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)

Febrile respiratory illnesses with respiratory failure are one of the most common reasons for admission to the intensive care unit. Most causes of febrile respiratory illness are bacterial and viral agents of community-acquired pneumonia. However, a small number of rare and highly contagious agents can initially present as febrile respiratory illnesses, which can lead to an epidemic that can greatly impact the health care system. This impact includes sustained mass critical care, with potential scarcity of critical resources (eg, positive-pressure ventilators), spread of disease to health care workers, sustained spread within the community, and extensive morbidity and mortality. The main agents of febrile respiratory illness that would lead to an epidemic include influenza, the coronavirus that causes severe acute respiratory syndrome, smallpox, viral hemorrhagic fever, plague, tularemia, and anthrax. Recognition of these agents occurs largely based on epidemiological clues, and management consists of antibiotics, antivirals, supportive care, and positive-pressure ventilation. Acute respiratory failure and acute respiratory distress syndrome occur with these agents, so a lung-protective (low tidal volume) ventilation strategy is indicated. Additional respiratory care measures, such as nebulized medications, bronchoscopy, humidified oxygen, and airway suctioning, potentiate aerosolization of the virus or bacteria and increase the risk of transmission to health care workers and patients. Thus, appropriate personal protective equipment, including an N95 mask or powered air-purifying respirator, is indicated. A basic understanding of the epidemiology, clinical findings, diagnosis, and treatment of these agents will provide a foundation for early isolation, evaluation, infection control, and public health involvement and response in cases of a febrile respiratory illness that causes respiratory failure.
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PMID:Severe febrile respiratory illnesses as a cause of mass critical care. 1817 59

A new strain of coronavirus has caused an outbreak of severe acute respiratory syndrome (SARS) from 2002 to 2003 resulting in 774 deaths worldwide. By protein chip array profiling technology, a number of serum biomarkers that might be useful in monitoring the clinical course of SARS patients were identified. This book chapter describes how the protein chip array profiling was carried out for this study. Briefly, SARS patients' serum samples were first fractionated in Q Ceramic HyperD ion exchange sorbent beads by buffers at different pH. Serum protein fractions thus obtained were then bound onto a copper (II) immobilized metal affinity capture (IMAC30 Cu [II]) ProteinChip Array or a weak cation-exchange (CM10) ProteinChip Array. After washing and addition of sinapinic acid, the chips were read in a Protein Biological System (PBS) IIc mass spectrometer. Ions were generated by laser shots and flied in a time of flight mode to the ion detector according to their mass over charge (m/z) ratio. The serum profiling spectra in SARS patients were acquired, baseline subtracted and analyzed in parallel with those from the control subjects by Ciphergen ProteinChip Software 3.0.2 with their peak intensities compared by a nonparametric two sample Mann-Whitney-U test. More than twelve peaks were differentially expressed in SARS patients with one at m/z of 11,695 (later identified to be serum amyloid A protein), which had increase in peak intensity correlating with the extent of SARS-coronavirus induced pneumonia as defined by a serial chest X-ray opacity score. The remaining biomarkers could also be useful in the study of other clinical parameters in SARS patients.
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PMID:Application of ProteinChip array profiling in serum biomarker discovery for patients suffering from severe acute respiratory syndrome. 1822 Feb 40

Although multiple viruses utilize host cell cyclophilins, including severe acute respiratory syndrome (SARS) and human immunodeficiency virus type-1(HIV-1), their role in infection is poorly understood. To help elucidate these roles, we have characterized the first virally encoded cyclophilin (mimicyp) derived from the largest virus discovered to date (the Mimivirus) that is also a causative agent of pneumonia in humans. Mimicyp adopts a typical cyclophilin-fold, yet it also forms trimers unlike any previously characterized homologue. Strikingly, immunofluorescence assays reveal that mimicyp localizes to the surface of the mature virion, as recently proposed for several viruses that recruit host cell cyclophilins such as SARS and HIV-1. Additionally mimicyp lacks peptidyl-prolyl isomerase activity in contrast to human cyclophilins. Thus, this study suggests that cyclophilins, whether recruited from host cells (i.e. HIV-1 and SARS) or virally encoded (i.e. Mimivirus), are localized on viral surfaces for at least a subset of viruses.
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PMID:Structural, biochemical, and in vivo characterization of the first virally encoded cyclophilin from the Mimivirus. 1834 30

SARS-CoV grows in a variety of tissues that express its receptor, although the mechanism for high replication in the lungs and severe respiratory illness is not well understood. We recently showed that elastase enhances SARS-CoV infection in cultured cells, which suggests that SARS development may be due to elastase-mediated, enhanced SARS-CoV infection in the lungs. To explore this possibility, we examined whether co-infection of mice with SARS-CoV and Pp, a low-pathogenic bacterium which elicits elastase production in the lungs, induces exacerbation of pneumonia. Mice co-infected with SARS-CoV and Pp developed severe respiratory disease with extensive weight loss, resulting in a 33~90% mortality rate. Mice with exacerbated pneumonia showed enhanced virus infection in the lungs and histopathological lesions similar to those found in human SARS cases. Intranasal administration of LPS, another elastase inducer, showed an effect similar to that of Pp infection. Thus, this study shows that exacerbated pneumonia in mice results from co-infection with SARS-CoV and a respiratory bacterium that induces elastase production in the lungs, suggesting a possible role for elastase in the exacerbation of pneumonia.
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PMID:Co-infection of respiratory bacterium with severe acute respiratory syndrome coronavirus induces an exacerbated pneumonia in mice. 1838 Aug 9

Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease with significant morbidity and mortality. An epidemic in 2003 affected 8,098 patients in 29 countries with 774 deaths. The aetiological agent is a new coronavirus spread by droplet transmission. Clinical and general laboratory manifestations included fever, chills, rigor, myalgia, malaise, diarrhoea, cough, dyspnoea, pneumonia, lymphopenia, neutrophilia, thrombocytopenia, and elevated serum lactate dehydrogenase (LD), alanine aminotransferase (ALT) and creatine kinase (CK) activities. Treatment has been empirical; initial potent antibiotic cover, followed by simultaneous ribavirin and corticosteroids, with or without pulse high-dose methylprednisolone, have been used. The postulated disease progression comprises (1) active viral infection, (2) hyperactive immune response, and (3) recovery or pulmonary destruction and death. We investigated serum LD isoenzymes and blood lymphocyte subsets of SARS patients, and found LD1 activity as the best biochemical prognostic indicator for death, while CD3+, CD4+, CD8+ and natural killer cell counts were promising predictors for intensive care unit (ICU) admission. Plasma cytokine and chemokine profiles showed markedly elevated Th1 cytokine interferon (IFN)-gamma, inflammatory cytokines interleukin (IL)-1beta, IL-6 and IL-12, neutrophil chemokine IL-8, monocyte chemoattractant protein-1 (MCP-1), and Th1 chemokine IFN-gamma-inducible protein-10 (IP-10) for at least two weeks after disease onset, but there was no significant elevation of inflammatory cytokine tumor necrosis factor (TNF)-alpha and anti-inflammatory cytokine IL-10. Corticosteroid reduced IL-8, MCP-1 and IP-10 concentrations from 5-8 days after treatment. Measurement of biochemical markers of bone metabolism demonstrated significant but transient increase in bone resorption from Day 28-44 after onset of fever, when pulse steroid was most frequently given. With tapering down of steroid therapy, there was a decrease in bone resorption marker together with an increase in bone formation markers round Day 50, suggesting that some of the bone loss might be reversed. Our research studies on the chemical pathology and clinical immunology of SARS should have implications for the pathophysiology and therapy of this potentially lethal infection.
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PMID:Severe acute respiratory syndrome: clinical and laboratory manifestations. 1845 12

The newly emergent human coronavirus HKU1 (HCoV-HKU1) was first identified in Hong Kong in 2005. Infection by HCoV-HKU1 occurs worldwide and causes syndromes such as the common cold, bronchitis, and pneumonia. The CoV main protease (M(pro)), which is a key enzyme in viral replication via the proteolytic processing of the replicase polyproteins, has been recognized as an attractive target for rational drug design. In this study, we report the structure of HCoV-HKU1 M(pro) in complex with a Michael acceptor, inhibitor N3. The structure of HCoV-HKU1 provides a high-quality model for group 2A CoVs, which are distinct from group 2B CoVs such as severe acute respiratory syndrome CoV. The structure, together with activity assays, supports the relative conservation at the P1 position that was discovered by sequencing the HCoV-HKU1 genome. Combined with structural data from other CoV M(pro)s, the HCoV-HKU1 M(pro) structure reported here provides insights into both substrate preference and the design of antivirals targeting CoVs.
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PMID:Structure of the main protease from a global infectious human coronavirus, HCoV-HKU1. 1856 31

The human coronaviruses (HCoV) OC43 and 229E are common causes of upper respiratory tract infections. Severe diseases were rare, however, until the emergence of the severe acute respiratory syndrome (SARS)-CoV in 2003. Since then, other novel CoV (NL63 and HKU1) have been described, and they have caused respiratory infections worldwide. Potentially exposed laboratory workers or animal handlers with rapidly progressive pneumonia not responding to standard antibacterial coverage must be isolated with contact and droplet, and for specific situations, airborne precautions, till rapid tests of respiratory and faecal samples are negative for SARS-CoV. Generally, the viral loads collected at different anatomical sites correlate with the severity of symptoms and mortality. Shedding of SARS-CoV peaks at day 10 after the onset of symptoms, which theoretically allows ample time for antiviral treatment. The disease is characterized by uncontrolled replication of the virus and a prominent pro-inflammatory response. No randomized controlled trials with a specific anti-coronavirus agent have been conducted with respect to therapy or prophylaxis. Reports using historical matched controls have suggested that treatment with interferon alfacon-1 (a synthetic interferon) combined with steroid, protease inhibitors together with ribavirin, or convalescent plasma containing neutralizing antibody, could be useful. Prophylaxis with interferon or hyperimmune globulin may be considered for unprotected exposure. The role of immunomodulators to decrease excessive inflammation remains elusive. Other non-SARS-CoV infections are generally milder in immunocompetent hosts, and scientific data on antiviral treatment of these viruses are scarce.
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PMID:The management of coronavirus infections with particular reference to SARS. 1856 70

The relationship between immunosenescence and the host response to virus infection is poorly understood at the molecular level. Two different patterns of pulmonary host responses to virus were observed when gene expression profiles from severe acute respiratory syndrome coronavirus (SARS-CoV)-infected young mice that show minimal disease were compared to those from SARS-CoV-infected aged mice that develop pneumonitis. In young mice, genes related to cellular development, cell growth, and cell cycle were downregulated during peak viral replication, and these transcripts returned to basal levels as virus was cleared. In contrast, aged mice had a greater number of upregulated immune response and cell-to-cell signaling genes, and the expression of many genes was sustained even after viral clearance, suggesting an exacerbated host response to virus. Interestingly, in SARS-CoV-infected aged mice, a subset of genes, including Tnfa, Il6, Ccl2, Ccl3, Cxcl10, and Ifng, was induced in a biphasic pattern that correlated with peak viral replication and a subsequent influx of lymphocytes and severe histopathologic changes in the lungs. We provide insight into gene expression profiles and molecular signatures underlying immunosenescence in the context of the host response to viral infection.
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PMID:Genomic analysis reveals age-dependent innate immune responses to severe acute respiratory syndrome coronavirus. 1863 70

31 samples of blood serum of pregnant women with acute respiratory virus infection and pneumonia symptoms who had been administered into hospital were analyzed. Antibacterial and antifungal treatment was ineffective. Autumn-winter-spring seasonality was detected. In connection with above-mentioned, an attempt was made to find out the etiology of a disease using viroloy methods. Primers of hantaviruses, Crimea-and-Congo hemorrhage fever, coronaviruses, SARS, Leptospirosis and virus hepatitis. Genome of B hepatitis virus was discovered in 3 samples, C--in one sample, G--in four samples. The test for other primers was negative. It was shown that in case of serious clinical course only abortion can save mother's life. It is necessary to find out aetiology of the disease, primers and other pathogenic organisms of virus infections.
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PMID:[Etiology of infectious diseases in pregnant women with symptoms of fever and lung syndrome]. 1871 99

Although the 2003 severe acute respiratory syndrome (SARS) outbreak was controlled, repeated transmission of SARS coronavirus (CoV) over several years makes the development of a SARS vaccine desirable. We performed a comparative evaluation of two SARS vaccines for their ability to protect against live SARS-CoV intranasal challenge in ferrets. Both the whole killed SARS-CoV vaccine (with and without alum) and adenovirus-based vectors encoding the nucleocapsid (N) and spike (S) protein induced neutralizing antibody responses and reduced viral replication and shedding in the upper respiratory tract and progression of virus to the lower respiratory tract. The vaccines also diminished haemorrhage in the thymus and reduced the severity and extent of pneumonia and damage to lung epithelium. However, despite high neutralizing antibody titres, protection was incomplete for all vaccine preparations and administration routes. Our data suggest that a combination of vaccine strategies may be required for effective protection from this pathogen. The ferret may be a good model for SARS-CoV infection because it is the only model that replicates the fever seen in human patients, as well as replicating other SARS disease features including infection by the respiratory route, clinical signs, viral replication in upper and lower respiratory tract and lung damage.
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PMID:Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines. 1875 23


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