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)

A number of studies have illustrated the effectiveness of hematopoietic growth factors in managing treatment-related cytopenias in patients with human immunodeficiency virus (HIV) infection. One of these factors, granulocyte-macrophage colony-stimulating factor, has been shown to restore absolute neutrophil counts in patients with acquired immunodeficiency syndrome (AIDS) and Kaposi's sarcoma receiving a combination of zidovudine (AZT) and interferon alfa. A combination of granulocyte colony-stimulating factor and erythropoietin has also been demonstrated to alleviate both neutropenia and anemia in patients with advanced AIDS or AIDS-related complex receiving zidovudine. Hematopoietic growth factors, in combination with each other and with antiretroviral agents, thus have an important supportive role to play in the treatment of patients with HIV disease.
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PMID:Antiretroviral therapy and immunomodulators in patients with AIDS. 201 46

In vitro studies have shown that 3'-azido-3'-deoxythymidine (zidovudine, AZT) and interferon synergistically inhibit the replication of the human immunodeficiency virus type 1 (HIV) in peripheral blood mononuclear cells at concentrations achievable in patients. Interferon alfa can cause lesions to regress in patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma (KS). Although zidovudine has no significant effect on the regression of these lesions, it does have antiviral activity in these patients as manifested by a decline in serum HIV antigen. However, when used separately, the two drugs can have serious side effects in some patients. In addition, the development of zidovudine-resistant strains has been noted in patients with advanced HIV disease receiving zidovudine for nine months or longer. Three in vivo trials have been initiated to assess possible advantages of combination therapy with zidovudine and interferon alfa in patients with AIDS-related KS. The incidence of serious adverse reactions, therapeutic efficacy, and the rate of emergence of zidovudine-resistant strains of HIV were evaluated. Preliminary results indicate that combination therapy with interferon alfa and zidovudine can safely be administered to patients with AIDS-related KS in doses that elicit antitumor and antiviral responses and discourage the potential emergence of zidovudine-resistant HIV strains.
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PMID:Antiretroviral therapy in combination with interferon for AIDS-related Kaposi's sarcoma. 201 47

The possible mechanisms of neutropenia associated with both human immunodeficiency virus (HIV) infection and drug treatment in adults are examined, and the current and investigational strategies for managing neutropenia are reviewed. Neutropenia associated with HIV arises from diverse mechanisms, including cellular immune dysfunction, direct effects on progenitor cells, humoral immune dysfunction, and vitamin deficiencies. Drug-induced neutropenia may be related to direct cytotoxic effects, immunologic mediators, and the effects of vitamin depletion on the bone marrow. Bone marrow toxicity in patients receiving zidovudine appears to be more frequent in those patients with advanced disease, low CD4 cell counts, a pretreatment anemia, low serum vitamin B12 levels, and low or low normal serum folic acid levels. Patients with AIDS also are at increased risk for adverse events associated with folate antagonists and sulfonamides compared with other patient populations. Lithium therapy has improved neutrophil counts in patients receiving zidovudine; however, the toxicities associated with use of lithium, combined with the lower dosages of zidovudine now recommended, may obviate its use. The use of colony-stimulating factors appears promising for increasing the number and function of circulating neutrophils. Although concomitant use of interferon alfa and zidovudine may result in a strong synergistic anti-HIV effect, dose-limiting neutropenia has been reported in patients receiving the combination. There are currently no controlled data assessing the effectiveness of intravenous immune globulin in the treatment of HIV-related or drug-related neutropenia. In evaluating neutropenia, the clinician must attempt to discern whether the neutropenia is more likely related to disease state(s) or drug therapies. Potential management strategies include modulation of the disease state, discontinuation or dose reduction of the offending agent, or administration of exogenous immune enhancer.
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PMID:Neutropenia in patients infected with human immunodeficiency virus. 203 44

A variety of cellular proteins have been found to bind to related DNA sequences in the enhancer elements of the human immunodeficiency virus, the kappa immunoglobulin gene, the class I major histocompatibility complex gene, and the beta-interferon gene. Recently, lambda gt11 gene expression cloning using ligated oligonucleotide probes complementary to these DNA binding motifs has been performed. An identical cDNA clone encoding a cellular protein, referred to as HIV-EP1, MBP-1, or PRDII-BF1, that binds to each of these sequences has been identified. This cDNA potentially encodes a 298-kDa cellular protein with two widely separated zinc finger binding domains, each of which binds to the same DNA sequence. As part of an effort to examine the chromosomal organization of cellular genes encoding transcription factors, we report the chromosomal mapping of the gene encoding this zinc finger protein (ZNF40) to chromosome 6p22.3-24.
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PMID:Localization of the zinc finger DNA-binding protein HIV-EP1/MBP-1/PRDII-BF1 to human chromosome 6p22.3-p24. 203

In this pilot study, 12 patients with chronic delta hepatitis were studied. The diagnosis was based on the presence of antibodies to the hepatitis delta antigen in the serum and hepatitis delta virus RNA and hepatitis delta antigen in the serum and liver. All patients were also positive for hepatitis B surface antigen. The infection was presumed to have been transmitted by intravenous drug abuse in six of the patients, blood transfusion in one and by sexual contact in four (two had antibodies to human immunodeficiency virus in their serum, but did not show signs of acquired immunodeficiency syndrome). In one further patient, the source of infection was unknown. Interferon alfa-2b (INTRON A, Schering-Plough Corporation) was initiated at 5 million units per day subcutaneously for at least 4 months, being reduced by half if side effects occurred. Serum alanine aminotransferase levels, hepatitis delta virus RNA and hepatitis delta antigen were measured at monthly intervals for up to 12 months in some patients. Interferon therapy resulted in decreased serum levels of these three markers. On cessation of therapy, most patients experienced a relapse over 6 months, but alanine amino transferase levels could be normalized once more by restarting interferon therapy. In conclusion, interferon decreased hepatic inflammation by the inhibition of hepatitis delta virus replication, although relapse occurred when interferon was stopped and long-term therapy is required to achieve permanent control of the disease. Care will be required when treating patients with advanced or decompensated liver disease.
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PMID:Therapy of chronic delta hepatitis with interferon alfa-2b. 207 75

Gamma interferon (gamma-INF) production was studied and two-color fluorescence flow cytometry analysis was done on the peripheral blood mononuclear cells (PBMC) in allogeneic bone marrow transplant recipients. Gamma INF was not detected in any patients within a year after transplantation whether PBMC was stimulated with PHA or not. A year after transplantation, gamma-INF was produced in the normal level in the stimulated and unstimulated PBMC. The number of suppressor-inducer T cells (CD4+2H4+) was decreased and that of suppressor T cells (CD11+CD8+) was normal. The numbers of helper-inducer T cells (CD4+4B4+) and helper T cells (CD4+2H4-) were normal. The numbers of activated helper-inducer T cells (CD4+HLA-DR+) and suppressor-cytotoxic T cells (CD8+HLA-DR+) were elevated. In the NK cells, Leu7+ CD16-cells were elevated, whereas Leu7+CD16+ cells and Leu7-CD16+ cells were normal. Leu7+CD8+ cells were elevated. These results indicated immunodeficiency after transplantation.
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PMID:Gamma interferon production and two-color fluorescence flow cytometry analysis of peripheral blood mononuclear cells in allogeneic bone marrow transplant recipients. 210 21

Translational effects of the RNA leader and Tat protein of human immunodeficiency virus type 1 (HIV-1) were investigated in rabbit reticulocyte lysate. Hybrid RNA species with natural or mutated HIV-1 leader fused to human interferon- gamma mRNA were produced in vitro from recombinant plasmids. HIV-1 leader RNA was found to inhibit translation through two mechanisms. A 3-fold trans-inhibition of translation was demonstrated by mixing hybrid HIV-1 leader RNA with indicator interferon mRNA. By comparison, HIV-1 leader caused a 50-fold cis-inhibition in lysate in which two trans-inhibitory factors, double-stranded RNA-dependent protein kinase and (2'-5')oligoadenylate synthetase, were suppressed. In contrast, purified HIV-1 Tat protein produced in Escherichia coli enhanced by 4-fold translation from HIV-1 leader-interferon mRNA but not from interferon mRNA lacking HIV sequences or from total poly(A)+ RNA. Translation of mRNA containing either a single base substitution in the loop of the "trans-acting responsive" sequence (TAR) or an alternative stem-loop in TAR was nevertheless stimulated by Tat. The enhancement of translation by Tat was largely due to relief of cis-inhibition, since the effect was found even in lysate in which double-stranded RNA-dependent protein kinase was inhibited with 2-aminopurine. These results suggest that translation is an important level of control in the replication cycle of HIV-1.
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PMID:Direct evidence for translational regulation by leader RNA and Tat protein of human immunodeficiency virus type 1. 212 Jul 1

Homosexual men who were human immunodeficiency virus (HIV) seropositive at enrollment into the Pittsburgh portion of the Multicenter AIDS Cohort Study had elevated titers of serum alpha and gamma interferon (IFN) within 24 months prior to development of AIDS. In contrast, subjects who developed AIDS relatively early after seroconversion to HIV during this study did not have increased levels of alpha or gamma IFN.
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PMID:Relation of alpha and gamma interferon levels to development of AIDS in homosexual men. 212 42

Natural killer (NK) cells may be of significance in host defense against viral infections. In the present study, NK cell function was examined in relation to different phases of human immunodeficiency virus (HIV) infection. Peripheral blood mononuclear cells were tested for NK cell activity using K562 cell targets in a 51Cr-release assay. NK cell responses of 26 HIV-seronegative homosexual men were not significantly different from those of 30 heterosexual controls. NK activity was significantly lower in cells from 32 homosexual men with documented, early-phase HIV infection (average of 14 months; range of 3-27 months) as compared with that of seronegative men. The NK cell response decreased with time, since men within the first year of infection (n = 15; average of 7.8 months; range of 3-12 months) had greater NK cell activity than did those with longer duration of infection (n = 17; average of 18.3 months; range of 13-27 months). The decrease in NK cell activity did not correlate with altered numbers of cells bearing CD16 (NK) markers in these subjects. NK cell-mediated lysis and cell numbers were most severely depressed in a separate group of HIV-seropositive men who had acquired immune deficiency syndrome (AIDS). In vitro treatment with alpha-interferon (alpha-IFN) significantly enhanced NK activity of effector cells obtained from men within the first year of HIV infection but not in those with longer-term infection. Our results indicate that NK cell function decreases over time within the first 2 years of HIV infection in homosexual men, and is lowest in HIV-seropositive men with overt AIDS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Natural killer cell responses in homosexual men with early HIV infection. 214 Oct 73

We report that 11 human immunodeficiency virus 1 (HIV-1)-seropositive patients, including three AIDS patients, were able to generate a cellular immune response to the intradermal injection of low doses (2-10 micrograms) of recombinant interleukin 2 (rIL-2). A dose-dependent zone of induration appeared at the site of injection, peaked at 24 hr, and was accompanied by the local accumulation of T cells, monocytes, and Langerhans cells. Despite the reductions in the CD4+ T-cell counts in the peripheral blood of most patients, CD4+ T-cells could still be mobilized with rIL-2 injections into the skin. The total number of immigrant cells was equivalent to those in HIV-1-seronegative patients, although the CD4+/CD8+ ratio of the dermal population was reduced. In response to rIL-2, major histocompatibility complex (MHC) class II antigen was expressed on the surface of keratinocytes, Langerhans cells, lymphocytes, and macrophages. In addition, the gamma interferon (IFN-gamma)-induced protein IP-10 rapidly appeared in dermal inflammatory cells and keratinocytes. A majority of HIV-1-seropositive patients demonstrated low or absent responses to common skin-test antigens. Those with positive zones of induration were often defective in the cellular expression of the IFN-gamma-induced MHC class II antigen. The simultaneous administration of rIL-2 and soluble antigen at widely separated cutaneous sites led to an enhancement of skin-test antigen reactivity in seropositive patients. The results suggest that local administration of rIL-2 to seropositive patients may act systemically, stimulating cellular immunity to recall antigens, and thus may be of potential benefit in the defense against opportunistic pathogens encountered in HIV-1 infection.
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PMID:Cutaneous response to recombinant interleukin 2 in human immunodeficiency virus 1-seropositive individuals. 214 21


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