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)

We have stably expressed in CD4+ lymphoid cells the herpes simplex virus type 1 thymidine kinase (HSV1-TK) gene under the control of the human immunodeficiency virus (HIV) promoter and transactivation response element sequences. Upon HIV infection these regulatory sequences were transactivated, switching on high-level expression of HSV1-TK. This in turn caused the death of HIV-infected cells when they were cultured in the presence of acyclovir, a nucleoside analog that becomes toxic after phosphorylation by HSV1-TK. The elimination of HIV-infected cells resulted in the arrest of HIV spreading in the culture. Complete protection of HSV1-TK-expressing cells was obtained using acyclovir concentrations that are commonly detected in the plasma of patients treated for HSV1 infection. Thus, expression of this DNA construct generates a pool of CD4+ booby-trapped cells that, as a population, are resistant to HIV infection. Our data provide a rationale for the use of suicide genes in the design of gene therapy of HIV infection.
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PMID:Selective killing of CD4+ cells harboring a human immunodeficiency virus-inducible suicide gene prevents viral spread in an infected cell population. 134 66

In immature thymocytes, T cell receptor for antigen (TCR) mobilization leads to an active T cell suicide process, apoptosis, which is involved in the selection of the T cell repertoire. We have proposed that inappropriate induction of such a cell death program in the mature CD4+ T cell population could account for both early qualitative and late quantitative CD4+ T lymphocyte defects of human immunodeficiency virus (HIV)-infected individuals (Ameisen, J.C., and A. Capron. 1991. Immunol. Today. 4:102). Here, we report that the selective failure of CD4+ T cells from 59 clinically asymptomatic HIV-infected individuals to proliferate in vitro to TCR mobilization by major histocompatibility complex class II-dependent superantigens and to pokeweed mitogen (PWM) is due to an active CD4+ T cell death process, with the biochemical and ultrastructural features of apoptosis. Activation-induced cell death occurred only in the CD4+ T cell population from HIV-infected asymptomatic individuals and was not observed in T cells from any of 58 HIV-seronegative controls, including nine patients with other acute or chronic infectious diseases. Activation-induced CD4+ T cell death was prevented by cycloheximide, cyclosporin A, and a CD28 monoclonal antibody (mAb). The CD28 mAb not only prevented apoptosis but also restored T cell proliferation to stimuli, including PWM, superantigens, and the tetanus and influenza recall antigens. These findings may have implications for the understanding of the pathogenesis of acquired immune deficiency syndrome and for the design of specific therapeutic strategies.
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PMID:Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals. 134 69

The programmed cell death theory of acquired immunodeficiency syndrome (AIDS) pathogenesis postulates that most immunological and non-immunological defects in human immunodeficiency virus (HIV)-infected people are related to a single mechanism, the inappropriate expression in mature CD4+ T cells and other cell-populations such as neurons of an activation-induced physiological cell suicide program that plays an essential role during embryogenesis in the maturation of both the immune and the nervous systems. The theory is discussed in the context of a series of recent experimental findings indicating that mature T cells can, as immature thymocytes, undergo programmed cell death in response to T-cell receptor mobilization in various physiological and pathological circumstances including murine and human acquired immunodeficiency of retroviral origin. These findings provide new insights into the pathogenesis of AIDS and may have implications for the design of therapeutic strategies.
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PMID:The programmed cell death theory of AIDS pathogenesis: implications, testable predictions, and confrontation with experimental findings. 135 69

A major characteristic of human immunodeficiency virus (HIV) infection is progressive decline in T CD4+ lymphocytes. Ten years after infection, on average, this cell subpopulation disappears and AIDS develops. In the asymptotic phase T CD4+ lymphocytes no longer respond, in vitro or in vivo, to certain memory antigens constrained by the class II histocompatibility complex, or in vitro to polyclonal activators like pokeweed mitogen. They retain, however, some proliferative response activity and constitute only a small proportion of the T CD4+ population. Indirect mechanisms of depletion are therefore sought. We have proposed a hypothesis for a single mechanism: a programmed death process, apoptosis, reactivated in mature T CD4+ lymphocytes of seropositives. Unlike necrosis, apoptosis has a role in embryogenesis, in the adult in certain cell populations and, in immature thymocytes, in T lymphocyte selection and establishment of self-tolerance. T CD4+ lymphocytes of infected subjects lose their ability to proliferate in vitro, as they undergo a form of suicide in response to certain stimuli. In vivo T CD4+ cell activation induced by various infectious agents, including HIV, progressively reduces the subpopulation, independently of the virus' cytopathogenic effect. Tests were performed that explored the T CD4+ lymphocyte response to super-antigens, which mimic and amplify the effect of memory antigens by way of CMH II molecules of Ag-presenting cells and certain nu beta chains of the alpha beta receptor for the Ag which are expressed by a third of human mature T CD4+ lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Programmed death (apoptosis) of T CD4 lymphocytes and AIDS pathogenesis]. 135 12

During human immunodeficiency virus (HIV) infection there is a profound and selective decrease in the CD4+ population of T lymphocytes. The mechanism of this depletion is not understood, as only a small fraction of all CD4+ cells appear to be productively infected with HIV-1 in seropositive individuals. In the present study, crosslinking of bound gp120 on human CD4+ T cells followed by signaling through the T cell receptor for antigen was found to result in activation-dependent cell death by a form of cell suicide termed apoptosis, or programmed cell death. The data indicate that even picomolar concentrations of gp120 prime T cells for activation-induced cell death, suggesting a mechanism for CD4+ T cell depletion in acquired immune deficiency syndrome (AIDS), particularly in the face of concurrent infection and antigenic challenge with other organisms. These results also provide an explanation for the enhancement of infection by certain antibodies against HIV, and for the paradox that HIV appears to cause AIDS after the onset of antiviral immunity.
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PMID:Crosslinking CD4 by human immunodeficiency virus gp120 primes T cells for activation-induced apoptosis. 140 55

From 1988 to 1991, 139 runaways aged 11-19 years in the New York City area (n = 70 males, 69 females) were recruited from four shelters. Each runaway participated in a semistructured interview assessing beliefs and behavioral intentions regarding human immunodeficiency virus (HIV) testing. When asked how they would respond to being seropositive for HIV, 29% of runaways reported that they would engage in self-destructive acts and/or harm others (e.g., suicide, unprotected sex), 80% anticipated extreme distress, 47% expected difficulty securing housing and food, and 61% believed that friends were likely to avoid them. When presented with specific alternatives, fewer runaways anticipated self-destructive acts. Drug use, rather than sexual behaviors, would lead runaways to get tested for HIV. These results suggest that health-care providers must anticipate emotional distress and potential self-destructive behavior following receipt of documentation of HIV positive serostatus among runaways. Furthermore, prior to testing, youths' access to food, shelter, medical care, and social support must be secured.
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PMID:Beliefs and behavioral intentions regarding human immunodeficiency virus testing among New York City runaways. 142 Feb 11

Medicine, law, and social values are not static and must be re-examined periodically. This edition of the ACP Ethics Manual covers emerging issues in medical ethics and revisits some old issues. The overview of the evolution of medical ethics, which appeared in previous editions of the Manual, has been eliminated to allow more space for the consideration of today's ethical dilemmas. Other changes include a revised chapter on end-of-life care, discussion of physician-assisted suicide, revised sections on conflicts of interest and on medical risk to the physician and patient, given developments in human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS), and discussion of sexual contact between physician and patient. A statement on disclosure of errors and a section on care of the physician's family have also been added. The sections on confidential information told by a patient's family or friend to the physician; on physician-pharmaceutical industry relations; on physicians in training; and on the impaired physician have been expanded. Sections on advertising, peer review, and resource allocation have been revised. The literature of biomedical ethics expands at a rate that does not allow a bibliography to remain current, so an exhaustive list of references or suggested readings is not included in this manual. Instead, only cited references are listed.
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PMID:American College of Physicians Ethics Manual. Third edition. 849 78

During a 5-year period (July 1, 1985 to June 30, 1990), a systematic investigation of medicolegal autopsy cases with regard to the occurrence of human immunodeficiency virus (HIV) infection was carried out at the Department of Forensic Medicine in Stockholm, Sweden. Cases where a positive result was obtained from enzyme-linked immunosorbent assay and Western blotting were counted as HIV-positive (85 instances among 16,938 deaths, or 0.50%). Of these deaths, 21 (25%) were suicides. The number and proportion of suicides among HIV-positive homo- and bisexual males increased during the study period but remained unchanged for infected intravenous drug addicts. This increase of suicides among homo- and bisexual males could be related to the duration of the infection and to the manifestation of acquired immunodeficiency syndrome (AIDS) symptoms. Only 1 of the 21 suicides occurred in a hospital; 17 were committed in the homes of the deceased and 3 outdoors. Medicinal drug overdosage was the dominant choice of suicide method. Six of 12 homo- and bisexual males who committed suicide were of non-Swedish origin, i.e. immigrants, likely to have a less stable social network and thereby probably receiving less psychosocial support than the native population.
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PMID:Suicide related to human immunodeficiency virus infection in Stockholm. 156 96

We investigated factors influencing attitudes and practices among San Francisco physicians toward physician-assisted suicide in the context of AIDS. To explore this topic a questionnaire was developed for use in comparing two physician groups. This self-administered instrument was completed by 69 physician members of the San Francisco County Community Consortium (CCC), a community-based clinical research organization whose members care for persons with human immunodeficiency virus (HIV) disease. A comparison group consisted of 86 randomly sampled San Francisco physicians recruited from the California Medical Association mailing list. Anonymity of respondents was maintained. Chi-squares and t-tests were conducted to compare physician groups with regard to demographics and experiences with AIDS. Factor analytic techniques and correlational analyses were used to identify attitudinal and behavioral predictors of willingness to assist in a patient suicide. Twenty-three percent of the total sample would be likely to grant the patient's initial request for assistance in committing suicide. When faced with an adamant request, CCC members would be more likely to assist than comparison group physicians. Ethical beliefs were the strongest predictor of physicians' intention to assist. Identification with the AIDS patient also had significant predictive value.
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PMID:Physicians' attitudes toward assisted suicide in AIDS. 161 71

Activation-induced programmed cell death, or apoptosis, is a physiological cell suicide process involved in the negative thymic selection of the T-cell repertoire. We have proposed that the inappropriate re-emergence in the mature CD4+ T-cell population of such a death program could explain both the early dysfunction and the late depletion of CD4+ T-cells from human immunodeficiency virus (HIV)-infected individuals. We present evidence showing that the selective failure of T-cells from 10 HIV-infected asymptomatic individuals (with normal CD4+ T-cell counts) to proliferate in vitro to pokeweed mitogen and to self-major histocompatibility complex class-II T-cell receptor mobilization by superantigens is due to the induction by these stimuli of CD4+ T-cell death. This death process has characteristic features of apoptosis, including DNA fragmentation into multiples of a 200 base pair unit, and the preventive effect of the protein synthesis inhibitor cycloheximide. These findings suggest that in vivo CD4+ T-cell suicide upon activation might account, independently of any HIV-mediated cytopathic effect, for the progressive depletion of CD4+ T-cells that leads to AIDS.
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PMID:[Activation of CD4+ T-lymphocytes in asymptomatic HIV infected patients induce the program action of lymphocyte death by apoptosis]. 167 28


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