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)

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

The host factors involved in the restriction of tumor growth were studied in nude mice transplanted with a cloned line of chronically human immunodeficiency virus (HIV)-infected U937 cells. HIV-infected and uninfected U937 cells exhibited the same growth patterns in culture. However, HIV-infected cells were not tumorigenic when injected subcutaneously in nude mice, whereas large solid tumors were observed in mice injected with uninfected U937 cells. Injection of nude mice with antibody to alpha/beta interferon (IFN-alpha/beta) enabled HIV-infected U937 cells to grow progressively in approximately 90 to 100% of mice. HIV-infected U937 cells formed solid tumors in the majority (60 to 90%) of either immunosuppressed (splenectomized, irradiated, and anti-asialo-GM1-treated) or genetically immunodeficient (bg/nu/xid) nude mice. In mice treated with antibodies to IFN-alpha/beta with established HIV-positive tumors, a direct correlation was found between p24 antigenemia and tumor size. Treatment of established HIV-positive U937 cell tumors with human IFN-alpha or mouse IFN-alpha/beta resulted in a clear-cut inhibition of both tumor growth and p24 HIV antigenemia. In contrast, treatment with tumor necrosis factor alpha markedly inhibited tumor growth but did not significantly decrease serum p24 levels. 3'-Azido-3'-deoxythymidine treatment did not affect either tumor growth or the levels of serum p24 antigen. These data indicate that endogenous IFN-alpha/beta is a crucial factor in the restriction of both tumor growth and p24 antigenemia in mice injected with HIV-infected tumor cells. Moreover, the results suggest that the development of HIV-1 p24 antigenemia in athymic immunosuppressed mice may represent an interesting in vivo model for anti-HIV therapy.
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PMID:Human immunodeficiency virus (HIV)-infected tumor xenografts as an in vivo model for antiviral therapy: role of alpha/beta interferon in restriction of tumor growth in nude mice injected with HIV-infected U937 tumor cells. 190 15

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

Zidovudine (AZT) is a potent inhibitor of the replication of the human immunodeficiency virus (HIV), and it has been shown to improve survival in advanced HIV disease. We conducted a randomized, double-blind trial in adults with asymptomatic HIV infection who had CD4+ cell counts of fewer than 500 per cubic millimeter on entry into the study. The subjects (92 percent male) were randomly assigned to one of three treatment groups: placebo (428 subjects); zidovudine, 500 mg per day (453); or zidovudine, 1500 mg per day (457). After a mean follow-up of 55 weeks (range, 19 to 107), 33 of the subjects assigned to placebo had the acquired immunodeficiency syndrome (AIDS), as compared with 11 of those assigned to receive 500 mg of zidovudine (P = 0.002; relative risk, 2.8; 95 percent confidence interval, 1.4 to 5.6) and 14 of those assigned to receive 1500 mg of zidovudine (P = 0.05; relative risk, 1.9; 95 percent confidence interval, 1.0 to 3.5). In the three treatment groups, the rates of progression (per 100 person-years) to either AIDS or advanced AIDS-related complex were 7.6, 3.6, and 4.3, respectively. As compared with those assigned to placebo, the subjects in the zidovudine groups had significant increases in the number of CD4+ cells and significant declines in p24 antigen levels. In the 1500-mg zidovudine group, severe hematologic toxicity (anemia or neutropenia) was more frequent than in the other groups (P less than 0.0001). In the 500-mg zidovudine group, nausea was the only toxicity that was significantly more frequent (in 3.3 percent) than in the placebo group (P = 0.001). We conclude that zidovudine is safe and effective in persons with asymptomatic HIV infection and fewer than 500 CD4+ cells per cubic millimeter. Additional study will be required to determine whether such treatment will ultimately improve survival for persons infected with HIV.
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PMID:Zidovudine in asymptomatic human immunodeficiency virus infection. A controlled trial in persons with fewer than 500 CD4-positive cells per cubic millimeter. The AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. 238 74


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