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

After administration of Adriamycin, bleomycin, vincristine (ABV) as palliative chemotherapy in advanced AIDS-related Kaposi's sarcoma (AIDS.KS) patients with low Karnosfsky performance scores, the authors attempted to estimate the overall biological cost/benefit relating to the disease. The authors analyzed data from 20 consecutive AIDS patients with advanced Kaposi's sarcoma presenting skin and visceral involvement treated with ABV every 3 weeks. An increased rate of infections, HIV and ABV-related side effects was observed. The performance amelioration (about 30%) was not significantly correlated with AIDS.KS clinical remission. CD4 count at baseline (p < 0.05), ABV therapy duration (p < 0.001), the achieved AIDS.KS clinical amelioration score (p < 0.01) and the improved Karnofsky score (p < 0.001) were significant predictors of life expectancy which was unrelated to the rate of side effects. The authors conclude that ABV palliative chemotherapy can assist in protracting life expectancy and improving the Karnofsky score.
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PMID:Experience with adriamycin, bleomycin, vincristine (ABV) palliative chemotherapy in advanced AIDS-related Kaposi's sarcoma. 895 23

A spectrum of adverse drug reactions that are caused by the combined action of drugs and viruses has been described: ampicillin rash in acute infectious mononucleosis; Reye's syndrome; hypersensitivity reactions to sulphonamides in patients with HIV infection; drug-induced agranulocytosis; paracetamol (acetaminophen) hepatotoxicity; aspirin (acetylsalicyclic acid)-induced asthma; Epstein-Barr virus-associated lymphoma and methotrexate; and AIDS-related Kaposi's sarcoma and nitrite use. Changes in pharmacokinetics have been reported for: caffeine, sulfamethoxazole and fluconazole in patients with HIV infection; theophylline, following influenza and influenza vaccination; and recently, dipyrone metabolites in carriers of the hepatitis B virus. In addition increased drug- and drug metabolite-related toxicity has been observed in virally infected cells. Pathogenetic mechanisms for the interaction between drugs and viruses are varied, and include biological mechanisms (often immunological) and changes in drug metabolism. The combined effects of chemical and biological exposure provide a unique model for the study of disease induction.
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PMID:Role of viral infections in the induction of adverse drug reactions. 901 Jun 40

Sequences of a new herpesvirus with homology to gammaherpesvirinae were recently identified in AIDS-associated Kaposi's sarcoma (KS). Subsequently this novel virus, called KS-associated virus (KSHV) or human herpesvirus (HHV) 8 was detected in classical KS and AIDS-associated body cavity based lymphomas by polymerase chain reaction. In this report major and minor capsid proteins of HHV-8 were molecularly cloned and produced as recombinant proteins in Escherichia coli. Sera from 69 HIV-1 infected patients with KS, 30 HIV-1 infected patients without KS and 106 control individuals were tested by enzyme-linked immunosorbent assay for anti-HHV-8 capsid IgM and IgG antibodies. Sera from four patients were tested over periods ranging from 18 months to 6 years. IgG antibodies directed against HHV-8 capsid antigens were detected in patients with AIDS-associated KS and in some AIDS patients without KS. Seroconversion with IgM and IgG antibodies directed against HHV-8 capsid proteins occurred more than 1 year prior to diagnosis of KS. In a considerable portion of KS patients no IgM or IgG antibodies against HHV-8 capsid proteins were detected. In these patients there was an inverse relationship between antibodies against HHV-8orf26 and the CD4/CD8 ratio, suggesting that the inconsistency of anti-HHV-8orf26 antibodies is due at least partly to an impaired immune response. No reactivity against HHV-8 capsid antigens was detected in the vast majority of sera from HIV-negative control individuals. Our findings indicate that a specific humoral immune response against capsid proteins is raised in HHV-8 infected individuals, and that anti-capsid antibodies can be used to diagnose HHV-8 infection. The correlation between occurrence of anti-HHV-8 antibodies and KS supports the hypothesis of a causative role of HHV-8.
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PMID:Detection of antibodies against viral capsid proteins of human herpesvirus 8 in AIDS-associated Kaposi's sarcoma. 908 32

Recently, two clinical trials demonstrated an antitumour effect of systemic high-dose beta-hCG therapy and of different regimens of local beta-hCG injections in AIDS-related Kaposi's sarcoma. We report the efficacy and safety of subcutaneous beta-hCG treatment (low-dose (2500-25000 IU/day) or high dose (25000-100000 IU/day)) in eight patients with advanced HIV disease in whom systemic chemotherapy and radiation were contraindicated or had failed. During therapy, serum hCG-concentrations as well as LH and FSH were measured. In the low-dose regimen one partial response was achieved. In the high-dose regimen, one patient maintained his response without further improvement. Three patients had stable disease and four patients disease progression. Serious side effects related to beta-hCG therapy were not observed. In conclusion, systemic beta-hCG-therapy for Kaposi's sarcoma is safe but associated with regression only in a minority of patients with advanced HIV-disease.
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PMID:Beta-human choriogonadotropin therapy and HIV-related Kaposi's sarcoma. 911 Sep 21

Primary murine embryonic fibroblasts transfected with HIV-1 TAT demonstrated decreased levels of high energy phosphates (ATP, GTP, UTP/CTP), adenine nucleotides (ATP, ADP, AMP), and both NAD+/NADH redox pairs, resulting in a substantial loss of redox poise. A greater than 50% decrease in intracellular reduced glutathione (GSH) concentration was accompanied by the extracellular appearance of acidic fibroblast growth factor (FGF-1). Addition of either N-acetyl-L-cysteine or glutathione ester (GSE), but not L-2-oxothiazolidine 4-carboxylate, partially restored intracellular GSH levels and resulted in loss of extracellular FGF-1. Treatment of FGF-1-transduced cells with buthionine sulfoximine (BSO) resulted in a time- and dose-dependent decrease in total cellular GSH concentration that was accompanied by the extracellular appearance of FGF-1. Inclusion of GSE during BSO treatment eliminated the extracellular appearance of FGF-1. BSO treatment of cells transfected with a mutant form of FGF-1, in which all three cysteine residues were replaced with serines, also decreased total cellular GSH concentration but failed to induce the extracellular appearance of FGF-1. Collectively, these results suggest that HIV-1 TAT induces a condition of oxidative stress, which mediates cellular secretion of FGF-1, an observation relevant to the pathophysiologic development and progression of AIDS-associated Kaposi's sarcoma.
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PMID:Glutathione depletion associated with the HIV-1 TAT protein mediates the extracellular appearance of acidic fibroblast growth factor. 950 19

Raynaud's phenomenon is a common vascular side effect of chemotherapy drug regimens. Chemotherapy-induced Raynaud's phenomenon leading to acral gangrene has rarely been reported. In this report, one patient who developed gangrene after bleomycin and vincristine/vinblastine chemotherapy for AIDS-related Kaposi's sarcoma and another HIV-infected patient who exhibited symptoms of severe Raynaud's phenomenon related to the same regimen are presented. Because the combination of bleomycin and vinca alkaloids is commonly used for the treatment of AIDS-related Kaposi's sarcoma, clinicians should be aware of the risk of provoking acral necrosis in patients who develop Raynaud's phenomenon under chemotherapy. The literature is reviewed, and clinical symptoms, pathophysiology, and treatment options are discussed.
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PMID:Raynaud's phenomenon and acral necrosis after chemotherapy for AIDS-related Kaposi's sarcoma. 951 87

Both clinical and experimental evidence indicates that AIDS-related Kaposi's sarcoma (AIDS-KS) has a multifactorial pathogenesis with factors such as HIV viral load, latent virus induction, and opportunistic infections contributing to disease progression. However, a consistent feature that unites these apparently diverse putative etiologic agents is sustained serum elevations of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha). While virtually every cell responds to TNF-alpha with gene activation, the extent of TNF-alpha-mediated cellular signaling is regulated by a delicate balance between signal activation and signal arresting events. Reactive oxygen intermediates (ROI), which are generated as a consequence of TNF-alpha membrane interaction, are part of this TNF-alpha-initiated cellular activation cascade. Previous studies in our laboratory have shown that AIDS-KS cells possess impaired oxygen intermediate scavenging capacities, thereby establishing conditions permissive for the intracellular retention of ROI. In this study, we used cellular capacity to upregulate the cytoprotective enzyme superoxide dismutase (SOD) to address the extent of cellular response to TNF-alpha. Concurrent with the SOD analyses, nucleotide profiles were obtained to assess cellular bioenergetic responses during TNF-alpha challenge. Proliferative growth levels of mitochondrial (Mn)SOD activities showed an activity spectrum ranging from lowest activity in AIDS-KS cells, to intermediate levels in matched, nonlesional cells from the AIDS-KS donors, to highest activities in HIV normal fibroblasts. In contrast, following TNF-alpha challenge, the AIDS-KS and KS donor nonlesional cells showed a 11.89- and 5.86-fold respective increase in MnSOD activity, while the normal fibroblasts demonstrated a 1.35-fold decrease. Subsequent thiol redox modulation studies showed that only the normal fibroblast cultures showed a potentiation of TNF-alpha-mediated MnSOD upregulation following GSH depletion. In addition, provision of the GSH precursor, N-acetylcysteine during TNF-alpha challenge only diminished MnSOD activity and mitochondrial compartmentalization in the AIDS-KS cells, a finding that likely reflects the lower levels of reduced thiols in this cellular population. Our data, which show that a perturbation in their cellular thiol redox status accentuates AIDS-KS cellular responsiveness to TNF-alpha, suggest a biochemical rationale for the recognized TNF-alpha AIDS-KS clinical correlation.
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PMID:Thiol redox modulation of tumor necrosis factor-alpha responsiveness in cultured AIDS-related Kaposi's sarcoma cells. 951 60

The aim of this study was to identify a safe and tolerable dose of recombinant interferon-beta (IFN-beta) used in conjunction with a fixed dose of zidovudine in patients with early-stage, good-prognosis AIDS-related Kaposi's sarcoma. We conducted a phase I, dose-escalation controlled trial of 22.5, 45 of 90 million units of IFN-beta given by daily subcutaneous injection with 500 mg per day of oral zidovudine. At the time of this study, this was standard of care for HIV infection. Patients were sequentially enrolled at three medical centers. Tumor response, drug tolerance, antiviral studies and CD4 changes were assessed. Four patients were enrolled at each dose level, and escalation proceeded when at least four patients had tolerated two weeks of therapy without dose-limiting toxicity. ACTG Kaposi's sarcoma tumor response criteria were used to assess response. Fifteen patients were enrolled. The combination of IFN-beta and zidovudine was well tolerated, and the dose-limiting toxicities were local skin necrosis and systemic symptoms. Despite generally good prognostic characteristics, only two patients achieved a clinical complete response and three addition patients had stable disease for a prolonged period of time (range 24-44 weeks). There was no correlation between baseline CD4 cell counts and tumor response, nor between the antiviral effect of IFN-beta as measured by decreases in immune-complex dissociated p24 antigen and tumor response. Higher doses of IFN-beta did not result in more tumor responses or in greater antiviral activity. The maximum tolerated dose of IFN-beta in combination with 500 mg per day of zidovudine was 45 million units by subcutaneous injection per day. IFN-beta is well tolerated in patients with AIDS-related Kaposi's sarcoma when used in conjunction with zidovudine. However, the antitumor response rate in good-prognosis patients is low. Further studies of this agent should be in the context of four-drug antiretroviral regimens where viral suppression is greatest and any antitumor activity of IFN-beta may be observed.
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PMID:Open-label phase I study of combination therapy with zidovudine and interferon-beta in patients with AIDS-related Kaposi's sarcoma: AIDS Clinical Trials Group Protocol 057. 955 13

Nitrite inhalants have been commonly abused substances in the United States. Nitrite inhalants and AIDS was a popular topic in the early 1980s, when the cause of AIDS was not known. With the discovery of HIV, concern about nitrite use in the USA waned. However, nitrite inhalant use is associated with behavioral relapse and HIV transmission among gay men, with decreased lymphocyte counts and natural killer cell activity in a few laboratory studies, and it remains a candidate cofactor in the pathogenesis of AIDS-related Kaposi's sarcoma. Discouraging nitrite use continues to be a worthwhile public health goal.
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PMID:Nitrite inhalants: history, epidemiology, and possible links to AIDS. 964 94

AIDS-associated Kaposi's sarcoma (AIDS-KS), the most common malignant complication of human immunodeficiency virus infection, is characterized by neoplastic proliferation of mesenchymal cells. AIDS-KS cells release and respond to an array of cytokines through specific plasma membrane receptors. Specific targeting of potent cytotoxic agents to cell surface receptors/antigens on Kaposi's sarcoma cells may provide effective therapy for this malignancy. We have identified a new target in the form of an interleukin 13 (IL-13) receptor that is overexpressed in the five AIDS-KS cell lines examined. Radiolabeled IL-13 cross-linked to a single protein of about Mr 70,000 in AIDS-KS cells. We utilized a chimeric cytotoxic protein composed of IL-13 and a truncated Pseudomonas exotoxin (IL13-PE38QQR), which was found to be specifically and highly cytotoxic to AIDS-KS cells, as determined by protein synthesis inhibition and clonogenic assays. IL13-PE38QQR demonstrated significant antitumor activity in a human epidermoid carcinoma xenograft model. Normal human umbilical vein-derived endothelial, lymphoid, and bone marrow precursor cells expressed low levels of IL-13 receptors, and IL-13 toxin was not cytotoxic to them. Thus, IL-13 receptor on AIDS-KS cells may represent a novel plasma membrane protein(s) that could be utilized to target therapeutic agents.
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PMID:Receptor for interleukin 13 on AIDS-associated Kaposi's sarcoma cells serves as a new target for a potent Pseudomonas exotoxin-based chimeric toxin protein. 981 66


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