Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both viral effect and immune-mediated mechanism are involved in the pathogenesis of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infection. In this study, we showed that in SARS patient sera there were autoantibodies (autoAbs) that reacted with A549 cells, the type-2 pneumocytes, and that these autoAbs were mainly IgG. The autoAbs were detectable 20 days after fever onset. Tests of non-SARS-pneumonia patients did not show the same autoAb production as in SARS patients. After sera IgG bound to A549 cells, cytotoxicity was induced. Cell cytotoxicity and the anti-epithelial cell IgG level were positively correlated. Preabsorption and binding assays indicated the existence of cross-reactive epitopes on SARS-CoV spike protein domain 2 (S2). Furthermore, treatment of A549 cells with anti-S2 Abs and IFN-gamma resulted in an increase in the adherence of human peripheral blood mononuclear cells to these epithelial cells. Taken together, we have demonstrated that the anti-S2 Abs in SARS patient sera cause cytotoxic injury as well as enhance immune cell adhesion to epithelial cells. The onset of autoimmune responses in SARS-CoV infection may be implicated in SARS pathogenesis.
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PMID:Antibody to severe acute respiratory syndrome (SARS)-associated coronavirus spike protein domain 2 cross-reacts with lung epithelial cells and causes cytotoxicity. 1604 40

Severe acute respiratory syndrome (SARS) is a significant emerging infectious disease. Humans infected with the etiological agent, SARS-associated coronavirus (SARS-CoV), primarily present with pneumonitis but may also develop hepatic, gastrointestinal, and renal pathology. We inoculated common marmosets (Callithrix jacchus) with the objective of developing a small nonhuman primate model of SARS. Two groups of C. jacchus were inoculated intratracheally with cell culture supernatant containing SARS-CoV. In a time course pathogenesis study, animals were evaluated at 2, 4, and 7 days after infection for morphological changes and evidence of viral replication. All animals developed a multifocal mononuclear cell interstitial pneumonitis, accompanied by multinucleated syncytial cells, edema, and bronchiolitis in most animals. Viral antigen localized primarily to infected alveolar macrophages and type-1 pneumocytes by immunohistochemistry. Viral RNA was detected in all animals from pulmonary tissue extracts obtained at necropsy. Viral RNA was also detected in tracheobronchial lymph node and myocardium, together with inflammatory changes, in some animals. Hepatic inflammation was observed in most animals, predominantly as a multifocal lymphocytic hepatitis accompanied by necrosis of individual hepatocytes. These findings identify the common marmoset as a promising nonhuman primate to study SARS-CoV pathogenesis.
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PMID:Pneumonitis and multi-organ system disease in common marmosets (Callithrix jacchus) infected with the severe acute respiratory syndrome-associated coronavirus. 1604 31

Experimental studies were performed to determine the role of a newly isolated reovirus (ReoV) from a severe acute respiratory syndrome (SARS) patient in the etiology of this newly described serious respiratory syndrome. Four cynomologus macaques were inoculated with this reovirus (BYD1) in an attempt to replicate the infection and pathology observed in SARS. The body temperature of the infected monkeys was monitored three times a day, and blood and fecal samples were periodically collected for specific immunology determinations. On days 7 and 33 after inoculation, necropsies for pathological accessment and pathogen isolation were performed. The four infected macaques developed a fever on days 3 and 4 after inoculation, and maintainted a febrile state for 4-6 days. The highest temperature in the animals recorded was 40.4 degrees C. After a recovery phase, the macaques developed a second febrile condition. Antibody titers against the reovirus injected by the intravenous route occurred in higher number than those in the nasal cavity. Four macaque monkeys demonstrated diffuse alveolar damage, characterized by hemorrhagic pneumonia, serosanguineous exudates, formation of hyaline membranes, and type II pneumocyte hyperplasia, which were similar to those that have been noted in SARS patients. Lymphocytes decreased in the cortex of the lymph node and in the white pulp of the spleen. ReoV was detected in pneumonic tissue by virus isolation and RT-PCR. The macaques infected with the newly isolated reovirus developed a fever, diffuse alveolar damage and pulmonary interstitial inflammation similar to that noted in SARS patients. This evidence demonstrates that ReoV might have a primary role in the etiology of SARS.
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PMID:Experimental infection of macaques with the human reovirus BYD1 strain: an animal model for the study of the severe acute respiratory syndrome. 1610 46

Infectious diseases that do not primarily affect the gastrointestinal tract can cause severe diarrhea. The pathogenesis of this kind of diarrhea includes cytokine action, intestinal inflammation, sequestration of red blood cells, apoptosis and increased permeability of endothelial cells in the gut microvasculature, and direct invasion of gut epithelial cells by various infectious agents. Of the travel-associated systemic infections presenting with fever, diarrhea occurs in patients with malaria, dengue fever and SARS. Diarrhea also occurs in patients with community-acquired pneumonia, when it is suggestive of legionellosis. Diarrhea can also occur in patients with systemic bacterial infections. In addition, although diarrhea is rare in patients with early Lyme borreliosis, the incidence is higher in those with other tick-borne infections, such as ehrlichiosis, tick-borne relapsing fever and Rocky Mountain spotted fever. Unfortunately, it is often not established whether diarrhea is an initial symptom or develops during the course of the disease. The real incidence of diarrhea in some infectious diseases must also be questioned because it could represent an adverse reaction to antibiotics.
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PMID:Diarrhea caused by primarily non-gastrointestinal infections. 1626 4

Severe acute respiratory syndrome (SARS) is a recently discovered viral disease, characterized by fever, cough, acute fibrinous pneumonia and high infectivity. Specific pathogen-free (SPF) chickens were immunized with inactivated SARS coronavirus and their eggs were harvested at regular intervals. Yolk immunoglobulin (IgY) was extracted using the water dilution method, followed by further purification on a Sephadex G-75 column. SDS-polyacrylamide gel electrophoresis (SDS-PAGE), Western blot and neutralization test results showed that the IgY obtained was of a high purity and had a strong reactive activity with a neutralization titer of 1:640. Lyophilization and stability tests showed that lyophilized anti-SARS coronavirus IgY had promising physical properties, with no significant reduction in reactive activity and good thermal stability. All these data suggest that the anti-SARS coronavirus IgY could be a new useful biological product for specific antiviral therapy against SARS.
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PMID:Preparation and evaluation of anti-SARS coronavirus IgY from yolks of immunized SPF chickens. 1632 77

SARS is a new type of infectious pneumonia that emerged in China in November 2002. It spread around the world through an outbreak in Hong Kong in March 2003. Patients were reported in 29 countries, and around 800 people died, although a majority of these cases were in Asian countries. Within a month after the virus that causes SARS was isolated, its entire genome sequence became available. The result is the acknowledgement of a novel coronavirus, now called SARS coronavirus (SCoV), that is different from other already known existing human and animal coronaviruses. Since a number of scientists from distinct fields have participated in the research on this emerging virus, a plenty of information has become available, and now SARS-CoV has become one of the best-studied members among coronaviruses. In this review, I would like describe on SCoV virology by comparison with other well-studied coronaviruses. It covers the taxonomy, structure of virion, viral genome and proteins, unique replication strategy, receptors and viral pathogenesis. In the last part, I mention with my personal speculation about the origin and evolution of SCoV.
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PMID:[SARS coronavirus]. 1636 82

Severe acute respiratory syndrome (SARS) coronavirus (SCoV) causes a recently emerged human disease associated with pneumonia. The 5' end two-thirds of the single-stranded positive-sense viral genomic RNA, gene 1, encodes 16 mature proteins. Expression of nsp1, the most N-terminal gene 1 protein, prevented Sendai virus-induced endogenous IFN-beta mRNA accumulation without inhibiting dimerization of IFN regulatory factor 3, a protein that is essential for activation of the IFN-beta promoter. Furthermore, nsp1 expression promoted degradation of expressed RNA transcripts and host endogenous mRNAs, leading to a strong host protein synthesis inhibition. SCoV replication also promoted degradation of expressed RNA transcripts and host mRNAs, suggesting that nsp1 exerted its mRNA destabilization function in infected cells. In contrast to nsp1-induced mRNA destablization, no degradation of the 28S and 18S rRNAs occurred in either nsp1-expressing cells or SCoV-infected cells. These data suggested that, in infected cells, nsp1 promotes host mRNA degradation and thereby suppresses host gene expression, including proteins involved in host innate immune functions. SCoV nsp1-mediated promotion of host mRNA degradation may play an important role in SCoV pathogenesis.
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PMID:Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression by promoting host mRNA degradation. 1691 15

The Centers for Disease Control and Prevention (CDC) recommend that SARS-coronavirus (SARS-CoV) testing be considered in epidemiologically high-risk patients hospitalized with community-acquired pneumonia (CAP) if no alternative diagnosis is identified after 72 h. The aim of this study was to identify routine laboratory variables that might indicate the need for SARS-CoV testing. Routine hematological/biochemical variables in patients with laboratory-confirmed SARS (2003) were compared with those in consecutive patients hospitalized June-December 2004 with radiologically confirmed CAP. Stepwise logistic regression analyses were performed to identify discriminating variables at baseline and by day 3 of hospitalization. Nasopharyngeal aspiration and antigen detection for influenza virus and respiratory syncytial virus using an immunofluorescence assay (IFA) were routinely performed in patients with CAP. Altogether, 181 patients with CAP (who remained undiagnosed by IFA) and 303 patients with SARS were studied. The mean intervals from symptom onset to admission were 3.1 and 2.8 days, respectively (p > 0.05). The etiological agent of CAP was identified retrospectively in only 39% of cases, the majority being bacterial pathogens. At baseline, age and absolute neutrophil count (ANC) were the only independent discriminating variables (p < 0.0001). Using a value of <4.4 x 10(9)/l as the cutoff for ANC, the sensitivity and specificity of ANC for discriminating SARS were 64 and 95%, respectively (AUC 0.90). By day 3 of hospitalization, age (p < 0.0001), change in ANC (p = 0.0003), and change in bilirubin (p = 0.0065) were discriminating variables. A model combining age <65 years, a change in ANC of >-3 x 10(9)/l, and a change in bilirubin of > or =0 mmol/l had a sensitivity of 43% and a specificity of 95% for SARS (AUC 0.90). There are only a few laboratory features (including lymphopenia) that clearly discriminate SARS from other causes of CAP. Nevertheless, when evaluating epidemiologically high-risk patients with CAP and no immediate alternative diagnosis, a low ANC on presentation along with poor clinical and laboratory responses after 72 h of antibiotic treatment may raise the index of suspicion for SARS and indicate a need to perform SARS-CoV testing.
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PMID:Role of laboratory variables in differentiating SARS-coronavirus from other causes of community-acquired pneumonia within the first 72 h of hospitalization. 1707 67

Severe acute respiratory distress syndrome (SARS) caused by SARS-associated coronavirus (SARS-CoV) is a systemic infection that clinically manifests as progressive pneumonia. During the initial phases of infection the virus causes pauci-inflammatory alveolar and interstitial edema that result in imaging abnormalities dominated by ground glass opacities (GGO). Severe SARS cases can develop radiologic and pathologic findings of diffuse alveolar damage. Although radiologic evidence of acute bronchiolitis is absent, SARS-CoV also infects ciliated airway epithelium, probably accounting for respiratory transmissibility of the virus. Radiologic recovery from SARS can be complete, but computed tomography images often show persistent GGO and reticular opacities, some of which reflect pathologic findings of fibrosis. Long-term follow-up imaging of survivors shows gradual decrease of GGO and reticulation with persistent air trapping in some patients. The latter is evidence of small airway disease that is not radiologically evident at the onset of the disease.
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PMID:Radiology of severe acute respiratory syndrome (SARS): the emerging pathologic-radiologic correlates of an emerging disease. 1711 Aug 51

Coronaviruses (CoVs), a genus containing about 26 known species to date, cause highly prevalent diseases and are often severe or fatal in humans and animals. In 2003, a previously unknown coronavirus was identified to be the etiological agent of a global outbreak of a form of life-threatening pneumonia called severe acute respiratory syndrome (SARS). No efficacious therapy is currently available, and vaccines and drugs are under development to prevent SARS-CoV infection in many countries. The CoV main protease (M(pro)), which plays a pivotal role in viral gene expression and replication through a highly complex cascade involving the proteolytic processing of replicase polyproteins, is an attractive target for drug design. This review summarizes the recent advances in biological and structural studies, together with development of inhibitors targeting CoV M(pro)s. It is expected that inhibitors targeting CoV M(pro)s could be developed into wide-spectrum antiviral drugs against existing and possible future emerging CoV-associated diseases.
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PMID:Drug design targeting the main protease, the Achilles' heel of coronaviruses. 1716 63


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