Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Functional studies assessed the cytolytic activity of the amino terminal peptide (FP-I; 23 residues 519-541) of the glycoprotein 41,000 (gp41) of the Human Immunodeficiency Virus Type-1 (HIV-1). Synthetically prepared FP-I efficiently hemolyzed human red blood cells at 37 degrees C, with 40% lysis at 32 microM. Kinetic studies indicated that FP-I induced maximal hemolysis in 30 min, probably through tight binding of the peptide with the red cell membrane. The Phe-Leu-Gly-Phe-Leu-Gly (residues 526-531) motif in FP-I apparently plays a critical role in lysis of red cells, since no hemolytic activity was observed for an amino-acid-substituted FP-I in which the unique Phe-Leu-Gly-Phe-Leu-Gly was converted to Ala-Leu-Gly-Ala-Leu-Gly. As neither smaller constituent peptides (e.g., residues 519-524 and residues 526-536) nor a N-terminal flanking peptide (e.g., residues 512-523) induced red cell hemolysis, the entire 23-residue (519-541) sequence of FP-I may be required for hemolytic activity. FP-I was also cytolytic with CD4(+)-bearing Hut-78 cells, with 40% lysis at approx. 150 microM. These results are consistent with an earlier hypothesis that the N-terminal peptide of gp41 may partially contribute to the in vivo cytopathic actions of HIV-1 infection (Gallaher, W.R. (1987) Cell 50, 327-328).
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PMID:The amino-terminal peptide of HIV-1 glycoprotein 41 lyses human erythrocytes and CD4+ lymphocytes. 135 63

This study was conducted to determine if soluble CD4 (ST4) altered the pharmacokinetics of 2',3'-dideoxycytidine (ddC) in nonhuman primates. Each of six monkeys received 5 mg/kg of ddC iv in the absence and presence of two different iv regimens of ST4. The ST4 regimens produced steady-state plasma concentrations of 10.3 micrograms/ml (N = 3) and 22.2 micrograms/ml (N = 3) for 30 min following ddC administration. Pharmacokinetic parameters for ddC and ST4 were calculated based on plasma and urine concentrations of ddC and plasma concentrations of ST4. Following combined ddC and ST4 administration, in both the low- and high-dose ST4 groups, plasma concentration-time profile of ddC were similar for each monkey, and no statistical differences were observed in the pharmacokinetic parameters compared with those obtained when ddC was given alone. Complete urinary excretion data for ddC was obtained in 3 of the 6 animals studied. At the low ST4 dose, one animal had a reduced renal clearance of ddC, whereas at the high ST4 dose two animals recorded an increased renal clearance of ddC. ST4 plasma concentrations were comparable to in vitro concentrations of antiviral activity, with pharmacokinetic parameters similar to those reported previously. The kinetic information provides a basis for rational dosage design for combination chemotherapeutic regimens of ddC and ST4 in human immunodeficiency virus infection.
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PMID:Pharmacokinetic evaluation of drug interactions with anti-human immunodeficiency virus drugs. V. Effect of soluble CD4 on 2',3'-dideoxycytidine kinetics in monkeys. 135 14

We report the findings of an epidemiological study conducted between June 1989 and February 1990 on a population of leprosy patients in southern Senegal (Bignona major endemic disease sector). Two types of population were studied: patients living in urban areas and inmates of leprosaria. The global HIV seroprevalence (HIV 2 in all cases) of the leprosy-patient population was 1.15% (3/257): 0.8% (1/130) for the urban group and 1.5% (2/127) for the leprosaria. The seroprevalence rate does not differ significantly from that for the control group studied and for blood donors (1/221). The diagnosis of leprosy in the seropositive subjects had been established before 1980. None of them showed any sign of relapse. The immunodepression associated with the presence of HIV was only moderate: it was reflected in a lowering of the CD4 count and of the CD4/CD8 ratio, but with no clinical sign of AIDS.
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PMID:[Epidemiological study of HIV seroprevalence in a leprosy patient population in Senegal]. 135 46

A case of histiocytosis X (Langerhans type) associated with bullous pulmonary emphysema and acquired immune deficiency, regarding CD4 positive cells, is described. Previous history was remarkable for skin lesions which first appeared in 1981 and progressively worsened, diabetes insipidus diagnosed in 1986, and bullous pulmonary emphysema detected in 1988. Biopsy results of skin lesions were consistent with histiocytosis X. Thyroid gland involvement was found by means of cytological examination. The search for HIV infection (also performed by means of immunoblotting and PCR) was negative. To our knowledge the immunodeficiency detected in histiocytosis X affects the T suppressor lymphocyte subset, so we thought this peculiar case was worth describing.
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PMID:A case of Langerhans histiocytosis with HIV-like immunodeficiency. 135 92

In order to evaluate the reliability of CD4 and CD8 T lymphocyte counts in large scale studies, a quality control study was performed in 12 French laboratories. CD4 and CD8 counts, assessed by various haematological and immunological techniques, were compared in order to assess possible differences between the laboratories and the techniques used. Our data showed that (a) the consistency of CD4 measurements was satisfactory since the between-laboratory coefficient of variation for absolute CD4 cell numbers above 200/mm3 was around 15% instead of 5-10% for all laboratories but one; (b) the major sources of variability arose from the use of automatic devices in the two-step measurement procedure: immunophenotyping and haematological counting. These data suggest that multicentre assays of CD4 and CD8 counts result in some increase in their variability. Nevertheless the results of large multicentric trials can be extrapolated with confidence in the routine care of HIV+ patients. Together, the results justified the involvement of several experienced laboratories in a clinical trial of HIV-related disease.
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PMID:Consistency of routine measurements of CD4+, CD8+ peripheral blood lymphocytes. 135 37

Nutritional status and food intake of HIV+ and HIV- homosexual men that were free from enteric pathogens were compared. Food intake (7-day weighed record), anthropometry, and D-xylose excretion were measured in 44 patients (9 HIV-, 35 HIV+). HIV+ patients were found to be thinner, based on anthropometric measurements of skinfold thickness (p < 0.05) and percentage body fat (p < 0.05), and they also tended to be lighter than the HIV- patients. No differences were observed in the arm muscle mass or the food intake of the two groups. In the HIV+ patients, regression analysis was used to correlate changes in nutritional status with progression of the disease, using CD4+ lymphocyte count as a measure of severity. A decrease in CD4 count positively correlated with a decrease in weight (r = 0.48, p < 0.01), body mass index (r = 0.41, p < 0.05), and arm muscle area (r = 0.42, p < 0.01). Energy intake (r = 0.67, p < 0.01), serum albumin (r = 0.52, p < 0.01), and D-xylose excretion (r = 0.57, p < 0.0001) also positively correlated with CD4 count. Multiple regression analysis revealed a relationship between CD4 count, weight, and energy intake, indicating that as the disease progresses, a decline in weight is seen parallel to a reduction in food intake. These data indicate that changes in body composition and nutritional status are present throughout the stages of HIV disease, though no causal relationships can be interpreted from this study. The initial changes appear to be due to loss of fat stores, as determined by anthropometry.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nutritional status and food intake in human immunodeficiency virus infection. GI/HIV Study Group. 135 53

Formation of large syncytia and rapid cell killing are characteristics of the Zairian human immunodeficiency virus type 1 isolate HIV-1-NDK, which is highly cytopathic for CD4+ lymphocytes in comparison with the HIV-1-LAV prototype. Chimeric viruses containing different combinations of HIV-1-NDK genetic determinants corresponding to the splice donor, the packaging signal, and the coding sequence of the p18gag protein together with the HIV-1-NDK EcoRI5278-XhoI8401 fragment were obtained by polymerase chain reaction-directed recombination. Phenotypic analysis of recombinant viruses indicated that 75 amino acids from the N-terminal part of HIV-1-NDK p18gag protein together with the HIV-1-NDK envelope glycoprotein are responsible for enhanced fusogenicity of HIV-1-NDK in CD4+ lymphocytes as well as for enhanced infectivity of HIV-1-NDK in some CD4- cells lines. The HIV-1-NDK splice donor/packaging sequence and the sequence encoding the gag protein p25 were not important for the variation observed in HIV-1 fusogenicity.
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PMID:The human immunodeficiency virus (HIV) gag gene product p18 is responsible for enhanced fusogenicity and host range tropism of the highly cytopathic HIV-1-NDK strain. 135 91

There have been reported cases of long-term symptomless human immunodeficiency virus type 1 (HIV-1) infection, but it is not clear whether the benign course of infection was due to host, viral, or other unknown factors. During follow-up of subjects with transfusion-acquired HIV-1 infection in New South Wales, Australia, we identified a group of 6 subjects who had been infected through a single common donor. We were therefore able to study the contributions of various factors to the course of infection. Throughout follow-up (range 6.8-10.1 years after infection), 5 of the recipients and the donor (last follow-up 10.2 years after infection of the first recipient) remained clinically free of symptoms, with normal CD4 cell counts and no p24 antigenaemia. HIV-1 was isolated from only 1 recipient; the isolate did not induce syncytia in a SUPT1 co-culture assay and had a limited in-vitro host range. 1 infected recipient (who had received extensive immunosuppressive treatment for systemic lupus erythematosus) developed Pneumocystis carinii pneumonia and died 4.3 years after infection. The frequency of progression to AIDS or a CD4 cell count below 0.50 x 10(9)/l was significantly lower among the 6 subjects with a common donor (1/6) than among 101 other HIV-infected transfusion recipients for whom data from 7 years of follow-up were available (94/101; p less than 0.0001). These findings suggest that the subjects were infected by a less virulent strain of HIV-1. The identification of this group of subjects should stimulate a search for other similar groups, which will provide important information on the immunopathogenesis of HIV-1 disease.
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PMID:Long-term symptomless HIV-1 infection in recipients of blood products from a single donor. 809 79

A cohort of 139 hemophiliacs was typed for HLA D region genes by means of restriction fragment length polymorphisms (RFLPs) detected by HLA DQ and DR gene probes. Disease progression was studied in the 65 HIV antibody-positive patients, who were infected by contaminated clotting factor before 1985. Strong associations were found between disease progression in HIV-infected patients and allelic DNA fragments revealed by a DQ alpha cDNA probe. A 5.5 kb fragment was reduced in frequency and a 4.6 kb fragment increased in frequency (p less than 0.005) in the faster progressing group, as measured both by development of CDC Category IV clinical symptoms and CD4 number less than 200 x 10(6)/l. These results correlate with DR types deduced from the RFLP patterns revealed by DR beta and DQ alpha gene probes. A decrease in DR4 and an increase in both DR5 and the DR3 subtype found in the A1 B8 DR3 haplotype were associated with disease progression (p less than 0.05).
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PMID:Progression of HIV-related disease is associated with HLA DQ and DR alleles defined by restriction fragment length polymorphisms. 135 76

An assay based on production of HIV antigen in cultures of CD4+ lymphocytes infected 'in vitro' with cell-free virus was established. Using this assay it was possible to isolate, propagate and reliably determine the zidovudine susceptibility of HIV isolates from all patients despite differences in cellular tropism and syncytium inducing capacity. Using this assay, differences in zidovudine susceptibility of 52 serial isolates obtained from 16 patients before and after initiation of therapy were examined. HIV with a 10- to 100-fold reduced susceptibility to zidovudine were isolated from 13 patients as early as 4 months after initiation of therapy. Number of months of zidovudine treatment was strongly associated with development of viral resistance, and high CD4 cell counts tended to be associated with lower rates of development of resistance. That patients can harbor mixtures of virus strains with different susceptibility to zidovudine was confirmed by the differences in susceptibility between isolates obtained simultaneously from CD4+ lymphocyte and plasma, and by the differences in susceptibility between virus strains isolated from clones of CD4+ lymphocytes.
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PMID:Development of resistance to zidovudine in HIV strains isolated from CD4+ lymphocytes and plasma during therapy. 135 26


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