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

Thirty-five patients with active chronic hepatitis B (ACH-B) were evaluated. They were in stable replicative phase (HBeAg +; DNA polymerase and ALT stable in two determinations at least one month apart) and had not been infected by delta virus or HIV-1. Thirty-four patients were heterosexual and no patient was a drug abuser except one. The 23 initial cases were followed up for 15 months without therapy. The subsequent 12 cases were treated with maximal doses of 2.5 megaunits/m2 of lymphoblastoid alpha interferon (IFN-L) daily for two weeks and three times a week during 10 more weeks. While in the controls only two cases (8.69%) lost the DNA-polymerase activity and HBeAg, 5 treated patients (41.66%; p less than 0.05) developed seroconversion to nonreplicative phase. No patient from the control series lost the HBsAg; however, this happened in 2 treated patients (16.66%). These results show that IFN-L is effective in heterosexual patients with ACH-B in replicative phase without delta virus or HIV-I co-infection.
 ...
PMID:[Treatment of chronic hepatitis B with lymphoblastoid alpha interferon]. 261 34

Azidothymidine (AZT) and interferon alpha (IFN-alpha) are among the drugs showing strong in vitro activity against the human immunodeficiency virus type-1 (HIV-1). Each drug, however, has significant toxicity against normal marrow progenitor cells that frequently proves dose-limiting in patients. In this study, AZT and recombinant IFN-alpha 2a (rIFN-alpha 2a) were tested as single agents and in combination against normal myeloid (CFU-GM) and erythroid (BFU-E) colony forming cells in a standard methylcellulose culture assay. The data were analyzed using a quantitative computerized analysis based on the median-effect principle and the isobologram equation as described by Chou and Talalay (Adv Enz Regul 22:27, 1984). The ED90 for BFU-E and CFU-GM inhibition was then compared with previously measured in vivo plasma levels of each drug and the ED90 for the anti-HIV-1 effect in vitro. We demonstrate that (a) the drugs are strongly synergistic in inhibiting marrow progenitor cell growth and that this synergism occurs at drug levels that are within the range of measured plasma levels in phase I clinical trials, (b) BFU-E are more sensitive than CFU-GM to the inhibiting effects of AZT, rIFN-alpha 2a or both drugs in combination, (c) the drug concentrations in combination that synergistically inhibit bone marrow progenitors are much higher than those required to inhibit HIV-1 replication in vitro, and (d) the anti-HIV-1 effect for the combination of AZT and rIFN-alpha 2a was clearly superior to the effect of AZT or rIFN-alpha 2a alone as indicated by the combination index and the dose-reduction index. These data suggest that substantially lower doses of AZT and rIFN-alpha than those currently being tested in clinical trials might not only maintain a strong synergistic anti-HIV-1 effect but might also avoid significant hematologic toxicity.
 ...
PMID:Synergistic cytotoxic effect of azidothymidine and recombinant interferon alpha on normal human bone marrow progenitor cells. 276 64

Virus shedding was detected in 77% of homosexual subjects and in only 6% of heterosexual controls. The overall virus isolation rate in homosexual subjects was not significantly different among HIV-seropositive (79%) and HIV-seronegative (74%) individuals. In about 20% of homosexual subjects, virus shedding from multiple sites was observed. The most frequently isolated virus was cytomegalovirus (CMV) (41%), followed by enteroviruses (23%), herpes simplex virus (HSV) (7%), and adenoviruses (6%). In the control group, about 50% of subjects were seronegative for HSV-1 and 2, and about 70% were negative for CMV and Epstein-Barr virus (EBV). Only 2% of homosexuals were seronegative for CMV, about 5% for HSV-1 and 2, and about 20% for EBV. No differences were found in antibody levels against varicella-zoster virus (VZV) among the control and homosexual groups. The proportion of seronegatives for Coxsackie and hepatitis viruses was significantly higher in control than in homosexual subjects. However, no differences in the proportion of seronegatives for measles, mumps, and rubella were observed. No HIV-antibody-negative individual was detected with an OKT4/OKT8 ratio of less than 0.75. On the other hand, only HIV-positive subjects, with a ratio of less than 0.75, had high serum IFN alpha titers. The results suggest that the high rate of virus shedding among HIV-negative homosexual subjects might be a factor in the development of AIDS in this high-risk population.
 ...
PMID:Virus isolation and immune studies in a cohort of homosexual men. 290 92

21 patients with AIDS and Kaposi's sarcoma were enrolled in an open therapeutic trial to determine the in vivo anti-retroviral activity of recombinant interferon-alpha (IFN-alpha). 8 (38%) showed a complete or partial anti-tumour response. The mean pretreatment CD4 count for the responders was 399 cells/microliter vs 154 cells/microliter for the non-responders. All 5 of the patients with more than 400 CD4 cells/microliter pretreatment showed a significant reduction in tumour, whereas none of the 7 patients with under 150 CD4 cells/microliter had any response. 5 of the 6 complete or partial responders with greater than 50 pg/ml of human immunodeficiency virus (HIV) p24 before IFN therapy showed a 75% or greater reduction by 12 weeks of therapy, with 3 patients having persistently negative HIV cultures. The anti-viral effects were also most pronounced in the patients with the highest CD4 counts. These data demonstrate the potential benefits, both anti-tumour and anti-retroviral, of treatment with IFN-alpha in the early stages of HIV infection and Kaposi's sarcoma.
 ...
PMID:Anti-retroviral effects of interferon-alpha in AIDS-associated Kaposi's sarcoma. 290 54

Mononuclear leukocytes from human immunodeficiency virus (HIV)-seronegative and -seropositive homosexual men lysed HIV-infected U937 cells to a significantly greater degree than uninfected U937 cells. Depletion of cell subsets with monoclonal antibodies and complement indicated that the effector cells were primarily of the CD16+ phenotype. Acid-stable alpha interferon (IFN-alpha) production induced by the HIV-infected cells correlated with, although was not an absolute requisite for, preferential lysis of the infected targets. The activity of these CD16+, natural killer (NK) cells decreased in relation to the duration of HIV infection and the presence of acquired immunodeficiency syndrome. Pretreatment of peripheral blood mononuclear cells from HIV-seronegative subjects, but not HIV-seropositive men, with IFN-alpha or recombinant interleukin-2 enhanced lysis of both uninfected and HIV-infected U937 cells. These results suggest that IFN-alpha-associated, NK-like mechanisms are active in the cytotoxic response against HIV-infected cells and that HIV infection results in an early and progressive depression of such responses. Prospective investigations may be useful in determining the role of this NK cell response in the natural history and pathogenesis of HIV infection and the efficacy of therapeutic modalities.
 ...
PMID:Association of alpha interferon production with natural killer cell lysis of U937 cells infected with human immunodeficiency virus. 291 35

HIV infection induces both immune deficiency and immune stimulation. Central to the pathology of HIV infection is reduction in the numbers and function of CD4 T cells. Impaired functions include decreased proliferation, IL-2 receptor expression and production of lymphokines (IL-2 and gamma interferon (IFN]. HIV infection stimulates B cells and CD8 T cells. This is seen relatively soon after HIV infection. Increased activation and immaturity are seen in both these cell groups. In vitro studies confirm HIV stimulation of these cells. Studies have been conducted on patients with AIDS and opportunistic infection (OI) or Kaposi's sarcoma (KS), with AIDS-related complex (ARC) or with persistent generalized lymphadenopathy (PGL), as well as on asymptomatic HIV-seropositive and -seronegative homosexually active men. The latter group has been followed at 6-month intervals for the past 2-3 years. Those who seroconverted (became HIV-infected) were studied to investigate early changes following HIV infection. To delineate the immunopathology of infection with HIV, serial testing of seropositive individuals was carried out to determine the rate of CD4-T-cell reduction. Lowered CD4-T-cell number and percentage and CD4/CD8 ratio correlate with the occurrence of AIDS and with survival after AIDS-KS diagnosis. Seropositive individuals, however, differed markedly in the rate of CD4-T-cell reduction; in some, no reduction in CD4 cells occurred over a two-year period of observation. We propose that, in individuals in which CD4 levels have reached a plateau, effective host resistance to further CD4 cytoreduction has occurred.
 ...
PMID:Immune pathogenesis of AIDS and related syndromes. 295 95

Some strains of human immunodeficiency virus type 1 (HIV-1) can infect primary monocytes and monocyte-derived macrophages in vitro. In this report, the effect of cytokines on the production of one of these strains that shows a tropism for mononuclear phagocytes, designated HIV-1JR-FL, was studied. Primary peripheral blood mononuclear phagocytes infected with HIV-1JR-FL were treated with the hematopoietic factors: granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), macrophage colony-stimulating factor (M-CSF), and gamma-interferon (gamma-IFN). The M-CSF, GM-CSF, IL-3, and gamma-IFN were able to alter HIV-1 production under different conditions.
 ...
PMID:Cytokines alter production of HIV-1 from primary mononuclear phagocytes. 304 75

We evaluated the response to therapy and outcome in patients with HIV-associated KS. Eighteen of 26 patients with newly diagnosed KS were treated continuously with IFN until progression of the disease occurred. In most patients with progressive disease, chemotherapy, usually with vinca alcaloid derivatives was instituted. Results were disappointing: 10 of 26 patients (38.5%) died after a median follow-up period of 4.5 months. Survival was shortest in patients who developed opportunistic infections, malignant lymphoma, or had a low OKT4/OKT8 ratio. Only one patient showed a complete remission and one patient had a partial remission under IFN therapy. Five additional patients had stable disease. Chemotherapy was without measureable effect on KS in patients who had progressive disease under IFN. IFN therapy was associated with various, not life-threatening adverse effects and was best tolerated by patients with a low OKT4/OKT8 ratio. Our results indicate that only a small portion of AIDS patients with KS seem to benefit from a continuous treatment with IFN.
 ...
PMID:Kaposi's sarcoma in AIDS patients: long-term treatment with recombinant interferon alpha-2a and chemotherapy. 313 32

Preclinical and clinical studies with an azidothymidine (AZT)/interferon-alpha (IFN-alpha) combination resulted in a marked and synergistic antiretroviral activity. The administration of the two drugs in HIV-seropositive patients affected with Kaposi's sarcoma, however, induced neutropenia, thrombocytopenia, and, in some cases, anemia. A possible means to improve the therapeutic index of AZT and/or IFN-alpha in AIDS patients could be the addition of hematopoietic growth factors. In vitro activity of cytokines on the hematotoxicity of the AZT-IFN-alpha association has not yet been studied. We have performed an in vitro study to evaluate the toxicity of AZT, IFN-alpha, or both on peripheral blood hematopoietic progenitors (CFU-GM and BFU-E) and to assess the activity of interleukin 1 (IL-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), or both in modifying AZT-IFN-alpha hematotoxicity. Results indicate that AZT, IFN-alpha, and combinations of the two have a dose-dependent inhibitory effect on the in vitro growth of peripheral blood hematopoietic progenitors. Combinations of AZT and IFN-alpha inhibited CFU-GM and BFU-E proliferation in an additive manner. Neither IL-1 nor GM-CSF alone was able to induce a significant reduction of AZT-induced damage. Only the addition to the cultures of both cytokines partially curbed the antiproliferative activity of AZT at low dosages.
 ...
PMID:Azidothymidine and interferon-alpha in vitro effects on hematopoiesis: protective in vitro activity of IL-1 and GM-CSF. 749 65

We investigated the CD8+CD57+ alveolar cell functions and their immunoregulatory role in lungs from HIV-seropositive patients with the clinical presentation of lymphocytic alveolitis at different stages of human immunodeficiency virus (HIV) disease. We previously reported, at Stage IV of HIV infection, an expansion of CD8+CD57+ alveolar lymphocytes mirroring the decline of local anti-HIV cytotoxic T-lymphocyte (CTL) responses, and demonstrated that sorted CD8+CD57+ alveolar lymphocytes inhibited the effector phase of these HIV-specific CTL. In the present study, we show that the expansion of CD8+CD57+ alveolar T cells can also be detected at stages II and III of HIV disease, although at a lower degree than observed at Stage IV of HIV infection. When sorted, these CD8+CD57+ alveolar lymphocytes block effector killer cells such as allospecific CTL, natural killer (NK), and lymphokine-activated killer (LAK) cells. The mechanism of action of these inhibitory T-lymphocytes has been further studied and we demonstrated that: (1) cell-to-cell contact between inhibitor and killer is not required, (2) nonstimulated alveolar CD8+CD57+lymphocytes but not CD57- lymphocytes spontaneously release a solube inhibitor of cytolytic functions (ICF). This inhibitory activity of alveolar CD8+CD57+ cells is mediated by a glycosylated protein which is distinct from tumor necrosis factor-alpha (TNF alpha), TNF beta, transforming growth factor-beta 1 (TGF beta 1), TGF beta 2, interferon alpha (IFN alpha), interferon gamma (IFN gamma), and prostaglandins. The release of such an inhibitor of killer cell functions by CD8+CD57+ lymphocytes in the lungs, which are an important interface between the sterile body and the antigen-laden environment, may play a role in the local control of cell immunity.
 ...
PMID:Alveolar CD8+CD57+ lymphocytes in human immunodeficiency virus infection produce an inhibitor of cytotoxic functions. 751 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>