Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus (HIV-1) isolates from 8 Ethiopian and 8 Swedish AIDS patients, none of them treated with antiviral drugs, were compared for sensitivity to azido-deoxy-thymidine (AZT), dideoxy-inosine (ddI) and interferon-alpha. HIV was isolated from peripheral blood mononuclear class, identified by Western blot and nucleotide sequencing, and passaged 1-3 times. Sensitivity to the 3 drugs, expressed as ED50s relative to positive controls, was determined by culturing HIV in the presence of drugs in a range of concentrations and assaying the supernatant for p24 antigen and the virus pellet for reverse transcriptase (RT). Dose-dependent anti-HIV activity for AZT was seen in the 8 Ethiopian isolates, and ED50s for p24 antigen and RT activity were correlated. 1 Ethiopian HIV isolate was sensitive to ddI, and another, to interferon-alpha. 1 Swedish HIV was resistant to AZT, and on analysis had a mutation from threonine to tyrosine at position 215. There were no significant differences between ED50s for interferon in the Swedish and Ethiopian HIVs. Combined data for each drug showed correlation between the p24 antigen and RT activities of the Ethiopian and Swedish HIVs. Since there was no resistance observed in the Ethiopian HIV to AZT or ddI, low-dose treatment would probably slow progression of HIV infection in Ethiopians, if these drugs could be made available for clinical trials.
 ...
PMID:Response of Ethiopian human immunodeficiency virus type 1 isolates to antiviral compounds. 128 93

There is an increasingly body of evidence, obtained both in vitro and in vivo, showing that exogenous opioids have a variety of effects on cells of the immune system. The consequence is that opiates at pharmacological concentrations suppress cell-mediated immunity, as reflected by depressed T-dependent antibody production by B lymphocytes, altered T lymphocyte functions such as proliferation, delayed-type hypersensitivity, graft-versus-host responses and decreased cytotoxic NK cell activity. The macrophage/monocyte oxidative burst and phagocytosis are also impaired, effects probably mediated by various opioid receptor types as they are blocked or reversed by naloxone, an opioid antagonist. Other possible mechanisms of interaction remain to be elucidated: exogenous opioids can act on neurons of the central nervous system, thereby activating the neuroendocrine system with a subsequent increase in serum glucocorticoid levels. Another potential link between the central nervous system and lymphoid tissue is the sympathetic nervous system, via which opioid-induced activation could result in noradrenergic inhibition of the immune system. The clinical consequences of these suppressive effects on the immune system are seen in the striking increase in the incidence of infections in intravenous opioid addicts. The advent of AIDS and the identification of intravenous drug abusers as a critical risk group have propelled interest in this area. Data obtained both in vitro and in vivo with various experimental models shows that morphine increases susceptibility to bacterial and viral infections, the latter effect possibly being related to a depressive effect of opioids on gamma-interferon levels. The dosage and time of administration strongly influence the results: it appears that chronic opioid treatment in vivo induces a state of immune tolerance, with normal resistance to viral infections, whereas short or single administration has a detrimental effect. In the former context, other factors such as a morphine-induced increase in CD4+ cell numbers may tend to enhance the infectivity of HIV-infected subjects.
 ...
PMID:Opiates and immune function. Consequences on infectious diseases with special reference to AIDS. 130 43

Mice infected with LP-BM5 murine leukemia viruses develop a syndrome, termed mouse AIDS (MAIDS), characterized by increasingly severe immunodeficiency and progressive lymphoproliferation. Virus-infected mice were examined for the ability to resist acute infection and to control chronic infection with the protozoan Toxoplasma gondii, a major opportunistic pathogen of individuals infected with human immunodeficiency virus. Mice infected with the retroviruses for 2 or 4 weeks responded normally to challenge with the parasite, but mice inoculated with the protozoan 8 or 12 weeks after viral infection died with acute disease due to T. gondii. Increased sensitivity to acute infection was associated with a reduced ability to produce gamma interferon (IFN-gamma) and with established changes in CD4+ T-cell function. Mice latently infected with T. gondii and then inoculated with the retrovirus mixture were found to reactivate the parasite infection, with 30 to 40% of dually infected animals dying between 5 and 16 weeks after viral infection. Reactivation was associated with reduced proliferation and impaired production of IFN-gamma in response to stimulation with soluble T. gondii antigens or to concanavalin A. Continuing resistance to lethal reactivation in the remaining mice was shown to require CD8+ T cells and expression of IFN-gamma. In addition, it was found that chronic infection with T. gondii altered the course of MAIDS by inhibiting the progression of splenomegaly and immunodeficiency and reducing the expression of both the helper and etiologic defective viruses. These results support previous studies which indicate that infection with T. gondii is controlled by synergistic interactions between CD4+ and CD8+ T cells, the functions of which are progressively impaired during the course of MAIDS.
 ...
PMID:Opportunistic infections and retrovirus-induced immunodeficiency: studies of acute and chronic infections with Toxoplasma gondii in mice infected with LP-BM5 murine leukemia viruses. 132 58

In recent years, the antiviral armamentarium has expanded considerably. Currently available agents are virustatic, inhibiting specific steps in the process of viral replication. No agent is active against nonreplicating or latent viruses. Acyclovir is useful in the treatment of genital herpes, herpes simplex encephalitis, mucocutaneous herpetic infection, varicella infection in the immunosuppressed host, and herpes zoster infection in the normal and the immunosuppressed host. It can also be used for prevention of herpesvirus infection in immunocompromised patients. Ganciclovir is indicated for the treatment of cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome (AIDS) and is effective in the management of organ-specific cytomegalovirus infection in other immunocompromised patients. Chronic hepatitis C and condyloma acuminatum due to human papillomavirus respond to therapy with interferon alfa-2b. Patients with human immunodeficiency virus infection and CD4 lymphocyte counts of less than 500 cells/mm3 should be treated with zidovudine. Amantadine is useful in a therapeutic and prophylactic role in the management of influenza A virus infection. With the expanded use of and indications for antiviral therapy, clinically significant resistance to these agents has been encountered with increasing frequency.
 ...
PMID:Antiviral agents. 134 78

To improve evaluation of new antiretroviral drugs in the acquired immunodeficiency syndrome (AIDS), sensitive biological markers that accurately predict response to treatment are needed. Two possible markers are endogenous interferon (E-IFN), which is a cytokine involved in the pathophysiology of AIDS, and serum triglycerides (TG), which are raised in patients with AIDS, possibly reflecting enhanced cytokine activity. E-IFN, TG, body-mass index, CD4 count, and HIV p24 were measured in 19 patients (15 with AIDS, 4 with AIDS-related complex), who were part of the phase II licensing trial of zidovudine (ZDV). 10 received ZDV and 9 received placebo. Rapid, significant, and sustained declines from initial values in E-IFN and TG concentrations were observed in ZDV patients but not in placebo patients. Baseline values of E-IFN and TG concentrations after 4 months on ZDV treatment were both important contributors to long-term survival. The findings suggest that these indicators of abnormal cytokine expression may be useful measures of not only disease severity but also efficacy of antiretroviral therapy in AIDS.
 ...
PMID:Endogenous interferon and triglyceride concentrations to assess response to zidovudine in AIDS and advanced AIDS-related complex. 134 48

Anemia and neutropenia are common complications of HIV infection. Antiretroviral therapy with zidovudine exacerbates bone marrow suppression by inhibiting proliferation of blood cell progenitor cells. In addition, treatment for opportunistic infections or malignancies can involve the use of myelosuppressive drugs. As a consequence, severe anemia and neutropenia can result, thereby limiting the utilization of antiretroviral drugs. Since antiretroviral therapy can increase survival, drugs that ameliorate myelosuppression are important adjuncts in the treatment of HIV-infected patients. Three hematopoietic growth factors are effective in the treatment of anemia or neutropenia. In four placebo-controlled trials, erythropoietin (EPO) at doses up to 600 U/kg/wk decreased mean transfusion requirements by 37%, increased mean hematocrit by 4.5% and corrected anemia in the majority of patients receiving zidovudine over a 12-week period. In a separate study, granulocyte colony-stimulating factor (G-CSF) corrected leukopenia and isolated neutrophil defects in 22 patients with AIDS without altering HIV expression. When erythropoietin was added to the regimen, combined G-CSF and EPO corrected both anemia and leukopenia and lessened subsequent zidovudine toxicity. Similarly, granulocyte macrophage-colony-stimulating factor (GM-CSF) corrected leukopenia and pre-existing neutrophil defects in patients with HIV infection. In controlled and uncontrolled trials, GM-CSF also appears to reduce toxicity from zidovudine, ganciclovir, and antineoplastic therapy. New combinations of hematopoietic stimulants are being used to decrease the toxicity from combination antiretroviral therapy with alpha interferon and cytotoxic chemotherapy in the treatment of AIDS-related malignancies.(ABSTRACT TRUNCATED AT 250 WORDS)
AIDS Res Hum Retroviruses 1992 Jun
PMID:Hematopoietic growth factors as adjuncts to antiretroviral therapy. 138 Feb 56

Adriamycin (ADR) is an anticancer drug commonly used in the treatment of HIV-related cancers. Due to its effect on DNA metabolism, ADR might be able to modulate HIV replication in monocyte-macrophages (M/M), resting cells potentially less sensitive to the toxic effect of this drug. Thus, we assessed the efficacy of ADR against HIV replication in both lymphocytes and M/M. We further investigated the mechanism(s) of action of ADR and its potential synergistic activity with zidovudine (AZT) or alpha-interferon (IFN alpha). ADR consistently inhibited viral replication in M/M: 50% viral inhibition was obtained with 0.005 micrograms/ml ADR, while greater 90% viral inhibition was obtained with 0.05 micrograms/ml ADR. No cell toxicity was seen in M/M at concentrations up to 0.5 micrograms/ml. No anti-HIV activity was shown by ADR in lymphocytes at concentrations up to 0.05 micrograms/ml, that is also the toxic dose 50% (TCID50 for these cells). ADR neither inactivates HIV virions nor affects HIV binding with CD4 receptors. No inhibition of HIV reverse transcriptase by ADR was found at concentrations at least 2,000-fold greater than the 50% HIV inhibitory concentration in M/M. Molecular analysis by polymerase chain reaction (PCR) suggests that ADR substantially affects virus DNA production at concentrations that inhibit viral replication. Finally, late stages of HIV replication were not affected by ADR. At least additive effects of the association ADR + AZT and ADR + IFN alpha were obtained against de novo HIV infection of M/M.(ABSTRACT TRUNCATED AT 250 WORDS)
AIDS Res Hum Retroviruses 1992 Jul
PMID:Selective inhibition of HIV replication by adriamycin in macrophages but not in lymphocytes. 138 99

Since prevalent cohorts may be biased by the duration of human immunodeficiency virus (HIV) infection (onset bias), it is useful to assess the potential predictive value of markers in incident cohorts of HIV-positive subjects for whom the date of seroconversion is known or can reliably be estimated. Of 131 homosexual men with HIV-1 seroconversion from New York City and Washington, DC, who were evaluated annually beginning in 1982, 60 developed acquired immunodeficiency syndrome (AIDS) by the end of 1989. The prognostic significance of immunologic markers (proportion of CD4+ T-lymphocytes, neopterin, beta 2-microglobulin, serum interferon, and anti-p24 antibody) and of a virologic marker (HIV p24 antigen) was determined using measurements made at defined time intervals after the known or estimated date of HIV seroconversion. When measurements made 3 years after seroconversion were used, all markers except anti-p24 antibody were found to be significant estimators of AIDS risk in univariate analyses. In multivariate Cox regression modeling, the maximum information was obtained by including neopterin, interferon, and the CD4+ T-lymphocyte proportion. The predictive value of markers after HIV seroconversion could change considerably from one interval to another. Elevated levels of beta 2-microglobulin and neopterin significantly predicted the development of Kaposi's sarcoma. These two markers were highly correlated (r = 0.74). The authors conclude that immunologic markers can be important for an HIV staging system for estimating prognosis and facilitating early therapeutic intervention in HIV-positive patients.
 ...
PMID:Immunologic markers of progression to acquired immunodeficiency syndrome are time-dependent and illness-specific. 138 11

A multi-centre, randomized, open-label trial was conducted to evaluate the safety and efficacy of recombinant interferon (rIFN) alpha-2c versus rIFN gamma in patients with recurrent or persistent condylomata acuminata (CA). Thirty-three such patients were treated either with 6 micrograms rIFN alpha-2c or with 0.1 mg rIFN gamma (both equivalent to 2 x 10E6 IU), single dose, subcutaneously 3 times a week for 6 weeks. In case of no complete clearance at week 10, a second course of treatment with the other type of rIFN was given. There was no significant difference in the complete clearance proportions at week 10 between the two treatment groups (3/16 vs 6/17). No relapses occurred in these patients during the 16 weeks' follow-up. Further clearances during the follow-up resulted in a total complete clearance proportion of 14/33 at the end of study. The treatment was well tolerated. Repeated interferon therapy has its place in treating persistent or recurrent condylomas.
Int J STD AIDS
PMID:Clinical study with recombinant interferon gamma versus interferon alpha-2c in patients with condylomata acuminata. 139 Oct 62

Chagas' disease, caused by Trypanosoma cruzi, is an important cause of morbidity in many countries in Latin America. The important modes of transmission are by the bite of the reduviid bug and blood transfusion. The organism exists in three morphological forms: trypomastigotes, amastigotes, and epimastigotes. The mechanism of transformation and differentiation is currently being explored, and signal transduction pathways of the parasites may be involved in this process. Parasite adherence to and invasion of host cells is a complex process involving complement, phospholipase, penetrin, neuraminidase, and hemolysin. Two clinical forms of the disease are recognized, acute and chronic. During the acute stage pathological damage is related to the presence of the parasite, whereas in the chronic stage few parasites are found. In recent years the roles of tumor necrosis factor, gamma interferon, and the interleukins in the pathogenesis of this infection have been reported. The common manifestations of chronic cardiomyopathy are arrhythmias and thromboembolic events. Autoimmune, neurogenic, and microvascular factors may be important in the pathogenesis of the cardiomyopathy. The gastrointestinal tract is another important target, and "mega syndromes" are common manifestations. The diagnosis and treatment of this infection are active areas of investigation. New serological and molecular biological techniques have improved the diagnosis of chronic infection. Exacerbations of T. cruzi infection have been reported for patients receiving immuno-suppressive therapy and for those with AIDS.
 ...
PMID:Chagas' disease. 142 18


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