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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have designed two software systems allowing the study of proteins through a comparison to those stored in data banks. The first one, "Automat", locates in a systematic manner all identities shared by a given protein and the proteins in a data bank. The second, "Critic" enables the selection of specific segments in a given molecule by comparing them with those gathered in a data bank. These sites were termed "critical" since they mostly correspond to functional sites (active sites) of the well-known proteins which were studied with the aid of this program (somatostatin, insulin, IL2, etc). Automat allowed us to reveal homologies between HIV-1 and the CD4, which have remained unsolved until now. These similitudes proved to be critical sites (according to Critic). The putative involvement of these sites in the physiopathological processes as induced by HIV-1 are worth considering since the results of our experiments are consistent with this assumption.
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PMID:Critical sites: a semantic approach to protein sequences. Application to the HIV-1 envelope molecule. 129 44

India has launched a liberalization of its economy with restructuring, privatization, and increased imports in order to achieve higher economic performance. This drive also affected the pharmaceutical industry and drug distribution, but in a negative manner. In the 1980s there were 9000 drug manufacturers that together produced up to 60,000 different preparations. In 1992, only 20,000 drugs were produced. The Voluntary Health Organization of India (VHAI) has fought for 10 years for a rational policy on medicines to halt the production of worthless or outright harmful products. For instance, anabolic steroids are sold as nutritional supplements to children, and the banned clioquinol is regularly used against diarrhea despite an international boycott. In recent years unscrupulous manufacturers have sold contaminated water as glucose for infusion bags and anti-D-immunoglobulin which was contaminated with HIV-infected blood. In northern India, a criminal organization bought up used cannulas from hospitals and repacked them for resale as new supplies. While a new medicine policy is formulated, there is a serious shortage of life-saving drugs such as insulin and rifampicin. In the last years, prices have exploded as some products have become six times more expensive. The whole national health system has undergone cost cuts to comply with an ultimatum from the World Bank and the International Monetary Fund; otherwise, sorely needed dollar loans would not be forthcoming. Funds for fighting tuberculosis and malaria have been trimmed, although AIDS and family planning budgets have been increased. One-fourth of the state health expenditures go to combat AIDS, since about 1 million people are infected with HIV. The pharmaceutical industry has also been embroiled in a patent protection wrangle with American drug exporters who claim that Retrovir or AZT (developed by Burroughs Wellcome) was pirated by the Cipla firm, whereas Cipla countered that it was ferreted out from scientific journals.
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PMID:[India: an expensive and dangerous drug]. 130 Jun 63

We have characterized an inhibitory RNA element in the human immunodeficiency virus type 1 (HIV-1) gag coding sequence that prevents gag expression. The inhibition exerted by this element could be overcome by the presence of the Rev-responsive element in cis and of Rev protein in trans. To understand the mechanism of function, we inactivated the inhibitory element by mutagenesis while maintaining an intact gag coding region. A constitutive high level of Rev-independent gag expression was achieved only after the introduction of 28 point mutations over a large region of 270 nucleotides within the gag coding region. To our knowledge, this is the first demonstration of inactivation of a negative RNA element within a coding region without alteration of the expressed protein. Elimination of the inhibitory element in the p17gag region, named INS-1, offered the opportunity to detect a second inhibitory element in the gag-pol region. The presence of either INS element is sufficient to inhibit gag expression, demonstrating that multiple INS elements acting independently can inhibit HIV RNA expression. Expression of gag from Rous sarcoma virus, a retrovirus that does not require Rev-like regulatory proteins, revealed that the Rous sarcoma virus p19gag region does not contain inhibitory elements. These results demonstrate the presence of a strong inhibitory element acting at the level of mRNA and provide a general method for the removal of such elements from mRNA coding regions. The inhibitory element functions in the absence of any HIV-1 proteins, suggesting that cellular factors are responsible for this inhibition.
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PMID:Mutational inactivation of an inhibitory sequence in human immunodeficiency virus type 1 results in Rev-independent gag expression. 143 10

This report details the structure-activity relationships of the HIV gag substrate analog Val-Ser-Gln-Asn-Leu psi[CH(OH)CH2]Val-Ile-Val (U-85548E), an inhibitor exhibiting subnanomolar affinity towards HIV type-1 aspartic proteinase (HIV-1 PR). Our data show that the P1-P2' tripeptidyl sequence provides the minimal chemical determinant for HIV-1 PR binding. We describe the structure-activity properties of Leu psi[CH(OH)CH2]Val substitution in other peptidyl ligands of nonviral substrate origin (e.g., angiotensinogen, insulin and pepstatin). Furthermore, the aspartic proteinase selectivities of a few key compounds are summarized relative to evaluation against human renin, human pepsin, and the fungal enzyme, rhizopuspepsin. These studies have led to the rational design of nanomolar potent inhibitors of both HIV-1 and HIV-2 PR. Finally, a 2.5 A resolution X-ray crystallographic structure of U-85548E complexed to synthetic HIV-1 PR dimer (Jaskolski et al., Biochemistry 30, 1600 [1991]) provided a 3-D picture of the inhibitor bound to the enzyme active site, and we performed computer-assisted molecular modeling studies to explore the possible binding modes of the above series of Leu psi[CH(OH)CH2]Val substituted HIV-1 PR inhibitors.
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PMID:HIV protease (HIV PR) inhibitor structure-activity-selectivity, and active site molecular modeling of high affinity Leu [CH(OH)CH2]Val modified viral and nonviral substrate analogs. 147 85

Human T-lymphoblastoid cells H9, CEM and CEM-clone 5 were selected for growth in RPMI 1640 supplemented with transferrin 5 micrograms/ml, insulin 5 micrograms/ml and sodium selenite 5 ng/ml. After 40 days of adaptation to serum-free medium, these cells displayed growth, morphology, and expression of CD4 similar to serum-supplemented cultures. Infection of these cells with two strains of HIV-1 (LAV and NDK) and a strain of HIV-2 (ROD) was as efficient in serum-free as in serum-supplemented medium as demonstrated by reverse transcriptase activity in the culture supernatants of infected cells. Furthermore, HIV-induced cytopathogenicity was observed in serum-free cultures, demonstrating that both HIV infection and cytopathic effect did not require the presence of serum components. Electron microscopy showed that mature viral particles were produced from infected cells cultured in serum-free medium. Finally, the ability of monoclonal antibody OKT4 A to inhibit infection by HIV-1 LAV but not by HIV-1 NDK was the same with and without serum in the culture medium, demonstrating that both CD4-dependent and CD4-independent infections can occur in the total absence of serum. Human T-lymphoblastoid cells adapted for growth in serum-free medium provide therefore a complementary tool for the study of HIV infection and cytopathogenicity under defined conditions.
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PMID:Human T-lymphoblastoid cells selected for growth in serum-free medium provide new tools for study of HIV replication and cytopathogenicity. 172 73

To test whether clinically stable human immunodeficiency virus (HIV) infection, like other infections, is associated with insulin resistance and increased insulin clearance, we measured the sensitivity to insulin and insulin clearance using the euglycemic insulin clamp technique in 10 clinically stable outpatients with symptomatic HIV infection (Centers for Disease Control [CDC] group IV) and 10 healthy controls. During administration of 0.8 and 4 mU insulin.kg-1.min-1, HIV-infected men had 40% (P less than .02) and 83% (P less than .01) higher rates of insulin clearance when compared with healthy controls. Despite significantly lower steady-state insulin concentrations (42 +/- 2 v 52 +/- 4 microU/mL, P less than .05, and 255 +/- 17 v 392 +/- 14 microU/mL, P less than .001, patients v controls), patients and controls had similar total glucose uptake (7.99 +/- 0.81 v 7.92 +/- 0.44 mg.kg-1.min-1 and 14.00 +/- 0.81 v 13.65 +/- 0.65 mg.kg-1.min-1, patients v controls). In the postabsorptive state, no differences were found between patients and controls in insulin levels (7 +/- 1 microU/mL in both) and endogenous glucose production (2.52 +/- 0.07 and 2.24 +/- 0.17 mg.kg-1.min-1, respectively), but plasma glucose levels in the patients (5.02 +/- 0.15 mmol/L) were significantly lower when compared with controls (5.46 +/- 0.14 mmol/L, P less than .05). The results indicate that HIV-infected men have increased rates of insulin clearance and increased sensitivity of peripheral tissues to insulin, which makes HIV infection unique with regard to glucose and insulin metabolism.
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PMID:Insulin sensitivity and insulin clearance in human immunodeficiency virus-infected men. 164 Aug 55

Relationships with retroviruses have recently been found in different human pathologies as autoimmune diseases which would be associated with the presence and eventually the expression of retroviral sequences. Detection of the presence of HTLV-1 and HIV-1 homologous sequences and their expression was realised on lymphocytes of 14 patients with polyendrocrinopathies (Basedow-Graves' disease and insulin-dependent diabetes) and four relatives of one index case. No antibodies to HTLV-1 and HIV-1 could be detected by Western blot and Elisa tests. HTLV-1 related sequences were revealed by Southern blot (SB) in 5 out of 18 subjects' DNA. Analyses of all DNA were performed by polymerase chain reaction (PCR). Seven DNA, including the 5 previously positive in SB, and two relatives (father and grandfather), negative in SB, contained HTLV-1-gag related sequences, but neither pol nor pX regions. Concerning HIV-1, all 18 DNA examined were negative by both methods. DNA of ten clinically healthy donors were found to be negative with the same tests.
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PMID:Detection of HTLV-1 gag related sequences in leucocyte DNA from patients with polyendocrinopathies (Basedow-Graves' disease and insulin-dependent diabetes). 190 39

The main principles of this hypothesis are very general: (i) signal-detection from background noise is one central issue in electronics; (ii) an important source of misunderstanding at different levels of communication is the fact that a given signal may have different meanings in different contexts; (iii) the unique role of chance in developmental biology is generally appreciated (37). In AIDS the basic defect would be the human specific inability to distinguish between the amino acid sequence of neuroleukin and peptides derived from the gp120 envelope protein of HIV, resulting in a slowly progressing failure of the CD4+ T cell-mediated immunity. In IDDM the postulated HLA class II-dependent hypersensitivity to immunological noise could predispose to random contacts between cells with a different signalling language. In the ensuing dialogue neuroleukin secreted by T cells would imply a continuous demand for insulin secretion to pancreatic beta cells resulting in diabetes. This hypothesis does not contradict with the provocative ideas proposed by Duesberg concerning the relationships between HIV and AIDS (24) and the known data on the genesis of IDDM.
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PMID:Are syntax errors due to the amino acid sequence of neuroleukin involved in the pathogenesis of the acquired immunodeficiency syndrome (AIDS) and insulin dependent diabetes mellitus (IDDM)? 204 84

We have employed a recombinant plasmid, pBHIV1, carrying the long terminal repeat (LTR) of the human immunodeficiency virus-1 (HIV-1) linked to the reporter chloramphenicol acetyl transferase (cat) gene and to the aminoglycoside phosphotransferase (aph) gene as a selectable marker. We have introduced pBHIV1 in rat 208F and human MRCSV40TGR fibroblasts and obtained stable geneticin resistant RFBHIV1-1 and SVTGHIV-1 transfectant cells respectively. Both RFBHIV1-1 and SVTGHIV1-1 cells express CAT activity from the HIV LTR promoter. The response to insulin, epidermal growth factor, hydrocortisone and dexamethasone was studied on the LTR regulated CAT activity in both cell lines. It was found that, at optimal concentrations, insulin, epidermal growth factor and hydrocortisone regulate positively the expression of CAT from the HIV LTR in rat RFBHIV1-1 but not in human SVTGHIV1-1 cells. On the other hand dexamethasone at 10(-5) M stimulated CAT activity in both types of cells.
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PMID:Response of human immunodeficiency virus long terminal repeat to growth factors and hormones. 224 Oct 99

The traditional method for calculating risk in prospective and retrospective studies is based on the assumption that the study population is homogeneous. Risk is therefore estimated as an overall average for the entire population, when in fact some individuals may be at high risk and others at little or no risk. This paper introduces an alternate approach to risk estimation. The calculations are equally simple and utilize the same data. Yet, the new approach allows for heterogeneity and can detect it when it exists. The new method was applied to HIV seroconversion data from a follow-up study, age-at-onset distribution for Huntington disease, and age-specific prevalence of insulin-treated diabetes. These analyses were intended to demonstrate both applicability of the method to different types of data and the accuracy of the estimates when compared with the known parameters. The HIV analysis predicted a high-risk subgroup constituting about 17% of the cohort. This estimate closely approximates the actual 16% who reportedly engaged in high-risk activities and had a 15-fold higher seroconversion rate than the rest of the cohort. There is no evidence from genetic linkage studies for heterogeneity in Huntington disease. The present results, however, suggested that 14%-18% of individuals who are susceptible to the disease have a much lower risk than others. Diabetes data was chosen because the model is clearly too simplistic for this disease, and the analysis did reveal lack of fit of the model.
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PMID:A simple method to detect and estimate heterogeneity: application to Huntington disease, diabetes, and HIV seroconversion. 252 Nov 97


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