Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper examines the debate over the human immunodeficiency virus (HIV) as the cause of acquired immunodeficiency syndrome (AIDS) from an historical perspective. The changing criteria for proving the link between putative pathological agents and diseases are discussed, beginning with Robert Koch's research on anthrax in the late nineteenth century. Various versions of 'Koch's postulates' are analyzed in relation to the necessity and sufficiency arguments of logical reasoning. In addition, alterations to Koch's postulates are delineated, specifically those required by the discovery of rickettsiae and viruses in the early twentieth century and by the immunological testing developed after mid-century to demonstrate the links between elusive viral agents and two diseases, hepatitis B and infectious mononucleosis. From this perspective, an examination of the AIDS debate is constructed. Molecular biologist Peter Duesberg's argument that HIV is not the cause of AIDS is analyzed in light of his contention that a version of Koch's postulates has not been satisfied. Additional research findings through 1990 relating to the etiology of AIDS are also noted.
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PMID:Koch's postulates and the etiology of AIDS: an historical perspective. 134 26

This survey of the clinical and epidemiological features of human cowpox, a rare but relatively severe zoonotic infection, is based on 54 cases, many unpublished, which we have studied since 1969. Patients present with painful, haemorrhagic pustules or black eschars, usually on the hand or face, accompanied by oedema, erythema, lymphadenopathy, and systemic involvement. Severe, occasionally fatal, cases occur in eczematous and immunosuppressed individuals, although cowpox has not yet been reported in anyone infected with the human immunodeficiency virus. Variations in the clinical features are described, and the differential clinical diagnosis of cowpox, parapox, herpes virus, and anthrax infections is discussed. The role of the laboratory in diagnosis is described, and the value of electron microscopy in providing rapid confirmation is emphasized. Care in taking a detailed history will assist in the initial clinical diagnosis, and a history of contact with domestic cats, particularly during July-October, is important. The possible influence of smallpox vaccination on the incidence and severity is discussed and discounted.
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PMID:Human cowpox 1969-93: a review based on 54 cases. 799 88

Since the terrorist attacks of September 11, 2001, and the anthrax exposures in the following weeks, concern that smallpox could be used as a biologic weapon has increased. Public health departments and the U.S. military have begun the process of vaccinating soldiers and civilian first-responders. Smallpox vaccination carries some serious risks: approximately one in 1 million primary vaccinees and one in 4 million revaccinees will die from adverse vaccine reactions. The most serious side effects of smallpox vaccine include progressive vaccinia, postvaccinial central nervous system disease, and eczema vaccinatum. Some of these reactions can be treated with vaccinia immune globulin or cidofovir. Proper patient screening and site care are essential. Family physicians must learn to screen potential vaccinees for contraindications (e.g., immunodeficiency, immunosuppression, certain skin and eye diseases, pregnancy, lactation, allergy to the vaccine or its components, moderate or severe intercurrent illness) and to treat vaccine-associated adverse reactions.
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PMID:Smallpox vaccine: contraindications, administration, and adverse reactions. 1367 38

Pro-hormone or pro-protein convertases are a conserved family of eukaryotic serine proteases found in the secretory pathway. These endoproteases mature precursors for peptides and proteins that perform a wide range of physiologically important and clinically relevant functions. The first member of this family to be identified was Kex2 in the yeast Saccharomyces cerevisiae. One mammalian member of this family - furin - is responsible for processing substrates that include insulin pro-receptor, human immunodeficiency virus gp160 glycoprotein, Ebola virus glycoprotein, and anthrax protective antigen. Recent determination of the crystal structures for the catalytic core domains of both Kex2 and furin - the first for any members of this family - provide remarkable insights and a new level of understanding of substrate specificity and catalysis by the pro-protein convertases.
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PMID:The kindest cuts of all: crystal structures of Kex2 and furin reveal secrets of precursor processing. 1510 34

Human immunodeficiency virus (HIV) and Mycobacterium tuberculosis annually cause 3 million and 2 million deaths, respectively. Last year, 600,000 individuals, doubly infected with HIV and M. tuberculosis, died. Since World War I, approximately 150 million people have succumbed to these two infections--more total deaths than in all wars in the last 2,000 years. Although the perceived threats of new infections such as SARS, new variant Creutzfeldt-Jakob disease and anthrax are real, these outbreaks have caused less than 1,000 deaths globally, a death toll AIDS and tuberculosis exact every 2 h. In 2003, 40 million people were infected with HIV, 2 billion with M. tuberculosis, and 15 million with both. Last year, 5 million and 50 million were newly infected with HIV or M. tuberculosis, respectively, with 2 million new double infections. Better control measures are urgently needed.
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PMID:Annulling a dangerous liaison: vaccination strategies against AIDS and tuberculosis. 1581 88

The problem of biological security raises alarm due to the real growth of biological threats. Biological security includes a wide scope of problems, the solution of which becomes a part of national security as a necessary condition for the constant development of the country. A number of pathogens, such as human immunodeficiency virus, exotic Ebola and Lassa viruses causing hemorrhagic fever,rotaviruses causing acute intestinal diseases, etc. were first discovered in the last century. Terrorist actions committed in the USA in 2001 using the anthrax pathogen made the problem of biological danger even more important. In Russian Federation, biological threats are counteracted through the united state policy being a part of general state security policy. The biological Security legislation of Russian Federation is chiefly based on the 1992 Federal Law on Security. On the basis of cumulated experience, the President of Russia ratified Basics of Russian Federation's State Policy for Chemical and Biological Security for the Period through 2010 and Beyond on 4 December, 2003. The document determines the main directions and stages of the state development in the area of chemical and biological security. The Federal target program Russian Federation's National Program for Chemical and Biological Security is being developed, and its development is to be completed soon in order to perfect the national system for biological security and fulfill Basics of Russian Federation's State Policy for Chemical and Biological Security for the Period through 2010 and Beyond, ratified by the President. The new global strategy for control over infectious diseases, presented in the materials of Saint Petersburg summit of the Group of Eight, as well as the substantive part of its elements in Sanitary International Standards, are to a large degree an acknowledgement of the Russian Federation's experience and the algorithm for fighting extremely dangerous infections. This Russia's experience has resulted in the following global achievements: smallpox elimination in the USSR (1936); the USSR's suggestions on the program of smallpox elimination in the world and 2 billion doses of the vaccine transferred to the possession of the WHO (since 1958); the global elimination of the disease (1980); effective control over avian influenza at the epizootic stage, recognized internationally at Beijing International Congress, 17-18 January, 2006.
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PMID:[Important issues of biological safety]. 1822 6

The field of bioinformatics has become a major part of the drug discovery pipeline playing a key role in improvement and acceleration of this time and money consuming process. Here we review the application of the informational spectrum method (ISM), a virtual spectroscopy method for structure/function analysis of proteins, in identification of functional protein domains representing candidate therapeutic targets for drugs against human immunodeficiency virus (HIV)-1, anthrax, highly pathogenic influenza virus H5N1 and cardiovascular diseases.
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PMID:Discovery of new therapeutic targets by the informational spectrum method. 1885

Furin is a ubiquitously expressed proprotein convertase (PC) that plays a vital role in numerous disease processes including cancer metastasis, bacterial toxin activation (e.g. anthrax and Pseudomonas), and viral propagation (e.g. avian influenza and human immunodeficiency virus). To identify small molecule inhibitors of furin and related processing enzymes, we performed high-throughput screens of chemical diversity libraries utilizing both enzyme-based and cell-based assays. The screens identified partially overlapping sets of compounds that were further characterized for affinity, mechanism, and efficacy in additional cellular processing assays. Dicoumarols were identified as a class of compounds that inhibited furin non-competitively and reversibly with Ki values in the micromolar range. These compounds inhibited furin/furin-like activity both at the cell surface (protecting against anthrax toxin) and in the secretory pathway (blocking processing of the metastasis factor membrane-type 1 matrix metalloproteinase/MT1-MMP) at concentrations close to Ki values. Compounds tested exhibited distinct patterns of inhibition of other furin-family PCs (rat PACE4, human PC5/6 and human PC7), showing that dicoumarol derivatives might be developed as either generic or selective inhibitors of the PCs. The extensive clinical use, high bioavailability and relatively low toxicity of dicoumarols suggests that the dicoumarol structure will be a good starting point for development of drug-like inhibitors of furin and other PCs that can act both intracellularly and at the cell surface.
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PMID:Inhibition of furin/proprotein convertase-catalyzed surface and intracellular processing by small molecules. 1933 39

We performed a comprehensive alanine scan of human alpha-defensin HNP1 and tested the ability of the resulting analogs to kill Staphylococcus aureus, inhibit anthrax lethal factor, and bind human immunodeficiency virus-1 gp120. By far, the most deleterious mutation for all of these functions was W26A. The activities lost by W26A-HNP1 were restored progressively by replacing W26 with non-coded, straight-chain aliphatic amino acids of increasing chain length. The hydrophobicity of residue 26 also correlated with the ability of the analogs to bind immobilized wild type HNP1 and to undergo further self-association. Thus, the hydrophobicity of residue 26 is not only a key determinant of the direct interactions of HNP1 with target molecules, but it also governs the ability of this peptide to form dimers and more complex quaternary structures at micromolar concentrations. Although all defensin peptides are cationic, their amphipathicity is at least as important as their positive charge in enabling them to participate in innate host defense.
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PMID:Trp-26 imparts functional versatility to human alpha-defensin HNP1. 2022 Jan 36

This review presents successful applications of carbohydrate molecules in drug delivery, vaccine development, cancer, HIV and various other diseases based on advances in glycobiology and glycochemistry. Carbohydrate-mediated delivery could be site specific/cell specific. Carbohydrate-based delivery system has been successfully utilized for the delivery of macromolecular drugs, antigen, and potential therapeutic drug candidates. Lectin, the high affinity carbohydrate-binding nonimmune glycoproteins has specific and noncovalent binding sites for defined carbohydrates. Endogenous surface lectins of cancer cells participate in the regulation of tumor cell growth. The oligosaccharides constitute potential recognition sites for carbohydrate-mediated interactions between cells and drug carriers bearing suitable site directing molecules. The recognition of carbohydrate immunodeterminants has created great attention in the development of carbohydrate-based vaccines. Peptide mimotopes provide a strategy to augment human immunodeficiency virus 1 (HIV-1) specific carbohydrate reactive immune responses. Experimental cancer and HIV vaccines are being developed in attempts to overcome weak immunological responses to carbohydrate-rich surface antigens using carriers, adjuvants, and novel carbohydrate antigen constructs. Current carbohydrate-based vaccines are used for prostate cancer, typhus, pneumonia, and meningitis; vaccines for malaria, anthrax, and leishmaniasis are under development. This article discusses the current research involved in the role of carbohydrate molecules in targeted controlled drug delivery, immunology, and vaccine development.
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PMID:Carbohydrate molecules: an expanding horizon in drug delivery and biomedicine. 2166 77


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