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Biomedical subjects

R M Cunningham

Publications and source records attributed to R M Cunningham.

At least 19 recordsLinked to original sources
PubMed2004

Fold-specific substitution matrices for protein classification.

MOTIVATION: Methods that focus on secondary structures, such as Position Specific Scoring Matrices and Hidden Markov Models, have proved useful for assigning proteins to families. However, for assigning proteins to an attribute class within a family these methods may introduce more free parameters than are needed. There are fewer members and there is less variability among sequences within a family. We describe a method for organizing proteins in a family that exhibits up to an order of magnitude reduction in the number of parameters. The basis is the log odds ratio commonly used to measure similarity. We adapt this to characterize the sequence dissimilarities that give rise to attribute differentiation. This leads to the definition of Class Attribute Substitution Matrices (CLASSUM), a dual of the BLOSUM. RESULTS: The method was applied to classify sequences hierarchically in the lambda and kappa subgroups of the immunoglobulin superfamily. Positions conferring class were identified based on the degree of amino acid variability at a position. The CLASSUM computed for these positions classified better than 90% of test data correctly compared with 35-50% for BLOSUM-62. The expected value for a random matrix is 14%. The results suggest that family-specific data-derived substitution matrices can improve the resolution of automated methods that use generic substitution matrices for searching for and classifying proteins.

Algorithms↗
PubMed1995

Person and environment in HIV risk behavior change between adolescence and young adulthood.

This article explores how personal and environmental variables influence change in human immunodeficiency virus (HIV)-related risk behaviors between adolescence and young adulthood. Repeated interviews with 602 youths from 10 cities across the United States provide the data. These interviews first occurred in 1984-1985 and 1985-1986 when the youths were adolescents and were repeated again in 1989-1990 and 1991-1992 when they were all young adults. A longitudinal multivariate analysis shows that 31% of the variance in HIV risk behaviors by inner-city young adults is predicted by a combination of adolescent risk behaviors, personal variables (suicidality, substance misuse, antisocial behavior), environmental variables (history of child abuse, poor relations with parents, stressful events, peer misbehavior, number of AIDS prevention messages), and interactions between variables (number of neighborhood murders with child abuse, number of neighborhood murders with substance misuse, and unemployment rates with antisocial behavior).

Adolescent↗
PubMed1994

The association of physical and sexual abuse with HIV risk behaviors in adolescence and young adulthood: implications for public health.

This paper explores the relationship between changes in HIV risk behaviors and physical and sexual abuse. A stratified random sampling procedure selected 602 youths from a sample of 2,787 patients seen consecutively at public health clinics in 10 cities. Face-to-face structured interviews conducted since 1984-85 provide a history of change in risk behavior from adolescence to young adulthood. Univariate and bivariate analyses assessed differences in demographic and number and type of risk behaviors between those experiencing single or multiple types of abuse and those with no abuse history at all. The results show that a history of physical abuse, sexual abuse, or rape is related to engaging in a variety of HIV risk behaviors and to a continuation or increase in the total number of these behaviors between adolescence and young adulthood. This information might help practitioners to both prevent initial involvement in HIV risk behaviors and to prevent continuation of behaviors as youths move into young adulthood.

Adolescent↗
PubMed1994

Inner-city youths and condom use: health beliefs, clinic care, welfare, and the HIV epidemic.

This paper examines questions concerning condom use and determinants of change in use by inner-city youths who appear to be in the direct path of the AIDS epidemic. Detailed information gathered in interviews with 548 youths in 1989-90 and 1991-92, provide a history of change in condom use and HIV-related high-risk behaviors. Condom use as a whole increased with time and age. Positive beliefs concerning condoms and awareness of HIV transmission were determinants of increases in use, and negative beliefs were determinants of decreases. Nevertheless, those youths who engaged in the highest HIV-risk behaviors (prostitution, IV drug use, and male homosexuality) were no more likely than lower-risk youths to increase their condom use. Financial need, indicated by receipt of welfare, appeared to be a significant barrier to increasing condom use. Also noteworthy was the negative association between using health clinics and condom use. Although youths with high-risk behaviors make more clinic visits, those visits do not result in condom use.

Adolescent↗
PubMed1989

Effects of staurosporine on protein kinase C and amylase secretion from pancreatic acini.

The effects of staurosporine, a recently isolated microbial alkaloid, on amylase secretion and protein kinase C activity of guinea pig pancreatic acini were investigated. Staurosporine at a concentration of 1 microM completely inhibited both acinar protein kinase C activity (IC50 = 5.5 +/- 1.4 nM) and amylase secretion induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (IC50 = 4.1 +/- 0.4 nM). At this concentration, staurosporine reduced amylase secretion elicited by maximally effective concentrations of carbachol and cholecystokinin by approximately 50% but did not appreciably alter the potencies of the two secretagogues. In the presence of staurosporine, amylase secretion induced by carbachol was linear for at least 60 min. Staurosporine had no effect on amylase release elicited by the Ca2+ ionophore A23187. It did, however, inhibit secretion induced by vasoactive intestinal peptide, although with a reduced potency relative to its effects on amylase release stimulated by TPA, carbachol, and cholecystokinin (IC50 = 34 +/- 17 nM). These results indicate that staurosporine is a potent inhibitor of protein kinase C activity in pancreatic acini and that protein kinase C has an important role as an intracellular mediator of digestive enzyme secretion induced by cholecystokinin and carbachol in the acinar cell. In addition, a separate staurosporine-insensitive coupling pathway, most likely involving Ca2+, appears to be equally important and can maintain long-term secretion in the absence of functional protein kinase C activity.

Alkaloids↗