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

The actions of retroviral infections, aging, and cocaine and morphine injection on cytokine production were investigated in C57BL/6 female mice. Retroviral infection with LP-BM5 murine leukemia virus was further developed as a model of murine acquired immunodeficiency syndrome (AIDS). The effects of cocaine and morphine on gamma-interferon (IFN) and tumor necrosis factor (TNF) production in vivo and with isolated spleen cells were measured by a sandwich enzyme-linked immunosorbent assay (ELISA) method. Serum IFN was generally not detected in any group except mice injected with saline and young mice infected with LP-BM5 virus. Splenocytes from mice with murine AIDS produced less IFN when stimulated in vitro by ConA. In aged mice, IFN production by spleen cells was severely suppressed by retroviral infection. Cocaine had a tendency to suppress IFN production by stimulated cells in vitro. Morphine tended to reduce IFN production by spleen cells from retrovirally infected animals. The serum TNF level in mice with murine AIDS was elevated creating higher levels in morphine and morphine plus cocaine treated uninfected mice while cocaine injection eliminated serum TNF. When stimulated in vitro by lipopolysaccharides (LPS), splenocytes from mice with murine AIDS also produced more TNF than uninfected controls. TNF production in vitro and in vivo was significantly increased by retroviral infection. Therefore, results indicate that cocaine and retroviral infection modulate TNF and IFN production.
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PMID:Modulation of tumor necrosis factor and gamma interferon production by cocaine and morphine in aging mice infected with LP-BM5, a murine retrovirus. 171 22

Kaposi's sarcoma (KS) is a malignant neoplasm that develops in 20% to 30% of all acquired immunodeficiency syndrome (AIDS) cases. Kaposi's sarcoma primarily involves the skin, but can progress to involve the lungs, gastrointestinal tract, and liver. alpha-Interferon alone or in combination with zivoduvine has activity in acquired immunodeficiency syndrome-related KS, especially in patients with limited disease and CD4 lymphocyte counts over 400/mm3. Patients with progressive or symptomatic visceral disease, however, can be treated more effectively with cytotoxic chemotherapy. We have used a combination of doxorubicin, bleomycin, and vincristine (ABV) and have achieved response rates of over 80%. Discontinuation of therapy, however, is associated with relapse shortly after response (2 to 3 months). Thus, we have begun studies to define a safe and effective maintenance therapy. Such therapies should include antiretroviral agents since most patients succumb to other human immunodeficiency virus complications, and since human immunodeficiency virus directly, through viral proteins, and indirectly, through the induction of cellular genes, induces KS growth. Additionally, agents with antitumor activity and possible antiviral activity, such as alpha-interferon, may be potentially effective in maintenance therapies. We recently studied 21 patients in a phase I study of recombinant interferon alpha-2b (INTRON-A, Schering-Plough Corp, Kenilworth, NJ) alone following ABV chemotherapy. A dose of 10 million units, given in daily subcutaneous injections, was the maximal tolerated dose; higher doses were associated with intolerable fatigue, diarrhea, and fevers. We are currently conducting a phase I/II trial studying the combination of zivoduvine (500 mg/d) and recombinant interferon alpha-2b (5, 10, and 15 million units) as maintenance in patients with advanced or progressive KS.
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PMID:Phase I/II trials of alpha-interferon alone or in combination with zidovudine as maintenance therapy following induction chemotherapy in the treatment of acquired immunodeficiency syndrome-related Kaposi's sarcoma. 171 42

Tryptophan (Trp) is an indispensable amino acid required for biosynthesis of proteins, serotonin and niacin. Indoleamine 2,3-dioxygenase (IDO) is induced by infections, viruses, lipopolysaccharides, or interferons (IFNs) and this results in significant catabolism of Trp along the kynurenine (Kyn) pathway. Intracellular growth of Toxoplasma gondii and Chlamydia psittaci in human fibroblasts in vitro is inhibited by IFN-gamma and this inhibition is negated by extra Trp in the medium. Similarly, growth of a number of human cell lines in vitro is inhibited by IFN-gamma and addition of extra Trp restores growth. Thus, in some in vitro systems, antiproliferative effects of IFN-gamma are mediated by induced depletion of Trp. We find that cancer patients given Type I or Type II IFNs can induce IDO which results in decreased serum Trp levels (20-50% of pretreatment) and increased urinary metabolites of the Kyn pathway (5 to 500 fold of pretreatment). We speculate that in vivo antineoplastic effects of IFNs and clinical side effects are mediated, at least in part, by a general or localized depletion of Trp. In view of reported increases of IFNs in autoimmune diseases and our earlier findings of elevated urinary Trp metabolites in autoimmune diseases, it seems likely that systemic or local depletion of Trp occurs in autoimmune diseases and may relate to degeneration, wasting and other symptoms in such diseases. We find high levels of IDO in cells isolated from synovia of arthritic joints. IFNs are also elevated in human immunodeficiency virus (HIV) patients and increasing IFN levels are associated with a worsening prognosis. We propose that IDO is induced chronically by HIV infection, is further increased by opportunistic infections, and that this chronic loss of Trp initiates mechanisms responsible for the cachexia, dementia, diarrhea and possibly immunosuppression of AIDS patients. In these symptoms, AIDS resembles classical pellagra due to dietary deficiency of Trp and niacin. In preliminary studies, others report low levels of Trp and serotonin, and elevated levels of Kyn and quinolinic acid in AIDS patients. The implications of these data in cancer, autoimmune diseases and AIDS are discussed.
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PMID:Implications of interferon-induced tryptophan catabolism in cancer, auto-immune diseases and AIDS. 172 46

Growing out of the successful transmission of leprosy to armadillos, making available large quantities of M. leprae, there have been remarkable recent advances in the knowledge of the leprosy bacillus. These bacilli and their isolated chemical constituents provide organisms for in vitro testing of new drugs, reagents for the study of the immunologic dysfunction in leprosy patients, development of early diagnostic methods, and the preparation of candidate vaccines. Leprosy is usually transmitted by the nasorespiratory route, but occasionally, there is transplacental infection. There are reports suggesting that patients have acquired leprosy by contact with wild M. leprae-infected armadillos in Louisiana and Texas. Perturbations in lymphocyte-macrophage interaction appear to be most closely related to the defective CMI in leprosy. The helper T/suppressor T cell populations vary markedly in lesions of the various forms of leprosy, with enhanced suppression of T-cell activity in lepromatous disease. Infiltration of IL-2 and gamma-interferon seems to stimulate CMI in situ in lesions of lepromatous leprosy. Vaccination of lepromatous patients with a killed M. leprae-plus-BCG preparation stimulates CMI and clears tissues of leprosy bacilli, providing an immunotherapeutic approach to the management of leprosy. Immunoprophylactic vaccine trials are in progress, and initial results should be available in 1991. Because of drug resistance, dapsone monotherapy of leprosy is no longer recommended. Multidrug regimens, composed of dapsone, rifampin, and clofazimine or a thioamide, are now required and appear to reduce the incidence of leprosy when applied assiduously. Newer experimental drugs that may eventually be included in these regimens include the fluoroquinolones, minocycline, and clarithromycin. There is no clear evidence that the early serologic diagnosis of leprosy is generally applicable. Favorable response to therapy in multibacillary patients, however, may be assessed by noting drops in levels of M. leprae-specific antigens in blood and urine and, to a lesser extent, levels of specific antibodies in serum. There are conflicting reports on the influence of AIDS on leprosy. There are no convincing data showing that AIDS and leprosy affect each other. Although chemotherapy offers the best current hope for the control of leprosy, effective immunoprophylaxis and improved socioeconomic conditions in endemic areas are thought to be essential in programs for the eradication of leprosy.
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PMID:Leprosy. 173 Jan 74

The value of ascites gamma interferon concentration and ascites adenosine deaminase activity in distinguishing tuberculosis from other causes of ascites was examined in a prospective study of 86 patients with ascites, including 16 with tuberculous peritonitis. Gamma interferon concentration was higher in tuberculous peritonitis than in the other causes of ascites (p less than 0.0001), and a cut-off between 3 and 9 u/ml reached a sensitivity and a specificity of 100%. The mean (+/- SD) gamma interferon level in tuberculous ascites was 39.3 +/- 18.3 u/ml in patients seronegative for HIV and 14.2 +/- 4.7 u/ml in patients with AIDS (p = 0.01). Adenosine deaminase activity in tuberculous ascites was also higher than in the other causes of ascites (p less than 0.0001), and a cut-off of 40 u/l reached a sensitivity of 100% and a specificity of 97%. The two false positives for adenosine deaminase test were true negatives for the gamma interferon test. There was no significant correlation between gamma interferon concentration and adenosine deaminase activity either in tuberculous ascitis or in any other group. This study suggests that ascites gamma interferon determination may be very useful in the screening of tuberculous peritonitis, but its cost makes it advisable to use adenosine deaminase activity as a routine test, at least in areas where tuberculosis is endemic.
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PMID:Diagnostic value of ascites gamma interferon levels in tuberculous peritonitis. Comparison with adenosine deaminase activity. 177 79

We have described a nonantibody type inhibitor of interferons (IFN) in the blood of patients with AIDS, advanced neoplastic disorders, and lupus erythematosus in earlier reports (1,2). In the present study we show that the semipurified inhibitor blocks the antiproliferative signal of IFN-alpha in Daudi cells and the membrane potential shifting ability of IFN-alpha is modulated by the interferon inhibitor preparation (IFI).
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PMID:Effect of an interferon inhibitor on the antiproliferative signal of interferon-alpha. 178 17

This paper aims to summarize current experience with alpha interferon and provide direction for future study. There are four areas in which alpha interferon has proven or potential activity: antiviral, premalignant, adjuvant and advanced disease settings. The three main viral diseases in which interferon alfa-2b has been shown to have activity are chronic viral hepatitis, acquired immunodeficiency syndrome, and human papilloma virus infections. In vitro studies suggest that alpha interferon may inhibit transformation of some premalignant conditions into malignant disease; e.g., vaginal intraepithelial neoplasia. In the adjuvant setting, it is possible that a biological response modifier, such as alpha interferon, may have a role in helping the immune system to destroy residual tumour cells following tumour bulk reduction with radiation or chemotherapy. A higher response rate has been seen in patients with small tumour bulk compared to those with large tumour bulk (e.g., malignant melanoma, ovarian carcinoma), and in patients with early, rather than late, disease (e.g., chronic myelogenous leukaemia, hairy cell leukaemia, multiple myeloma, non-Hodgkin's lymphoma). This may be due to efficacy in a small tumour bulk setting or due to an immunoadjuvant role. In advanced disease, the question is how best to exploit the possible synergistic effects between alpha interferon and other therapeutic modalities. The optimum dose, schedule and patient populations for combined treatment have yet to be determined. The major objective of this paper is to determine how best to capitalize upon the current state of knowledge to build for future trials of alpha interferon, and to determine whether the existing data suggest an adjuvant role for interferon after initial tumour regression.
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PMID:alpha Interferon: the potential drug of adjuvant therapy: past achievements and future challenges. 179 68

We evaluated clinical efficacy and tolerability of recombinant alpha 2a interferon (IFN), in a group of 16 patients with AIDS and ARC, including 3 children. All patients were followed up monthly for clinical and immunological studies. The frequency of oportunistic infections (OI) in AIDS, and the following symptoms in all patients were studied: fever, night sweats, fatigue, diarrhoea, weight loss. Immunological parameters (CD3+, CD4+, CD8+ lymphocytes, skin tests to recall antigens, NK activity, lymphoproliferative response to PHA) were also evaluated. Adult patients were treated with 3-6 million IU of r-alpha 2a IFN daily im for 3 months and the 3 times weekly up to 12 months. Pediatric cases were treated with lower doses of 0.5-1.5 million IU using the same time schedule. We observed clinical improvement and reduction of severe infections in 10/15 evaluable patients (4/4 ARC and 6/11 AIDS). Immunological parameters were transiently improved in one third of cases. We observed only mild side effects in r-alpha IFN treatment. We suggest therapy with r-alpha 2a IFN at low dosage should be tried in patients with AIDS for its beneficial effects on OI development.
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PMID:Recombinant alpha-2a interferon treatment in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC): clinical and immunological evaluation. 181 17

An immunomodulator, IMREG-1, derived from human leukocyte dialysates exerts a variety of effects on the cell-mediated immune system, including acceleration and amplification of delayed hypersensitivity to recall antigens, modulation of gamma-interferon production in response to antigen, and enhanced expression of the p55 portion of the receptor for interleukin-2 on CD4+ cells. On the basis of initial studies of IMREG-1 in patients with AIDS-Related Complex (ARC), a multicenter randomized, double-blind, placebo controlled trial of this agent was carried out. The results indicate that patients who received IMREG-1 had a lower risk of progression to frank AIDS than those who received placebo. A decline in the rate of reduction of numbers of CD4+ cells, as well as fewer symptoms were also observed in patients who received IMREG-1 as compared with placebo.
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PMID:Clinical and immunologic observations in patients with AIDS-related complex treated with IMREG-1. 182 5

Although 3'-azido-3'-deoxythymidine (zidovudine, AZT) has demonstrated efficacy in the treatment of human immunodeficiency virus (HIV) infection, there are limitations associated with its use. Consequently, other agents, such as 2',3'-dideoxycytidine (ddC) and 2',3'-dideoxyinosine (ddI), are being assessed for the treatment of patients with HIV infection. However, the most effective therapy for HIV infection may be combination therapy with zidovudine and any of a number of other therapies. To obtain maximum efficacy, combination regimens should include agents that do not share cross-resistance, have different mechanisms of action, and have different dose-limiting toxicities; the relative merits of a concurrent dosage schedule (limits drug failure) and a consecutive dosage schedule (limits toxicity) must also be considered. In addition, the shift between administering a starting regimen and a rescue regimen should be based on time on therapy, disease breakthrough, or drug complication. Eventually, the shift may be precipitated by the in vitro resistance patterns of individual viruses, as is now the case with antibiotics for infection. Several trials are currently in progress to assess combination therapy with zidovudine and ddC; initial results indicate that the combination may allow for improved efficacy and decreased side effects, compared with treatment with either drug alone. Trials of combination therapy with ddI, interferon alfa, and acyclovir are also in progress. It is hoped that these initial studies will pave the way for rational drug sequencing in the treatment of patients with acquired immunodeficiency syndrome.
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PMID:Treatment of AIDS with combinations of antiretroviral agents. 185 Jan 92


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