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)

Cutaneous patch and plaque lesions, and erythroderma may suggest mycosis fungoides both clinically and histopathologically in HIV+ patients. However, in some cases, this diagnosis is questionable. Five such cases are presented. When we compared these cases with cases of mycosis fungoides unassociated with HIV infection, we found less concordance among dermatopathologists in making a histopathological diagnosis, a greater proportion of CD8 than CD4 T cells in the cutaneous infiltrates, and no instances of demonstrated clonality of the cutaneous T-cell infiltrates in the HIV+ group. We conclude that CD8 T-cell predominant dermatoses may simulate mycosis fungoides in HIV+ patients.
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PMID:Mycosis fungoideslike T-cell cutaneous lymphoid infiltrates in patients with HIV infection. 769 9

Assembly and budding of retroviruses is believed to involve a complex interaction of envelope and capsid proteins at the host cell membrane. The nature of these interactions is, however, incompletely understood. Studies of the topography of the surface of HIV-1 have shown that the envelope glycoprotein projections (knobs) are arranged in a T = 7 levo rotational symmetry. Similarly, an icosahedral structure has been suggested for the p17 matrix of HIV-1. In an effort to investigate whether there is a structural interaction between these molecules, virions whose maturation was blocked by an inhibitor of HIV protease were studied using cytochemistry, morphometry, and 2D fast Fourier transform image enhancement. Analysis of the relationship between core morphology and the topographic distribution of envelope glycoprotein projections on HIV-1 provided structural evidence of an interaction between Env and Gag proteins. Furthermore, image enhancement revealed a periodic substructure in the Pr55gag plaque. Taken together, the data suggest an interaction between Pr55gag and the gp120-gp41 complex during assembly and budding of HIV-1. This interaction may, in part, contribute to determining the amount of Env glycoprotein that will be incorporated into a virion, and therefore play a role in the biology of HIV-1.
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PMID:Ultrastructural evidence of an interaction between Env and Gag proteins during assembly of HIV type 1. 773 97

N-alpha-acetyl-nona-D-arginine amide acetate (ALX40-4C) was developed as a competitive inhibitor of the binding of the HIV Tat protein to its RNA target TAR, which is an intracellular interaction dependent on a short, arginine-rich sequence in Tat. ALX40-4C is a simple mimic of that domain, which is stabilised against enzymatic degradation through inclusion of D-amino acids and terminal protection. The drug inhibits HIV-1 in vitro and is currently being assessed in vivo. In the work reported here, potential activities of the compound against other viruses were examined. As expected, there was little or no activity against most viruses examined, except against some herpesviruses: HSV-1, HSV-2 and CMV. Maximal inhibition of HSV-1 in a plaque reduction assay required pre-incubation with the drug. Maximal inhibition of HCMV, which replicates more slowly than HSV-1, requires exposure to the compound within the first few hours of infection. It appears that the drug inhibits an early step in HSV and HCMV infection. Such a mechanism is consistent with that of other cationic, herpesvirus inhibitors.
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PMID:Antiherpetic activities of N-alpha-acetyl-nona-D-arginine amide acetate. 779 7

The antiretroviral activity of two new lipophilic derivatives of azidothymidine (AZT), N4-hexadecyl-2'-deoxyribocytidylyl-(3',5')-3'-azido-2',3'-deoxythy midine (N4-hexadecyldC-AZT) and N4-palmitoyl-2'-deoxyribocytidylyl-(3',5')-3'-azido-2',3'-deoxythy midine (N4-palmitoyldC-AZT) was evaluated in comparison to AZT. In vitro the drugs were tested in human immunodeficiency virus 1 (HIV-1) infected CD4+ HeLa and H9 cells. The in vivo antiviral effect of these derivatives was analysed in Rauscher leukemia virus (RLV) infected mice. The derivatives were incorporated into small liposomes. In vitro both derivatives inhibited virus proliferation in both HIV-1 infected cell lines in a similar dose-responsive manner as AZT. In a plaque reduction assay, using HeLa cells, the IC50 values were 0.035 microM for AZT, 0.5 microM for N4-hexadecyldC-AZT and 4.5 microM for N4-palmitoyldC-AZT, whereas p24 antigen analysis on H9 cells gave IC50 values of 0.005 microM, 0.05 microM and 0.05 microM, respectively. RLV infected mice were treated with intermittent schedules i.p. or i.v. on days 1, 6, 11, and days 16 or 0, 3, 7, and 11 after infection. Regimens with further delayed drug application were on days 3, 7, and 11 and 7 and 11 only. While i.p. treatment with total doses of 380-1140 mg/kg free AZT resulted in 10-30% inhibition of RLV induced splenomegaly, the derivatives gave inhibitions of 37-94%. Late onset of treatment with the derivatives was significantly more effective as compared to free AZT. Intravenous treatment with N4-hexadecyldC-AZT was effective, but with AZT was inactive. The discrepancy in antiviral activity of the AZT derivatives found between the in vitro and in vivo test systems emphasizes the importance of investigating the activity of drug derivatives in vivo.
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PMID:New lipophilic alkyl/acyl dinucleoside phosphates as derivatives of 3'-azido-3'-deoxythymidine: inhibition of HIV-1 replication in vitro and antiviral activity against Rauscher leukemia virus infected mice with delayed treatment regimens. 794 15

The cultivable subgingival bacterial flora from three HIV-seropositive and CD4 cell depleted children with hemophilia were examined in this study. The numbers of CD4 cells of the subjected children ranged from 4.9 to 16.3 per mm3 blood. Streptococcus species, including, beta-hemolytic streptococcus identified as Streptococcus mutans and Streptococcus sanguis, were predominant in the subgingival plaque samples. Actinomyces species were also frequently found. Gram-negative rods other than Capnocytophaga species were not common in these samples. It is possible that the subgingival microbial flora are influenced by the CD4 cell decrease with HIV infection.
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PMID:A study of the subgingival microflora of HIV-seropositive and CD4 cell depleted children with hemophilia. 798 69

In California and Utah, researchers used the standard Airburst Test and the Tensile and Elongation Test to determine the stability of multiple replicates of several types of aged latex condoms (100 condoms/brand) from each brand of remaining stocks from an original National Institutes of Health-sponsored study. They used current stocks of lubricated and nonlubricated Trojan brands as controls. They physically stressed each condom as much as it would be during coitus just before ejaculation before submitting it to the 2 tests. They used a new bacteriophage assay, which can detect a single viral plaque-forming unit (PFU), to detect any leakage. The bacteriophage oX174 was used as a surrogate for HIV-1 and other viruses of sexually transmitted diseases. Each of the brands of condoms experienced some leakage. All of the Protex Contracept Plus condoms leaked. As for the remaining brands, the leakage rate varied from 0.9% to 22.8%. The Ramses Non-Lubricated condom, the original Mentor condom, and the LifeStyles Conture had the lowest percentage of condoms that leaked viral particles (0.9%, 4%, and 6.3%, respectively). Their leakage rates were lower than those of the 2 current stocks (25.7% for the lubricated Trojan controls and 11.8% for the nonlubricated Trojan controls). None of the leakages in the 3 brands were visibly detectable. Test conditions were intentionally demanding: a much smaller viral particle than HIV-1 (25% the diameter of HIV-1, close to the size of some hepatitis viruses), the enveloped and spherical shape of which enhances the potential for its passage through small holes, presence of a potent surface active agent, a longer test period than most coital acts (30 minutes), a constant pressure head during the test period, a high titer of virus and large volume of viral suspension with the condom. These results should be considered in the proper perspective.
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PMID:Viral leakage risk differences in latex condoms. 807 34

Previous studies have suggested that salivary secretions may act as inhibitors of HIV-1 replication in vitro. This inhibitory activity was determined to be associated mainly with secretions obtained from the human submandibular-sublingual glands, and subsequent electron micrographs revealed the association of viral particles with the salivary sediment. Fractionation of human submandibular-sublingual (HSMSL) saliva by size-exclusion chromatography was initiated, and resulting fractions were tested for their ability to modulate the replication of HIV-1 using a plaque assay on HeLa CD4+ cell monolayers. Results indicated that the filtration-sensitive inhibitory activity was primarily associated with the mucin-rich fractions, and the inhibitory activity was found to reduce the number of infectious units by 75%. To determine the identity of the salivary components involved, adsorption experiments involving the interaction of HIV particles with immobilized salivary components were performed. Immunological counter staining revealed an interaction of HIV particles as well as recombinant gp120 with the lower-molecular-weight mucin. Electron microscopic examination of the mucin-rich fractions-HIV incubates revealed the aggregation of virus particles by salivary components. These results suggest that human salivary mucins may have a role in modulating the infectivity of HIV-1.
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PMID:Interaction of HIV-1 and human salivary mucins. 808 29

Zidovudine treatment of individuals infected with human immunodeficiency virus type 1 (HIV-1) results in HIV-1 isolates with a reduced zidovudine sensitivity in vitro. This reduction is due to mutations causing amino acid substitutions at five codons (41, 67, 70, 215, and 219) on the reverse transcriptase enzyme of HIV. HIV-1 isolates were obtained 8 to 69 weeks after therapy discontinuation from 10 patients at different stages of disease. Zidovudine sensitivity was determined by the HeLa CD4+ plaque assay. The presence of the resistance-conferring mutations was determined by using a selective polymerase chain reaction. Sensitivity could be determined for six isolate pairs: one showed a decline in the 50% inhibitory zidovudine concentration after therapy discontinuation; four pairs did not show a change. The majority of changes in the five codons in isolates from all 10 patients were the result of a relative increase in the wild-type sequence. Complete changes from mutant to the wild type were seen for only two codons in isolates from two patients. This study of isolates from a small group of individuals at different stages of disease, who had been taking zidovudine for 1 to 2 years, shows that a period of 1 year without zidovudine may be required to achieve a change from a mutant or mixed virus population to a wild-type virus population.
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PMID:Effects of discontinuation of zidovudine treatment on zidovudine sensitivity of human immunodeficiency virus type 1 isolates. 810 17

Ribozymes are potentially powerful tools for the suppression of intracellular gene expression. However, the few reports that exist of their activities in bacteria have described mixed success. Chuat and Galibert (Chuat, J.-C., and Galibert, F. (1989) Biochem. Biophys. Res. Commun. 162, 1025-1029) failed to detect any trans-activities of hammerhead ribozymes in Escherichia coli, while Sioud and Drlica (Sioud, M., and Drlica, K. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 7303-7307) reported complete inhibition of expression of the gene for a nonbacterial protein, HIV-1 integrase, by trans-acting hammerhead ribozymes in E. coli. It is of interest to determine whether ribozymes can really be used in natural bacterial systems (Altman, S. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 10898-10900). We now report that a ribozyme designed to cleave the A2 gene of RNA coliphage SP, when transcribed from a plasmid in E. coli caused failure of the proliferation of progeny phage. Inactive ribozymes with altered catalytic sequences did not affect phage growth. These results indicate that it is mainly the catalytic activity of the ribozyme and not its function as an antisense molecule that is responsible for suppressing the proliferation of the RNA phage. Moreover, an analysis based on numbers of plaque-forming units and the function of the A2 protein indicated that antisense RNA may successfully compete with ribosomes in targeting mRNA while ribozymes in this study may not compete with ribosomes in naturally occurring bacterial transcription/translation-coupled systems.
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PMID:A hammerhead ribozyme inhibits the proliferation of an RNA coliphage SP in Escherichia coli. 815 67

Although Kaposi's sarcoma is not the most common cause of death in AIDS patients, it is often one of the initial opportunistic illnesses associated with human immunodeficiency virus infection. Extensive plaque formation and edema in the lower extremities may take on the appearance of cellulitis, and in dark-skinned persons, the lesions of the neoplasm may not be noticeable. Treatment is palliative; therapy for local effect is appropriate unless lesions are extensive or systemic involvement is present.
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PMID:Kaposi's sarcoma mimicking cellulitis. 824 91


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