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)

Kaposi's Sarcoma (KS) is an angioproliferative disease that is characterized by proliferation of spindle-shaped cells predominantly of vascular endothelial cell origin, neoangiogenesis, inflammatory cell infiltration, and edema. Although the lesions of classical KS and AIDS-associated KS (AIDS-KS) share common histological features, AIDS-KS occurs at a markedly higher frequency with a more aggressive clinical course. Immunohistochemical analyses of 26 evolutionarily staged AIDS-KS lesions derived from HIV-infected patients demonstrate significant cytoplasmic levels of Bcl-2, a protooncogene known to prolong cellular viability and to antagonize apoptosis. Bcl-2 expression increases as the pathological stage of KS advances. Immunohistochemical analyses of classical KS lesions demonstrate prevalent expression of Bcl-2 as well, indicating that upregulation of Bcl-2 may be important in the pathogenesis of both classical and AIDS-associated KS. Coexpression of Bcl-2 and factor VIII-related antigen in spindle-shaped cells present within KS lesions suggests that Bcl-2 is upregulated within the vascular endothelial spindle-shaped cells of KS. The consequences of upregulated Bcl-2 expression within KS lesions may be prolonged spindle cell viability which, when coupled with dysregulated cellular proliferation due in part to synergistic activities of inflammatory and angiogenic cytokines and HIV-1 Tat protein, may result in the maintenance, growth, and progression of KS.
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PMID:Immunihistochemical detection of Bcl-2 in AIDS-associated and classical Kaposi's sarcoma. 864 47

Rectosigmoidoscopy and rectal biopsies specimens were taken from thirty six HIV infected patients in the Vargas Hospital of Caracas. There were thirty three males and three females. the mean age was thirty two years. Seventy three per cent were homosexuals. The sexual behaviour was the most important risk factor for the infection with the HIV. Forty four per cent of the rectosigmoidoscopies were abnormal, presenting hiperemic or petechiae mucosas. Alterations in rectal biopsies were reported on all specimens, twenty six with inespecific chronic rectitis. Two bipsies reported Kaposi's Sarcoma and eight bipsies demonstrated opportunistic agents.
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PMID:[Rectal biopsies from HIV-infected patients]. 876 55

Kaposi's Sarcoma (KS), the most common AIDS-associated malignancy, occurs with increased frequency in all HIV transmission groups, but at a particularly high rate in homosexual men. Recent studies suggest that KS pathogenesis involves exposure to an infectious agent, altered expression and response to cytokines, and modulation of growth by HIV gene products. KS varies in its clinical presentation from a relatively indolent process to a widely disseminated, aggressive disease. A variety of local and systemic treatments provide effective, but usually temporary, disease palliation. Insights into KS pathogenesis suggest a number of targeted therapeutic approaches that may eventually lead to improved disease management and disease cure.
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PMID:Acquired immunodeficiency syndrome-associated Kaposi's sarcoma. Biology and management. 909 38

This review attempts to put together the changes in the blood and bone marrow observed in those who are infected with human immunodeficiency virus (HIV). These are contribution of many published and unpublished data and experience on; blood counts, blood film and bone marrow films prepared and stained by MayGrunwald-Giemsa or Leishman stain. Some changes in haemostasis are also included. The salient changes are cytopaenias; leucopaenia, anaemia, thrombocytopaenia, and bone marrow hypoplasia, although the latter occurs, it is found in a minority of cases. Other changes include myelodysplasia, functionally defective cells, and enhanced bleeding tendency particularly in those with bleeding defects. There are also malignancies associated with HIV infection such as Kaposi's Sarcoma and malignant lymphomas. The pathogenesis of these events are multi-factorial, varied and involve; killing of cells by the virus, syncytial formation by the cells, destruction of the stem cells, immune and drugs effects. These mechanisms are modified by factors of viral, host environment and their interactions. Changes are commonly found in patients with acquired immunodeficiency syndrome (AIDS) but can be seen in some cases anytime during the course of the disease. Once developed the changes are progressive. The management of these complications remain individualised and symptomatic. Treatment trials with the haematopoesis growth factors, particularly colony stimulating factors are producing some encouraging results. However other cytokines, for example, interleukin-6 may be having untoward effect such as association with the causation of Kaposi's sarcoma and the malignant non-Hodgkin's lymphomas. While standard approaches to the management of the malignancies tend to be the practice, adjustments are usually necessary in most patients.
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PMID:Haematological changes in human immunodeficiency virus infection. Part I: Review article. 955 49

Human herpesvirus type 8 (HHV-8) has been identified as the most likely candidate to be involved in the development of Kaposi's Sarcoma (KS). HHV-8 has been associated with all forms of KS, primary effusion lymphoma, and multicentric Castleman's disease and detected in various non-neoplastic cells. Its presence in cells of the different hemopoietic lineages has not yet been investigated in a comprehensive and systematic manner. In this study we searched for the presence of HHV-8 in different subpopulations of peripheral blood mononuclear cells (PBMC) from patients with classic and AIDS-associated KS, as well as from HIV-1 sero-positive and sero-negative persons without KS. Thirty-four samples of PBMC were isolated from 30 patients. Subpopulations were isolated with immunomagnetic beads. Polymerase chain reaction for HHV-8 DNA was performed on PBMC and subpopulations with a primer pair selected from ORF26 of the viral genome. Polymerase chain reaction products were subsequently Southern blotted and hybridized. In patients with KS, HHV-8 DNA was detected in nine of 11 (81%) CD19+ cells, four of 11 (36%) CD2+ cells, three of 11 (27%) CD14+ cells, and nine of 11 (81%) of the remaining depleted cell populations (DP) that contain CD34 positive cells. In a subsequent set of experiments HHV-8 DNA was detected in 10 of 12 (83%) CD34 positive cell fractions. All cell subpopulations from the non-KS group were HHV-8 negative, with the exception of one positive B cell sample obtained from an HIV-infected patient. Our data demonstrate that in peripheral blood HHV-8 is detectable not only in CD19+ cells, as previously reported, but also in other cells, including T cells, monocytes, and cells devoid of specific lineage markers. We also show for the first time that CD34+ cells in peripheral blood of KS patients are a predominant HHV-8-harboring population, suggesting that they represent an additional important reservoir for this virus in vivo.
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PMID:Infection of circulating CD34+ cells by HHV-8 in patients with Kaposi's sarcoma. 1050 49

TLC D-99 is a unique liposomal formulation of doxorubicin that consists of phosphatidyl choline/cholesterol. The objectives of the study were to evaluate safety and efficacy of two doses of TLC D-99 in the treatment of patients with AIDS-related Kaposi's Sarcoma (KS). Forty HIV-infected persons with biopsy-proven KS were randomized to receive TLC D-99 at doses of either 10 (low) or 20 (high) mg/m2 every 2 weeks. Patients assigned to the low-dose arm could be escalated to the high-dose arm if their KS progressed after 3 cycles of therapy. Median age was 35 years (range, 26-47) and median CD4 count was 13 (range, 0-440). Nineteen patients were assigned to receive the low dose, and 21 patients were assigned to the high dose. Partial response occurred in 15% (6 of 40) of the patients or in 5% (1 of 19) and 24% (5 of 21) in the low- and high-dose arms, respectively; stable disease was observed in 65% (26 of 40) or in 68% (13 of 19) and 62% (13 of 21) in the low and high doses, respectively. Neutropenia was the major toxicity and was observed in 68 and 81% of patients with the low- and high-dose arms, respectively; grade 4 neutropenia was observed in 16 and 14%, respectively. Mild alopecia was noted in only 8%. Therefore, TLC D-99 is active against AIDS-related KS, and the response is dose-dependent.
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PMID:AIDS-related Kaposi's sarcoma: a phase II study of liposomal doxorubicin. The TLC D-99 Study Group. 1058 55

Kaposi's Sarcoma (KS) is a pathology which occurs with increased frequency and in a particularly aggressive form in AIDS patients. The HIV-1 Tat protein appears to be an important co-factor in the induction of the extensive neo-vascularization associated with AIDS-KS. Tat acts as a chemoattractant for endothelial cells in vitro, inducing both chemotactic and invasive responses. Several clinical trials have been performed testing the effectiveness of diverse biological agents in therapy of KS, among these the type I interferons. Type I IFNs have diverse biological functions besides their anti-viral activity, including anti-angiogenic properties. We have shown that IFN alpha and IFN beta are potent inhibitors of both primary and immortalized endothelial cell migration and morphogenesis in vitro as well as neo-angiogenesis induced by HIV-1 Tat in vivo. The inhibitory effect of IFN class I on HIV-Tat associated angiogenesis further supports its use as a therapy for epidemic Kaposi's sarcoma. The use of recombinant IFNs at the levels required to obtain a therapeutic effect are associated with side effects and toxicity, therefore we are now developing a gene therapy approach for constant and local delivery type I IFNs.
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PMID:Inhibition of angiogenesis by type I interferons in models of Kaposi's sarcoma. 1066 56

Kaposi's Sarcoma (KS) was first described one century ago as a disease occurring in elderly men manifested as an indolent cutaneous form. After the onset of human immunodeficiency virus type I (HIV-1) infection, KS became epidemic which, in association with HIV, presented as an aggressive, systemic disease. Recently, the recognition that a novel human herpes virus-8 (HHV-8) was highly prevalent among KS patients provided strong evidence to indicate that HHV-8 was the etiology of KS. The pathogenesis of KS in AIDS patients is still controversial, but there is evidence suggesting that KS is a cytokine-mediated disease, and that increased levels of inflammatory cytokines in AIDS patients were responsible for the aggressive pattern of the disease seen in such patients. The recently developed serological assays for detection of HHV-8 antibodies have made possible a better understanding of the prevalence of HHV-8 in different populations, and this has allowed a deeper understanding of HHV-8 epidemiology.
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PMID:Human Herpes Virus 8 and Kaposi's Sarcoma: A Review. 1108 63

The Lancet Letter reports use of chorionic gonadotropin (HCG) for treating Kaposi's Sarcoma (KS). Low doses of HCG were given intramuscularly, then escalated to 150,000 IU (and higher), three times a week. All patients had significant tumor regression. Delayed treatment or dosages under 100,000 IU resulted in recurring tumors. Another study, however, is apparently showing good results with 250, 500, 1,000 and 2,000 IU. HCG is quite expensive, costing from $3,150 per month for the generic to $10,800 per month for Profasi HP, Serono Laboratories' brand name version. Another study is trying systemic HCG therapy, and monitoring viral load, safety, and anti-tumor effects. HCG has an anti-HIV effect in the test tube.
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PMID:Human chorionic gonadtropin. 1136 54

Dr. Yuan Chang and her research group believe they have fulfilled the epidemiological criteria for establishing the KSHV (herpes virus) as the cause of Kaposi's Sarcoma (KS), but Dr. Gallo and others still question the virus's role. If KS is caused by KSHV, there is a possibility that an antiviral drug may have a therapeutic effect. Foscarnet, in one open-label study of five people with KS, proved to be effective in three of the cases by causing a remission and even clearing external (and in one case internal) lesions for more than a year after just one or two brief courses. Another retrospective analysis of 20,228 showed people with HIV/AIDS treated with foscarnet were 70 percent less likely to develop KS. Such research evidence warrants further study; one open-label trial for 25 people is recruiting. Call Clare Kenny or Lorrie Jondreau at (212) 263-5244 for more information.
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PMID:KS virus controversy. 1136 55


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