acute respiratory syndrome (SARS) outbreak is a previously unidentified coronavirus. While there is a wealth of epidemiological studies, little if any molecular characterization of SARS coronavirus (SCoV) proteins has been carried out. Here we describe the molecular characterization of SCoV E protein, a critical component of the virus responsible for virion envelope morphogenesis. We conclusively show that SCoV E protein contains an unusually short, palindromic transmembrane helical hairpin around a previously unidentified pseudo-center of symmetry, a structural feature which seems to be unique to SCoV. The hairpin deforms lipid bilayers by way of increasing their curvature, providing for the first time a molecular explanation of E protein's pivotal role in viral budding. The molecular understanding of this critical component of SCoV may represent the beginning of a concerted effort aimed at inhibiting its function, and consequently, viral infectivity.


id: cord-293403-o1i999hy
title: E-health in the East Asian tigers
author: Holliday, Ian
date: 2004-09-11
txt: ./txt/cord-293403-o1i999hy.txt
cache: ./cache/cord-293403-o1i999hy.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1386505604001807
doi: 10.1016/j.ijmedinf.2004.08.001
summary:
  OBJECTIVE: The article analyzes e-health progress in East Asia''s leading tiger economies: Japan, Hong Kong, Singapore, South Korea and Taiwan. In this article, we examine the progress of e-health in the five leading economies of East Asia: Japan, Hong Kong, Singapore, South Korea and Taiwan. Against the dual backdrop of sophisticated IT societies that make extensive use of the Internet and cost-effective healthcare systems driven in variable ways by actors from the public and private sectors, we now turn to a survey of e-health in the East Asian tigers. Throughout the region, the major quasi-autonomous state agencies, such as the national health insurance agencies in Japan, South Korea and Taiwan, the HKHA in Hong Kong and the two big healthcare clusters in Singapore, also have sites. Over the next 5 years, the HKHA is planning to create a Hong Kong Health Information Infrastructure, with the aim of networking all healthcare providers in the public, private and social welfare sectors.

abstract:
  OBJECTIVE: The article analyzes e-health progress in East Asia's leading tiger economies: Japan, Hong Kong, Singapore, South Korea and Taiwan. It describes five main dimensions of e-health provision in the tigers: policymaking, regulation, provision, funding and physician-patient relations. METHODS: We conducted a series of fieldwork interviews and analyzed key healthcare websites. RESULTS AND CONCLUSION: Our main finding is that the development of e-health in the region is less advanced than might be expected. Our explanation focuses on institutional, cultural and financial factors.


id: cord-293865-0yp9wd0j
title: Isolation is not the answer
author: May, Thomas
date: 2004
txt: ./txt/cord-293865-0yp9wd0j.txt
cache: ./cache/cord-293865-0yp9wd0j.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15190328/
doi: 10.1038/429603a
abstract: International scientific collaboration is the best defence against bioterror.
summary:
  New restrictions on the publication of sensitive information relevant to biological weapons, on access to ''select'' biological agents for research, and on the training of scientists from specified countries are some examples. Consequently, attention to the global dimensions of bioterror threats is particularly important, including strengthening international means to identify and contain outbreaks of infectious disease. Recognition of the true international nature of the bioterror threat should make the United States take a leading role in training foreign scientists, medical professionals and public-health personnel to build a global capacity for identifying and containing disease outbreaks. Apart from the obvious barriers that restrictions on access to scientific information and tools place on research, restrictions on scientific training for foreign nationals will delay those countries from developing expertise crucial to identifying and containing disease outbreaks -key to any global strategy against bioterrorism.


id: cord-295075-cqbayzat
title: “Teaching old drugs to kill new bugs”: structure-based discovery of anti-SARS drugs
author: Rajnarayanan, Rajendram V.
date: 2004-08-20
txt: ./txt/cord-295075-cqbayzat.txt
cache: ./cache/cord-295075-cqbayzat.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15358186/
doi: 10.1016/j.bbrc.2004.06.155
summary:
  Several old drugs that bind to SARS 3CLpro active site were selected and in silico derivatized to generate covalent irreversible inhibitors with enhanced affinity. Structural conclusions from active site similarity within the coronavirus family and virtual screening on homology models have provided some clues regarding the class of compounds that could interact with SARS protease. The present study employs in silico derivatization as a method to ''''teach old drugs to kill new bugs.'''' We have designed irreversible covalent inhibitors by selective derivatization of top non-covalent leads, which includes several old drugs especially a class of HIV inhibitors identified from virtual screening. The side chains of His163 and Phe140 and the main-chain atoms of Met165, Glu166, and His172 form the S1 subsite, which confers specificity towards Gln. Thus, specific covalent inhibitors of SARS 3CLpro could be designed by substituting the amino acid at the P1 0 position with a thiol specific reactive organic moiety like chloromethyl ketone.

abstract:
  Abstract Severe acute respiratory syndrome (SARS) main protease or 3C-like protease (3CLpro) is essential for the propagation of the coronaviral life cycle and is regarded as one of the main targets for structure-based anti-SARS drug design. It is an attractive approach to find new uses for old drugs as they have already been through extensive clinical testing and could easily be accelerated for clinical approval. Briefly, we performed virtual screening of a database of small molecules against SARS 3CLpro, analyzed inhibitor–protease complexes, and identified several covalent and non-covalent inhibitors. Several old drugs that bind to SARS 3CLpro active site were selected and in silico derivatized to generate covalent irreversible inhibitors with enhanced affinity. Furthermore, we show that pharmacophores derived from clusters of compounds resulting out of virtual screening could be useful probes for future structure–activity relationship studies (SARs) and fine-tune the lead molecules identified.


id: cord-296605-p67twx7a
title: Management of Critically Ill Patients with Severe Acute Respiratory Syndrome (SARS)
author: LAU, Arthur Chun-Wing
date: 2004-03-10
txt: ./txt/cord-296605-p67twx7a.txt
cache: ./cache/cord-296605-p67twx7a.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15912185/
doi: nan
summary:
  title: Management of Critically Ill Patients with Severe Acute Respiratory Syndrome (SARS) Most SARS patients would require high flow oxygen supplementation, 20–30% required intensive care unit (ICU) or high dependency care, and 13–26% developed acute respiratory distress syndrome (ARDS). The management of critically ill SARS patients requires timely institution of pharmacotherapy where applicable and supportive treatment (oxygen therapy, noninvasive and invasive ventilation). More than onethird of all the SARS patients required high flow oxygen therapy [4] , 20-30% required intensive care unit (ICU) admission or high dependency care, and 13-26% developed acute respiratory distress syndrome (ARDS) [5, 6] . Description and clinical treatment of an early outbreak of severe acute respiratory syndrome (SARS) in Guangzhou, PR China Evaluation of non-invasive positive pressure ventilation in treatment for patients with severe acute respiratory syndrome Clinical observation of non-invasive positive pressure ventilation (NIPPV) in the treatment of severe acute respiratory syndrome (SARS)

abstract:
  Severe acute respiratory syndrome (SARS) is frequently complicated with acute respiratory failure. In this article, we aim to focus on the management of the subgroup of SARS patients who are critically ill. Most SARS patients would require high flow oxygen supplementation, 20–30% required intensive care unit (ICU) or high dependency care, and 13–26% developed acute respiratory distress syndrome (ARDS). In some of these patients, the clinical course can progress relentlessly to septic shock and/or multiple organ dysfunction syndrome (MODS). The management of critically ill SARS patients requires timely institution of pharmacotherapy where applicable and supportive treatment (oxygen therapy, noninvasive and invasive ventilation). Superimposed bacterial and other opportunistic infections are common, especially in those treated with mechanical ventilation. Subcutaneous emphysema, pneumothoraces and pneumomediastinum may arise spontaneously or as a result of positive ventilatory assistance. Older age is a consistently a poor prognostic factor. Appropriate use of personal protection equipment and adherence to infection control measures is mandatory for effective infection control. Much of the knowledge about the clinical aspects of SARS is based on retrospective observational data and randomized-controlled trials are required for confirmation. Physicians and scientists all over the world should collaborate to study this condition which may potentially threaten human existence.


id: cord-298083-4h3tg6hg
title: Antigenicity and receptor-binding ability of recombinant SARS coronavirus spike protein
author: Ho, Tin-Yun
date: 2004-01-23
txt: ./txt/cord-298083-4h3tg6hg.txt
cache: ./cache/cord-298083-4h3tg6hg.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/14706633/
doi: 10.1016/j.bbrc.2003.11.180
summary:
  In order to analyze the antigenicity and receptor-binding ability of SARS-CoV S protein, we expressed the S protein in Escherichia coli using a pET expression vector. By biotinylated ELISA and Western blot using biotin-labeled S protein as the probe, we identified 130-kDa and 140-kDa proteins in Vero cells that might be the cellular receptors responsible for SARS-CoV infection. Taken together, these results suggested that recombinant S protein exhibited the antigenicity and receptor-binding ability, and it could be a good candidate for further developing SARS vaccine and anti-SARS therapy. These data suggested that comparison of primary amino acid sequences does not provide insight into the receptor-binding specificity or antigenic properties of SARS-CoV S protein. To analyze the antigenicity of recombinant S protein, we performed Western blot and ELISA using sera from SARS patients or from spike-immunized rabbits.

abstract:
  Severe acute respiratory syndrome (SARS) is an emerging infectious disease associated with a novel coronavirus and causing worldwide outbreaks. SARS coronavirus (SARS-CoV) is an enveloped RNA virus, which contains several structural proteins. Among these proteins, spike (S) protein is responsible for binding to specific cellular receptors and is a major antigenic determinant, which induces neutralizing antibody. In order to analyze the antigenicity and receptor-binding ability of SARS-CoV S protein, we expressed the S protein in Escherichia coli using a pET expression vector. After the isopropyl-β-d-thiogalactoside induction, S protein was expressed in the soluble form and purified by nickel-affinity chromatography to homogeneity. The amount of S protein recovered was 0.2–0.3 mg/100 ml bacterial culture. The S protein was recognized by sera from SARS patients by ELISA and Western blot, which indicated that recombinant S protein retained its antigenicity. By biotinylated ELISA and Western blot using biotin-labeled S protein as the probe, we identified 130-kDa and 140-kDa proteins in Vero cells that might be the cellular receptors responsible for SARS-CoV infection. Taken together, these results suggested that recombinant S protein exhibited the antigenicity and receptor-binding ability, and it could be a good candidate for further developing SARS vaccine and anti-SARS therapy.


id: cord-298312-tvc39eg7
title: China’s rural electricity market—a quantitative analysis
author: Yang, Ming
date: 2004-06-30
txt: ./txt/cord-298312-tvc39eg7.txt
cache: ./cache/cord-298312-tvc39eg7.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0360544203002846
doi: 10.1016/j.energy.2003.12.002
summary:
  Historical data for over 20 years were collected on rural economic development, households, population, per capita income, community infrastructure development, capital investment, electricity consumption, output values in agriculture sector, and township and village enterprises (TVEs). We forecast electricity demand in the rural areas of the six provinces and tried to identify the best investment market in terms of high growth rate of electricity demand and greatest impact on rural electrification and economic development. Between 1995 and 2001, two additional hot topics have been added to China''s power literature: (1) continued reform of the power industry aiming at establishing a full retail market for power sector competition; and (2) rural electricity market development. In this study, we focused on electricity market analysis and power demand forecasting for the rural areas-county level and below.

abstract:
  Abstract The objective of this paper is to quantify the development of the rural electricity market at county level and below in China. A sectorial energy demand analysis and forecasting model was developed to analyze six Chinese provinces with different economic backgrounds. Historical data for over 20 years were collected on rural economic development, households, population, per capita income, community infrastructure development, capital investment, electricity consumption, output values in agriculture sector, and township and village enterprises (TVEs). This paper concludes that by 2010, annual electricity demand will increase at a rate between −1.40% and 15.60% (depending on the sectors and provinces). It also recommends a preferred order for future rural electricity investment: Jiangsu, Hebei, Henan, Shaanxi, Liaoning and Xinjiang, i.e. from the most to the least developed provinces, if the investment objectives are to find the best market return and the greatest impact on rural market development.


id: cord-300731-i2ow33bk
title: A Review of Multi-Threat Medical Countermeasures against Chemical Warfare and Terrorism
author: Cowan, Fred M.
date: 2004-11-17
txt: ./txt/cord-300731-i2ow33bk.txt
cache: ./cache/cord-300731-i2ow33bk.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15605928/
doi: 10.7205/milmed.169.11.850
summary:
  Although sites and mechanisms of action and the pathologies caused by different chemical insults vary, common biochemical signaling pathways, molecular mediators, and cellular processes provide targets for MTMC drugs. The biochemical pathways associated with chemical toxicity can involve proteases, inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1, IL-8, and other molecules such as platelet activating factor (PAF), N-methyl-D-aspartate (NMDA) glutamate receptors, acetylcholine (ACh), substance P, and poly(ADP-ribose) polymerase (PARP) (for review, see Ref. 14). These mediators and receptors can influence inflammatory responses associated with cellular processes such as degranulation, apoptosis, and necrosis that contribute to pathologies caused by chemical agents. Therefore, many classes of compounds used as countermeasures to chemical warfare agents such as PARP inhibitors, proteases inhibitors, adenosine agonists, and NMDA receptor antagonist, although not chiefly thought of as anti-inflammatory drugs, have anti-inflammatory pharmacology (Table I ) (for review, see Ref. 14) .

abstract:
  The Multi-Threat Medical Countermeasure (MTMC) hypothesis has been proposed with the aim of developing a single countermeasure drug with efficacy against different pathologies caused by multiple classes of chemical warfare agents. Although sites and mechanisms of action and the pathologies caused by different chemical insults vary, common biochemical signaling pathways, molecular mediators, and cellular processes provide targets for MTMC drugs. This article will review the MTMC hypothesis for blister and nerve agents and will expand the scope of the concept to include other chemicals as well as briefly consider biological agents. The article will also consider how common biochemical signaling pathways, molecular mediators, and cellular processes that contribute to clinical pathologies and syndromes may relate to the toxicity of threat agents. Discovery of MTMC provides the opportunity for the integration of diverse researchers and clinicians, and for the exploitation of cutting-edge technologies and drug discovery. The broad-spectrum nature of MTMC can augment military and civil defense to combat chemical warfare and chemical terrorism.


id: cord-301286-ska85bts
title: Lymphocyte apoptosis in acute respiratory syncytial virus bronchiolitis
author: ROE, M F E
date: 2004-06-10
url: https://www.ncbi.nlm.nih.gov/pubmed/15196254/
doi: 10.1111/j.1365-2249.2004.02512.x
abstract:
  Respiratory syncytial virus (RSV) infection may have an effect on the development of T cell memory responses. RSV bronchiolitis in infants is associated with a transient decline in circulating lymphocytes. We hypothesized that the mechanism underlying this lymphopenia is apoptosis. Blood was taken from 32 infants during primary RSV bronchiolitis and three months later. Using flow cytometry, we found that absolute numbers of both CD3+/CD4+ T-helper lymphocytes (P = 0·029) and CD3+/CD8+ cytotoxic lymphocytes (CTL) (P = 0·043) were significantly reduced during acute infection. Up-regulated expression both of Fas (P < 0·001) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor (P < 0·001) was found during acute illness on both CD3+/CD4+ and CD3+/CD8+ lymphocytes, when compared with convalescent samples. Expression of Fas on CD4+ lymphocytes was inversely related to CD4+ number (P = 0·03). Plasma levels of soluble Fas ligand (P = 0·028) and caspase-1 (P = 0·037), determined by enzyme-linked immunosorbent assay, were increased during bronchiolitis. Plasma interleukin-18, a product of caspase-1 activity, was not raised. Taken together, these data suggest that in acute RSV infection, CD4+ helper lymphocytes and CD8+ cytotoxic lymphocytes are primed to undergo apoptosis. This is a mechanism through which lymphopenia may occur and T cell memory may be altered.


id: cord-304899-vruq4r7z
title: Syndrome respiratoire aigu sévère : une épidémie singulière de pneumonie virale
author: Guihot, Amélie
date: 2004-03-31
txt: ./txt/cord-304899-vruq4r7z.txt
cache: ./cache/cord-304899-vruq4r7z.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0755498204985818
doi: 10.1016/s0755-4982(04)98581-8
summary:
  L''agent infectieux étiologique a rapidement été identifié comme étant un nouveau Coronavirus, baptisé Coronavirus associé au Sras (Sras-CoV).La transmission du virus est interhumaine, par les particules respiratoires principalement. n Chine du Sud-Est, au début de l''année 2003, une épidémie de pneumopathie hautement contagieuse et potentiellement mortelle a été signalée par les autorités sanitaires chinoises.Cette entité clinique d''étiologie inconnue a été baptisée Syndrome respiratoire aigu sévère (Sras) par l''Organisation mondiale de la santé (OMS). La ribavirine est un analogue nucléosidique utilisé comme anti-viral dans le traitement de l''hépatite C chronique (Rébétol ® ), en association avec l''interféron α .La ribavirine possédant une activité in vitro contre plusieurs virus respiratoires (virus syncytial respiratoire, virus de la grippe), elle a été utilisée empiriquement par plusieurs équipes chez des patients atteints de Sras.

abstract:
  Résumé Agent infectieux Le Syndrome respiratoire aigu sévère (Sras) est une pneumopathie fébrile initialement observée en Chine à la fin de l’année 2002. L’agent infectieux étiologique a rapidement été identifié comme étant un nouveau Coronavirus, baptisé Coronavirus associé au Sras (Sras-CoV). La transmission du virus est interhumaine, par les particules respiratoires principalement. Clinique et traitement La gravité clinique est variable, allant de la simple fièvre au syndrome de détresse respiratoire aigu. Il n’existe pas de traitement spécifique. Cependant, la ribavirine combinée à des corticoïdes a été utilisée avec succès dans un certain nombre de cas. Épidémiologie Au cours du premier semestre de l’année 2003, la dissémination du virus a été extrêmement rapide, évoluant sur un mode pandémique, contaminant plus de 8000 patients, dont 774 en sont décédés. Le réservoir viral, probablement d’origine animale, reste inconnu à ce jour. L’épidémie semble être actuellement jugulée, mais des ré-émergences sporadiques ou épidémiques sont possibles et ont été décrites en Chine dans la province de Guangdong début janvier 2004. Summary Infectious agent The severe acute respiratory syndrome (SARS) is a febrile pneumonia initially observed in China at the end of 2002. The infectious agent has rapidly been identified as a new coronavirus, baptised SARS-associated coronavirus (CoV-SARS). Transmission is inter-human, via respiratory particles mainly. Clinical presentation and treatment The clinical presentation is highly variable, from a mild fever to an acute respiratory distress syndrome. There is no specific treatment. Ribavirin associated with steroids have been used with success in numerous cases. Epidemiology During the first half of 2003, the spreading of the virus has been very fast, with a pandemic mode of evolution. More than 8 000 people were infected and 774 died. The reservoir of the virus, which may be animal, is still unknown. The epidemic seems to be controlled, but sporadic or epidemic re-emergences may occur and have been observed in China duting January 2004.


id: cord-305341-nokybn2a
author: Zeng, Fanya
date: 2004-03-19
txt: ./txt/cord-305341-nokybn2a.txt
cache: ./cache/cord-305341-nokybn2a.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0006291X04002104
doi: 10.1016/j.bbrc.2004.01.166
summary:
  title: Characterization of humoral responses in mice immunized with plasmid DNAs encoding SARS-CoV spike gene fragments Another interesting finding was that mouse antibodies elicited separately by plasmids encoding S1 and S2 subunits cooperatively neutralized SARS-CoV but neither the S1 nor S2 specific antibodies did, suggesting the possible role of both S1 and S2 subunits in host cell docking and entry. Animals vaccinated with DNA encoding secreting form of E2 glycoprotein of classical swine fever virus (CSFV) showed both CSFV specific antibody response and protection upon viral challenge though the native E2 was anchor membrane protein ( [28, 29] and Zeng et al., unpublished data). In the mice experiment, it was demonstrated that SARS-CoV specific antibodies could be induced by immunization with plasmids encoding S1, S2 and fragment of S1 subunit. The first paper on immunizing masques with structural genes of SARS-CoV, however, reported that co-delivery of three viral genes encoding S1, nucleocapsid (N), and membrane (M) protein could elicit a high titer of neutralizing antibody and T-cell response [24] .

title:
  Characterization of humoral responses in mice immunized with plasmid DNAs encoding SARS-CoV spike gene fragments

abstract:
  The immunological characteristics of SARS-CoV spike protein were investigated by administering mice with plasmids encoding various S gene fragments. We showed that the secreting forms of S1, S2 subunits and the N-terminus of S1 subunit (residues 18–495) were capable of eliciting SARS-CoV specific antibodies and the region immediate to N-terminus of matured S1 protein contained an important immunogenic determinant for elicitation of SARS-CoV specific antibodies. In addition, mice immunized with plasmids encoding S1 fragment developed a Th1-mediated antibody isotype switching. Another interesting finding was that mouse antibodies elicited separately by plasmids encoding S1 and S2 subunits cooperatively neutralized SARS-CoV but neither the S1 nor S2 specific antibodies did, suggesting the possible role of both S1 and S2 subunits in host cell docking and entry. These results provide insights into understanding the immunological characteristics of spike protein and the development of subunit vaccines against SARS-CoV.


id: cord-307073-vatfdilt
author: Narita, M.
date: 2004-08-11
url: https://api.elsevier.com/content/article/pii/S0021997504000660
doi: 10.1016/j.jcpa.2004.05.001
title:
  Encephalomalacic Lesions in Pigs Dually Infected with Porcine Reproductive and Respiratory Syndrome Virus and Pseudorabies Virus

abstract:
  Four pigs (group 1) were infected with an aerosol containing porcine reproductive and respiratory syndrome virus (PRRSV) followed 7 days later by pseudorabies virus (PRV). Three further pigs (group 2) received PRRSV alone, two (group 3) received PRV alone, and two (group 4) remained as uninfected controls. Despite the admittedly small numbers of animals, the experiment appeared to throw light on aspects of synergy. Thus, the group 1 pigs showed severe neurological signs characterized by ataxia and muscular tremors. Total cell numbers in the bronchoalveolar lavage fluid were increased in all PRRSV-infected pigs, and PRRSV antigen was detected in the alveolar macrophages. Total cell numbers in the cerebrospinal fluid of group 1 pigs were considerably greater than those demonstrated in group 3, but no PRV antigen was found. Pigs of groups 1 and 2 showed pulmonary lesions, characterized by interstitial pneumonia and PRRSV antigen immunolabelling. Non-suppurative encephalitis was found in five of the six pigs of groups 1 and 3. In particular, one group 1 animal had severe necrotizing encephalitis with intranuclear inclusion bodies and associated immunolabelling of PRV antigen. The other three group 1 pigs had prominent malacic lesions, with macrophages. These neuropathological findings strongly suggested that PRRSV infection in pigs enhances the severity of brain lesions caused PRV.


id: cord-307968-sqe7h05t
title: Human Challenge Pilot Study with Cyclospora cayetanensis
author: Alfano-Sobsey, Edith M.
date: 2004-04-17
txt: ./txt/cord-307968-sqe7h05t.txt
cache: ./cache/cord-307968-sqe7h05t.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15200870/
doi: 10.3201/eid1004.030356
summary:
  We describe a pilot study that attempted to infect human volunteers with Cyclospora cayetanensis. In addition, data from Cryptosporidium human volunteer studies demonstrated that the 50% infectious dose (ID 50 ) differed (from 9 to 1,042 oocysts), depending on the isolate used in the study (10) . For these reasons, we attempted to vary the inocula by selecting oocysts from persons in different geographic regions (Haiti, Missouri, and Georgia) and increasing the numbers All oocysts in stool samples in this study were stored in potassium dichromate (2.5%), and most of the final inoculum preparations were disinfected with bleach (5.25%). Cryptosporidium parvum has been stored in 2.5% potassium dichromate (for <6 weeks to >12 weeks) and remained infectious in human volunteers, cell culture, and animals (11, 12) . However, the effects of potassium dichromate and bleach on the Cyclospora oocysts used in this study are unknown, since methods to evaluate infectivity and viability were not available.

abstract:
  We describe a pilot study that attempted to infect human volunteers with Cyclospora cayetanensis. Seven healthy volunteers ingested an inoculum of Cyclospora oocysts (approximately 200–49,000 oocysts). The volunteers did not experience symptoms of gastroenteritis, and no oocysts were detected in any stool samples during the 16 weeks volunteers were monitored.


id: cord-308576-iw8oobbe
title: Expression and purification of SARS coronavirus membrane protein
author: Wuxing, Dai
date: 2004
txt: ./txt/cord-308576-iw8oobbe.txt
cache: ./cache/cord-308576-iw8oobbe.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15641679/
doi: 10.1007/bf02831095
summary:
  To construct a recombinant plasmid Pet23a-M, the gene encoding severe acute respiratory syndrome (SARS) coronavirus membrane protein was amplified by RT-PCR and cloned into the expression plasmid Pet23a. To screen and prepare effective SARS virus vaccine and diagnostic antigens, we designed a pair of primers to amplify the gene encoding SARS coronavirus membrane protein and cloned it into an expression plasmid Pet23a. Coli BI.21 ( D E 3 ) and induced by I P T G , Western-blot showed that the expressed 27 kD protein which was characterized by SDS-PAGE and purified by metal chelated chromatography could react with antibodies in sera of SARS patients during convalescence, demonstrating the recombinant protein possessed the biological activity of membrane protein.

abstract:
  To construct a recombinant plasmid Pet23a-M, the gene encoding severe acute respiratory syndrome (SARS) coronavirus membrane protein was amplified by RT-PCR and cloned into the expression plasmid Pet23a. Results of restriction endonuclease analysis, PCR detection and DNA sequencing analysis revealed that the cloned DNA sequence was the same as that reported. The recombinants were transformed intoEscherichia coli (E. Coli) BL21 (DE3) and induced by Isopropyl-β-D-thiogalactopyranoside (IPTG). The expression of 27 kD (1 kD=0.992 1 ku) protein was detected by SDS-PAGE and pured by metal chelated chromatography. Results of Western-blot showed that this expressed protein could react with antibodies in sera of SARS patients during convalescence. This provided the basis for the further study on SARS virus vaccine and diagnostic agents.


id: cord-308833-ei1faruy
author: Zheng, Xiaohong
date: 2004
txt: ./txt/cord-308833-ei1faruy.txt
cache: ./cache/cord-308833-ei1faruy.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32214716/
doi: 10.1007/bf03182817
summary:
  In this research, high voltage static electricity and ultraviolet technologies were integrated to an air purifying device which can be used to trap and kill airborne bacteria and viruses in central air-conditioning systems. This provides a basis for using this particular phage strain as a viral simulant in place of SARS CoV and other airborne viruses in the tests for evaluation of bioaerosol removal and inactivation by different types of air purifiers. Fig. 4(a) shows that the plaques formed on a GSM plate were used to sample the airflow containing phage aerosol generated with a source suspension with 10 5 pfu/mL when the integrated air purifier was turned off. In addition to particle removal test, airborne bacteria were also sampled in the experimental room with the integrated air purifier. Based upon the integrated technology of high voltage electric field, ultraviolet ray, composite silver material, and activated carbon fibers, an air purifying device has been developed to prevent airborne bacteria and virus spread through central air-conditioning system.

title:
  Experimental investigation of integrated air purifying technology for bioaerosol removal and inactivation in central air-conditioning system

abstract:
  In this research, high voltage static electricity and ultraviolet technologies were integrated to an air purifying device which can be used to trap and kill airborne bacteria and viruses in central air-conditioning systems. An experimental platform was built to mimic the central air system, in which the efficacy of the newly built device was examined. In addition to the standard physical and chemical tests, bacteriophages were used to simulate airborne viruses in the experimental system. The bacteriophage suspension was aerosolized into the air with ultrasonic wave atomization. The result showed that more than 86% removal efficiency of micro-particles (<10 micron in diameter) were removed after the device was in operation in a building and more than 95% of bacteriophages in the experimental system. It is concluded that the integrated air purifier is suitable for controlling air quality and preventing virus transmission through the central air system.


id: cord-312797-hohzjx74
title: Human Metapneumovirus: A New Player among Respiratory Viruses
author: Hamelin, Marie-Ève
date: 2004-04-01
txt: ./txt/cord-312797-hohzjx74.txt
cache: ./cache/cord-312797-hohzjx74.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15034830/
doi: 10.1086/382536
summary:
  Despite the fact that prospective and case-control studies have been limited, the epidemiology and clinical manifestations associated with hMPV have been found to be reminiscent of those of the human respiratory syncytial virus, with most severe respiratory tract infections occurring in infants, elderly subjects, and immunocompromised hosts. In addition, studies have shown that hMPV is not a new pathogen, with serological evidence of human infection dating from 1958 in The Netherlands [4] and viral isolation for the past 10-20 years in Europe and Canada [4, 7] . Symptoms of both upper and lower respiratory tract infections have been associated with hMPV in young children, although most reports are biased towards description of the most severe symptomatology in hospitalized subjects. Virological features and clinical manifestations associated with human metapneumovirus: a new paramyxovirus responsible for acute respiratory-tract infections in all age groups

abstract:
  The human metapneumovirus (hMPV) is a newly described member of the Paramyxoviridae family belonging to the Metapneumovirus genus. Since its initial description in 2001, hMPV has been reported in most parts of the world and isolated from the respiratory tract of subjects from all age groups. Despite the fact that prospective and case-control studies have been limited, the epidemiology and clinical manifestations associated with hMPV have been found to be reminiscent of those of the human respiratory syncytial virus, with most severe respiratory tract infections occurring in infants, elderly subjects, and immunocompromised hosts. Additional research is needed to define the pathogenesis of this viral infection and the host's specific immune response.


id: cord-312848-vbadg8ki
author: Jeong, Jae-Ho
date: 2004-08-26
txt: ./txt/cord-312848-vbadg8ki.txt
cache: ./cache/cord-312848-vbadg8ki.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0168170204002850
doi: 10.1016/j.virusres.2004.07.003
summary:
  In the present study, we analyzed the S glycoprotein gene to characterize 10 winter dysentery (WD) coronavirus strains circulated in Korea during 2002–2003 and compared the nucleotide (nt) and deduced amino acid (aa) sequences with the other known BCoV. The phylogenetic analysis of the entire S glycoprotein gene revealed that the aa sequences of all Korean WD strains were more homologous to each other and were very closely related to respiratory bovine coronavirus (RBCV) strain OK and enteric bovine coronavirus (EBCV) strain LY-138, but were distinct from the other known BCoVs. Based on the phylogenetic analysis of the hypervariable region of the S1 subunit, all Korean WD strains clustered with the respiratory strain OK, BCQ3994 and the enteric strain LY-138, while the Canadian BCQ calf diarrhea and WD strains, and the American RBCV LSU, French EBCV F15 and avirulent VACC, L9, and Mebus strains clustered on a separate major branch.

title:
  Molecular analysis of S gene of spike glycoprotein of winter dysentery bovine coronavirus circulated in Korea during 2002–2003

abstract:
  Since the molecular analysis of spike (S) glycoprotein gene of bovine coronavirus (BCoV) has been conducted and compared mainly among American and Canadian isolates and/or strains, it is unclear whether BCoV circulated in the other countries are distinctive in genetic characteristics. In the present study, we analyzed the S glycoprotein gene to characterize 10 winter dysentery (WD) coronavirus strains circulated in Korea during 2002–2003 and compared the nucleotide (nt) and deduced amino acid (aa) sequences with the other known BCoV. The phylogenetic analysis of the entire S glycoprotein gene revealed that the aa sequences of all Korean WD strains were more homologous to each other and were very closely related to respiratory bovine coronavirus (RBCV) strain OK and enteric bovine coronavirus (EBCV) strain LY-138, but were distinct from the other known BCoVs. Based on the phylogenetic analysis of the hypervariable region of the S1 subunit, all Korean WD strains clustered with the respiratory strain OK, BCQ3994 and the enteric strain LY-138, while the Canadian BCQ calf diarrhea and WD strains, and the American RBCV LSU, French EBCV F15 and avirulent VACC, L9, and Mebus strains clustered on a separate major branch. These data suggest that the WD strains circulated in Korea had a genetic property of both RBCV and EBCV and were significantly distinct from the ancestral enteric strain.


id: cord-312865-nno2yjae
title: SARS CTL vaccine candidates; HLA supertype‐, genome‐wide scanning and biochemical validation
author: Sylvester‐Hvid, C.
date: 2004-04-23
txt: ./txt/cord-312865-nno2yjae.txt
cache: ./cache/cord-312865-nno2yjae.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15104671/
doi: 10.1111/j.0001-2815.2004.00221.x
summary:
  One would therefore expect that an effective vaccine should induce mucosal immunity such as that effected by secretory immunoglobulin A (IgA), which specifically prevents an infectious agent from penetrating the mucosal epithelium, and by cytotoxic T lymphocytes (CTLs), which specifically eradicate infected cells (5) . Human CTLs are specific for peptides presented in the context of human leukocyte antigen (HLA) molecules [generically known as ''''major histocompatibility complex (MHC) molecules'''']. Thus, 13 of the 15 peptides predicted to be good binders to A*0301 were found to bind to another member of the A3 supertype, HLA-A*1101. Similarly, nine of the 15 peptides predicted to be good binders to A*1101 were found to bind to HLA-A*0301 (Table 1) Once all nine supertypes have been tested, we would project to have found well over 100 different vaccine candidates. Immunogenicity of a human immunodeficiency virus (HIV) polytope vaccine containing multiple HLA A2 HIV CD8(þ) cytotoxic T-cell epitopes

abstract:
  Abstract: An effective Severe Acute Respiratory Syndrome (SARS) vaccine is likely to include components that can induce specific cytotoxic T‐lymphocyte (CTL) responses. The specificities of such responses are governed by human leukocyte antigen (HLA)‐restricted presentation of SARS‐derived peptide epitopes. Exact knowledge of how the immune system handles protein antigens would allow for the identification of such linear sequences directly from genomic/proteomic sequence information (Lauemoller et al., Rev Immunogenet 2001: 2: 477–91). The latter was recently established when a causative coronavirus (SARS‐CoV) was isolated and full‐length sequenced (Marra et al., Science 2003: 300: 1399–404). Here, we have combined advanced bioinformatics and high‐throughput immunology to perform an HLA supertype‐, genome‐wide scan for SARS‐specific CTL epitopes. The scan includes all nine human HLA supertypes in total covering >99% of all individuals of all major human populations (Sette & Sidney, Immunogenetics 1999: 50: 201–12). For each HLA supertype, we have selected the 15 top candidates for test in biochemical binding assays. At this time (approximately 6 months after the genome was established), we have tested the majority of the HLA supertypes and identified almost 100 potential vaccine candidates. These should be further validated in SARS survivors and used for vaccine formulation. We suggest that immunobioinformatics may become a fast and valuable tool in rational vaccine design.


id: cord-312899-ot5pvtbl
title: In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds
author: Chen, F
date: 2004-09-30
txt: ./txt/cord-312899-ot5pvtbl.txt
cache: ./cache/cord-312899-ot5pvtbl.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S1386653204000551
doi: 10.1016/j.jcv.2004.03.003
summary:
  Commercial antiviral agents and pure chemical compounds extracted from traditional Chinese medicinal herbs were screened against 10 clinical isolates of SARS coronavirus by neutralisation tests with confirmation by plaque reduction assays. Interferon-beta-1a, leukocytic interferon-alpha, ribavirin, lopinavir, rimantadine, baicalin and glycyrrhizin showed antiviral activity. We report in this study on the in vitro antiviral susceptibility of 10 isolates of SARS coronavirus to commercially available antiviral agents and pure chemical compounds including baicalin, glycyrrhizin, and chlorogenic acid extracted from traditional Chinese herbs. Further testing by neutralization tests Table 3 Comparison of antiviral activity of 10 compounds against 10 strains of SARS-CoV in fRhK4 cell line, against the prototype strains (39849) with the other 9 isolates of SARS coronavirus against the active compounds confirmed detectable inhibitory activities for leukocytic interferon-alpha, interferon-beta-1a, ribavirin, lopinavir, rimantadine, and baicalin.

abstract:
  Abstract Effective antiviral agents are urgently needed to combat the possible return of severe acute respiratory syndrome (SARS). Commercial antiviral agents and pure chemical compounds extracted from traditional Chinese medicinal herbs were screened against 10 clinical isolates of SARS coronavirus by neutralisation tests with confirmation by plaque reduction assays. Interferon-beta-1a, leukocytic interferon-alpha, ribavirin, lopinavir, rimantadine, baicalin and glycyrrhizin showed antiviral activity. The two interferons were only active if the cell lines were pre-incubated with the drugs 16h before viral inoculation. Results were confirmed by plaque reduction assays. Antiviral activity varied with the use of different cell lines. Checkerboard assays for synergy were performed showing combinations of interferon beta-1a or leukocytic interferon-alpha with ribavirin are synergistic. Since the clinical and toxicity profiles of these agents are well known, they should be considered either singly or in combination for prophylaxis or treatment of SARS in randomised placebo controlled trials in future epidemics.


id: cord-314386-cxq9v218
title: SARS Coronavirus Detection
author: Nitsche, Andreas
date: 2004-07-17
url: https://www.ncbi.nlm.nih.gov/pubmed/15324554/
doi: 10.3201/eid1007.030678
abstract:
  We developed a set of three real-time reverse transcription–polymerase chain reaction (PCR) assays that amplify three different regions of the SARS-associated coronavirus (SARS-CoV), can be run in parallel or in a single tube, and can detect <10 genome equivalents of SARS-CoV. The assays consider all currently available SARS-CoV sequences and are optimized for two prominent real-time PCR platforms.


id: cord-316723-srenbxa7
author: Zhao, Jincun
date: 2004-11-23
txt: ./txt/cord-316723-srenbxa7.txt
cache: ./cache/cord-316723-srenbxa7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15797360/
doi: 10.1016/j.jcv.2004.09.024
summary:
  Amino acid residues 450–650 of the spike (S) glycoprotein of SARS-CoV (S450-650) contains dominant epitopes for anti-viral antibodies (Abs) in patient sera. However, so far there is no enzyme-linked immunosorbent assay (ELISA) available for easier and more sensitive detection of anti-S Abs. Our computer-assisted analysis suggested that amino acid residues 450-650 of the S glycoprotein (S450-650) of SARS-CoV is largely solvent accessible and likely to contain dominant B cell epitopes. (2004) showing that residues 441-700 of the S protein of SARS-CoV contained dominant epitope(s) for anti-S Abs in patient sera, as determined in WB assays. All patient sera were tested for anti-SARS-CoV IgG Abs using an ELISA kit produced by Huada Institute (see below). Sera from three convalescent SARS patients and two healthy individuals were serial diluted and tested in the S450-650-based ELISAs, which detected anti-S IgG Abs in a specific and sensitive manner, with the reactivity end point from 1:400 to 1:800 diluted patient sera (Fig. 2) .

title:
  Development and evaluation of an enzyme-linked immunosorbent assay for detection of antibodies against the spike protein of SARS-coronavirus

abstract:
  BACKGROUND: Severe acute respiratory syndrome (SARS) is caused by infection with SARS-associated coronavirus (CoV). Amino acid residues 450–650 of the spike (S) glycoprotein of SARS-CoV (S450-650) contains dominant epitopes for anti-viral antibodies (Abs) in patient sera. OBJECTIVES: To develop and evaluate an ELISA system for detection of anti-S Abs in patient sera. STUDY DESIGN: Express recombinant S450-650 in E. Coli and evaluate the sensitivity and specificity of an ELISA system based on the S450-650 polypeptide. RESULTS: The S450-650-based ELISA detected IgG Abs in 41 out of 51 serum samples from 22 hospitalized patients with probable SARS, a result closely correlated with that obtained with a virus-based ELISA (r = 0.75, k = 0.8). Differential anti-S IgG responses were observed amongst SARS patients. Some of them produced anti-S Abs early during their infection, while others failed to make IgG Abs against the S450-650 polypeptide. None of the serum samples from 100 healthy blood donors was positive in the S450-650-based assay. CONCLUSION: The S450-650-based ELISA can detect anti-S IgG Abs with high sensitivity and specificity.


id: cord-319792-16upcncw
author: Zhu, Jieqing
date: 2004-06-18
txt: ./txt/cord-319792-16upcncw.txt
cache: ./cache/cord-319792-16upcncw.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0006291X0400912X
doi: 10.1016/j.bbrc.2004.04.141
summary:
  Following the rule: formation of the 6-helix bundle of the fusion core from severe acute respiratory syndrome coronavirus spike protein and identification of potent peptide inhibitors Severe acute respiratory syndrome coronavirus (SARS-CoV) has been identified as a new distinct pathological entity [1] [2] [3] and the disease infected more than 8000 people and killed 774 worldwide, mostly in Asia, before it was brought under control in July between the winter and spring in 2002-2003 (WHO website: www.who.int). The genomic sequencing reveals that, as with other enveloped RNA viruses, including the coronaviruses [10] [11] [12] , SARS-CoV envelope spike (S) protein contains highly conserved heptad repeat regions (HR1 and HR2), which have been shown as important in virus membrane fusion and successfully used as targets for virus entry/fusion inhibitors in a number of viruses [13] [14] [15] [16] [17] [18] , including a coronavirus, mouse hepatitis virus (MHV) [12] .

title:
  Following the rule: formation of the 6-helix bundle of the fusion core from severe acute respiratory syndrome coronavirus spike protein and identification of potent peptide inhibitors

abstract:
  Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is a newly identified member of Family Coronaviridae. Coronavirus envelope spike protein S is a class I viral fusion protein which is characterized by the existence of two heptad repeat regions (HR1 and HR2) (forming a complex called fusion core). Here we report that by using in vitro bio-engineering techniques, SARS-CoV HR1 and HR2 bind to each other and form a typical 6-helix bundle. The HR2, either as a synthetic peptide or as a GST-fusion polypeptide, is a potent inhibitor of virus entry. The results do show that SARS-CoV follows the general fusion mechanism of class I viruses and this lays the ground for identification of virus fusion/entry inhibitors for this devastating emerging virus.


id: cord-321691-46la29tm
title: SARS Antibody Test for Serosurveillance
author: Hsueh, Po-Ren
date: 2004-09-17
txt: ./txt/cord-321691-46la29tm.txt
cache: ./cache/cord-321691-46la29tm.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15498156/
doi: 10.3201/eid1009.040101
summary:
  A peptide-based enzyme-linked immunosorbent assay (ELISA) can be used for retrospective serosurveillance of severe acute respiratory syndrome (SARS) by helping identify undetected chains of disease transmission. A peptide-based enzyme-linked immunosorbent assay (ELISA) can be used for retrospective serosurveillance of severe acute respiratory syndrome (SARS) by helping identify undetected chains of disease transmission. Such surveillance may be key to tracking the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) because mild and asymptomatic cases of SARS-CoV infection that do not meet the World Health Organization''s case definition (1) have been identified by immunoassays (2) (3) (4) , and SARS-CoV-like viruses have been isolated from wild mammals (5) . The diagnostic sensitivity of the peptide ELISA was 100% on a panel of 69 convalescent-phase serum samples from SARS patients provided as a reference panel by the Center for Disease Control, Department of Health, Taiwan. The peptide ELISA was evaluated for specificity on serum samples drawn from patients associated with typical and atypical respiratory pathogens other than SARS-CoV (National Taiwan University Hospital).

abstract:
  A peptide-based enzyme-linked immunosorbent assay (ELISA) can be used for retrospective serosurveillance of severe acute respiratory syndrome (SARS) by helping identify undetected chains of disease transmission. The assay was developed by epitope mapping, using synthetic peptides from the spike, membrane, and nucleocapsid protein sequences of SARS-associated coronavirus. The new peptide ELISA consistently detected seroconversion by week 2 of onset of fever, and seropositivity remained through day 100. Specificity was 100% on normal blood donor samples, on serum samples associated with infection by other pathogens, and on an interference panel. The peptide-based test has advantages of safety, standardization, and automation over previous immunoassays for SARS. The assay was used for a retrospective survey of healthy healthcare workers in Taiwan who treated SARS patients. Asymptomatic seroconversions were detected in two hospitals that had nosocomial disease.


id: cord-321797-2xhusfth
author: Lee‐Baggley, Dayna
date: 2004-03-11
txt: ./txt/cord-321797-2xhusfth.txt
cache: ./cache/cord-321797-2xhusfth.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32313437/
doi: 10.1111/j.1467-839x.2004.00131.x
summary:
  Hierarchical linear regression indicated that the use of wishful thinking in response to the threat of SARS was related to both avoiding public places and avoiding people perceived to be possible carriers of the SARS virus, but was not associated with the use of more adaptive health behaviors, such as using disinfectants and hand washing. Perception of SARS threat was significantly related to reports of both coping (wishful thinking and support seeking) and health behaviors (avoidant behavior, avoiding people perceived to be at risk for SARS and taking precautions). In sum, multivariate analyses controlling for differences in perceived threat of SARS, state anxiety and other ways of coping indicated that both wishful thinking and empathic responding were significantly associated with specific SARS-related health behaviors. 4 Controlling for differences in perceived threat of SARS, state anxiety and other ways of coping, support seeking was not significantly related to the SARS-related health behaviors examined in the present study.

title:
  Coping with the threat of severe acute respiratory syndrome: Role of threat appraisals and coping responses in health behaviors

abstract:
  The present study examines the psychological impact of severe acute respiratory syndrome (SARS) by exploring the coping strategies and health behaviors enacted in response to the SARS epidemic. Hierarchical linear regression indicated that the use of wishful thinking in response to the threat of SARS was related to both avoiding public places and avoiding people perceived to be possible carriers of the SARS virus, but was not associated with the use of more adaptive health behaviors, such as using disinfectants and hand washing. Conversely, those who reported engaging in empathic responding in response to the threat of SARS were both less likely to report avoiding people perceived as being at a high risk for SARS and more likely to report engaging in effective health behaviors. Support seeking was not a significant predictor of the health behaviors examined in the present study. Results are discussed in terms of coping with health threats and health promotion.


id: cord-321949-s1qu3odd
title: Rotavirus infection in adults
author: Anderson, Evan J
date: 2004-01-28
url: https://api.elsevier.com/content/article/pii/S1473309904009284
doi: 10.1016/s1473-3099(04)00928-4
abstract:
  Rotavirus has been recognised for 30 years as the most common cause of infectious gastroenteritis in infants and young children. By contrast, the role of rotavirus as a pathogen in adults has long been underappreciated. Spread by faecal-oral transmission, rotavirus infection in adults typically manifests with nausea, malaise, headache, abdominal cramping, diarrhoea, and fever. Infection can also be symptomless. Rotavirus infection in immuno-compromised adults can have a variable course from symptomless to severe and sustained infection. Common epidemiological settings for rotavirus infection among adults include endemic disease, epidemic outbreak, travel-related infection, and disease resulting from child-to-adult transmission. Limited diagnostic and therapeutic alternatives are available for adults with suspected rotavirus infection. Because symptoms are generally self-limiting, supportive care is the rule. Clinicians caring for adults with gastroenteritis should consider rotavirus in the differential diagnosis. In this review we intend to familiarise clinicians who primarily provide care for adult patients with the salient features of rotavirus pathophysiology, clinical presentation, epidemiology, treatment, and prevention.


id: cord-322529-3xn5v54s
author: Rodák, L.
date: 2004-06-30
txt: ./txt/cord-322529-3xn5v54s.txt
cache: ./cache/cord-322529-3xn5v54s.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15228549/
doi: 10.1111/j.1439-0450.2004.00746.x
summary:
  title: Verification of Sensitivity and Specificity of Group A Rotavirus Detection in Piglets Faeces with Monoclonal Blocking ELISA Methods Selected competitive blocking ELISA (CB‐ELISA) and electron microscopy (EM) were used for examination of 194 field faecal samples of piglets affected with diarrhoea. The sensitivity and specificity of the CB‐ELISA was verified both by inclusion of control samples containing transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhoea virus (PEDV) in each analysis and by comparative examination of samples with the commercial ELISA kit. Sensitivity comparison of three variants of the blocking ELISA method of rotavirus A detection were performed by box titrations in microtitre plate wells pre-coated with binding antibodies. Sensitivity of the CB-ELISA method and DAS-ELISA kit was compared by examination of faecal sample of experimentally infected piglet twofold diluted 2· to 1024·. By examination of positive faecal sample twofold diluted 2· to 1024·, at least 10 times higher sensitivity of CB-ELISA method was demonstrated (Table 2) .

title:
  Verification of Sensitivity and Specificity of Group A Rotavirus Detection in Piglets Faeces with Monoclonal Blocking ELISA Methods

abstract:
  Monoclonal antibodies to group A rotavirus Vp6 protein were prepared and used for verification of three blocking enzyme‐linked immunosorbent assay (ELISA) modifications to detect rotavirus A. Selected competitive blocking ELISA (CB‐ELISA) and electron microscopy (EM) were used for examination of 194 field faecal samples of piglets affected with diarrhoea. Rotavirus was detected in 43 samples (22.2%) by CB‐ELISA method, whereas in 26 (13.4%) samples by EM examination. However, of 26 samples positive by EM, rotavirus A was detected by CB‐ELISA in 19 (73.1%) samples; indicating the share of group A rotavirus in all cases of gastroenteritis caused by rotavirus. The sensitivity and specificity of the CB‐ELISA was verified both by inclusion of control samples containing transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhoea virus (PEDV) in each analysis and by comparative examination of samples with the commercial ELISA kit. The CB‐ELISA sensitivity was positively affected by examination of samples in the presence of chelating agent.


id: cord-322834-rl6yum7n
author: Wallinga, Jacco
date: 2004-09-15
txt: ./txt/cord-322834-rl6yum7n.txt
cache: ./cache/cord-322834-rl6yum7n.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15353409/
doi: 10.1093/aje/kwh255
summary:
  The available epidemic curves for SARS show marked differences between the affected regions with respect to the total number of cases and epidemic duration, even for those regions in which outbreaks started almost simultaneously and similar control measures were implemented at the same time. In this paper, we interpret the observed epidemic curves with regard to disease transmission potential and effectiveness of control measures, and we compare the epidemiologic profiles of SARS outbreaks in Hong Kong, Vietnam, Singapore, and Canada. The model uses values of k t = 0.18 for cases with a symptom onset date before March 12, 2003 , and k t = 0.08 for cases with a symptom onset date on or after March 12, 2003 ; these values correspond to the distribution of the number of secondary infections per case as observed during the severe acute respiratory syndrome (SARS) outbreak in Singapore (4).

title:
  Different Epidemic Curves for Severe Acute Respiratory Syndrome Reveal Similar Impacts of Control Measures

abstract:
  Severe acute respiratory syndrome (SARS) has been the first severe contagious disease to emerge in the 21st century. The available epidemic curves for SARS show marked differences between the affected regions with respect to the total number of cases and epidemic duration, even for those regions in which outbreaks started almost simultaneously and similar control measures were implemented at the same time. The authors developed a likelihood-based estimation procedure that infers the temporal pattern of effective reproduction numbers from an observed epidemic curve. Precise estimates for the effective reproduction numbers were obtained by applying this estimation procedure to available data for SARS outbreaks that occurred in Hong Kong, Vietnam, Singapore, and Canada in 2003. The effective reproduction numbers revealed that epidemics in the various affected regions were characterized by markedly similar disease transmission potentials and similar levels of effectiveness of control measures. In controlling SARS outbreaks, timely alerts have been essential: Delaying the institution of control measures by 1 week would have nearly tripled the epidemic size and would have increased the expected epidemic duration by 4 weeks.


id: cord-322877-jy1uvwre
title: Ocular screening in severe acute respiratory syndrome
author: Yuen, Kenneth S.C.
date: 2004-03-30
txt: ./txt/cord-322877-jy1uvwre.txt
cache: ./cache/cord-322877-jy1uvwre.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15059730/
doi: 10.1016/j.ajo.2003.09.060
summary:
  To investigate the ocular manifestations of patients with severe acute respiratory syndrome (SARS) and to monitor the possible ocular complications arising from the treatment regimen with high-dose systemic corticosteroid drugs. In March 2003, Hong Kong was seriously affected by a massive outbreak of SARS, and we took that opportunity to conduct a prospective observational study to investigate the probable ocular manifestations arising from SARS and the possible short-term complications resulting from the pulse or high-dose corticosteroid therapy. Patients were assessed with a comprehensive ocular examination including best-corrected visual acuity, intraocular pressure (IOP) by noncontact tonometer ([NCT] Xpert Noncontact Tonometer Plus; Reichert Ophthalmic Instruments, New York, New York, USA), slit-lamp, and binocular indirect ophthalmoscopy at baseline and at 2 months and 3 months. 2 With the unremarkable ophthalmologic findings of this study, routine ocular screening in patients with SARS for diagnosis or for complications may not be worthwhile.

abstract:
  To investigate the ocular manifestations of patients with severe acute respiratory syndrome (SARS) and to monitor the possible ocular complications arising from the treatment regimen with high-dose systemic corticosteroid drugs. DESIGN: Prospective, observational cohort case series. METHODS: Ninety eyes from 45 patients with the diagnosis of SARS during an epidemic outbreak in Hong Kong were analyzed. Relevant medical and ophthalmic histories were taken. Ophthalmic examinations, including best-corrected visual acuity, intraocular pressure, slit-lamp, and indirect ophthalmoscopy examination, were performed at baseline and at 2-month and 3-month follow-up. SETTING: Faculty practice in university hospital. RESULTS: Only two patients had mild elevated intraocular pressure at baseline and at subsequent follow-up. There was no loss of visual acuity, cataract progression, or increased cup–disk ratio. Fundus examinations were unremarkable in all patients. CONCLUSIONS: Our study did not demonstrate any ocular manifestations in patients with SARS. The treatment regimen of high-dose corticosteroid also did not show any significant ocular complications. Routine ocular screening of patients with SARS for diagnosis or for complications might not be indicated.


id: cord-323996-613j97y9
title: Serological survey on canine coronavirus antibodies in giant pandas by virus neutralization test
author: Jun, Qiao
date: 2004
txt: ./txt/cord-323996-613j97y9.txt
cache: ./cache/cord-323996-613j97y9.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/bf02844956
doi: 10.1007/bf02844956
summary:
  title: Serological survey on canine coronavirus antibodies in giant pandas by virus neutralization test In order to survey the infectious situation of canine coronavirus (CCV) in giant panda population, a virus neutralization test detecting specific antibodies against CCV in giant panda''s sera was established by using two-fold dilutions of serum and 100 TCID(50) of the virus. In recent years, it was reported that CCV could infect giant pandas and others precious wild animals (Mainka et aL 1994; He et aL 1996; Gao et aL 2003; Qiao et aL 2004) . Whether it is necessary to use CCV vaccine to protect this precious animal should be researched, in order to answer these questions, the 62 sera samples of giant panda were collected from zoos and reserve regions in Sichuan Province, China and used for serological investigation of neutralizing antibodies against CCV. Diagnosis of complex infection of canine distemper virus and canine coronavirus to giant panda by multi-PCR

abstract:
  In order to survey the infectious situation of canine coronavirus (CCV) in giant panda population, a virus neutralization test detecting specific antibodies against CCV in giant panda’s sera was established by using two-fold dilutions of serum and 100 TCID(50) of the virus. The 62 sera samples of giant pandas, which were gathered from zoos and reserve region of Sichuan Province, China were detected. The neutralization antibody titer of 1:4 was recognized as the positive criterion, 8 sera samples were detected to be positive, and the positive rate was 12.9%. The titers of neutralizing antibody ranged from 1:8 to 1:32. It was the first comprehensive investigation on neutralization antibodies against CCV in giant panda population in China. The results of study showed that the infection of CCV in giant panda population was universal, which has posed a threat to the health of giant panda. Therefore, it is incumbent on us to study safe and effective vaccines to protect giant panda against CCV infection.


id: cord-326094-8id2oh1n
title: Clinical prevention and population health Curriculum framework for health professions
author: Allan, Janet
date: 2004-12-31
txt: ./txt/cord-326094-8id2oh1n.txt
cache: ./cache/cord-326094-8id2oh1n.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0749379704002065
doi: 10.1016/j.amepre.2004.08.010
summary:
  10, 11 Another IOM report called for "transforming the content, methods, approaches, and settings used in health professions education" in response to the "changing needs of the population and changing demands of practice." 12 Healthy People 2010 13 encouraged the reexamination of clinical education by including an objective "to increase the proportion of schools of medicine, schools of nursing and health professional training schools whose basic curriculum for healthcare providers includes the core competencies in health promotion and disease prevention." The task of developing such a framework provided the impetus for the Association of Teachers of Preventive Medicine (ATPM) to join with the Associa-tion of Academic Health Centers to convene the Healthy People Curriculum Task Force, which is composed of a senior academic member and the executive director (or designee) from the following clinical health professional organizations: The Task Force also includes representation from the Student Health Alliance (a consortium of 11 health profession student organizations) and two resource groups, the Association of Schools of Public Health (ASPH) and Community-Campus Partnerships for Health.

abstract:
  Abstract The Clinical Prevention and Population Health Curriculum Framework is the initial product of the Healthy People Curriculum Task Force convened by the Association of Teachers of Preventive Medicine and the Association of Academic Health Centers. The Task Force includes representatives of allopathic and osteopathic medicine, nursing and nurse practitioners, dentistry, pharmacy, and physician assistants. The Task Force aims to accomplish the Healthy People 2010 goal of increasing the prevention content of clinical health professional education. The Curriculum Framework provides a structure for organizing curriculum, monitoring curriculum, and communicating within and among professions. The Framework contains four components: evidence base for practice, clinical preventive services–health promotion, health systems and health policy, and community aspects of practice. The full Framework includes 19 domains. The title “Clinical Prevention and Population Health” has been carefully chosen to include both individual- and population-oriented prevention efforts. It is recommended that all participating clinical health professions use this title when referring to this area of curriculum. The Task Force recommends that each profession systematically determine whether appropriate items in the Curriculum Framework are included in its standardized examinations for licensure and certification and for program accreditation.


id: cord-327819-7p05jk1h
title: Avian Influenza: A New Pandemic Threat?
author: Trampuz, Andrej
date: 2004-04-30
txt: ./txt/cord-327819-7p05jk1h.txt
cache: ./cache/cord-327819-7p05jk1h.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15065617/
doi: 10.4065/79.4.523
summary:
  13 The nomenclature of influenza viruses includes the type of virus (A, B, or C), host of origin (excluding humans), geographical site of origin, strain number, and year of isolation, followed in parentheses by the antigenic description of the hemagglutinin and neuraminidase glycoproteins, eg, A/chicken/Hong Kong/258/97 (H5N1). 18 Other control measures include continuous surveillance of influenza virus strains in humans and in birds, careful protection of cullers through appropriate personal protective equipment, restrictions on the movement of live poultry, and use of the human influenza vaccine to reduce the risk of coinfection in poultry workers and cullers. In 1997, the first documented direct transmission of an avian influenza virus to humans occurred in Hong Kong, when an H5N1 strain caused a severe respiratory disease in 18 previously healthy young adults, 6 of whom died. On January 23, 2004, authorities in Thailand reported an outbreak of highly pathogenic avian influenza among poultry, with laboratory-confirmed cases of H5N1 infection in humans.

abstract:
  In December 2003, the largest outbreak of highly pathogenic avian influenza H5N1 occurred among poultry in 8 Asian countries. A limited number of human H5N1 infections have been reported from Vietnam and Thailand, with a mortality rate approaching 70%. Deaths have occurred in otherwise healthy young individuals, which is reminiscent of the 1918 Spanish influenza pandemic. The main presenting features were fever, pneumonitis, lymphopenia, and diarrhea. Notably, sore throat, conjunctivitis, and coryza were absent. The H5N1 strains are resistant to amantadine and rimantadine but are susceptible to neuraminidase inhibitors, which can be used for treatment and prophylaxis. The widespread epidemic of avian influenza in domestic birds increases the likelihood for mutational events and genetic reassortment. The threat of a future pandemic from avian influenza is real. Adequate surveillance, development of vaccines, outbreak preparedness, and pandemic influenza planning are important. This article summarizes the current knowledge on avian influenza, including the virology, epidemiology, diagnosis, and management of this emerging disease.


id: cord-328271-ma3s7hrs
author: Madden, David L.
date: 2004-10-08
txt: ./txt/cord-328271-ma3s7hrs.txt
cache: ./cache/cord-328271-ma3s7hrs.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/3279901/
doi: 10.1002/ana.410230738
summary:
  title: Antibody to human and simian retrovirus, HTLV‐I, HTLV‐II, HIV, STLV‐III, and SRV‐I not increased in patients with multiple sclerosis We have tested sera from patients with multiple sclerosis, matched controls, and those with other neurological diseases, as well as sera from patients with the acquired immunodeficiency syndrome and controls and patients with tropical spastic paraparesis (TSP) and controls for antibody to human T‐lymphotropic virus type I (HTLV‐I), HTLV‐II, human immunodeficiency virus (HIV), simian T‐lymphotropic virus type III, or simian retrovirus type I by immunofluorescent activity test, and for HTLV‐I and HIV by the ELISA method. Sera from patients with multiple sclerosis and matched controls, and from patients with optic neuritis and Parkinson''s or other neuromuscular diseases did not have antibody to any of the retroviruses tested. None of the HTLV-I ELISA readings on samples from AIDS patients or controls or from MS patients, patients with optic neuritis, contro1s, and patients with other neurological diseases were above the cutoff of 0.36.

title:
  Antibody to human and simian retrovirus, HTLV‐I, HTLV‐II, HIV, STLV‐III, and SRV‐I not increased in patients with multiple sclerosis

abstract:
  We have tested sera from patients with multiple sclerosis, matched controls, and those with other neurological diseases, as well as sera from patients with the acquired immunodeficiency syndrome and controls and patients with tropical spastic paraparesis (TSP) and controls for antibody to human T‐lymphotropic virus type I (HTLV‐I), HTLV‐II, human immunodeficiency virus (HIV), simian T‐lymphotropic virus type III, or simian retrovirus type I by immunofluorescent activity test, and for HTLV‐I and HIV by the ELISA method. Sera from patients with multiple sclerosis and matched controls, and from patients with optic neuritis and Parkinson's or other neuromuscular diseases did not have antibody to any of the retroviruses tested. Specimens from TSP patients and some controls contained HTLV‐I antibody. We conclude from our study that only TSP patients had serological evidence of infection with one of the retroviruses studied.


id: cord-330558-autprmr4
title: ACE2, a new regulator of the renin–angiotensin system
author: Burrell, Louise M.
date: 2004-05-31
txt: ./txt/cord-330558-autprmr4.txt
cache: ./cache/cord-330558-autprmr4.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15109615/
doi: 10.1016/j.tem.2004.03.001
summary:
  Ang II is thought to be responsible for most of the physiological and pathophysiological effects of the RAS, and inhibitors of ACE that reduce the formation of Ang II have been highly successful in the management of hypertension, are standard therapy following myocardial infarction to delay the development of heart failure, and reduce the rate of progression of renal disease [2, 3] . Recently, however, the classical view of the RAS has been challenged by the discovery of the enzyme ACE2 [4, 5] , in addition to the increasing awareness that many angiotensin peptides other than Ang II have biological activity and physiological importance [6] . Blockade of the RAS with ACE inhibitors or Ang II type 1 receptor antagonists has clearly established its key role in the pathophysiology of an increasing number of diseases, including hypertension, heart failure, ventricular remodelling, renoprotection and diabetic complications.

abstract:
  Abstract Angiotensin-converting enzyme (ACE) is a zinc metalloproteinase and a key regulator of the renin–angiotensin system (RAS). ACE2 is a newly described enzyme identified in rodents and humans with a more restricted distribution than ACE, and is found mainly in heart and kidney. ACE2 cleaves a single residue from angiotensin I (Ang I) to generate Ang 1–9, and degrades Ang II, the main effector of the RAS, to the vasodilator Ang 1–7. The importance of ACE2 in normal physiology and pathophysiological states is largely unknown. ACE2 might act in a counter-regulatory manner to ACE, modulating the balance between vasoconstrictors and vasodilators within the heart and kidney, and playing a significant role in regulating cardiovascular and renal function.


id: cord-331244-zaguyxm5
title: Confronting the avian influenza threat: vaccine development for a potential pandemic
author: Stephenson, Iain
date: 2004-07-30
url: https://api.elsevier.com/content/article/pii/S1473309904011053
doi: 10.1016/s1473-3099(04)01105-3
abstract:
  Sporadic human infection with avian influenza viruses has raised concern that reassortment between human and avian subtypes could generate viruses of pandemic potential. Vaccination is the principal means to combat the impact of influenza. During an influenza pandemic the immune status of the population would differ from that which exists during interpandemic periods. An emerging pandemic virus will create a surge in worldwide vaccine demand and new approaches in immunisation strategies may be needed to ensure optimum protection of unprimed individuals when vaccine antigen may be limited. The manufacture of vaccines from pathogenic avian influenza viruses by traditional methods is not feasible for safety reasons as well as technical issues. Strategies adopted to overcome these issues include the use of reverse genetic systems to generate reassortant strains, the use of baculovirusexpressed haemagglutinin or related non-pathogenic avian influenza strains, and the use of adjuvants to enhance immunogenicity. In clinical trials, conventional surfaceantigen influenza virus vaccines produced from avian viruses have proved poorly immunogenic in immunologically naive populations. Adjuvanted or whole-virus preparations may improve immunogenicity and allow sparing of antigen.


id: cord-331616-arnuoufn
title: Virus PCR Assay Panels: An Alternative to the Mouse Antibody Production Test
author: Blank, Walter A.
date: 2004
txt: ./txt/cord-331616-arnuoufn.txt
cache: ./cache/cord-331616-arnuoufn.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15235643/
doi: 10.1038/laban0204-26
summary:
  The authors compare MAP testing with PCR-based detection methods, focusing on differences in animal use, laboratory requirements, sample size, and limits of detection. Until recently, the mouse antibody production (MAP) test was the primary method of screening for viruses of murine origin 6 ( Table 1) , but the application of modern molecular biology methods to this purpose presents certain advantages. Because PCR amplifies only DNA molecules, one detects viruses with RNA samples from the animals and test them for virus-specific antibodies using the enzymelinked immunosorbent (ELISA), indirect fluorescent antibody (IFA), or hemagglutination inhibition (HAI) assays. To prevent false-positive results due to contamination with PCR templates, reagent preparation, sample processing, and PCR amplification/product detection should all take place in separate laboratories. Comparison of the sensitivity of in vivo antibody production tests with in vitro PCR-based methods to detect infectious contamination of biological materials

abstract:
  Antibody production tests have traditionally been used to test biological materials for viral contamination. Now molecular biology techniques have emerged as an alternative. The authors compare MAP testing with PCR-based detection methods, focusing on differences in animal use, laboratory requirements, sample size, and limits of detection.


id: cord-332522-adul9nzf
title: Development of Taqman RT-nested PCR system for clinical SARS-CoV detection
author: Wu, Qingfa
date: 2004-04-02
txt: ./txt/cord-332522-adul9nzf.txt
cache: ./cache/cord-332522-adul9nzf.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15109816/
doi: 10.1016/j.jviromet.2004.02.011
summary:
  In this study, 12 sets of nested primers covering the SARS-CoV genome have been screened and showed sufficient sensitivity to detect SARS-CoV in RNA isolated from virus cultured in Vero 6 cells. To optimize further the reaction condition of those nested primers sets, seven sets of nested primers have been chosen to compare their reverse transcribed efficiency with specific and random primers, which is useful to combine RT with the first round of PCR into a one-step RT-PCR. Through investigations on a test panel of whole blood obtained from 30 SARS patients and 9 control persons, the specificity and sensitivity of the Taqman RT-nested PCR system was found to be 100 and 83%, respectively, which suggests that the method is a promising one to diagnose SARS in early stages. To compare the sensitivities of these 12 sets of nested primers, serial 10-fold di-lution genome cDNA of BJ01 that reverse transcribed with random primer was used as the template to carry out the nested PCR.

abstract:
  Severe acute respiratory syndrome (SARS) is an acute newly emerged infectious respiratory illness. The etiologic agent of SARS was named ‘SARS-associated coronavirus’ (SARS-CoV) that can be detected with reverse transcription-polymerase chain reaction (RT-PCR) assays. In this study, 12 sets of nested primers covering the SARS-CoV genome have been screened and showed sufficient sensitivity to detect SARS-CoV in RNA isolated from virus cultured in Vero 6 cells. To optimize further the reaction condition of those nested primers sets, seven sets of nested primers have been chosen to compare their reverse transcribed efficiency with specific and random primers, which is useful to combine RT with the first round of PCR into a one-step RT-PCR. Based on the sensitivity and simplicity of results, the no. 73 primer set was chosen as the candidate primer set for clinical diagnoses. To specify the amplicon to minimize false positive results, a Taqman RT-nested PCR system of no. 73 nested primer set was developed. Through investigations on a test panel of whole blood obtained from 30 SARS patients and 9 control persons, the specificity and sensitivity of the Taqman RT-nested PCR system was found to be 100 and 83%, respectively, which suggests that the method is a promising one to diagnose SARS in early stages.


id: cord-333405-ji58jbct
title: The challenge of emerging and re-emerging infectious diseases
author: Morens, David M.
date: 2004-07-08
txt: ./txt/cord-333405-ji58jbct.txt
cache: ./cache/cord-333405-ji58jbct.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15241422/
doi: 10.1038/nature02759
summary:
  Of the ''newly emerging'' and ''re-emerging/resurging'' diseases that have followed the appearance of AIDS (Fig. 1) , some have been minor curiosities, such as the 2003 cases of monkeypox imported into the United States 4 , whereas others, such as severe acute respiratory syndrome (SARS), which emerged in the same year 5 , have had a worldwide impact. The impact of both new and re-emerging infectious diseases on human populations is affected by the rate and degree to which they spread across geographical areas, depending on the movement of human hosts or of the vectors or reservoirs of infections. Immune deficiency associated with AIDS, and with chemotherapy for cancer, immune-mediated diseases and transplantation, has contributed to an enormous global increase in the numbers of immunosuppressed people over the past few decades (probably more than 1% of the world''s population), setting the stage for the re-emergence of many opportunistic infections.

abstract:
  Infectious diseases have for centuries ranked with wars and famine as major challenges to human progress and survival. They remain among the leading causes of death and disability worldwide. Against a constant background of established infections, epidemics of new and old infectious diseases periodically emerge, greatly magnifying the global burden of infections. Studies of these emerging infections reveal the evolutionary properties of pathogenic microorganisms and the dynamic relationships between microorganisms, their hosts and the environment.


id: cord-334366-gl5eqlkh
author: Murris-Espin, M.
date: 2004-06-30
txt: ./txt/cord-334366-gl5eqlkh.txt
cache: ./cache/cord-334366-gl5eqlkh.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0761842504720240
doi: 10.1016/s0761-8425(04)72024-0
abstract: Unknown
summary:
  title: Par rapport à la vancomycine, le linézolide améliore la guérison et la survie des patients atteints de pneumonias nosocomiales à Staphylococcus aureus méthicilline-résistant (SAMR) R.G. Wunderin Plusieurs études ont montré une efficacité du linézolide identique à celle de la vancomycine dans les infections nosocomiales à Gram positif [2] [3] [4] . Dans les pneumonies confirmées à SAMR par hémoculture ou prélèvement invasif, le bénéfice de survie dans le groupe linézolide était confirmé : 85 % vs 67 %, p = 0,05. En termes de guérison clinique, des résultats identiques étaient retrouvés dans le sous-groupe des pneumonies à SAMR confirmées par hémoculture ou prélèvement invasif. Cette étude, bien que rétrospective, donc imparfaite sur le plan méthodologique, mais reprenant les résultats de deux études méthodologiquement comparables et de qualité, souligne, en termes de survie, l''intérêt d''un traitement empirique précoce par linézolide en cas de pneumonie nosocomiale suspectée à SAMR.

title:
  Par rapport à la vancomycine, le linézolide améliore la guérison et la survie des patients atteints de pneumonias nosocomiales à Staphylococcus aureus méthicilline-résistant (SAMR) R.G. Wunderin


id: cord-335691-lsuwsm43
title: The Burden of Community-Acquired Pneumonia in Seniors: Results of a Population-Based Study
author: Jackson, Michael L.
date: 2004-12-01
txt: ./txt/cord-335691-lsuwsm43.txt
cache: ./cache/cord-335691-lsuwsm43.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15578365/
doi: 10.1086/425615
summary:
  To estimate rates of community-acquired pneumonia and to identify risk factors for this disease, we conducted a large, population-based cohort study of persons aged ⩾65 years that included both hospitalizations and outpatient visits for pneumonia. In multivariate analysis, age, male sex, current smoking, diabetes mellitus, congestive heart failure, lung cancer, serious nonlung cancer, COPD, asthma without COPD, dementia, stroke, receipt of prednisone, use of home oxygen services, greater number of outpatient visits, and hospitalization for pneumonia in the year prior to the study start date were independently associated with risk of all CAP (table 3) . A population-based study involving 4175 elderly persons in Finland found that crude CAP rates did not differ between men and women and that male sex was not significantly associated with CAP after accounting for age and certain chronic medical conditions and risk factors, including asthma, receipt of immunosuppressive therapy, and heart disease [21] .

abstract:
  Background. Pneumonia is recognized as a leading cause of morbidity in seniors. However, the overall burden of this disease—and, in particular, the contribution of ambulatory cases to that burden—is not well defined. To estimate rates of community-acquired pneumonia and to identify risk factors for this disease, we conducted a large, population-based cohort study of persons aged ⩾65 years that included both hospitalizations and outpatient visits for pneumonia. Methods. The study population consisted of 46,237 seniors enrolled at Group Health Cooperative who were observed over a 3-year period. Pneumonia episodes presumptively identified by International Classification of Diseases, Ninth Revision, Clinical Modification codes assigned to medical encounters were validated by medical record review. Characteristics of participants were defined by administrative data sources. Results. The overall rate of community-acquired pneumonia ranged from 18.2 cases per 1000 person-years among persons aged 65–69 years to 52.3 cases per 1000 person-years among those aged ⩾85 years. In this population, 59.3% of all pneumonia episodes were treated on an outpatient basis. In multivariate analysis, risk factors for community-acquired pneumonia included age, male sex, chronic obstructive pulmonary disease, asthma, diabetes mellitus, congestive heart failure, and smoking. Conclusions. On the basis of these data, we estimate that roughly 915,900 cases of community-acquired pneumonia occur annually among seniors in the United States and that ∼1 of every 20 persons aged ⩾85 years will have a new episode of community-acquired pneumonia each year.


id: cord-336063-66qoykl1
title: Recognition of Functional Sites in Protein Structures()
author: Shulman-Peleg, Alexandra
date: 2004-06-04
url: https://www.sciencedirect.com/science/article/pii/S0022283604004139
doi: 10.1016/j.jmb.2004.04.012
abstract:
  Recognition of regions on the surface of one protein, that are similar to a binding site of another is crucial for the prediction of molecular interactions and for functional classifications. We first describe a novel method, SiteEngine, that assumes no sequence or fold similarities and is able to recognize proteins that have similar binding sites and may perform similar functions. We achieve high efficiency and speed by introducing a low-resolution surface representation via chemically important surface points, by hashing triangles of physico-chemical properties and by application of hierarchical scoring schemes for a thorough exploration of global and local similarities. We proceed to rigorously apply this method to functional site recognition in three possible ways: first, we search a given functional site on a large set of complete protein structures. Second, a potential functional site on a protein of interest is compared with known binding sites, to recognize similar features. Third, a complete protein structure is searched for the presence of an a priori unknown functional site, similar to known sites. Our method is robust and efficient enough to allow computationally demanding applications such as the first and the third. From the biological standpoint, the first application may identify secondary binding sites of drugs that may lead to side-effects. The third application finds new potential sites on the protein that may provide targets for drug design. Each of the three applications may aid in assigning a function and in classification of binding patterns. We highlight the advantages and disadvantages of each type of search, provide examples of large-scale searches of the entire Protein Data Base and make functional predictions.


id: cord-336605-d4loia11
author: Zhang, Xue Wu
date: 2004-05-15
txt: ./txt/cord-336605-d4loia11.txt
cache: ./cache/cord-336605-d4loia11.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0968089604002214
doi: 10.1016/j.bmc.2004.03.035
summary:
  To allow structure-based design of drugs directed at SARS-CoV main proteinase, we predicted its binding pockets and affinities with existing HIV, psychotic and parasite drugs (lopinavir, ritonavir, niclosamide and promazine), which show signs of inhibiting the replication of SARS-CoV. Except four drugs (lopinavir, ritonavir, niclosamide and promazine), we also conducted the docking studies of two other molecules, PNU and UC2, for their molecular formulas are close to those of niclosamide and promazine, respectively (Fig. 2) , and they both are the inhibitors of HIV-1 reverse transcriptase. Figure 3 displays the overall structures of docking for four drugs (lopinavir, ritonavir, niclosamide and promazine) and two inhibitors (PNU and UC2) to SARS-CoV main proteinase. Thus, the four drugs and two inhibitors studied here can basically bind to the active site of SARS-CoV main proteinase, a cleft between domains I and II.

title:
  Old drugs as lead compounds for a new disease? Binding analysis of SARS coronavirus main proteinase with HIV, psychotic and parasite drugs

abstract:
  The SARS-associated coronavirus (SARS-CoV) main proteinase is a key enzyme in viral polyprotein processing. To allow structure-based design of drugs directed at SARS-CoV main proteinase, we predicted its binding pockets and affinities with existing HIV, psychotic and parasite drugs (lopinavir, ritonavir, niclosamide and promazine), which show signs of inhibiting the replication of SARS-CoV. Our results suggest that these drugs and another two HIV inhibitors (PNU and UC2) could be used as templates for designing SARS-CoV proteinase inhibitors.


id: cord-339062-tq0f6d01
title: Transmission cycles, host range, evolution and emergence of arboviral disease
author: Weaver, Scott C.
date: 2004
txt: ./txt/cord-339062-tq0f6d01.txt
cache: ./cache/cord-339062-tq0f6d01.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15378043/
doi: 10.1038/nrmicro1006
summary:
  RNA viruses, including HIV 1,2 , dengue virus (DENV) 3, 4 and possibly the severe acute respiratory syndrome (SARS) coronavirus [5] [6] [7] , have caused recent pandemics by changing their host range to amplify in humans. In this review, we focus on selected viruses such as Venezuelan equine and Japanese encephalitis viruses (VEEV and JEV, respectively), which cause epidemics by adapting to domestic animals and exploiting them as amplification hosts. After identification of VEEV as a cause of human disease, experimental animal models revealed that equine infection results in a high titre VIRAEMIA; the animals therefore serve as highly efficient amplification hosts in the presence of abundant competent mosquito vectors 12 However, studies of dengue virus ecology in sylvatic habitats of west Africa 72 and Malaysia 73, 74 have identified transmission cycles involving non-human primates as reservoir hosts and arboreal, tree-hole dwelling Aedes (Stegomyia) spp.

abstract:
  Many pandemics have been attributed to the ability of some RNA viruses to change their host range to include humans. Here, we review the mechanisms of disease emergence that are related to the host-range specificity of selected mosquito-borne alphaviruses and flaviviruses. We discuss viruses of medical importance, including Venezuelan equine and Japanese encephalitis viruses, dengue viruses and West Nile viruses.


id: cord-339514-0aa58pi6
title: Assembly of human severe acute respiratory syndrome coronavirus-like particles
author: Ho, Yu
date: 2004-06-11
txt: ./txt/cord-339514-0aa58pi6.txt
cache: ./cache/cord-339514-0aa58pi6.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S0006291X04008253
doi: 10.1016/j.bbrc.2004.04.111
summary:
  Viral particles of human severe acute respiratory syndrome coronavirus (SARS CoV) consist of three virion structural proteins, including spike protein, membrane protein, and envelope protein. In this report, virus-like particles were assembled in insect cells by the co-infection with recombinant baculoviruses, which separately express one of these three virion proteins. Sucrose gradient purification followed by Western blot analysis and immunogold labeling showed that the spike protein could be incorporated into the virus like particle also. Recombinant baculoviruses encoding E, M, and S protein genes were used to infect Sf21 insect cell, and the expression of each protein was checked by Western blot at 4 dpi (data not shown). The packaging signal of coronavirus RNA was previously identified by using defective interfering viral particles [26] , since the SARS-CoV is a highly infectious virus, it would be much more feasible to identify this signal by using VLPs. Moreover, S protein-containing VLPs should be able to specifically target to the host cell of the SARS CoV and serve as a safe and efficient tool to deliver Western analysis confirmed the presence of S and E proteins mainly in fractions 16-18.

abstract:
  Viral particles of human severe acute respiratory syndrome coronavirus (SARS CoV) consist of three virion structural proteins, including spike protein, membrane protein, and envelope protein. In this report, virus-like particles were assembled in insect cells by the co-infection with recombinant baculoviruses, which separately express one of these three virion proteins. We found that the membrane and envelope proteins are sufficient for the efficient formation of virus-like particles and could be visualized by electron microscopy. Sucrose gradient purification followed by Western blot analysis and immunogold labeling showed that the spike protein could be incorporated into the virus like particle also. The construction of engineered virus-like particles bearing resemblance to the authentic one is an important step towards the development of an effective vaccine against infection of SARS CoV.


id: cord-339976-tg2jkss7
author: Wang, Haibin
date: 2004-07-01
txt: ./txt/cord-339976-tg2jkss7.txt
cache: ./cache/cord-339976-tg2jkss7.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15229153/
doi: 10.1373/clinchem.2004.031237
abstract: nan
summary:
  title: Detection and Monitoring of SARS Coronavirus in the Plasma and Peripheral Blood Lymphocytes of Patients with Severe Acute Respiratory Syndrome Reliable and sensitive determination of the SARS CoV load would aid in the early identification of infected individuals, provide guidance for treatment (especially the use of steroid hormones and antiviral agents), and aid in monitoring of a patient''s clinical course and outcome. The method could detect the CoV load during the SARS course, as demonstrated in Fig. 1B , representative data from the 44 patients tested. High frequency of point mutations clustered within the adenosine triphosphatebinding region of BCR/ABL in patients with chronic myeloid leukemia or Ph-positive acute lymphoblastic leukemia who develop imatinib (STI571) resistance Serial analysis of the plasma concentration of SARS coronavirus RNA in pediatric patients with severe acute respiratory syndrome Quantitative analysis and prognostic implication of SARS coronavirus RNA in the plasma and serum of patients with severe acute respiratory syndrome

title:
  Detection and Monitoring of SARS Coronavirus in the Plasma and Peripheral Blood Lymphocytes of Patients with Severe Acute Respiratory Syndrome


id: cord-340611-7ftnttm0
author: Gensheimer, K. F
date: 2004-06-30
url: https://doi.org/10.1016/j.ics.2004.01.021
doi: 10.1016/j.ics.2004.01.021
title:
  Challenges and opportunities in pandemic influenza planning: lessons learned from recent infectious disease preparedness and response efforts

abstract:
  Abstract The impact of the next pandemic influenza is likely to be far greater, by orders of magnitude, than most bioterrorism (BT) scenarios. A written pandemic emergency plan and establishment of emergency management teams are critical to mounting a coordinated and effective response to what will be a catastrophic event. Members of these teams should include public health, medical, emergency response and public safety officials, organized at each local, state and federal level. The tragic events of September 11, 2001 and the subsequent anthrax attacks have substantially increased funding and support for bioterrorism planning in the United States. Thus, public health officials have an unprecedented opportunity to strengthen current systems' planning efforts by promoting dual use bioterrorism/pandemic influenza plans. Combining lessons learned from the 2001 terrorist incidents, recent preevent smallpox vaccine programs and the history of past influenza pandemics, more effective strategies can be developed. For example, enhanced influenza surveillance systems can provide data that will not only provide early identification of a novel influenza strain, but will provide more timely recognition of other outbreaks of infectious diseases, including public health threats that may initially present as an influenza-like illness (ILI). In recent years, we have witnessed emerging and reemerging infectious disease threats that have presented us with challenges similar to those posed by an influenza pandemic. Such events highlight the need for advance planning to ensure an optimal response to a health emergency that is certain to be unpredictable, complex, rapidly evolving and accompanied by considerable public alarm. While advance warning for a terrorist attack is unlikely, the warning already exists for a possible new influenza strain, as evidenced by the recent cases of H5N1 in Hong Kong and the rapid global spread of cases of Severe Acute Respiratory Syndrome.


id: cord-344383-7s4gnxs4
title: Atypical SARS in Geriatric Patient
author: Tee, Augustine K.H.
date: 2004-02-17
txt: ./txt/cord-344383-7s4gnxs4.txt
cache: ./cache/cord-344383-7s4gnxs4.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15030694/
doi: 10.3201/eid1002.030322
summary:
  We describe an atypical presentation of severe acute respiratory syndrome (SARS) in a geriatric patient with multiple coexisting conditions. On the basis of epidemiologic data (contact tracing linking her to one of the three original index cases in Singapore) (12) , the index patient''s cause of death was determined to be SARS (Figure 3 ). Since the issue of a global alert on atypical pneumonia by the World Health Organization on March 12, reported cases of SARS increased daily and appeared in other countries, including Canada, the United States, Europe, and Africa. Our case serves to highlight atypical signs and symptoms of SARS, especially the resolving fever, delay in establishing a positive contact history, and the nonspecific chest radiographic appearance that could be affected by concurrent coexisting conditions, such as cardiac failure. A cluster of cases of severe acute respiratory syndrome in Hong Kong Severe acute respiratory syndrome (SARS) in Singapore: clinical features of index patient and initial contacts

abstract:
  We describe an atypical presentation of severe acute respiratory syndrome (SARS) in a geriatric patient with multiple coexisting conditions. Interpretation of radiographic changes was confounded by cardiac failure, with resolution of fever causing delayed diagnosis and a cluster of cases. SARS should be considered even if a contact history is unavailable, during an ongoing outbreak.


id: cord-345088-krb1eidw
author: Shen, S
date: 2004-09-01
txt: ./txt/cord-345088-krb1eidw.txt
cache: ./cache/cord-345088-krb1eidw.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S0042682204003988
doi: 10.1016/j.virol.2004.06.016
summary:
  title: A single amino acid mutation in the spike protein of coronavirus infectious bronchitis virus hampers its maturation and incorporation into virions at the nonpermissive temperature Here, we report the emergence and isolation of two temperature sensitive (ts) mutants and a revertant in the process of cold-adaptation of coronavirus infectious bronchitis virus (IBV) to a monkey kidney cell line. Evidence presented demonstrated that the Q(294)-to-L(294) mutation, located at a highly conserved domain of the S1 subunit, might hamper processing of the S protein to a matured 180-kDa, endo-glycosidase H-resistant glycoprotein and the translocation of the protein to the cell surface. In virus-infected cells, the Endo-H sensitive, 155-kDa form of ts291602 was abundant at the nonpermissive temperature, clearly indicating that the mutant S protein was trimmed in the ER and cis-Golgi but was not transported to the trans-Golgi.

title:
  A single amino acid mutation in the spike protein of coronavirus infectious bronchitis virus hampers its maturation and incorporation into virions at the nonpermissive temperature

abstract:
  The spike (S) glycoprotein of coronavirus is responsible for receptor binding and membrane fusion. A number of variants with deletions and mutations in the S protein have been isolated from naturally and persistently infected animals and tissue cultures. Here, we report the emergence and isolation of two temperature sensitive (ts) mutants and a revertant in the process of cold-adaptation of coronavirus infectious bronchitis virus (IBV) to a monkey kidney cell line. The complete sequences of wild type (wt) virus, two ts mutants, and the revertant were compared and variations linked to phenotypes were mapped. A single amino acid reversion (L(294)-to-Q) in the S protein is sufficient to abrogate the ts phenotype. Interestingly, unlike wt virus, the revertant grows well at and below 32 °C, the permissive temperature, as it carries other mutations in multiple genes that might be associated with the cold-adaptation phenotype. If the two ts mutants were allowed to enter cells at 32 °C, the S protein was synthesized, core-glycosylated and at least partially modified at 40 °C. However, compared with wt virus and the revertant, no infectious particles of these ts mutants were assembled and released from the ts mutant-infected cells at 40 °C. Evidence presented demonstrated that the Q(294)-to-L(294) mutation, located at a highly conserved domain of the S1 subunit, might hamper processing of the S protein to a matured 180-kDa, endo-glycosidase H-resistant glycoprotein and the translocation of the protein to the cell surface. Consequently, some essential functions of the S protein, including mediation of cell-to-cell fusion and its incorporation into virions, were completely abolished.


id: cord-346629-770qyee8
title: Phylogenetic analysis of avian infectious bronchitis virus strains isolated in Japan
author: Mase, M.
date: 2004-07-15
txt: ./txt/cord-346629-770qyee8.txt
cache: ./cache/cord-346629-770qyee8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15290359/
doi: 10.1007/s00705-004-0369-9
summary:
  title: Phylogenetic analysis of avian infectious bronchitis virus strains isolated in Japan To define the origin and evolution of recent avian infectious bronchitis virus (IBV) in Japan, a genetic analysis was performed. By phylogenetic analysis based on the S1 gene including the sequence of the hypervariable regions, IBV isolates in Japan were classified into five genetic groups, which included two already-known groups (Mass and Gray). In this study, to define the origin and evolution of recent IBV in Japan, we determined the nucleotide sequences of IBV isolated in Japan using the reverse transcriptase-polymerase chain reaction (RT-PCR) method coupled with direct sequencing, and analyzed the sequences phylogenetically with viruses isolated in other countries. By phylogenetic analysis, the IBV isolates in Japan used in this study were divided into five genetic groups (Fig. 1 ). Typing of field isolates of infectious bronchitis virus based on the sequence of the hypervariable region in the S1 gene

abstract:
  To define the origin and evolution of recent avian infectious bronchitis virus (IBV) in Japan, a genetic analysis was performed. By phylogenetic analysis based on the S1 gene including the sequence of the hypervariable regions, IBV isolates in Japan were classified into five genetic groups, which included two already-known groups (Mass and Gray). Among them, three major genetic groups were associated with the recent outbreaks of IB in Japan. One group is indigenous to Japan and could not be placed within the known existing groups in other countries. The remaining two groups, which have emerged recently, are related to isolates in China and Taiwan.


id: cord-347410-6muxz6c5
author: Phillips, Sally
date: 2004-10-19
txt: ./txt/cord-347410-6muxz6c5.txt
cache: ./cache/cord-347410-6muxz6c5.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S8755722304000729
doi: 10.1016/j.profnurs.2004.07.003
abstract: nan
summary:
  Agencies within the Department of Health and Human Services (HHS) have been working to address readiness and response capabilities, but private organizations and professional associations also have a role to play. In keeping with the Public Health Security and Bioterrorism Preparedness and Response Act of 2002, HHS developed a department-wide strategic plan to delineate its priorities. htm) have strategic activities in education, training, licensure, and credentialing for the public health care workforce and for hospital readiness. Under the directive, HHS established the Healthcare Sector Coordinating Council, which has responsibility for activities such as communicating potential risks, threats, and vulnerabilities to private organizations. A coordinating group comprising nurses from university, public health, and response settings, with a secure system that would allow collaboration on issues like identifying and providing a roster of volunteers, would be a good national, consistent approach to identifying and addressing vulnerabilities.

title:
  Readiness and response to public health emergencies: Help needed Now from professional nursing associations


id: cord-350328-wu1ygt6w
title: SARS: responding to an unknown virus
author: Tambyah, P. A.
date: 2004-07-14
txt: ./txt/cord-350328-wu1ygt6w.txt
cache: ./cache/cord-350328-wu1ygt6w.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15252720/
doi: 10.1007/s10096-004-1175-8
summary:
  The severe acute respiratory syndrome (SARS) is an emerging infection caused by a novel coronavirus which first appeared in southern China at the end of 2002. The severe acute respiratory syndrome (SARS) is a newly recognized coronavirus infection that emerged in southern China [1] with subsequent global spread to 29 countries [2] [3] [4] [5] . The newly infected individuals traveled onward to their homes or next destinations in the USA, Canada, Singapore, Hong Kong and Ireland sparking off epidemics of varying degrees of severity in each of those countries, mainly in hospitals but also in their respective communities. A directive had gone out from the Hong Kong Department of Health on 21 February 2003 to maintain strict infection control with droplet precautions for all cases of "atypical" community-acquired pneumonia because of concerns that highly pathogenic avian influenza might be easily transmissible from person to person. Severe acute respiratory syndrome (SARS) in Singapore: clinical features of index patient and initial contacts

abstract:
  The severe acute respiratory syndrome (SARS) is an emerging infection caused by a novel coronavirus which first appeared in southern China at the end of 2002. In early 2003, through a single incident, it spread to Hong Kong, Singapore, Canada and Vietnam. For busy clinicians in large public hospitals, the response to the virus was initially based on ensuring a high level of protection for staff. However, as the epidemic progressed and more information became available about the virus, procedures were rationalized and the virus is currently under control worldwide. There are, however, numerous unanswered questions concerning super-spreading events, the modes of transmission of the virus and, perhaps most importantly, the rapid detection of the virus early in the course of disease. These issues need to be addressed in case the virus becomes more widespread in the near future.


id: cord-350513-ho32ajsx
author: Chen, Paul Chih‐Hsueh
date: 2004-05-07
txt: ./txt/cord-350513-ho32ajsx.txt
cache: ./cache/cord-350513-ho32ajsx.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15141389/
doi: 10.1002/path.1575
abstract: nan
summary:
  Tissue and cellular tropism of the coronavirus associated with severe acute respiratory syndrome: an in‐situ hybridization study of fatal cases. Using in situ hybridization (ISH), To et al demonstrated the presence of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) in pneumocytes and in the surface enterocytes of the small intestine. Supplementing their findings, we report here our recent study, which suggests that the SARS-CoV may not be exclusively located in pneumocytes, but also in pulmonary macrophages. Under low magnification, scattered cells containing dark bluish signals, which represented the SARS-CoV, were visualized ( Figure 1A , nuclear fast red counterstain) within the damaged alveolar spaces, small bronchioles, and even the vascular lumina. Tissue and cellular tropism of the coronavirus associated with severe acute respiratory syndrome: an in-situ hybridization study of fatal cases Chen and Hsiao make an interesting observation on the pathology of severe acute respiratory syndrome (SARS).

title:
  Re: To KF, Tong JH, Chan PK, et al. Tissue and cellular tropism of the coronavirus associated with severe acute respiratory syndrome: an in‐situ hybridization study of fatal cases. J Pathol 2004; 202: 157–163


id: cord-351354-10rusr6j
title: Diagnostic Criteria during SARS Outbreak in Hong Kong
author: Chan, Louis Y.
date: 2004-06-17
txt: ./txt/cord-351354-10rusr6j.txt
cache: ./cache/cord-351354-10rusr6j.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15224676/
doi: 10.3201/eid1006.030618
abstract: nan
summary:
  Before the etiologic agent was identified, the diagnosis of SARS was made according to a set of clinical-epidemiologic criteria as suggested by the Centers for Disease Control and Prevention (CDC) (1-3). These criteria remained important in the initial diagnosis and prompt isolation of patients because the overall sensitivity of initial reverse transcriptase-polymerase chain reaction (RT-PCR) testing for SARSassociated coronavirus (SARS CoV) RNA on upper respiratory specimens ranged from approximately 60% to 70% (though sensitivity improved with a second test) (4, 5) . By using paired serologic testing to determine SARS-CoV infection (3), we evaluated the relative importance of the clinical-epidemiologic diagnostic criteria during an outbreak. Probable SARS case-patients were those who met the CDC clinical criteria for severe respiratory illness of unknown etiology (3), and met the epidemiologic criterion for exposure in either a close or a possible contact. Our findings showed that 5.9% of cases defined as probable SARS on the basis of clinical-epidemiologic criteria had no serologic evidence of coronavirus infection.


id: cord-353308-e4s8el0s
title: Severe acute respiratory syndrome: review and lessons of the 2003 outbreak
author: Parashar, Umesh D
date: 2004-05-20
txt: ./txt/cord-353308-e4s8el0s.txt
cache: ./cache/cord-353308-e4s8el0s.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15155694/
doi: 10.1093/ije/dyh198
abstract: nan
summary:
  This dramatic chain of transmission brought to the world''s attention this new respiratory disease, called severe acute respiratory syndrome (SARS), and clearly illustrated the potential for SARS to spread extensively from a single infected person and to rapidly disseminate globally through air travel. Diarrhoea has been reported at presentation in approximately 25% of patients, although this symptom was observed in as many as 73% of all patients affected by an outbreak at an apartment complex in Hong Kong that is believed to have resulted from fecal-oral/respiratory transmission of SARS-CoV. [53] [54] [55] [56] Given that profuse watery diarrhoea is seen in a significant proportion of patients and SARS-CoV can be shed in large quantities in stool, faeces remain a possible source of virus and fecal-oral or fecal-respiratory spread are the leading hypotheses for a large outbreak affecting more than 300 people at an apartment complex in Hong Kong. Fatal severe acute respiratory syndrome is associated with multiorgan involvement by coronavirus (SARS-CoV)


id: cord-354130-mi7saerx
title: Microbiological Monitoring in Individually Ventilated Cage Systems
author: Compton, Susan R.
date: 2004
txt: ./txt/cord-354130-mi7saerx.txt
cache: ./cache/cord-354130-mi7saerx.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15514655/
doi: 10.1038/laban1104-36
summary:
  The limitations of molecular methods are that they are relatively expensive, they can yield both false negative and false positive results, their high sensitivity makes them prone to cross-contamination, and many substances found in blood, feces, and other animal tissues can function Methods such as exposing sentinels to soiled bedding, as used traditionally with mice housed in static isolator cages, also require reassessment for their applicability in IVC systems. There are many ways of detecting an infectious agent that has been transmitted to one or more rodents housed in IVCs. The most direct method of surveillance is to monitor the colony mice themselves for evidence of an infection. The decreased intercage spread of an infectious agent means that infections are sporadic and confined to just a few cages at a time, and it is therefore essential to use an adequate sample size when monitoring mice housed in IVC systems.

abstract:
  Housing rodents in IVC racks has many advantages over conventional cages but also presents unique challenges related to health monitoring. The authors review the issues to consider in design of a sentinel program using IVC systems.


id: cord-354209-g1zynbul
title: Fear and Stigma: The Epidemic within the SARS Outbreak
author: Person, Bobbie
date: 2004-02-17
txt: ./txt/cord-354209-g1zynbul.txt
cache: ./cache/cord-354209-g1zynbul.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15030713/
doi: 10.3201/eid1002.030750
summary:
  While other NCID/CDC response teams dealt with laboratory investigations, surveillance, communica-tion, and clinical infection control practices, the Community Outreach Team worked to implement rapid public health strategies to document, monitor, and assist in ameliorating specific problems associated with fear, stigmatization, and discrimination attributed to the SARS outbreak in the United States. The team carried out the following activities: 1) facilitated group discussions with key opinion leaders within the Asian community in the United States; 2) collected and monitored the CDC Public Response Service data; 3) collected and monitored Asian-language newspapers, Internet sites, and other information sources; 4) reviewed polling data and other communication information; 5) conducted community visits, panel discussions, and media interviews; 6) solicited information from state and regional minority health liaisons nationwide; 7) developed ongoing relationships with the Asian-American communities; particularly in major metropolitan areas throughout the United States; and 8) determined new datagathering strategies as needed.

abstract:
  Because of their evolving nature and inherent scientific uncertainties, outbreaks of emerging infectious diseases can be associated with considerable fear in the general public or in specific communities, especially when illness and deaths are substantial. Mitigating fear and discrimination directed toward persons infected with, and affected by, infectious disease can be important in controlling transmission. Persons who are feared and stigmatized may delay seeking care and remain in the community undetected. This article outlines efforts to rapidly assess, monitor, and address fears associated with the 2003 severe acute respiratory syndrome (SARS) epidemic in the United States. Although fear, stigmatization, and discrimination were not widespread in the general public, Asian-American communities were particularly affected.


id: cord-354407-zzxjv666
author: Campanacci, Valérie
date: 2004-06-07
txt: ./txt/cord-354407-zzxjv666.txt
cache: ./cache/cord-354407-zzxjv666.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/12925794/
doi: 10.1107/s0907444903016779
summary:
  title: Structural genomics of the SARS coronavirus: cloning, expression, crystallization and preliminary crystallographic study of the Nsp9 protein The aetiologic agent of the recent epidemics of Severe Acute Respiratory Syndrome (SARS) is a positive‐stranded RNA virus (SARS‐CoV) belonging to the Coronaviridae family and its genome differs substantially from those of other known coronaviruses. The crystal structure of the main (or 3CL) protease of transmissible gastroenteritis virus, a related coronavirus, has been determined and was used to construct a model of the SARS-CoV 3CL protease, facilitating future drug design against this important target (Anand et al., 2003) . In the related mouse hepatitis virus, which is a group 2 coronavirus, the SARS-CoV Nsp9 corresponds to a 12 kDa cleavage product (P1a-12) that is found preferentially in the perinuclear region of infected cells, where it co-localizes with other components of the viral replication complex (Bost et al., 2000) .

title:
  Structural genomics of the SARS coronavirus: cloning, expression, crystallization and preliminary crystallographic study of the Nsp9 protein

abstract:
  The aetiologic agent of the recent epidemics of Severe Acute Respiratory Syndrome (SARS) is a positive‐stranded RNA virus (SARS‐CoV) belonging to the Coronaviridae family and its genome differs substantially from those of other known coronaviruses. SARS‐CoV is transmissible mainly by the respiratory route and to date there is no vaccine and no prophylactic or therapeutic treatments against this agent. A SARS‐CoV whole‐genome approach has been developed aimed at determining the crystal structure of all of its proteins or domains. These studies are expected to greatly facilitate drug design. The genomes of coronaviruses are between 27 and 31.5 kbp in length, the largest of the known RNA viruses, and encode 20–30 mature proteins. The functions of many of these polypeptides, including the Nsp9–Nsp10 replicase‐cleavage products, are still unknown. Here, the cloning, Escherichia coli expression, purification and crystallization of the SARS‐CoV Nsp9 protein, the first SARS‐CoV protein to be crystallized, are reported. Nsp9 crystals diffract to 2.8 Å resolution and belong to space group P6(1/5)22, with unit‐cell parameters a = b = 89.7, c = 136.7 Å. With two molecules in the asymmetric unit, the solvent content is 60% (V (M) = 3.1 Å(3) Da(−1)).


