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Biomedical subjects

J A Kelly

Publications and source records attributed to J A Kelly.

At least 145 records · Page 8Linked to original sources

Psychological factors that predict AIDS high-risk versus AIDS precautionary behavior.

Men (N = 526) who patronized gay bars in three cities completed measures of sexual behavior covering the previous 3 months and psychological measures theoretically pertinent to AIDS risk. Thirty-seven percent of the sample reported engaging in unprotected anal intercourse, the behavior most strongly associated with transmission of human immunodeficiency virus (HIV) infection. Perceived peer norms concerning the acceptability of safer sex practices, AIDS health locus of control scores, risk behavior knowledge, age, and accuracy of personal risk estimation, but not personal HIV serostatus knowledge, were associated with high-risk and precaution-taking behavior.

Acquired Immunodeficiency Syndrome↗

The impact of community-based groups to help persons reduce HIV infection risk behaviours.

In addition to widescale AIDS education campaigns, interventions are also needed which can directly assist in the development of skills to reduce HIV infection. Cognitive-behavioural and skills training approaches have long been used to help individuals learn to change other behaviour patterns related to health and can be applied to AIDS. Several approaches (self-management skills training, assertiveness training, and problem-solving) are discussed in relation to HIV risk reduction counselling. Examples and outcome data from prior risk reduction groups for gay men are summarised. Involvement in multiple-session group intervention can produce rapid and clinically meaningful changes in high-risk behaviour patterns. Issues pertinent to the field implementation of such interventions are discussed.

Group Processes↗

The stigma of AIDS: fear of disease and prejudice toward gay men.

Three hundred college students were presented with vignettes describing an ill person; the vignettes were identical except the illness was identified as either AIDS or leukemia and the individual was described as either homosexual or heterosexual. After reading one vignette, each subject completed a set of measures sensitive to interpersonal evaluation, prejudicial attitudes, and willingness to interact casually with the portrayed individual. The findings indicate the presence of highly stigmatizing attitudes towards AIDS patients and suggest that the public views AIDS patients and gay persons with similar attitudinal prejudice. The need for greater attention to AIDS by social and behavioral researchers is discussed.

Acquired Immunodeficiency Syndrome↗

AIDS risk behavior patterns among gay men in small southern cities.

Men entering gay bars in three small southern cities were administered questionnaires to assess AIDS (acquired immunodeficiency syndrome) risk knowledge, perceived norms concerning the social acceptability of AIDS risk precautions, and personal sexual behavior. Seventy-seven percent (N = 355) of male patrons completed the measures. While risk knowledge levels were high, respondents did not perceive strong norms favoring risk reduction precautions. Rates of risk behavior were considerably higher than those reported for gay men in large urban epicenters.

Adult↗

A skills-training group intervention model to assist persons in reducing risk behaviors for HIV infection.

Fifteen gay men with a history of recent high-risk sexual activities attended seven group sessions that provided risk education, training in self-management skills pertinent to risk reduction, sexual assertiveness training, and problem solving with respect to health consciousness, social supports, and efficacy of risk-reduction change. Before and after intervention, subjects completed measures of AIDS risk knowledge, sexual practices occurring over 4-month retrospective periods, and self-monitored records of ongoing sexual activities and participated in role plays assessing behavioral assertiveness skill for resisting high-risk coercions. Eight-month follow-up data were also collected. Subjects exhibited substantial and well-maintained change following intervention in behaviors relevant to HIV infection risk, including frequency of unprotected anal intercourse (which decreased to near-zero levels), condom use (which increased to almost 90% of intercourse occasions), and in an index that reflects the multiplicative function of risk behaviors frequency by the number of partners with whom high-risk behaviors occurs. This demonstration provides further evidence that skills-training approaches can assist individuals in implementing behavior changes to reduce risk for AIDS and identifies a model relevant to counseling efforts in AIDS prevention programs, HIV counseling and testing programs, drug abuse and STD clinics, and other applied settings.

Adolescent↗

Crystallographic mapping of beta-lactams bound to a D-alanyl-D-alanine peptidase target enzyme.

X-ray crystallography has been used to examine the binding of three members of the beta-lactam family of antibiotics to the D-alanyl-D-alanine peptidase from Streptomyces R61, a target of penicillins. Cephalosporin C, the monobactam analog of penicillin G and (2,3)-alpha-methylene benzylpenicillin have been mapped at 2.3 A resolution in the form of acyl-enzyme complexes bound to serine 62. On the basis of the positions of these inhibitors, the binding of a tripeptide substrate for the enzyme, L-lysyl-D-alanyl-D-alanine, has been modeled in the active site. The binding of both inhibitors and substrate is facilitated by hydrogen-bonding interactions with a conserved beta-strand (297-303), which is antiparallel to the beta-lactam's acylamide linkage or the substrate's peptide bond. The active site is similar to that in beta-lactamases.

Anti-Bacterial Agents↗

An objective test of AIDS risk behavior knowledge: scale development, validation, and norms.

Efforts to curtail the spread of AIDS emphasize changing risk practices. An objective measure of practical knowledge about AIDS risk behaviors can permit the more accurate assessment of the impact of such prevention programs. This paper describes the construction of a standardized 40-item test of AIDS risk behavior knowledge and presents data on the validity, reliability, and psychometric characteristics of the measure in addition to norms for several populations. Knowledge scores of risk behavior may serve as a useful dependent measure when evaluating the impact of applied or experimental AIDS prevention programs, especially with groups at potential risk for the syndrome.

Acquired Immunodeficiency Syndrome↗

Studying enzyme-beta-lactam interactions using X-ray diffraction.

The interaction of representative beta-lactam antibiotics with a bacterial enzyme target has been mapped in three dimensions using X-ray diffraction data to 2.25 A resolution. Examination of complexes of cephalosporin C, benzylmonobactam, and alpha-(2,3)-methylenepenicillin G with the D-alanyl-D-alanine transpeptidase-carboxypeptidase from Streptomyces R61 shows that the enzyme's reactive serine has acylated the beta-lactam ring of each inhibitor. The known half-lives of the three acyl complexes can be correlated with the distance of the drug's carboxylate (or sulfonate) group from complementary groups on the DD-peptidase.

Anti-Bacterial Agents↗

Behavioral intervention to reduce AIDS risk activities.

Behavior change can curtail the spread of acquired immune deficiency syndrome (AIDS). In this study, 104 gay men with a history of frequent AIDS high-risk behavior completed self-report, self-monitoring, and behavioral measures related to AIDS risk. The sample was randomly divided into experimental and waiting-list control groups. The experimental intervention provided AIDS risk education, cognitive-behavioral self-management training, sexual assertion training, and attention to the development of steady and self-affirming social supports. Experimental group participants greatly reduced their frequency of high-risk sexual practices and increased behavioral skills for refusing sexual coercions, AIDS risk knowledge, and adoption of "safer sex" practices. Change was maintained at the 8-month follow-up.

Acquired Immunodeficiency Syndrome↗

Relative bioavailability of pilocarpine from a novel ophthalmic delivery system and conventional eyedrop formulations.

Pupillary responses to pilocarpine following topical application in a novel ophthalmic delivery system (NODS) and a conventional eyedrop formulation have been compared in eight healthy subjects in a single dose crossover study. The magnitude of the miotic and light reflex responses to NODS 40, 80, and 170 micrograms and to a single 2% Minims eyedrop (delivering 518 micrograms) were recorded by infrared television pupillography over periods of 24 hours. Dosage comparisons of drug responses were obtained by interpolation and yielded the equivalence of one eyedrop to 67 +/- 11 micrograms pilocarpine from the NODS formulation. These findings indicate that in a comparison of total doses delivered pilocarpine has an approximately eight-fold greater bioavailability from NODS than from a conventional eyedrop formulation.

Adult↗

Structure and function of disk aggregates of the coat protein of tobacco mosaic virus.

Experiments have been carried out on the coat protein of tobacco mosaic virus (TMVP) to test for the occurrence of the previously postulated RNA-induced direct switching, during in vitro assembly of tobacco mosaic virus (TMV), of the subunit packing from the cylindrical bilayer disk to the virus helical arrangement. No evidence was found for such RNA-induced switching and no evidence for the direct participation of the bilayer disk in either the nucleation or elongation phases of the in vitro virus assembly. Instead, virus assembly proceeds by an initiation step involving the binding of the RNA to the previously characterized two-plus turn helical aggregate that is formed from small oligomers of subunits. However, a bilayer disk, which has been characterized in high ionic strength crystals, has been observed in low ionic strength virus assembly solutions only as a transient species upon depolymerization of dimers of bilayer disks formed in solution at high ionic strength, and not as an equilibrium species of TMVP.

Capsid Proteins↗

Studies on the mechanisms of oxidation in the erythrocyte by metabolites of primaquine.

The interaction of certain metabolites of the 8-aminoquinoline antimalarial primaquine with both normal and glucose-6-phosphate dehydrogenase (G6PD)-deficient erythrocytes and with haemoglobin preparations was studied in an attempt to elucidate the mechanisms of methaemoglobin formation and haemolytic anaemia associated with the use of primaquine. Studies using erythrocytes revealed that oxidation of haemoglobin and reduced glutathione (GSH) was due to the metabolites rather than the parent drug. Incubation of free haemoglobin with 5-hydroxylated metabolites of primaquine also led to oxidation of oxyhaemoglobin and GSH. Oxidation of GSH also occurred in the absence of oxyhaemoglobin. The results suggest a dual mechanism for these oxidative effects, involving autoxidation of the 5-hydroxy-8-aminoquinolines and their coupled oxidation with oxyhaemoglobin. The initial products of these processes would be drug metabolite free radicals, superoxide radical anions, hydrogen peroxide and methaemoglobin. Further free radical reactions would lead to oxidation of GSH, more haemoglobin and probably other cellular constituents. NADPH had no effect on the oxidative effects of the primaquine metabolites in these experiments. In the G6PD-deficient erythrocyte, the oxidation of haemoglobin and GSH leads to Heinz body formation and eventually to haemolysis, the mechanisms of which are as yet unclear. The possible role of oxygen free radicals in the mode of action of 8-aminoquinolines against the malaria parasite is also briefly discussed.

Aminoquinolines↗

The active-site-serine penicillin-recognizing enzymes as members of the Streptomyces R61 DD-peptidase family.

Homology searches and amino acid alignments, using the Streptomyces R61 DD-peptidase/penicillin-binding protein as reference, have been applied to the beta-lactamases of classes A and C, the Oxa-2 beta-lactamase (considered as the first known member of an additional class D), the low-Mr DD-peptidases/penicillin-binding proteins (protein no. 5 of Escherichia coli and Bacillus subtilis) and penicillin-binding domains of the high-Mr penicillin-binding proteins (PBP1A, PBP1B, PBP2 and PBP3 of E. coli). Though the evolutionary distance may vary considerably, all these penicillin-interactive proteins and domains appear to be members of a single superfamily of active-site-serine enzymes distinct from the classical trypsin or subtilisin families. The amino acid alignments reveal several conserved boxes that consist of strict identities or homologous amino acids. The significance of these boxes is highlighted by the known results of X-ray crystallography, chemical derivatization and site-directed-mutagenesis experiments.

Amino Acid Sequence↗