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)

Synthetic peptides described as dog renin inhibitors were found to effectively inhibit the aspartyl protease of human immunodeficiency virus (HIV). The selection of oligopeptides for the HIV protease inhibition study was based on 1) the current strategy of inhibiting aspartyl proteases with transition state analogs, and 2) our previous observations regarding optimal structural differentiation at the P2 position among human, dog, and rat renin inhibitors. In an in vitro assay system consisting of recombinant HIV protease and a synthetic decapeptide substrate (at pH 5.5), results show that HIV protease was unaffected by statine-containing analogs carrying histidine at the P2 position whereas analogs containing valine at the same position yielded anti-protease IC50 values ranging from 50 to 500 nM. As anticipated, some analogs were also shown to inhibit processing of recombinant polyprotein substrate by HIV protease in vitro. The anti-viral activity of three inhibitors was studied in HIV-infected CEM and MT-2 cells. Results showed that one compound, Ac-Naphthylalanyl-Pro-Phe-Val-Statine-Leu-Phe-NH2 (antiprotease IC50 value = 0.4 microM), protected the infected cells effectively with IC50 values (0.73 microM for CEM cells and 0.88 microM for MT-2 cells). This antiviral effect is comparable to those obtained with AZT and ddC in parallel studies of MT-2 cells.
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PMID:A rational approach in the search for potent inhibitors against HIV proteinase. 186 85

Depression or psychosis in a previously asymptomatic individual infected with the human immunodeficiency virus (HIV) may be psychogenic, related to brain involvement by the HIV or both. Although prognosis and treatment differ depending on etiology, computed tomography (CT) and magnetic resonance imaging (MRI) are usually unrevealing in early HIV encephalopathy and therefore cannot differentiate it from psychogenic conditions. Thirty of 32 patients (94%) with HIV encephalopathy had single-photon emission computed tomography (SPECT) findings that differed from the findings in 15 patients with non-HIV psychoses and 6 controls. SPECT showed multifocal cortical and subcortical areas of hypoperfusion. In 4 cases, cognitive improvement after 6-8 weeks of zidovudine (AZT) therapy was reflected in amelioration of SPECT findings. CT remained unchanged. SPECT may be a useful technique for the evaluation of HIV encephalopathy.
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PMID:Single-photon emission computed tomography in human immunodeficiency virus encephalopathy: a preliminary report. 186 65

Since 1982, high-grade B-cell non-Hodgkin's lymphomas (NHLs) have been reported among persons with human immunodeficiency virus (HIV) infection (1); in 1985, CDC revised the surveillance case definition for acquired immunodeficiency syndrome (AIDS) to include certain high-grade NHLs. Recent surveillance findings indicate that NHLs occur among approximately 3% of all adults with AIDS reported to CDC. This report characterizes the occurrence of NHLs in a cohort of persons with AIDS or severe HIV infection who have received long-term zidovudine (AZT)-based therapy.
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PMID:Opportunistic non-Hodgkin's lymphomas among severely immunocompromised HIV-infected patients surviving for prolonged periods on antiretroviral therapy--United States. 187 May 60

Zidovudine (AZT), the only currently approved drug for treatment of human immunodeficiency virus (HIV) in AIDS, is known to be metabolized by mammalian systems to a variety of metabolites including 3'-azido-3'-deoxy-5'-O-glucuronide (GAZT). Interferons (IFNs) are known to alter the microsomal enzyme system responsible for the metabolism of some compounds. The aim of the present study was to investigate the effect of combination therapy of recombinant (r) IFN-beta and AZT on the rates of metabolism of AZT in AIDS patients. AZT was given orally (200 mg every 4 h) for 8 weeks prior to initiation of rIFN-beta therapy (45 X 10(6) U/day, s.c.). Serum samples from 8 patients were obtained prior to and at days 3 and 15 following initiation of rIFN-beta therapy. Serum was analyzed by high-performance liquid chromatography (HPLC) for both AZT and GAZT. The serum data were analyzed by a computer-assisted pharmacokinetics program that calculates rates of AZT metabolism. The half life for AZT was increased approximately two-fold by day 15. The rate of metabolism of AZT was diminished from 1.43 h-1 prior to IFN-beta therapy, to 0.4 h-1 and 0.05 h-1 at days 3 and 15, respectively. The volume of distribution of AZT was 2 l/kg at day 0 and increased to 3.2 and 3.5 l/kg on days 3 and 15, respectively. In conclusion, the results indicate that rIFN-beta inhibits the rate of AZT metabolism in AIDS patients.
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PMID:Metabolic interaction of recombinant interferon-beta and zidovudine in AIDS patients. 191 75

As the AIDS epidemic progresses, concern about the risk of occupational transmission of the causative organism, human immunodeficiency virus (HIV), is increasing. In this article, we summarize the risk of occupational acquisition of HIV in the health care setting and specify protocol and equipment that can reduce this risk in the radiology department. Accidental needle-stick injury is the most common form of exposure to infected blood, which is the only body fluid implicated to date in the occupational transmission of HIV. Prospective cohort studies demonstrate a 0.3-0.4% risk of infection for each needle-stick event. The most important instruction to health care workers that can reduce this risk is the following: Do not recap needles. Other risk-reduction measures include the adoption of universal precautions against transmission of infectious disease; sharp-instrument precautions; the use of protective garb to prevent skin and mucous membrane contamination when blood or bloody body fluid may splash; the availability of stable, puncture-resistant disposal containers for sharp instruments; the exclusion of breakable glass syringes; and the accessibility of resuscitation equipment in all rooms in order to avoid direct mouth-to-mouth contact. These and other measures discussed here are designed to prevent exposure of skin or mucous membrane to blood. If exposure does occur, the contaminated area should be washed immediately. A multicenter research protocol to evaluate the effectiveness of zidovudine (AZT) therapy in preventing seroconversion after exposure to HIV-contaminated blood recommends AZT therapy after massive exposure (e.g., injection of measurable quantities of blood) and endorses it for serious parenteral exposure (e.g., deep needle sticks).
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PMID:AIDS risk and risk reduction in the radiology department. 192 8

Health care workers may be occupationally exposed to human immunodeficiency virus (HIV). The risk of infection is highest with accidental needlestick and similar percutaneous exposures. Emphasis should be placed on avoiding this type of accident. Strategies to prevent accidents and to manage exposures once they have occurred should be developed in each work environment. It is to be hoped that a combination of better infection control, safer devices and technologies, and postexposure prophylaxis with zidovudine (AZT) or other chemotherapeutic agents will help prevent infection in health care providers caring for HIV-infected patients.
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PMID:Transmission of HIV in health care workers. 194 92

Presently, there is no consensus regarding the most appropriate diagnostic and therapeutic approach to patients with human immunodeficiency virus (HIV)-associated lymphoepithelial lesions of the major salivary glands. A retrospective review of 60 consecutive patients with lymphoepithelial lesions is presented. Thirty-eight cases were associated with HIV infection. Lesions associated with HIV infection were usually bilateral, multiple, cystic, and associated with lymphadenopathy. In contrast, in those cases without HIV infection, the lesions tended to be solitary and solid. In the HIV-infected group, treatment included surgery, radiotherapy, zidovudine (AZT), and/or cyst aspiration. All therapeutic regimens, other than aspiration alone, were found to be effective. Eighteen of the patients with HIV infection developed the acquired immunodeficiency syndrome (AIDS) during the study period. Surgical treatment is probably not necessary in the majority of HIV-associated cases. Depending upon individual circumstances, treatment with AZT or low-dose radiotherapy is recommended. A diagnostic and therapeutic algorithm is presented as a guide to the management of future cases.
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PMID:Major salivary gland lymphoepithelial lesions and the acquired immunodeficiency syndrome. 195 83

We recently synthesized phospholipid analogs with antiviral nucleosides in the polar headgroup and demonstrated their antiretroviral activity in vitro in human immunodeficiency virus-infected cells (Hostetler, K.Y., Stuhmiller, L.M., Lenting, H.B.M., van den Bosch, H. and Richman, D.D. (1990) J. Biol. Chem. 265, 6112-6117). Dideoxynucleoside analogs of cytidine diphosphate diglyceride (CDP-DG) represent one class of such phospholipid prodrugs from which the antiviral active principle may be released through established pathways of cellular phospholipid metabolism. We now demonstrate that the liponucleotides of dideoxycytidine, 3'-deoxythymidine and 3'-azido-3'-deoxythymidine (AZT, Zidovudine) can substitute to varying extents for CDP-DG in the biosynthesis of phosphatidylinositol, phosphatidylglycerol or diphosphatidylglycerol by rat liver subcellular fractions. In all three biosynthetic pathways dideoxycytidine diphosphate diglyceride was the most active donor of the phosphatidyl unit. The nearly stoichiometric formation of dideoxycytidine-5'-monophosphate during phosphatidylinositol biosynthesis supports the rationale that the antiretroviral liponucleotides may provide cells with a depot form from which the antiviral drug can be released in 5'-monophosphorylated form, thus bypassing the initial phosphorylation of free dideoxynucleosides.
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PMID:Cytidine diphosphate diglyceride analogs of antiretroviral dideoxynucleosides: evidence for release of dideoxynucleoside-monophosphates by phospholipid biosynthetic enzymes in rat liver subcellular fractions. 195 49

Mutations at amino acid positions 67, 70, 215, and 219 in the human immunodeficiency virus type 1 (HIV-1) pol gene correlate with the emergence of resistance to zidovudine (AZT). These four positions were monitored in viral RNA extracted from infected peripheral blood mononuclear cells (PBMC) and viral stocks obtained after coculture with uninfected lymphocytes. Genotype determinations were made using the self-sustained sequence replication (3SR) and differential bead-based sandwich hybridization (BBSH) assay. The hybridization results obtained by 3SR and BBSH analyses were verified by dideoxynucleotide sequencing of the 3SR products. Correlation of 3SR and BBSH with polymerase chain reaction and Southern hybridization analyses of the PBMC and corresponding viral isolates indicated that PBMC and corresponding HIV-1 isolates may differ in their genotypes at the monitored amino acid positions, variations from the wild-type nucleotide sequence may occur proximal to the codons being monitored, and viral isolates possessing the same genotypes at the four monitored amino acid positions showed a threefold variation in their ID50 measurements.
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PMID:Use of self-sustained sequence replication amplification reaction to analyze and detect mutations in zidovudine-resistant human immunodeficiency virus. 195 9

AZT inhibited replication of an immunodeficiency-inducing strain of feline leukemia virus (FeLV-FAIDS) in vitro at concentrations as low as 0.005 microgram/mL. This antiviral activity was augmented an additional 25-30% when AZT was combined with human recombinant alpha-interferon (2b) (IFN alpha). Administration of AZT alone or in combination with IFN alpha, beginning at the time of exposure to a 100% persistent viremia-inducing dose of FeLV-FAIDS, abrogated the progression of viral infection and protected treated animals from induction of persistent antigenemia and disease. Low levels of antigenemia were detected intermittently in some AZT-treated cats throughout the 6 week treatment and 40 week observation period. Combination of AZT with IFN alpha appeared even more effective than AZT alone. In this treatment group even transient antigenemia was undetectable throughout the therapy and posttherapy observation periods, and latent virus could not be reactivated from bone marrow cells of protected animals. These results provide additional evidence that early treatment with AZT or AZT/IFN alpha therapy can be effective in completely aborting retroviral infections.
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PMID:Therapy of presymptomatic FeLV-induced immunodeficiency syndrome with AZT in combination with alpha interferon. 196 30


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