Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As we enter the second decade of confronting human immunodeficiency virus (HIV)-induced disease, progress in the prophylaxis and treatment of acquired immunodeficiency syndrome (AIDS)-related opportunistic infections is encouraging. While the infectious manifestations of HIV become more manageable, AIDS-related malignancies remain problematic. In the era of infection prophylaxis and antiretroviral therapy, the incidence of Kaposi's sarcoma (KS) and aggressive non-Hodgkin's lymphoma (NHL) appears to be increasing. Mounting evidence suggests that KS may result from infection with an as yet unidentified sexually transmitted agent. The increase in NHL cases may result from patients surviving longer with severe immune compromise with a possible contribution of antiretroviral therapy itself. Despite effective cosmetic treatments, survival in recently diagnosed KS patients is actually shorter than patients diagnosed with KS earlier in the epidemic. The addition of growth factors to the chemotherapeutic regimen of patients with AIDS-related NHL has not yet been translated into a survival advantage. In vitro antiviral activity and clinical evidence of possible synergy with other antiretrovirals suggests that continued investigation of alpha-interferon in treatment of AIDS-related malignancies is a priority for the second decade of challenging AIDS.
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PMID:Acquired immunodeficiency syndrome and related malignancies: a topical overview. 165 43

Human immunodeficiency virus (HIV) infection is associated with multiple defects in immune regulation and hematopoiesis. These defects include decreased proliferation of hematopoietic progenitor cells and increased destruction of mature cells. There are also disturbances of regulatory cytokines. As a result, hematopoietic cytopenias are common and the tolerance of myelosuppressive therapy is poor. One successful approach to the management of these clinical problems is the use of hematopoietic growth factors. To date, three agents have been studied in patients with HIV infection. In a Phase I trial, granulocyte macrophage-colony stimulating factor (GM-CSF) corrected leukopenia and pre-existing neutrophil defects in patients with HIV infection. In uncontrolled trials, GM-CSF also appears to reduce toxicity from zidovudine, ganciclovir, alpha-interferon, and antineoplastic therapy. In a placebo-controlled trial, erythropoietin (EPO) decreased transfusion requirements and corrected anemia in the majority of patients receiving zidovudine. In a Phase I/II trial, granulocyte colony-stimulating factor (G-CSF) also corrected leukopenia and neutrophil defects in patients with AIDS without altering HIV expression. Combined G-CSF and EPO treatment corrected both anemia and leukopenia and reduced zidovudine toxicity. New combinations of hematopoietic stimulants are being used to decrease the toxicity from cytotoxic chemotherapy in the treatment of AIDS-related malignancies. Future treatments with other recombinant cytokines may result in both reduction in myelosuppression from drug therapy and, possibly, reconstitution of the immune and hematopoietic systems of HIV-infected patients.
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PMID:The use of hematopoietic growth factors in HIV infection and AIDS-related malignancies. 171 6

Infection by human immunodeficiency virus type 1 (HIV-1) causes acquired immunodeficiency syndrome (AIDS) after a long clinical latency. This disease is associated with a spectrum of cancers. Here we report that wild-type p53 is a potent suppressor of Tat, a major transactivator of HIV-1. Reciprocally, Tat inhibits the transcription of p53. Downregulation of p53 by upregulated tat may be important for the establishment of productive viral infection in a cell and also may be involved in the development of AIDS-related malignancies.
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PMID:Reciprocal modulations between p53 and Tat of human immunodeficiency virus type 1. 777 31

HHV-6 infection has been associated with several malignancies including non-Hodgkin's lymphoma and Hodgkin's disease by the presence of high antibody titer and/or the presence of HHV-6 DNA. To understand their oncogenic potential, SalI restriction fragments from HHV-6 strain U1102 were transfected into NIH3T3 cells to assess transforming ability. A 3.9-kbp SalI-L DNA fragment spanning the junction of the direct repeat left (DRL) and unique long segment (UL) regions of HHV-6 induced foci of morphologically altered cells. The SalI-L transformed NIH3T3 focal lines induced tumors in nude mice within 2 weeks. The retention of HHV-6 specific DNA observed in SalI-L transformed cells and their tumor-derived lines suggest a possible maintenance function. Since both HHV-6 infection as well as transforming fragments from other DNA viruses have been shown to transactivate the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR), SalI-L was examined for transactivation activity. SalI-L up-regulated HIV-1 LTR CAT 10-15 fold in both monkey CV-1 and human T Jurkat cells. The further study of the SalI-L transforming fragment exhibiting transactivation of HIV-1 LTR will elucidate whether these two activities are encoded by a single gene and will aid in the understanding of the interaction between HHV-6 and HIV-1 as it relates to progression of AIDS and/or AIDS-related malignancies.
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PMID:A transforming fragment within the direct repeat region of human herpesvirus type 6 that transactivates HIV-1. 813 19

The incidence of three malignancies has increased in conjunction with the epidemic of human immunodeficiency virus (HIV) disease, and they are currently considered acquired immunodeficiency syndrome (AIDS)-defining conditions. These are Kaposi's sarcoma, associated with AIDS since the onset of the epidemic in 1981; intermediate or high-grade B-cell lymphoma, which became AIDS-defining in 1985; and cervical carcinoma in HIV-infected women, formally recognized as an AIDS-defining diagnosis on January 1, 1993. Approximately 40% of all patients with AIDS have developed cancer during the course of HIV infection. Further, as survival has improved in HIV disease, the incidence of these malignancies has increased. It is thus expected that greater numbers of patients with AIDS-related lymphoma and cervical cancer will be diagnosed in the years ahead. The epidemiologic factors associated with neoplastic disease differ among patients with the three AIDS-related malignancies. The pathogenesis of neoplastic disease also differs. The specific etiologic steps in the development of AIDS-related Kaposi's sarcoma and lymphoma are currently unknown. However, a great deal of information has already been acquired, which may have bearing on the pathogenesis of malignant disease in general, as well as the elucidation of future therapeutic modalities. The specific epidemiologic, etiologic, and clinical characteristics of the AIDS-related malignancies will be described herein. It is hoped that this review will serve to outline our current understanding of this area, to introduce the questions and controversies which are apparent in the field, and to mention those areas in which future research might be focused.
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PMID:AIDS-related malignancies: the emerging epidemic. 835 Mar 62

Phosphorylation of proteins on serine, threonine and tyrosine is one of the significant regulatory mechanisms in gene expression and post-translational modifications in both eukaryotes and prokaryotes. Protein tyrosine phosphorylation in particular is implicated in cell proliferation, differentiation and certain pathological modifications including transformation. The overall protein tyrosine phosphorylation is modulated by protein tyrosine kinases (PTK) and protein tyrosine phosphatases (PTP). There are several viruses known to contain PTK and PTPs. A computer-based protein sequence search using the FAST P programme was used to investigate whether, theoretically, a sequence for a putative protein tyrosine phosphatase is present in the genomic sequence of the human immunodeficiency virus (HIV). A conserved motif GXGXXG characteristic of both PTK and PTP was found at the 5' LTR region of the HIV genome. Interesting sequence similarities with regulatory proteins of other retroviruses, viz. VPx of HIV-2 and X-protein of HTLV-1, and some transforming proteins were also observed. The implication of the possible phosphorylation event in association with the HIV regulatory proteins tat, rev and nef in AIDS-related malignancies is discussed.
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PMID:Tyrosine phosphorylation as a possible regulatory mechanism in the expression of human immunodeficiency virus genes. 874 91

AIDS-related malignancies (ARM) include AIDS-defining cancers such as Kaposi's sarcoma, non-Hodgkin's lymphoma and cervical carcinoma. In addition, certain other malignancies are also increased with human immunodeficiency virus (HIV) infection. New antiretroviral agents and better prophylaxis and treatment of HIV-related opportunistic infections are prolonging the lives of HIV-infected individuals. There will thus likely be a continued rise in the incidence and prevalence of ARM in the long term, even if effective antiretroviral and other AIDS-related therapies reduce their appearance in the short term. There are presently no curative regimens for the common ARM, with the possible exception of some lymphomas. Survival is shortened by most, and treatment is often toxic and poorly tolerated. Gene therapies may thus offer a useful adjunct to conventional treatment strategies for selected ARM. Although some gene therapy strategies may work well in the HIV setting, the chronic viral infection, immunodeficient status of the host, the tendency for HIV-infected individuals to have altered drug metabolism and an increased rate of adverse drug reactions will likely present special challenges. This review summarizes the state-of-the-art in the fledgling field of gene therapy for ARM, and explores areas for future research.
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PMID:Gene therapy strategies for AIDS-related malignancies. 947 51

Considerable progress has recently been achieved in understanding the pathogenesis of human immunodeficiency virus type 1 (HIV-1), and in improving the efficacy of antiretroviral therapies for the treatment of patients with the acquired immunodeficiency syndrome (AIDS). The pharmacological properties of new drugs are very effective in establishing a long-term suppression of HIV-1 replication, and have remarkably increased the survival period of patients with AIDS. However, current antiretroviral therapies are still far from eradicating HIV-1 from patients, and do not prevent the development of AIDS-related malignancies, which affect 40% of individuals infected by HIV-1. The malignancies that are considered AIDS-related are: Kaposi's sarcoma, non-Hodgkin lymphoma, intraepithelial cervical carcinoma and anal neoplasia. Their incidence is expected to increase as the survival period of patients with AIDS lengthens. Also, the cost of antiretroviral therapies poses a limit to the development of successful global intervention to tackle the worldwide spreading of AIDS, that, by the year 2000, will affect 40 million individuals. Some 90% of these new infections are occurring in developing countries, which can not afford the cost of antiretroviral therapies, and are not able to ensure a proper follow up of patients with AIDS. In addition, cultural and ethical problems make difficult the achievement of an adequate education of how to prevent the spreading of AIDS among populations of poorer countries. On these grounds, the field of AIDS research is evaluating alternative therapeutic approaches for the treatment and prevention of AIDS.
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PMID:The standpoint of AIDS research and therapy programs. 971 60

In the US over one million persons are currently infected with the HIV, over half a million have had AIDS, and over 300,000 have died from AIDS. Worldwide, it is estimated that more than 17 million people are currently infected with HIV, and over 1,200,000 cases of AIDS have been reported to the World Health Organization. By some estimates, up to 40% of patients with AIDS will ultimately develop some form of cancer. Non-Hodgkin's lymphoma, Kaposi's sarcoma and invasive cervical cancer have a higher incidence in persons with HIV infection and all three are AIDS-defining illnesses. In addition, several reports suggest that a number of other malignancies may occur at an increased incidence in persons with HIV infection, including squamous-cell carcinoma of the head, neck and anus, plasmacytoma, melanoma, small-cell lung cancer, basal-cell cancer, and germ-cell tumours. Clinicians should become familiar with HIV-related malignancies as their incidence is expected to further increase as more effective therapies for HIV and associated opportunistic infections allow patients to live longer in an advanced state of immunodeficiency. In the current article, we will review the clinical and therapeutic aspects of the most common AIDS-related malignancies including non-Hodgkin's and Hodgkin's lymphomas, Kaposi's sarcoma and anogenital epithelial neoplasias.
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PMID:AIDS-related malignancies. 978 31

For people immunosuppressed by human immunodeficiency virus (HIV), we expect an increase in cancer incidence similar to that documented in transplant patients. We examined the cancer spectrum in an HIV-infected cohort, specifically malignancies not currently associated with acquired immunodeficiency syndrome (AIDS), in relation to the general population. Cancer incidence data for residents of Harris County, Texas, diagnosed between 1975 and 1994, were linked to HIV/AIDS registry data by Soundex code and date of birth to identify malignancies in an HIV-infected cohort of 14,986 persons. Incidence of cancer in this cohort was compared to the general population by standardized incidence ratio (SIR) analysis. From the HIV-infected cohort, 2289 persons (15%) were identified as having one or more malignancies, with 97% occurring in males. The linkage alone identified 29.5% of the malignancies, of which only 28.7% were diagnosed in males. Adjusting for age, HIV-infected men and women had incidences of cancer that were 16.7 [95% confidence interval (CI) 16.1-17.3] and 2.9 (95% CI 2.3-3.7) times that expected for the general population of Harris County, Texas. Besides Kaposi's sarcoma, non-Hodgkin's lymphoma, cervix cancer and brain lymphoma, non-AIDS related malignancies of Hodgkin's lymphoma, non-melanotic skin cancer in males and colon cancer in females, exhibited significant SIRs of 5.6 (95% CI 3.6-8.4), 6.9 (95% CI 4.8-9.5) and 4.0 (95% CI 1.1-10.2). Increased incidences of lung, prostate and breast malignancies were not seen in this HIV cohort. Persons infected with HIV appear to be at increased risk for the non-AIDS related malignancies, Hodgkin's lymphoma, non-melanotic skin cancer in males and colon cancer in females.
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PMID:HIV-related malignancies: community-based study using linkage of cancer registry and HIV registry data. 1063 60


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