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Biomedical subjects

K Hein

Publications and source records attributed to K Hein.

At least 19 recordsLinked to original sources
PubMed1999

An extrachromosomal switch recombination substrate reveals kinetics and substrate requirements of switch recombination in primary murine B cells.

Ig class switch recombination occurs in B lymphocytes upon activation, and is targeted to distinct switch (S) regions by cytokine-mediated induction of switch transcripts spanning the entire S region and the adjacent constant region gene segments. Using a novel type of switch recombination substrate, constructed according to the intron-exon structure of the IgH locus, but with heterologous elements, we here have tested the structural requirements for targeting and the kinetics of switch recombination in activated primary murine B cells. When transfected at various times after activation, up to 10% of the transfected B cells perform recombination of the substrate within 12 h. Switch recombination in primary B cells is restricted to the first 72 h after onset of activation, then rapidly decreases to background levels, as obtained in plasmacytoma cells or with substrates carrying no S region sequences. In terms of structural requirements, switch recombination is targeted to any transcription unit that contains an intronic S region and depends on processing of the primary transcript by splicing.

Animals↗
PubMed1998

Processing of switch transcripts is required for targeting of antibody class switch recombination.

Antibody class switching is mediated by somatic recombination between switch regions of the immunoglobulin heavy chain gene locus. Targeting of recombination to particular switch regions is strictly regulated by cytokines through the induction of switch transcripts starting 5' of the repetitive switch regions. However, switch transcription as such is not sufficient to target switch recombination. This has been shown in mutant mice, in which the I-exon and its promoter upstream of the switch region were replaced with heterologous promoters. Here we show that, in the murine germline targeted replacement of the endogenous gamma1 promoter, I-exon, and I-exon splice donor site by heterologous promoter and splice donor sites directs switch recombination in activated B lymphocytes constitutively to the gamma1 switch region. In contrast, switch recombination to IgG1 is inhibited in mutant mice, in which the replacement does not include the heterologous splice donor site. Our data unequivocally demonstrate that targeting of switch recombination to IgG1 in vivo requires processing of the Igamma1 switch transcripts. Either the processing machinery or the processed transcripts are involved in class switch recombination.

Adenoviridae↗
PubMed1995

Molecular analysis and mapping of two genes encoding maize glutathione S-transferases (GST I and GST II).

Maize glutathione S-transferase (GST) isozymes are encoded by a gene family comprising at least five genes, three of which (Gst I, II and III) have recently been isolated and sequenced. The enzymes are active as homo or heterodimers and exhibit intraspecific polymorphism including a "null" variant for the two major isoforms expressed in roots. Northern blot analyses performed on total root RNA from "null" and "plus" genotypes, using Gst I- and Gst II-specific probes, indicated that the Gst I gene controls the expression of the two major GST isoforms expressed in roots. Gst I and Gst II were mapped by RFLP analysis using an F2 population of 149 individuals previously characterized. Gst I was localized on the long arm of chromosome 8, while two putative Gst II loci were mapped to chromosome 8 (70 cM from Gst I) and 10, respectively.

Alleles↗
PubMed1995

Comparison of HIV+ and HIV- adolescents: risk factors and psychosocial determinants.

According to the World Health Organization, half of the 14 million people with human immunodeficiency virus (HIV) worldwide were infected between the ages of 15 and 24 years. However, details about HIV-positive (HIV+) youths' risk-related behavior and social context have not been previously reported. OBJECTIVES. To outline detailed sexual and drug use practices, social and psychological status of HIV+ youth compared with a cohort of HIV-negative (HIV-) youth; and to examine the ability of the health belief and risk-taking models to predict sexual and drug use acts of HIV+ youth. METHODS. HIV testing was conducted on and a 207-item structured interview covering HIV risk-related acts, protective factors and background information was administered to 72 HIV+ and 1142 HIV- adolescents aged 13 through 21 years receiving care in an adolescent clinical care unit of a large medical center in New York City. Data were analyzed for adolescents reporting sexual intercourse (71 HIV+ and 722 HIV-) by logistic regression analysis of five domains to identify variables significantly associated with HIV seropositivity. RESULTS. Logistic regressions indicated significant differences in sexual risk acts based on serostatus and gender. Anonymous, blinded seroprevalence testing identified 11% more HIV+ adolescents than would have been identified by current counseling and testing practices. HIV+ adolescents were significantly more likely to be sexually abused (33 vs 21%, P < .05), engage in anal sex and survival sex (32 vs 4%, P < .01), unprotected sex with casual partners (42 vs 23%, P < .05), have had sex under the influence of drugs (52 vs 27%, P < .01), have a sexually transmitted disease (59 vs 28%, P < .01), use multiple drugs (43 vs 9%, P < .01) and engage in multiple problem behaviors (72 vs 30%, P < .01) than HIV- young people. HIV+ females reported more oral (69 vs 45%, P < .01) and/or anal (42 vs 12%, P < .01) intercourse compared to HIV- females. HIV+ males reported significantly higher rates of both insertive (82 vs 46%, P < .05) and receptive (51 vs 4%, P < .01) oral and anal (53 vs 13%, P < .01) intercourse than HIV- males. Protective factors were not significantly different for HIV+ and HIV- young people. CONCLUSIONS. Routine, confidential HIV counseling and testing should be considered for adolescents having unprotected sexual intercourse when age-specific services are available for HIV+ youth. Prevention programs should consider adolescents' history of abuse, homelessness, and other social as well as psychological dimensions in designing comprehensive care strategies to address HIV+ adolescents' multiple problem behaviors and living situations. Current theoretical models of health behaviors should be reconsidered, given the lack of their association to HIV risk acts of HIV+ youth. Age-specific services and interventions for HIV+ youth are urgently needed as HIV is spreading among youth worldwide.

Acquired Immunodeficiency Syndrome↗
PubMed1993

An evaluation of an AIDS risk reduction education and skills training (ARREST) program.

PURPOSE: With the increasing rate of HIV infection among adolescents, there is an urgent need for interventions that will provide teenagers with information, the ability to make decisions, and the assertiveness and communication skills required for effective prevention and risk reduction. This study evaluated an AIDS Risk Reduction Education and Skills Training (ARREST) program designed for adolescents, ages 12-16 years. METHODS: Eighty-seven inner-city, African-American (36%) and Latino (55%) adolescents were recruited from community-based after-school programs, and randomly assigned to either the ARREST intervention or a wait-list control group. Adolescents assigned to the ARREST intervention participated in three 90-minute intervention sessions. ARREST was evaluated by comparing pre- and post-test scores on a battery of self-report measures and videotaped role-play simulations. RESULTS: Analyses revealed significant post-test differences between the ARREST and wait-list control groups, with teens in the ARREST group demonstrating significant changes in knowledge and negative attitudes about HIV/AIDS, perception of risk, and appropriate concern about contracting AIDS. Most importantly, adolescents in the ARREST group demonstrated a significant increase in behavioral skills for negotiating prevention and risk reduction, and resisting peer pressures to engage in risk-related sexual and drug-use behaviors. CONCLUSIONS: ARREST was effective in meeting its short-term objectives for changes in knowledge and behavioral skills, which are important prerequisites for behavior change. Replication with long-term follow-up assessment is needed, however, to determine this intervention's effectiveness at changing risk-related sexual and drug-use behaviors.

Acquired Immunodeficiency Syndrome↗
PubMed1993

The evaluation of targeted outreach in an adolescent HIV/AIDS program.

PURPOSE: Most HIV infected youth are unaware of their serostatus. Among adolescents who know they are HIV positive, only a small percentage are currently receiving care in age-specific programs. Establishing effective links between prevention and service programs is critical in reaching this group of young people. METHODS: A specific outreach strategy was designed to develop more referrals from a wider variety of agencies to better serve youth at risk for HIV. A needs assessment of community-based agencies was the basis for: 1. overcoming barriers to care, 2. specifying the target population, 3. assessing existing referrals, and 4. selecting agencies for different levels of intensity of outreach. RESULTS: Six barriers faced by potential referring agencies were identified and corresponding solutions created which were incorporated into the outreach strategy. A comparison was made of referrals in the years before, during and after the outreach strategy was instituted. A significant difference by (chi 2 analysis) was noted in the number of agencies (p < 0.05), number of individuals (p < 0.01), number of appointments kept (p < 0.01), and the number of HIV+ youth enrolled (p < 0.01) during the year when the plan was fully implemented compared to previous and subsequent years. CONCLUSIONS: Systematic targeted outreach programs are an efficient way to maximize the time and effort of outreach staff. The result was an increase in the number and diversifity of referrals. This strategy could be used by groups caring for adults or younger children who want to expand services to include adolescents or by groups providing HIV/AIDS care who want to specifically serve adolescents.

Adolescent↗
PubMed1993

Human immunodeficiency virus-infected adolescents: the first 50 patients in a New York City program.

To address the unique manifestations of human immunodeficiency virus (HIV) among adolescents aged 13 through 21 years, a comprehensive evaluation and treatment program for high-risk and HIV-positive adolescents was developed in New York City in 1987. Among HIV-infected youth, mean age of testing was 18.2 years. One third of the HIV-positive patients were female and four fifths were African-American or Hispanic. No significant differences were found between HIV-positive (n = 50) and HIV-negative (n = 43) patients for age at first intercourse, injecting or other illicit drug use, history of sexually transmitted diseases, or survival sex (exchange of sex for money or drugs). HIV-positive males were more likely than HIV-negative males to have engaged in anal intercourse and to report a history of sexual abuse. Among infected females, 82% acquired HIV through heterosexual intercourse. Almost half (48%) of HIV-positive adolescents had significant immune dysfunction at the time of their initial visit (CD4 < 500/mm3) and were eligible for zidovudine. Many HIV-positive adolescents continued high-risk behaviors such as intercourse without condoms, particularly those with ongoing dependence on drugs or alcohol. With the epidemic of HIV infection increasing nationwide among adolescents, specialized, comprehensive programs are needed to counsel and treat HIV-infected adolescents and youth in high-risk situations.

Acquired Immunodeficiency Syndrome↗