Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1175175 (SARS)
 19,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The current study investigated the association between the use of recreational drugs at the time of sexual activity and high-risk sexual behavior in a Toronto cohort of 249 homosexual and bisexual men over a 5-year period commencing in 1984 to 1985 and concluding in 1989 to 1990. The main analysis was based on a total of 2536 visits. Univariate and multivariate Liang-Zeger regression models were used to relate the log of the sexual activity score (SARS) to the independent variables over the 20 follow-up visits while controlling for intercorrelations between variables from the same respondent. We found that there was a significant decline, over time, in the sexual activities that pose a higher risk of infection with human immunodeficiency virus. Recreational drugs still appear to be playing an important role in the continuation of higher-risk sexual activities. The use of poppers in conjunction with sex is a strong predictor of high-risk activity, as is use of alcohol and marijuana in conjunction with sex. Also, simultaneously strongly associated with higher-risk score is the Centers for Disease Control classification II. More emphasis needs to be placed on educating the population about the potential risks of combining reactional drugs with sexual activity.
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PMID:Ongoing high-risk sexual behaviors in relation recreational drug use in sexual encounters. Analysis of 5 years of data from the Toronto Sexual Contact Study. 827

Severe acute respiratory syndrome (SARS) has recently recognized as a new human infectious disease. A novel coronavirus was identified as the causative agent of SARS. This report summarizes the hematological findings in SARS patients and proposes a hypothesis for the pathophysiology of SARS coronavirus related abnormal hematopoiesis. Hematological changes in patients with SARS were common and included lymphopenia (68% - 90% of adults; 100% of children, n = 10), thrombocytopenia (20% - 45% of adults, 50% of children), and leukopenia (20% - 34% of adults, 70% of children). The possible mechanisms of this coronavirus on blood system may include (1) directly infect blood cells and bone marrow stromal cells via CD13 or CD66a; and/or (2) induce auto-antibodies and immune complexes to damage these cells. In addition, lung damage in SARS patients may also play a role on inducing thrombocytopenia by (1) increasing the consumption of platelets/megakaryocytes; and/or (2) reducing the production of platelets in the lungs. Since the most common hematological changes in SARS patients were lymphopenia and immunodeficiency. We postulate that hematopoietic growth factors such as G-CSF, by mobilizing endogenous blood stem cells and endogenous cytokines, could become a hematological treatment for SARS patients, which may enhance the immune system against these virus.
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PMID:The effect of SARS coronavirus on blood system: its clinical findings and the pathophysiologic hypothesis. 1284 98

The synthesis of the structurally unusual heterotricyclic compound 1-[3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridinyl]-2,8,9-trioxaadamantane-3,5,7-triol (trivially named bananin, BN) from pyridoxylidenephloroglucinol and a theoretical prospect on possible biological activities of BN are presented in this report. Pyridoxylidenephloroglucinol is synthesized by Knoevenagel condensation of the vitamin B6 aldehyde pyridoxal with phloroglucinol. Pyridoxylidenephloroglucinol rearranges to light-yellow (4'RS)-1',4'-dihydrobananin by refluxing in 5M hydrochloric acid. Air oxidation subsequently forms BN in the heat which immediately yields orange-yellow (4'RS)-4'-chloro-1',4'-dihydrobananin by 1,4-addition of hydrogen chloride. This intermediate could be isolated but, interestingly, not a BN hydrochloride. Brown BN is finally achieved by base-catalyzed elimination of hydrogen chloride from (4'RS)-4'-chloro-1',4'-dihydrobananin. Regarding possible biological activities, it was demonstrated that BN acts as zinc (Zn2+) chelator. Therefore, a target of interest could be the human immunodeficiency virus type 1 (HIV-1) zinc finger HIV-1 RNA-binding nucleocapsid protein p7 (NCp7). Through suggested zinc ejection from HIV-1 genomic RNA psi-element-binding and HIV-1-RNA-duplex packaging NCp7 by BN, thus rendering NCp7 functionally obsolete, it is deduced that HIV-1 replication and effective infectious virion encapsidation could be inhibited by BN. Furthermore, theoretical and structural considerations propose that BN is converted into bananin 5'-monophosphate (BNP) by the cell type-ubiquitous human enzyme pyridoxal kinase (EC 2.7.1.35). Together with the putative antilentiviral retinoid vitamin A-vitamin B6 conjugate analogue B6RA (Kesel, A. J. Biochem. Biophys. Res. Comm. 2003, 300, 793), BNP is postulated to serve as effector in a system of protein target sequences RX(D/E) of RNA virus components. Human immunodeficiency Retroviridae (HIVs) could possibly be influenced by B6RA and BNP. In addition, candidate targets of B6RA and BNP could be adsorption, transcription and/or viral RNA replication of an interestingly wide RNA virus selection including Picornaviridae (poliovirus, human coxsackievirus, hepatitis A virus), Flaviviridae (yellow fever virus, Dengue virus, West Nile virus, Kunjin virus, St. Louis encephalitis virus, hepatitis C virus), Togaviridae (rubella virus), Coronaviridae (human coronavirus, human SARS-associated coronavirus), Rhabdoviridae (rabies virus), Paramyxoviridae (human parainfluenza virus, measles virus, human respiratory syncytial virus), Filoviridae (Marburg virus, Ebola virus), Bornaviridae (Borna disease virus), Bunyaviridae (Hantaan virus), Arenaviridae (Lassa virus), and Reoviridae (human rotavirus). The postulated scope of 'metabolically trapped' BNP might resemble the antiviral spectrum of the RNA-viral virustatic ribavirin.
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PMID:A system of protein target sequences for anti-RNA-viral chemotherapy by a vitamin B6-derived zinc-chelating trioxa-adamantane-triol. 1452 57

The zoonotic introduction of an animal pathogen into the human population and the subsequent extension or alteration of its host range leading to the successful maintenance of the corresponding pathogen by human-to-human transmission pose a serious risk for world-wide health care. Such a scenario occurred for instance by the introduction of simian immunodeficiency viruses into the human population resulting in the human immunodeficiency viruses (HIV) and the subsequent AIDS pandemic or the proposed recent host range switch of the SARS coronavirus from a presently unknown animal species to humans. The occurrence of zoonotic transmissions of animal viruses to humans is a permanent threat to human health and is even increased by changes in the human lifestyle. In this review, the potential of the zoonotic transmission of bovine, feline and equine foamy retroviruses will be discussed in the light of well-documented cases of zoonotic transmissions of different simian foamy viruses to humans.
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PMID:Potential of zoonotic transmission of non-primate foamy viruses to humans. 1463 94

Spike (S) proteins of coronaviruses, including the coronavirus that causes severe acute respiratory syndrome (SARS), associate with cellular receptors to mediate infection of their target cells. Here we identify a metallopeptidase, angiotensin-converting enzyme 2 (ACE2), isolated from SARS coronavirus (SARS-CoV)-permissive Vero E6 cells, that efficiently binds the S1 domain of the SARS-CoV S protein. We found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells. 293T cells transfected with ACE2, but not those transfected with human immunodeficiency virus-1 receptors, formed multinucleated syncytia with cells expressing S protein. Furthermore, SARS-CoV replicated efficiently on ACE2-transfected but not mock-transfected 293T cells. Finally, anti-ACE2 but not anti-ACE1 antibody blocked viral replication on Vero E6 cells. Together our data indicate that ACE2 is a functional receptor for SARS-CoV.
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PMID:Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. 1464 84

The causative agent of severe acute respiratory syndrome (SARS) is a previously unidentified coronavirus, SARS-CoV. The RNA-dependent RNA polymerase (RdRp) of SARS-CoV plays a pivotal role in viral replication and is a potential target for anti-SARS therapy. There is a lack of structural or biochemical data on any coronavirus polymerase. To provide insights into the structure and function of SARS-CoV RdRp, we have located its conserved motifs that are shared by all RdRps, and built a three-dimensional model of the catalytic domain. The structural model permits us to discuss the potential functional roles of the conserved motifs and residues in replication and their potential interactions with inhibitors of related enzymes. We predict important structural attributes of potential anti-SARS-CoV RdRp nucleotide analog inhibitors: hydrogen-bonding capability for the 2' and 3' groups of the sugar ring and C3' endo sugar puckering, and the absence of a hydrophobic binding pocket for non-nucleoside analog inhibitors similar to those observed in hepatitis C virus RdRp and human immunodeficiency virus type 1 reverse transcriptase. We propose that the clinically observed resistance of SARS to ribavirin is probably due to perturbation of the conserved motif A that controls rNTP binding and fidelity of polymerization. Our results suggest that designing anti-SARS therapies can benefit from successful experiences in design of other antiviral drugs. This work should also provide guidance for future biochemical experiments.
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PMID:Molecular model of SARS coronavirus polymerase: implications for biochemical functions and drug design. 1465 87

It is unclear when, where and how novel pathogens such as human immunodeficiency virus (HIV), monkeypox and severe acute respiratory syndrome (SARS) will cross the barriers that separate their natural reservoirs from human populations and ignite the epidemic spread of novel infectious diseases. New pathogens are believed to emerge from animal reservoirs when ecological changes increase the pathogen's opportunities to enter the human population and to generate subsequent human-to-human transmission. Effective human-to-human transmission requires that the pathogen's basic reproductive number, R(0), should exceed one, where R(0) is the average number of secondary infections arising from one infected individual in a completely susceptible population. However, an increase in R(0), even when insufficient to generate an epidemic, nonetheless increases the number of subsequently infected individuals. Here we show that, as a consequence of this, the probability of pathogen evolution to R(0) > 1 and subsequent disease emergence can increase markedly.
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PMID:The role of evolution in the emergence of infectious diseases. 1466 40

The severe acute respiratory syndrome (SARS) has been one of the most epidemic diseases threatening human health all over the world. Based on clinical studies, SARS-CoV (the SARS-associated coronavirus), a novel coronavirus, is reported as the pathogen responsible for the disease. To date, no effective and specific therapeutic method can be used to treat patients suffering from SARS-CoV infection. RNA interference (RNAi) is a process by which the introduced small interfering RNA (siRNA) could cause the degradation of mRNA with identical sequence specificity. The RNAi methodology has been used as a tool to silence genes in cultured cells and in animals. Recently, this technique was employed in anti-virus infections in human immunodeficiency virus and hepatitis C/B virus. In this study, RNAi technology has been applied to explore the possibility for prevention of SARS-CoV infection. We constructed specific siRNAs targeting the S gene in SARS-CoV. We demonstrated that the siRNAs could effectively and specifically inhibit gene expression of Spike protein in SARS-CoV-infected cells. Our study provided evidence that RNAi could be a tool for inhibition of SARS-CoV.
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PMID:Silencing SARS-CoV Spike protein expression in cultured cells by RNA interference. 1498 13

We observed that 0 of 19 patients with human immunodeficiency virus type 1 (HIV-1) infection, including those with acquired immunodeficiency syndrome (AIDS), who were hospitalized together and who had close contact with 95 patients with severe acute respiratory syndrome (SARS) on the same hospital floor contracted SARS, whereas 6 of 28 medical workers who served on this floor contracted SARS while caring for these patients. Our investigation found that most of the patients with HIV-1/AIDS were receiving treatment of highly active antiretroviral therapy (HAART) during hospitalization. Coincidentally, a research group from Hong Kong recently reported that patients with SARS who received treatment with the anti-HIV-1 drug lopinavir-ritonavir experienced significantly better clinical outcomes than did those who did not receive lopinavir-ritonavir. On the basis of these observations and studies, we propose that HAART should be considered for patients with SARS and their close contacts when the SARS epidemic reemerges.
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PMID:Consideration of highly active antiretroviral therapy in the prevention and treatment of severe acute respiratory syndrome. 1503 38

Over the last decade, there was noted a large advancement of knowledge on living organisms and their products posing a potential occupational risk. Novel risk factors, often new to science, were identified, the role and significance of already known factors better comprehended, and occupational groups endangered by biological hazards more thoroughly recognized. Novel viruses and prions, emerging in different parts of the world, may pose a particular threat to health and life of health care workers, agriculture workers and veterinarians. A new coronavirus (SCoV) that evoked a rapid outbreak of disease described as severe acute respiratory syndrome (SARS) in the first half of 2003 may serve as an example. The disease was particularly common among health care workers. Previously discovered zoonotic viruses, Nipah virus in pigs and Hendra virus in horses, may be a cause of fatal encephalitis in animal farmers. Hantaviruses (Puumala, Hantaan, Sin Nombre and others) infecting field rodents may be a cause of hemorrhagic fever with renal syndrome (HFRS) or pulmonary syndrome (HPS) in farmers and laboratory workers. Prions responsible for inducing a zoonotic variant of Creutzfeldt-Jakob disease (vCJD) are considered to be a potential cause of work-related infections in agricultural and health care workers, however, this assumption has not as yet been supported by any conclusive evidence. In many countries, blood-borne occupational infections with hepatitis C virus (HCV) is the major epidemiological problem among health care workers, mostly because no vaccine against this virus has been produced to date. Vaccinations effectively restricted the number of occupational infections with hepatitis B virus (HBV), and work-related infections with human immunodeficiency virus (HIV) causing acquired immunodeficiency syndrome (AIDS) are very rare. Hazardous bioserosols, occurring in many work environments, pose an occupational health hazard of particular importance. Many new biological factors present in organic dusts that may induce work-related allergic and immunotoxic diseases among farmers and workers of the agricultural and wood industries have been identified. Droplet aerosols, which are generated from water, oils, oil-water emulsions and other liquids in various work environments, may contain infectious agents (Legionella spp.) as well as allergic and/or toxic agents. It has been shown that allergens and endotoxins produced by Gram-negative bacteria occurring in oil mist from metalworking fluids may cause occupational respiratory diseases in workers of the metallurgic industry.
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PMID:[Occupational bio hazards: current issues]. 1515 65


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