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)

It has been suggested that immunocompromised, HIV-infected patients are at risk of developing HPV infection and SIL. The well documented role of HPV and SIL in cervical carcinogenesis should lead to frequent, careful evaluation of HIV infected women. Forty-four cervical smears from 23 patients (20 HIV and 3 AIDS) were reviewed. While 11 of the 23 patients produced negative smears, 11 had abnormal cytological findings on at least one occasion. Sixteen smears (36 percent) from 10 patients (43%) showed evidence of HPV and/or SIL. Two smears (two patients) were assigned to the benign epithelial atypia category. (One of these showed keratosis which may indicate HPV infection.) Six smears (three patients) represented either a severe Trichomonas, fungal (Candida sp.), or Herpes infection. Three smears were deemed unsatisfactory for diagnosis due to severe acute inflammation or obscuring blood. Five biopsies were available. In four, histologic findings supported the original cytologic diagnosis. One patient with a negative smear had a biopsy showing condyloma. This study further supports an association of HPV and/or cervical dysplasia with HIV. Careful evaluation and follow-up of HIV-infected women is essential.
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PMID:Cervical cytology findings in women infected with the human immunodeficiency virus. 828 57

Selenium is an essential trace element in nutrition for the prevention of disease in humans. Epidemiological studies indicate an association between low nutritional selenium status and increased risks of cardiomyopathy, cardiovascular disease, and carcinogenesis in various sites of the body. The role of selenium supplementation in the prevention and treatment of AIDS-related pathology has been considered. Selenoproteins discovered in mammalian cells may account for the essentiality of selenium in the body's antioxidant defense; thyroid hormone function; immune system function, particularly the cellular immunity; formation of sperm; and functioning of the prostate gland. The seleno-organic compounds, primarily L-(+)-selenomethionine, generally are recognized as safe and effective forms of selenium supplementation. The nutritionally recommended dose of elemental selenium is estimated at 50 to 200 micrograms [corrected] per day. There is, however, increased discussion of a pharmacological dose of selenium, significantly higher than the nutritional dose of the microelement, to treat active conditions. One way of increasing the tissue levels of selenium is to combine its ingestible form with a nutrient bioavailability enhancing compound.
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PMID:Selenium: a quest for better understanding. 879 24

In 1980, two carotenoids, beta-carotene (BC) and canthaxanthine (CX) with and without pro-vitamin A activity, respectively, were orally administered to female Swiss albino mice and were found to substantially prevent skin carcinogenesis induced by benzo(a)pyrene (BP). This preventive effect was observed in darkness by means of photocarcinogenic enhancement (PCE) following UV (300 to 400 nm) irradiation. In 1984, the same experiment produced antitumorigenic activity when applied to breast carcinogenesis induced in mice by 8-methoxypsoralen (8-MOP) plus UV-A light and, in 1985, when directed toward gastric carcinogenesis induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). These data suggested a rationale for human intervention to prevent, by carotenoid supplementation, a second primary malignancy after the primary malignancy has been radically excised. In the 1980s, a pilot clinical study (15 cases) showed a longer than expected disease-free interval in all surviving patients. It was also subsequently found that, if treated daily with 20 mg of BC and intermittently with retinol 150 to 300,000 IU daily for seven days just prior to menses, women suffering from cyclical mastalgia were relieved from pain, without any toxic side effects. When BC was given in high daily doses (60 mg) to 60 drug addicts suffering from AIDS-related complex (ARC), they recovered from their objective and subjective symptoms (but not from lymphadenopathy) with improvement in their general health and increased performance status. At higher doses, BC (with or without hyperthermia) was effective even in patients in advanced stages of AIDS. A debate has arisen concerning a recent statement by the U.S. Government that "beta-carotene supplements do not protect Americans against cancer or heart disease, and may actually increase the risk of deadly lung tumors in smokers".
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PMID:Carotenoids in cancer, mastalgia, and AIDS: prevention and treatment--an overview. 921 91

The National Institute of Environmental Health Sciences (NIEHS) has several new initiatives involving chemical mixtures and has recognized the need to develop new experimental approaches to enhance our efforts in this area. Responding to recent increases in nominations of complex occupational exposures for toxicologic assessment by the U.S. National Toxicology Program, the NIEHS and the National Institute for Occupational Safety and Health have begun a program to characterize exposures through field studies, identify biomarkers of exposure in workers, and recreate relevant mixed exposures in a laboratory setting. A second initiative with the National Center for Environmental Health/Centers for Disease Control and Prevention will examine blood samples from the U.S. National Health and Nutrition Examination Survey population surveys for selected endocrine-disrupting agents and for common patterns of persistent xenobiotics, providing critical information for the design of animal studies to assess risks of relevant chemical mixtures to humans. New toxicology testing methods (lower cost, faster) will enhance our ability to study chemical mixtures (e.g., dioxin and dioxinlike chemicals, combination AIDS therapies). Ongoing method development efforts involve in vitro functional toxicology assays, screens for estrogenic activity, and carcinogenesis studies in transgenic mice. A major scientific initiative with mixtures involves studies of individual and mixtures of dioxin and dioxinlike chemicals to determine if toxic equivalence factors predict carcinogenic potency in traditional and transgenic bioassays. Complementing these studies is an increased emphasis on physiologically based pharmacokinetic modeling, an activity central to the proper interpretation of chemical mixture studies.
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PMID:Current approaches toward chemical mixture studies at the National Institute of Environmental Health Sciences and the U.S. National Toxicology Program. 986 Aug 84

Epstein-Barr virus (EBV) was first reported as the causative virus of Burkitt's lymphoma in 1964. Since then, EBV has also been associated with infectious mononucleosis, AIDS and transplant-related B cell lymphomas, and nasopharyngeal cancer. The virus has further been linked with T cell lymphomas, Hodgkin disease, and NK leukemia or LGL leukemia, establishing a concept of a wide spectrum of EBV associated malignant disorders. EBV DNA encodes several proteins such as EBNA1-6, LMP 1, 2 and others. Recent studies have demonstrated that EBNA2, EBNA5, EBNA3A, EBNA 3C are essential for transformation, and that any gene product is not sufficient to transform cells by itself. Further there are different mechanisms of virus-associated transformation or carcinogenesis among EBV-associated malignant disorders. On the other hand, human T lymphotropic virus type I (HTLV-I) is known as a causative virus of adult T cell leukemia (ATL). However, precise molecular mechanisms of leukemogenesis in ATL still remains unclear. Some additional factors to HTLV-I infection are supposed to be involved in complete leukemogenesis. We demonstrated that HTLV-I infected T cells and primary ATL cells express EBV receptor/CD21 on the cell surface. Therefore, it is possible that EBV infection is one of the factors. We further investigated this possibility in 6 HTLV-I infected T cell lines and primary ATL cells from 18 patients with ATL. However, no EBV genome was detected in both T cell lines and primary ATL cells. EBV involved T-cell lymphoma has unique clinical manifestations as compared to non-EBV involved T-cell lymphoma. Therefore, it is still possible that a small group of ATL patients with unique clinical manifestations is associated with EBV.
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PMID:Epstein-Barr virus involvement in T-cell malignancy: significance in adult T-cell leukemia. 1034 73

Recently it has been proposed that reactive oxygen species (ROS) are involved in pathogenesis of many human diseases. An elevated level of these molecules causes oxidative stress and is toxic for living cells. Oxidative stress is the reason of many damages of cellular structures, as result of free radical reactions with proteins, lipids, nucleic acids etc. In most of human diseases overproduction of ROS is characteristic for early stage of disease. Some of infectious factors, e.g. viruses can cause oxidative stress by disturbance of cellular antioxidants system or induction of oxidative reactions. There is some evidence of presence of oxidative stress in early stage of HIV infection (glutathione and other antioxidants loss in serum and decreased activity of antioxidant enzymes). All these metabolic disturbances may be involved in AIDS pathogenesis, for example through incorrect induction of lymphocyte apoptosis, tumours related to AIDS and high rate of HIV mutation. This suggests a possible, important role of oxidative stress in AIDS pathogenesis and that administration of antioxidant drugs, by HIV infected patients, may offer protection against mechanisms responsible for lymphocyte apoptosis and AIDS related carcinogenesis.
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PMID:[Oxidation mechanisms and anti-oxidation in HIV infected patients--effect on disease progression]. 1035 46

In the present study, we have studied the level of oxidative DNA base damage in lymphocytes of HIV-infected intravenous drug users (IDUs) and a seronegative control group. Chromatin was isolated from the lymphocytes and then analyzed by gas chromatography/isotope-dilution mass spectrometry with selected-ion monitoring (GC/IDMS-SIM). Significantly greater levels of four oxidatively modified DNA bases were observed in chromatin samples from the symptomatic HIV-infected patients than in those from the seronegative patients. These were 5-hydroxyuracil, 5-hydroxycytosine, 8-hydroxyadenine and 8-hydroxyguanine. In the case of 5-hydroxyuracil and 8-hydroxyguanine, a statistically significant difference was also found between the control group and the asymptomatic HIV-positive patients. These results suggest that oxidative stress may play an important role in the pathogenesis of acquired immune deficiency syndrome (AIDS), and that administration of antioxidant drugs to HIV-infected patients may offer protection against AIDS-related carcinogenesis.
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PMID:Oxidative DNA base damage in lymphocytes of HIV-infected drug users. 1049 76

Programmed cell death or apoptosis is a widespread biological phenomenon. Apoptosis is characterized by typical cell features such as membrane blebbing, chromatin condensation, and DNA fragmentation. It involves a number of membrane receptors (e.g., Fas, TNFR) and a cascade of signal transduction steps resulting in the activation of a number of cysteine proteases known as caspases. Disordered apoptosis may lead to carcinogenesis and participates in the pathogenesis of Alzheimer disease, Parkinson disease, or AIDS. Programmed cell death plays an important role in the processes of gamete maturation as well as in embryo development, contributing to the appropriate formation of various organs and structures. Apoptosis is one of the mechanisms of action of various cytotoxic agents and teratogens. Teratogen-induced excessive death of embryonic cells is undoubtedly one of the most important events preceding the occurrence of structural abnormalities, regardless of their nature. Therefore understanding the mechanisms involved in physiological as well as in disturbed or dysregulated apoptosis may lead to the development of new methods of preventive treatment of various developmental abnormalities. The present review summarizes data on the mechanisms of programmed cell death and concentrates on apoptosis involved in normal or disturbed gametogenesis and in normal and abnormal embryonic development.
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PMID:The role of apoptosis in normal and abnormal embryonic development. 1057 78

3'-Azido-3'-deoxythymidine (AZT), a thymidine analogue widely used in the treatment of AIDS patients and for prevention of the onset of AIDS in HIV-seropositive individuals, causes tumors in mice exposed as adults or in utero. The purpose of this study was to investigate the potential mechanisms of AZT mutagenicity and carcinogenicity by quantifying the incorporation of AZT into cellular DNA, measuring AZT-induced thymidine kinase (TK) mutant frequencies (Mfs), and determining the percentage of loss of heterozygosity (LOH) in spontaneous or AZT-induced TK mutants in the human lymphoblastoid cell line, TK6. Cells were exposed to 300 microM AZT for 0, 1, 3, or 6 days, or to 0, 33, 100, 300, or 900 microM AZT for 3 days (n = 5 flasks/group). The effects of exposure concentration on incorporation of AZT into cellular DNA were evaluated by an AZT radioimmunoassay, and the effects of duration and concentration of AZT exposure on the TK Mfs were assessed by a cell-cloning assay. AZT was incorporated into DNA in a dose-related manner at concentrations up to 300 microM, above which no further increase was observed. TK Mf increased with the extended duration and with incremental concentrations of AZT exposure. There was a positive correlation (P = 0.036, coefficient = 0.903) between AZT-DNA incorporation and AZT-induced TK Mfs, suggesting that AZT incorporation into cellular DNA has a direct role in the genotoxicity of AZT. Southern blot analyses indicated that 84% (6.2 x 10(-6)/7.4 x 10(-6)) of AZT-induced mutants were attributable to LOH, consistent with the known mechanism of AZT as a DNA chain terminator. Considering the importance of LOH in human carcinogenesis, AZT-induced LOH warrants further study.
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PMID:Relationships between DNA incorporation, mutant frequency, and loss of heterozygosity at the TK locus in human lymphoblastoid cells exposed to 3'-azido-3'-deoxythymidine. 1077 14

Free radicals have been implicated in over a hundred disease conditions in humans, including arthritis, hemorrhagic shock, atherosclerosis, advancing age, ischemia and reperfusion injury of many organs, Alzheimer and Parkinson's disease, gastrointestinal dysfunctions, tumor promotion and carcinogenesis, and AIDS. Antioxidants are potent scavengers of free radicals and serve as inhibitors of neoplastic processes. A large number of synthetic and natural antioxidants have been demonstrated to induce beneficial effects on human health and disease prevention. However, the structure-activity relationship, bioavailability and therapeutic efficacy of the antioxidants differ extensively. Oligomeric proanthocyanidins, naturally occurring antioxidants widely available in fruits, vegetables, nuts, seeds, flowers and bark, have been reported to possess a broad spectrum of biological, pharmacological and therapeutic activities against free radicals and oxidative stress. We have assessed the concentration- or dose-dependent free radical scavenging ability of a novel IH636 grape seed proanthocyanidin extract (GSPE) both in vitro and in vivo models, and compared the free radical scavenging ability of GSPE with vitamins C, E and beta-carotene. These experiments demonstrated that GSPE is highly bioavailable and provides significantly greater protection against free radicals and free radical-induced lipid peroxidation and DNA damage than vitamins C, E and beta-carotene. GSPE was also shown to demonstrate cytotoxicity towards human breast, lung and gastric adenocarcinoma cells, while enhancing the growth and viability of normal human gastric mucosal cells. The comparative protective effects of GSPE, vitamins C and E were examined on tobacco-induced oxidative stress and apoptotic cell death in human oral keratinocytes. Oxidative tissue damage was determined by lipid peroxidation and DNA fragmentation, while apoptotic cell death was assessed by flow cytometry. GSPE provided significantly better protection as compared to vitamins C and E, singly and in combination. GSPE also demonstrated excellent protection against acetaminophen overdose-induced liver and kidney damage by regulating bcl-X(L) gene, DNA damage and presumably by reducing oxidative stress. GSPE demonstrated excellent protection against myocardial ischemia-reperfusion injury and myocardial infarction in rats. GSPE was also shown to upregulate bcl(2) gene and downregulate the oncogene c-myc. Topical application of GSPE enhances sun protection factor in human volunteers, as well as supplementation of GSPE ameliorates chronic pancreatitis in humans. These results demonstrate that GSPE provides excellent protection against oxidative stress and free radical-mediated tissue injury.
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PMID:Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention. 1096 38


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