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Biomedical subjects

J A Kelly

Publications and source records attributed to J A Kelly.

At least 37 records · Page 2Linked to original sources

Influence of a partner's HIV serostatus, use of highly active antiretroviral therapy, and viral load on perceptions of sexual risk behavior in a community sample of men who have sex with men.

OBJECTIVE: To assess the perceptions of gay and bisexual men concerning the risk of HIV transmission through various sexual practices with a new sex partner depending on that partner's disclosed HIV status, antiretroviral treatment status, and viral load. METHODS: Study participants read four different scenarios describing sexual situations with a new partner and rated each scenario for risk of HIV transmission. HIV status and antiretroviral treatment status disclosed by the new sex partner were varied across four scenarios: unknown HIV status; HIV-negative; HIV-positive and not taking highly active antiretroviral therapy (HAART); and HIV-positive and taking HAART with an undetectable viral load. RESULTS: Study participants were 472 men attending a gay pride festival who reported that they were HIV-negative. Eighty-nine percent of the men were white, and the mean age of the study participants was 35.8 years. Of the four scenarios, sex with an HIV-positive partner not taking HAART was rated as posing the greatest risk. Sex with an HIV-positive partner taking HAART who had an undetectable viral load was not consistently viewed as riskier than sex with an HIV-negative partner or a man with an unknown HIV status. CONCLUSIONS: The current study provides preliminary evidence for the effect of disclosure of HIV serostatus, use of HAART, and the presence of an undetectable viral load on the perceptions of sexual risk for HIV-negative men. The findings suggest that some gay and bisexual men judge risk based on the perceived HIV status of their sex partners and not on the general assumption that all sex partners entail equal risk, as many prevention campaigns have emphasized.

Adult↗

Evidence for a susceptibility gene, SLEV1, on chromosome 17p13 in families with vitiligo-related systemic lupus erythematosus.

Both systemic lupus erythematosus (SLE) and vitiligo are autoimmune disorders that have strong evidence of complex genetic contributions to their etiology, but, to date, efforts using genetic linkage to find the susceptibility genes for either phenotype have met with limited success. Since autoimmune diseases are thought to share at least some of their genetic origins, and since only a small minority (16 of 92) of the European-American pedigrees multiplex for SLE in our collection have one or more affected members with vitiligo, we hypothesized that these pedigrees might be more genetically homogeneous at loci important to both SLE and vitiligo and, hence, have increased power for detection of linkage. We therefore evaluated genomewide microsatellite-marker-scan data for markers at an average marker density of approximately 11 cM in these 16 European-American pedigrees and identified a significant linkage at 17p13, where the maximum multipoint parametric LOD score was 3.64 (P<4.3x10(-5)) and the nonparametric linkage score was 4.02 (P<2.8x10(-5)), respectively. The segregation behavior of this linkage suggests a recessive mode of inheritance with a virtually homogeneous genetic effect in these 16 pedigrees. These results support the hypotheses that SLE and vitiligo may share important genetic effects and that sampling on the basis of clinical covariates dramatically improves power to identify genetic effects.

Chromosome Mapping↗

Mutational analysis of the thyrotropin-releasing hormone-degrading ectoenzyme. similarities and differences with other members of the M1 family of aminopeptidases and thermolysin.

Thyrotropin-releasing hormone-degrading ectoenzyme (TRH-DE) is a TRH-specific peptidase which catalyzes the inactivation of the peptidergic signal substance TRH. As indicated by sequence alignment, TRH-DE and the other members of the M1 family of aminopeptidases have a distinct set of conserved amino acid residues in common. By replacing amino acid residues that are putatively involved in catalysis, we could demonstrate that the enzymatic activities of the mutants E408D, E442D, E464Q, E464D, Y528F, H507R, and H507F are dramatically decreased, essentially due to the changes of V(max). The mutant enzymes E408Q and E442Q are inactive, whereas the specific enzymatic activity of the mutants R488Q, R488A, and Y554F are similar to that of the wild-type enzyme. These data strongly suggest that E408, E442, Y528, and H507 are involved in the catalytic process of TRH-DE while E464 presumably represents the third zinc-coordinating residue and may be equivalent to E166 in thermolysin. In contrast, amino acid residues R488 and Y554 seem not to be involved in the catalytic mechanism of TRH-DE.

Amino Acid Sequence↗

Predictors of HIV risk behavior among Russian men who have sex with men: an emerging epidemic.

BACKGROUND: Russia is experiencing one of the sharpest increases in HIV incidence in the world. Almost no research has examined patterns of risk behavior among Russian men who have sex with men (MSM). DESIGN AND METHODS: A total of 434 MSM were surveyed in all of St. Petersburg's gay-identified clubs during June 2000. Men completed questionnaires about their sexual practices, AIDS risk knowledge, safer sex attitudes, behavior change intentions, perceived safer sex norms, and fatalism. RESULTS: Most MSM were bisexual; 79% had female partners in their lives and 37% had female partners in the previous 3 months. Sexually transmitted disease treatment was reported by 32% of the men, 23% had sold sex to gain money, and knowledge about critical HIV risk-reduction steps was low. Of all men surveyed, 38% had unprotected anal sex in the previous 3 months, consistent condom use was reported by only 30% of men, and most recent anal intercourse occasions 37% of particpants'. Regression analyses showed that high-risk behavior was predicted by poor safer sex attitudes, weak behavior change intentions, low knowledge about AIDS risk, perceived peer norms that did not support safer sex, and having a boyfriend. CONCLUSION: To avert a widespread epidemic, HIV prevention interventions for Russian MSM are critically needed. Factors predicting risk were consistent with those found among MSM in other countries early in the HIV epidemic. However, unique cultural factors, including frequent bisexual behavior, the 'newness' of openly gay communities in Russia and lack of community experience in dealing with AIDS, require HIV prevention program tailoring.

Adult↗

A 1.2-A snapshot of the final step of bacterial cell wall biosynthesis.

The cell wall imparts structural strength and shape to bacteria. It is made up of polymeric glycan chains with peptide branches that are cross-linked to form the cell wall. The cross-linking reaction, catalyzed by transpeptidases, is the last step in cell wall biosynthesis. These enzymes are members of the family of penicillin-binding proteins, the targets of beta-lactam antibiotics. We report herein the structure of a penicillin-binding protein complexed with a cephalosporin designed to probe the mechanism of the cross-linking reaction catalyzed by transpeptidases. The 1.2-A resolution x-ray structure of this cephalosporin bound to the active site of the bifunctional serine type D-alanyl-D-alanine carboxypeptidase/transpeptidase (EC ) from Streptomyces sp. strain R61 reveals how the two peptide strands from the polymeric substrates are sequestered in the active site of a transpeptidase. The structure of this complex provides a snapshot of the enzyme and the bound cell wall components poised for the final and critical cross-linking step of cell wall biosynthesis.

Acylation↗

Outcomes of a randomized small-group HIV prevention intervention trial for people with serious mental illness.

HIV prevalence is alarmingly high among persons with serious mental illness and severely mentally ill adults frequently engage in high-risk behavior practices. This study evaluated the effectiveness of a small-group HIV risk reduction intervention offered to 189 men and women in outpatient programs for severely mentally ill adults. Participants screened for HIV risk were randomly assigned to attend either a 7-session small-group cognitive-behavioral HIV risk reduction intervention or a time-matched comparison intervention and were followed at 3-month intervals for one year. Participants who attended the HIV risk reduction intervention increased their condom use, had a higher percentage of intercourse occasions protected by condoms, and held more positive attitudes toward condoms. Women showed greater response to the intervention than men. While many behavior change effects were present at 3-, 6- and 9-month followup assessments, most diminished by the 12-month followup. These results under-score the need for tailored but ongoing HIV prevention efforts integrated into community programs that serve people with serious mental illness.

Acquired Immunodeficiency Syndrome↗

HIV risk behavior and risk-related characteristics of young Russian men who exchange sex for money or valuables from other men.

One of the world's newest HIV epidemics is emerging now in Russia and other countries of Central and Eastern Europe. We report on the HIV risk characteristics of young Russian men who exchange sex for money or valuables, a group that constitutes almost one-fourth of men surveyed recently in gay-identified venues in St. Petersburg. Among 96 MSM who have sex for economic gain, most reported multiple male and female partners, 45% had unprotected anal intercourse with their male partners in the past three months, and many not only received but also gave money or valuables themselves to their male partners. Relative to men who did not give sex for economic gain (n = 326), those who did were younger (n = .0001), less well-educated (p = .0001), and more often unemployed (p = .02). They also were less knowledgeable concerning even basic HIV risk reduction steps (p = .02) and held many misconceptions about safer sex. Men who exchanged sex for economic gain had more male (p = .001) and female partners (p = .01) in the past three months than men who did not, and one-third had been treated for STDs. In the context of Russia's rapid cultural and social changes, economic turmoil, and gay communities not yet experienced in AIDS, HIV prevention programs must be tailored to risk patterns and dynamics different than those found in the gay communities of many western countries.

Adolescent↗

AIDS knowledge, attitudes, and behaviour in Russia: results of a population-based, random-digit telephone survey in St Petersburg.

In this paper, we report on the results of what we believe to be the first population-based, random-digit telephone AIDS survey conducted in Russia. Recent and rapidly increasing STD and HIV rates show the extremely urgent need for HIV prevention programmes in Russia. HIV sexual risk behaviour, knowledge, attitudes, and personal concern characteristics were assessed in a sample of men and women aged 15-55 years living in 435 St Petersburg households. Many factors related to high HIV risk were found in this study. Only 6% of respondents reported consistent condom use, and 78% reported that they never or seldom used condoms. At the same time, over 13% had 3 and more sexual partners during the last year and 12% had 10 and more lifetime partners. Occasional or frequent anal sex was reported by 13% of those surveyed. Two-thirds of respondents acknowledged personal risk for getting HIV but fewer than 25% indicated that they had taken steps to reduce the risks. One-third of respondents believed that condoms are not an effective protection against HIV. Forty-eight per cent of respondents believed that HIV could be transmitted through kissing, 56% through mosquito bites, and 29.2% through sharing cigarettes. HIV/AIDS prevention efforts for the general public and also targeted campaigns directed toward high-risk communities must be quickly undertaken in Russia.

Acquired Immunodeficiency Syndrome↗

Kinetic investigation of the specificity of porcine brain thyrotropin-releasing hormone-degrading ectoenzyme for thyrotropin-releasing hormone-like peptides.

Evidence indicates that neuronally released thyrotropin-releasing hormone (TRH) is selectively inactivated by TRH-degrading ectoenzyme (TRH-DE) (EC ). TRH-DE inhibitors may be used to enhance the therapeutic actions of TRH and to investigate the functions of TRH and TRH-DE in the central nervous system. Although TRH-DE appears to exhibit a high degree of specificity toward TRH, systematic specificity studies, which would facilitate inhibitor design, have not been previously conducted for this enzyme. In this paper we present the first description of TRH-DE specificity across a directed peptide library in which the histidyl (P(1)') residue of TRH was replaced by a series of amino acids. Peptides were synthesized using standard solid phase chemistry. Kinetic parameters were measured either by continuous or discontinuous fluorometric assays or by quantitative high pressure liquid chromatography. The P(1)' residue was found to influence significantly both the ability of the peptides to bind to TRH-DE, as measured by their K(i) values, and the ability of TRH-DE to catalyze their hydrolysis. Moderately bulky, uncharged P(1)' residues were found to bind preferentially to TRH-DE. Results from this screen provide valuable information for the development of TRH-DE inhibitors and have led to the identification of two potent, reversible TRH-DE inhibitors, l-pyroglutamyl-l-asparaginyl-l-prolineamide (K(i) = 17.5 micrometer) and Glp-Asn-Pro-7-amido-4-methyl coumarin (K(i) = 0.97 micrometer).

Aminopeptidases↗

Impact of medical and nonmedical factors on physician decision making for HIV/AIDS antiretroviral treatment.

To examine influences of medical factors (e.g., viral load) and nonmedical factors (e.g., patient characteristics) on treatment decisions for highly active antiretroviral therapy (HAART), we sent a survey to a random sample of 995 infectious disease physicians who treat patients with HIV/AIDS in the United States in August, 1998. The response rate was 53%. Respondents were asked to report their current practices with respect to antiretroviral treatment and the extent to which each of three medical and 17 nonmedical factors would influence them for or against prescribing HAART to a hypothetical HIV-positive patient. Most reported initiating HAART with findings of low CD4+ cell counts and high viral loads, and weighing CD4+ cell counts, viral load, and opportunistic infection heavily in their decisions to prescribe HAART. Patients' prior history of poor adherence was weighed very much against initiating HAART. Patient homelessness, heavy alcohol use, injection drug use, and prior psychiatric hospitalization were cited by most physicians as weighing against HAART initiation. Thus, most physicians in this sample follow guidelines for the use of HAART, and nonmedical factors related to patients' life situations are weighed as heavily as disease severity in treatment decisions. As HIV increasingly becomes a disease associated with economic disadvantage and other social health problems, it will be essential to develop interventions and care support systems to enable patients experiencing these problems to benefit from HIV treatment advances.

Anti-HIV Agents↗

The effect of arthroscopic irrigation fluid warming on body temperature.

The use of room temperature solutions for body cavity irrigation during surgical procedures can lead to the development of perioperative hypothermia. Hypothermia during this period causes patient discomfort, increases oxygen consumption, interferes with the clotting cascade, and increases the length of hospital stay. Perioperative hypothermia in anesthetized patients also contributes to extended sedation, delayed emergence, and prolonged recovery from neuromuscular blockade. Twenty-four adult American Society of Anesthesiologists (ASA) class I and II patients were randomly assigned to receive warmed arthroscopic irrigation solution or room-temperature irrigation solution in this randomized, prospective study. Tympanic temperatures were monitored every 15 minutes throughout the surgical and postanesthesia recovery periods. P < .05 was considered significant. Statistical comparison of the mean percent temperature decrease from preoperative baseline between the 2 groups did not support the hypothesis that patients receiving warmed irrigation solution would maintain a higher core body temperature than those receiving room temperature solution.

Adult↗

HIV prevention with young men who have sex with men: what young men themselves say is needed. Medical College of Wisconsin CITY Project Research Team.

Young men who have sex with men (YMSM), and particularly ethnic minority YMSM, experience high incidence HIV infection due to continued patterns of high-risk sexual behaviour. The intent of this research was to systematically solicit input and recommendations from YMSM themselves concerning the kinds of HIV prevention programmes that would best meet their needs and would address risk issues they believed are critical. In-depth qualitative interviews were conducted with a sample of 72 purposively selected YMSM to identify necessary components of HIV prevention targeting YMSM. Respondents noted a need for comprehensive HIV prevention programmes that addressed issues related to dating and intimacy, sexuality and arousal, drugs and alcohol, self-esteem and self-worth, abuse and coercion, and sexual identity. Respondents emphasized the importance of keeping programmes confidential, fun, comfortable, accepting and open to all YMSM regardless of sexual identity. Identified community resource needs included safe havens for youth, more peer educators and older MSM mentors, increased school-based sexuality education, and greater support from the society at large as well as from churches, the gay community and communities of Color. Implications of these findings for HIV prevention are discussed.

Adolescent↗

Cost-effectiveness of an HIV risk reduction intervention for adults with severe mental illness.

Small-group HIV prevention interventions that focus on individual behavioural change have been shown to be especially effective in reducing HIV risk among persons with severe mental illness. Because economic resources to fund HIV prevention efforts are limited, health departments, community planning groups and other key decision-makers need reliable information on the cost and cost-effectiveness (not solely on effectiveness) of different HIV prevention interventions. This study used an economic evaluation technique known as cost-utility analysis to assess the cost-effectiveness of three related cognitive-behavioural HIV risk reduction interventions: a single-session, one-on-one intervention; a multi-session small-group intervention; and a multi-session small-group intervention that taught participants to act as safer sex advocates to their peers. For men, all three interventions were cost-effective, but advocacy training was the most cost-effective of the three. For women, only the single-session intervention was cost-effective. The gender differences observed here highlight the importance of focusing on gender issues when delivering HIV prevention interventions to men and women who are severely mentally ill.

Adult↗

Coping strategies and emotional wellbeing among HIV-infected men and women experiencing AIDS-related bereavement.

AIDS influences the psychological coping not only of the person with the disease but also those close to that individual. Following a death from AIDS, family members and friends may experience atypical bereavement. Bereavement coping challenges can be especially difficult and pronounced for persons who are themselves HIV-positive. The prevalence of AIDS-related bereavement and psychosocial predictors of grief severity were examined in an ethnically diverse sample of 199 HIV-infected men and women. Eighty per cent of HIV-positive respondents had experienced the loss of someone close to AIDS, the majority of whom had sustained multiple and repetitive losses. Two-thirds of the participants who had experienced an AIDS-related loss reported grief symptoms in the past month. Hierarchical regression analyses revealed that grief was most closely associated with emotional suppression and avoiding coping strategies, with residual variance related to depression. Interventions for AIDS-related bereavement that reduce distress and maladaptive ways of coping are needed in order to meet the secondary prevention needs of bereaved people living with HIV/AIDS.

Acquired Immunodeficiency Syndrome↗

Life optimism, substance use, and AIDS-specific attitudes associated with HIV risk behavior among disadvantaged innercity women.

The development of more effective human immunodeficiency virus (HIV) prevention programs for disadvantaged women requires identification of factors associated with risk. In the present study, 158 women - all of whom met criteria indicative of HIV risk - were recruited in innercity primary healthcare clinics and administered measurements that assessed variables in three domains believed pertinent to HIV sexual risk behavior: (1) substance use in the past 3 months, (2) acquired immunodeficiency syndrome (AIDS)-specific cognitive and attitudinal factors, including AIDS risk knowledge, condom attitudes, perceived risk for AIDS, behavior change intentions, and perceived self-efficacy, and (3) life context variables, including self-esteem, fatalism, personal optimism toward the future, and current life satisfaction. When women were categorized into highest and lower groups based on their recent risk behavior, AIDS-specific cognitive and attitudinal factors, as expected, differentiated the groups. However, women at highest risk for HIV also most often used a variety of substances and scored lower in self-esteem, held views more characterized by personal fatalism and low optimism concerning the future, and had greater life dissatisfaction than women at lower risk. HIV prevention programs for disadvantaged women require attention not only to AIDS-specific knowledge, attitudes, and skills development but also to broader issues of life context that, if unaddressed, may limit women's ability and motivation to reduce risk for HIV/AIDS.

Acquired Immunodeficiency Syndrome↗

Lymphangioleiomyomatosis: abdominopelvic CT and US findings.

PURPOSE: To describe the abdominal computed tomographic (CT) and ultrasonographic (US) findings in patients with thoracic lymphangioleiomyomatosis (LAM) and to relate the prevalence of the findings to the severity of pulmonary disease. MATERIALS AND METHODS: Eighty patients with LAM underwent chest and abdominopelvic CT and abdominopelvic US. The images were reviewed prospectively by one radiologist, and the abdominal findings were recorded and correlated with the severity of pulmonary disease at thin-section CT. RESULTS: Sixty-one (76%) of 80 patients had positive abdominal findings. The most common abdominal findings included renal angiomyolipoma (AML) in 43 patients (54%), enlarged abdominal lymph nodes in 31 (39%), and lymphangiomyoma in 13 (16%). Less common findings included ascites in eight (10%), dilatation of the thoracic duct in seven (9%), and hepatic AML in three (4%). A significant correlation (P =.02) was observed between enlarged abdominal lymph nodes and increased severity of lung disease. CONCLUSION: There are characteristic abdominal findings in patients with LAM that, in conjunction with the classic thin-section CT finding of pulmonary cysts, are useful in establishing this diagnosis.

Abdomen↗

The emerging AIDS crisis in Russia: review of enabling factors and prevention needs.

Eastern Europe is experiencing increased rates of HIV/AIDS, and the Russian Federation is among the countries with the most alarming case rate increases. Behavioural and biological studies demonstrate that the transmission of HIV in Russia is occurring as a result of injection drug use, homosexual, and heterosexual risk behaviours. Factors that promote risk and therefore enable HIV transmission in Russia parallel those found in other countries, including epidemics of other sexually transmitted infections, economic instability, poverty, and social factors such as gender roles. Research is urgently needed to better understand and forecast the HIV epidemic in Russia, as well as to develop effective interventions to prevent a Russian AIDS crisis.

Acquired Immunodeficiency Syndrome↗