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)

The possibility of protecting human CD4+ lymphocytes from human immunodeficiency virus type 1 (HIV1) infection, through a suicide mechanism elicited by the HIV1 transcription apparatus itself, offers a potentially useful approach for gene therapy of the acquired immunodeficiency syndrome. A replication-defective lentiviral HIV1 vector (HYIRES-TK) was designed to carry both the hygromycin (Hy) phosphotransferase gene for positive selection and the thymidine kinase (TK) gene of herpes simplex virus driven by the viral long terminal repeat (LTR). The internal ribosome entry site (IRES) from encephalomyocarditis virus was placed between the two genes for their efficient simultaneous translation. Transient expression of active TK into transfected COS-1 cells was shown to be induced by Tat and Rev over a detectable basal level. By providing the missing viral proteins in trans, recombinant viruses were generated and used to transduce Jurkat cells. The Hy-resistant population of cells was sensitive to ganciclovir (GCV) and acyclovir (ACV), a result consistent with a basal level of TK expression. Cocultivation of transduced cells with cells chronically infected with HIV in the presence of 10 microM ACV, a concentration non-toxic for the uninfected cells, resulted in increased killing of cells transduced with the HY-IRES-TK vector. These data indicate that two genes can be expressed from the viral LTR in the context of an HIV1 vector, with the aid of an IRES sequence. The expression is inducible by the HIV proteins Tat and Rev and it is possible to specifically kill infected cells with subtoxic concentrations of drug. To decrease the sensitivity of the transduced cells towards GCV, a variant vector expressing a truncated TK was constructed. The truncated version was expressed at levels similar to those of wild-type TK but induced sensitivity towards GCV in transduced cells that was intermediate between that of untransduced cells and of cells expressing wild-type TK.
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PMID:Inducible expression of herpes simplex virus thymidine kinase from a bicistronic HIV1 vector. 992 18

The issue of "treatable depression" in terminally ill patients has been raised in discussions of physician-assisted suicide. However, the role of psychiatry in palliative care remains largely undefined. Studies have documented a major depression prevalence in hospitalized patients with acquired immunodeficiency syndrome (AIDS) and cancer of 17% to 36% and in terminally ill patients from 9% to 17%. No randomized, controlled trials of depression treatment in the terminally ill have been completed. Tricyclic antidepressants and selective-sertonin reuptake inhibitors (SSRIs) have been proven effective in randomized trials for major depression in patients with cancer or human immunodeficiency virus (HIV) infection. Psychostimulants have shown effectiveness by randomized trial in medical inpatients, but only by case series in the terminally ill. Randomized trials have shown the effectiveness of psychotherapies for depression in cancer (ie, cognitive behavioral) and HIV-infected patients (ie, interpersonal). An open trial suggests effectiveness for problem-solving therapy for terminally ill patients. In summary, the treatability of depression in the terminally ill remains to be proven by randomized trials.
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PMID:Treatment of Depression at the End of Life: Clinical and Ethical Issues. 1008 1

As there is still neither a known cure for the acquired immunodeficiency syndrome (AIDS) nor any vaccine to prevent infection with the human immunodeficiency virus (HIV), an AIDS diagnosis continues to denote a death sentence. One might think that approaching dying, death, and bereavement in the AIDS pandemic would be the same as with other terminal illnesses. However, that is not the case. No other single disease in the history of the American legal system has generated more litigation than this disease. This article examines some of the medico-legal issues associated with AIDS-related death such as estate planning, discrimination, insurance, long-term care, the right to die, and suicide as detailed in medical and legal discourse.
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PMID:Death and AIDS: a review of the medico-legal literature. 1012 40

Donor T cells are beneficial for engraftment, immune reconstitution, and antileukemic effects after allogeneic marrow transplantation, but they also cause graft-versus-host disease. Treatment with ganciclovir can control graft-versus-host disease if donor T cells are genetically engineered to express viral thymidine kinase. Clinical protocols with thymidine kinase-expressing T cells currently prescribe the curative use of ganciclovir for genetic immunosuppression only after clinical manifestations of graft-versus-host disease have appeared. The aim of this work was to compare early/preventive versus delayed/curative treatment of GVHD. Here, we found that ganciclovir administered early after experimental marrow transplantation was highly effective in preventing graft-versus-host disease caused by thymidine kinase-expressing T cells, and surviving recipient mice were able to mount a T cell-dependent B cell response. In contrast, curative ganciclovir administration later after transplantation was much less effective in treating graft-versus-host disease and surviving recipients had markedly impaired immune function. These findings should be considered in the development of future clinical trials using thymidine kinase-expressing T cells; to date, such trials have envisaged the use of GCV to treat only declared graft-versus-host disease. The use of thymidine kinase-expressing T cells for conditional elimination of activated T cells after allogeneic marrow transplantation offers a promising new approach for the control of graft-versus-host disease. The versatility of the thymidine kinase/ganciclovir system offers clinical options depending on whether thymidine kinase-expressing T cells are infused at the time of bone marrow transplantation or in a delayed manner, and depending on whether GCV is administered in an early/preventive or delayed/curative manner. The rationale underlying these options is more complex than it may appear and is likely to have a profound impact on the efficacy of such treatments. In the present work, we analyze the immunological impact when GCV is administered in an early/preventive or delayed/curative manner. Our results demonstrate that the delayed/curative strategy is clearly associated with severe immunological defects. To our knowledge, this is the first report of immunodeficiency subsequent to suicide gene therapy for GVHD.
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PMID:Immunological defects after suicide gene therapy of experimental graft-versus-host disease. 1056 98

Most vital statistics indicators of the health of Americans were stable or showed modest improvements between 1997 and 1998. The preliminary birth rate in 1998 was 14.6 births per 1000 population, up slightly from the record low reported for 1997 (14.5). The fertility rate, births per 1000 women aged 15 to 44 years, increased 1% to 65.6 in 1998, compared with 65.0 in 1997. The 1998 increases, although modest, were the first since 1990, halting the steady decline in the number of births and birth and fertility rates in the 1990s. Fertility rates for total white, non-Hispanic white, and Native American women each increased from 1% to 2% in 1998. The fertility rate for black women declined 19% from 1990 to 1996, but has changed little since 1996. The rate for Hispanic women, which dropped 2%, was lower than in any year for which national data have been available. Birth rates for women 30 years or older continued to increase. The proportion of births to unmarried women remained about the same at one third. The birth rate for teen mothers declined again for the seventh consecutive year, and the use of timely prenatal care (82.8%) improved for the ninth consecutive year, especially for black (73.3%) and Hispanic (74.3%) mothers. The number and rate of multiple births continued their dramatic rise; the number of triplet and higher-order multiple births jumped 16% between 1996 and 1997, accounting, in part, for the slight increase in the percentage of low birth weight (LBW) births. LBW continued to increase from 1997 to 1998 to 7.6%. The infant mortality rate (IMR) was unchanged from 1997 to 1998 (7.2 per 1000 live births). The ratio of the IMR among black infants to that for white infants (2.4) remained the same in 1998 as in 1997. Racial differences in infant mortality remain a major public health concern. In 1997, 65% of all infant deaths occurred to the 7.5% of infants born LBW. Among all of the states, Maine, Massachusetts, and New Hampshire had the lowest IMRs. State-by-state differences in IMR reflect racial composition, the percentage LBW, and birth weight-specific neonatal mortality rate for each state. The United States continues to rank poorly in international comparisons of infant mortality. Expectation of life at birth increased slightly to 76.7 years for all gender and race groups combined. Death rates in the United States continue to decline, including a drop in mortality from human immunodeficiency virus. The age-adjusted death rate for suicide declined 6% in 1998; homicide declined 14%. Death rates for children from all major causes declined again in 1998. A large proportion of childhood deaths, however, continue to occur as a result of preventable injuries.
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PMID:Annual summary of vital statistics--1998. 1058 72

Alternative high schools serve approximately 280,000 students nationwide who are at high risk for failing or dropping out of regular high school or who have been expelled from regular high school because of illegal activity or behavioral problems. Such settings provide important opportunities for delivering health promotion education and services to these youth and young adults. However, before this survey, the prevalence of health-risk behaviors among students attending alternative high schools nationwide was unknown. The Youth Risk Behavior Surveillance System (YRBSS) monitors the following six categories of priority health-risk behaviors among youth and young adults: behaviors that contribute to unintentional and intentional injuries; tobacco use; alcohol and other drug use; sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs) (including human immunodeficiency virus [HIV] infection); unhealthy dietary behaviors; and physical inactivity. The national Alternative High School Youth Risk Behavior Survey (ALT-YRBS) is one component of the YRBSS; it was conducted in 1998 to measure priority health-risk behaviors among students at alternative high schools. The 1998 ALT-YRBS used a three-stage cluster sample design to produce a nationally representative sample of students in grades 9-12 in the United States who attend alternative high schools. The school response rate was 81.0%, and the student response rate was 81.9%, resulting in an overall response rate of 66.3%. This report summarizes results from the 1998 ALT-YRBS. The reporting period is February-May 1998. In the United States, 73.6% of all deaths among youth and young adults aged 10-24 years results from only four causes--motor vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 1998 ALT-YRBS demonstrate that many students at alternative high schools engage in behaviors that increase their likelihood of death from these four causes. During the 30 days preceding the survey, 51.9% had ridden with a driver who had been drinking alcohol, 25.1% had driven a vehicle after drinking alcohol, 32.9% had carried a weapon, 64.5% had drunk alcohol, and 53.0% had used marijuana. During the 12 months preceding the survey, 15.7% had attempted suicide, and 29.0% had rarely or never worn a seat belt. Substantial morbidity among school-aged youth and young adults also results from unintended pregnancies and STDs, including HIV infection. ALT-YRBS results indicate that in 1998, a total of 87.8% of students at alternative high schools had had sexual intercourse, 54.1% of sexually active students had not used a condom at last sexual intercourse, and 5.7% had ever injected an illegal drug. Among adults aged > or = 25 years, 66.5% of all deaths result from two causes--cardiovascular disease and cancer. Most risk behaviors associated with these causes of death are initiated during adolescence. In 1998, a total of 64.1% of students at alternative high schools had smoked cigarettes during the 30 days preceding the survey, 38.3% had smoked a cigar during the 30 days preceding the survey, 71.2% had not eaten > or = 5 servings of fruits and vegetables during the day preceding the survey, and 81.0% had not attended physical education (PE) class daily. Comparing ALT-YRBS results with 1997 national YRBS results demonstrates that the prevalence of most risk behaviors is higher among students attending alternative high schools compared with students at regular high schools. Some risk behaviors are more common among certain sex and racial/ethnic subgroups of students. ALT-YRBS data can be used nationwide by health and education officials to improve policies and programs designed to reduce risk behaviors associated with the leading causes of morbidity and mortality among students attending alternative high schools.
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PMID:Youth risk behavior surveillance. National Alternative High School Youth Risk Behavior Survey, United States, 1998. 1069 8

The Lit protease in Escherichia coli K-12 strains induces cell death in response to bacteriophage T4 infection by cleaving translation elongation factor (EF) Tu and shutting down translation. Suicide of the cell is timed to the appearance late in the maturation of the phage of a short peptide sequence in the major head protein, the Gol peptide, which activates proteolysis. In the present work we demonstrate that the Gol peptide binds specifically to domains II and III of EF-Tu, creating the unique substrate for the Lit protease, which then cleaves domain I, the guanine nucleotide binding domain. The conformation of EF-Tu is important for binding and Lit cleavage, because both are sensitive to the identity of the bound nucleotide, with GDP being preferred over GTP. We propose that association of the T4 coat protein with EF-Tu plays a role in phage head assembly but that this association marks infected cells for suicide when Lit is present. Based on these data and recent observations on human immunodeficiency virus type 1 maturation, we speculate that associations between host translation factors and coat proteins may be integral to viral assembly in both prokaryotes and eukaryotes.
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PMID:The major head protein of bacteriophage T4 binds specifically to elongation factor Tu. 1080 48

A longitudinal study of human immunodeficiency virus (HIV)-infected individuals followed-up in 13 centres was performed to assess the influence of hepatitis C virus (HCV) on the clinical and immunological evolution of HIV-infected patients. Eight-hundred and twelve HIV-infected patients with known HIV acquisition date, 89 co-infected with HCV, were included in the cohort. Clinical progression was defined as: 30% decrease of Karnofsky's index; and/or 20% body weight loss; and/or acquired immune deficiency syndrome (AIDS)-defining illness; and/or death (except by accident, suicide, or overdose). Immunological progression was defined as a decrease of initial CD4 count to below 200 mm(-3). If immunological progression was not statistically different between groups (P=0.25), clinical progression was significantly faster in HCV-HIV co-infected patients in univariate (P=0.02) and multivariable survival analysis (hazard ratio=1.63, P=0.03). This argues for active management of hepatitis C chronic infection among HCV-HIV co-infected patients.
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PMID:Hepatitis C virus co-infection is a negative prognostic factor for clinical evolution in human immunodeficiency virus-positive patients. 1088 41

Priority health-risk behaviors, which contribute to the leading causes of mortality and morbidity among youth and adults, often are established during youth, extend into adulthood, are interrelated, and are preventable. The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health-risk behaviors among youth and young adults--behaviors that contribute to unintentional and intentional injuries; tobacco use; alcohol and other drug use; sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs) (including human immunodeficiency virus [HIV] infection); unhealthy dietary behaviors; and physical inactivity. The YRBSS includes a national school-based survey conducted by CDC as well as state, territorial, and local school-based surveys conducted by education and health agencies. This report summarizes results from the national survey, 33 state surveys, and 16 local surveys conducted among high school students during February through May 1999. In the United States, approximately three fourths of all deaths among persons aged 10-24 years result from only four causes: motor-vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 1999 national Youth Risk Behavior Survey demonstrate that numerous high school students engage in behaviors that increase their likelihood of death from these four causes--16.4% had rarely or never worn a seat belt; during the 30 days preceding the survey, 33.1% had ridden with a driver who had been drinking alcohol; 17.3% had carried a weapon during the 30 days preceding the survey; 50.0% had drunk alcohol during the 30 days preceding the survey; 26.7% had used marijuana during the 30 days preceding the survey; and 7.8% had attempted suicide during the 12 months preceding the survey. Substantial morbidity and social problems among young persons also result from unintended pregnancies and STDs, including HIV infection. In 1999, nationwide, 49.9% of high school students had ever had sexual intercourse; 42.0% of sexually active students had not used a condom at last sexual intercourse; and 1.8% had ever injected an illegal drug. Two thirds of all deaths among persons aged > or = 25 years result from only two causes--cardiovascular disease and cancer. The majority of risk behaviors associated with these two causes of death are initiated during adolescence. In 1999, 34.8% of high school students had smoked cigarettes during the 30 days preceding the survey; 76.1% had not eaten > or = 5 servings/day of fruits and vegetables during the 7 days preceding the survey; 16.0% were at risk for becoming overweight; and 70.9% did not attend physical education class daily. These YRBSS data are already being used by health and education officials at national, state, and local levels to analyze and improve policies and programs to reduce priority health-risk behaviors among youth. The YRBSS data also are being used to measure progress toward achieving 16 national health objectives for 2010 and 3 of the 10 leading health indicators.
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PMID:Youth Risk Behavior Surveillance--United States, 1999. State and local YRBSS Coordinators. 1098 Dec 82

Gay men and lesbians have special interests in documenting their preferences regarding advance care planning and end-of-life care. A 64-item survey instrument was developed to ascertain the preferences of this community regarding approaches to end-of-life care, viewpoints on physician-assisted suicide (PAS) and euthanasia, and practices regarding advance care planning. The survey was completed by 575 participants recruited through community-based health care and social service organizations serving the lesbian and gay community, primarily in the New York metropolitan area. Respondents represent a diverse group of women (36%) and men (63%) from various age, racial/ethnic, and religious/spiritual backgrounds; 10% were human immunodeficiency virus (HIV)-positive. Respondents' perspectives on end-of-life care are generally consistent with findings from other attitudinal studies of U.S. adults: a majority supported legalization of PAS and preferred a palliative approach to end-of-life care. However, the gay community sample revealed even stronger support for assisted suicide and palliative care. Although respondents completed advance directives at a higher rate than adults generally, the legal importance for gay men and lesbians to execute directives should encourage health care providers and community organizations to assume a larger educational role on advance care planning. Results confirm other reports on the need to address provider communication skills. It is speculated that the HIV epidemic was a major influence behind these results because of the overwhelming personal impact of the epidemic on most gay men and lesbians during the past two decades.
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PMID:Attitudes on end-of-life care and advance care planning in the lesbian and gay community. 1144 26


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