Biomedical subjects

B C Murphy

Publications and source records attributed to B C Murphy.

At least 19 recordsLinked to original sources

PubMed2006

CpG methylation accounts for a recurrent mutation (c.1222C>T) in the human PAH gene.

The human PAH gene (GenBank: U49897.1 (cDNA), AF404777 (gDNA)) harbors alleles that either cause or are associated with hyperphenylalaninemia and phenylketonuria (http://www.pahdb.mcgill.ca). Mutation analysis has identified approximately 500 alleles of which approximately 30 produce polymorphic core haplotypes. The c.1222C>T allele (p.R408W) is the most prevalent and widely encountered PKU-causing allele. Because it occurs on multiple locus-specific polymorphic haplotypes, it is probably not identical by descent in different populations. This mutation involves a CpG dinucleotide in a so-called "hypermutable" codon suggesting that c.1222C>T could be a recurrent allele following spontaneous methylation-mediated deamination of 5 mC. This concept is widely assumed and accepted but the 5mC status of hypermutable codons has seldom been confirmed. We show that the PAH c.1222C nucleotide is indeed methylated (c.1222 mC) in somatic genomes (leukocyte and brain) of H. sapiens. Examination of a representative region in exon 12 (and also in exon 7) in the PAH gene shows that 5 mC is restricted to cytosines in CpG dinucleotides in the hypermutable codons. The methylation pattern seen in human PAH exon 12 was also observed in the corresponding codon in three nonhuman primates. The finding offers at least one explanation for the high relative frequency of the c.1222C>T (p.R408W) allele in the human population.

Alleles↗

PubMed2001

Mothers' emotional expressivity and children's behavior problems and social competence: mediation through children's regulation.

The relations between mothers' expressed positive and negative emotion and 55-79-month-olds' (76% European American) regulation, social competence, and adjustment were examined. Structural equation modeling was used to test the plausibility of the hypothesis that the effects of maternal expression of emotion on children's adjustment and social competence are mediated through children's dispositional regulation. Mothers' expressed emotions were assessed during interactions with their children and with maternal reports of emotions expressed in the family. Children's regulation, externalizing and internalizing problems. and social competence were rated by parents and teachers, and children's persistence was surreptitiously observed. There were unique effects of positive and negative maternal expressed emotion on children's regulation. and the relations of maternal expressed emotion to children's externalizing problem behaviors and social competence were mediated through children's regulation. Alternative models of causation were tested; a child-directed model in which maternal expressivity mediated the effects of child regulation on child outcomes did not fit the data as well.

Affect↗

PubMed1998

Genotype/phenotype correlation in affected individuals of a family with a deletion of the entire coding sequence of the connexin 32 gene.

X-linked Charcot-Marie-Tooth disease (CMTX) is a peripheral nerve disorder that has been linked to mutations in the connexin 32 gene (Cx32). These mutations have been shown to be genetically heterogeneous, though recurrences of specific mutations in apparently unrelated families have been seen. The majority of mutations have been shown to be missense, resulting in non-conservative amino acid changes. A few mutations resulting in a premature termination of protein translation, including both nonsense mutations as well as frameshifting microdeletions, have been documented. We would like to report a deletion mutation that appears to eliminate the entire coding sequence of the Cx32 gene, but which has been shown to segregate with a clinical phenotype not unlike that seen in individuals with a less severe alteration of the Cx32 gene. The causes at a cellular level of the CMTX phenotype are still not fully clear, though there has been speculation that these may involve a dominant negative effect where the mutant connexin 32 suppresses the function of other connexins. Studies of kindreds such as this, where in CMTX-affected males the Cx32 gene product is totally absent, will help us to better understand the molecular mechanisms underlying the clinical phenotype associated with this disorder.

Aged↗

PubMed1998

Contemporaneous and longitudinal prediction of children's sympathy from dispositional regulation and emotionality.

The relation of 8- to 10-year-olds' teacher-reported dispositional sympathy to regulation and emotionality was examined with a longitudinal sample. In general, sympathy was correlated with adults' reports of regulation and low negative emotionality contemporaneously and, to some degree, 2 and 4 years prior. General emotional intensity interacted with some aspects of regulation in predicting sympathy; for example, attention focusing predicted sympathy but only for children low in general emotional intensity. In general, the pattern of correlations changed little from age 6-8 to age 8-10 years, although parent-reported negative emotionality was more highly negatively related to sympathy at the older age. Dispositional sympathy was associated with verbal or physiological markers of sympathy in a laboratory setting.

Arousal↗

PubMed1998

Shyness and children's emotionality, regulation, and coping: contemporaneous, longitudinal, and across-context relations.

The relations of teachers' and parents' reports of children's shyness (i.e., social inhibition) at ages 6-8, 8-10, and 10-12 years to dispositional regulation, emotionality, and coping were examined. Shyness was positively related to internalizing negative emotion, coping by doing nothing, and, for parent-rated shyness, behavioral inhibition/nonimpulsivity, attention focusing, and avoidant coping; it was negatively related to positive emotionality, instrumental coping, seeking support from teachers (at younger ages), and for teacher-rated shyness, attentional control. Often prediction held over several years and/or across reporters. Parent-reported internalizing negative emotion at age 4-6 predicted shyness at ages 6-8 and 8-10, but primarily for children low in attention shifting. Teacher-rated shyness was related to low social status; parent-rated shyness correlated with boys' adult-rated social status at age 4-6 and with style of social interaction, particularly for girls. The relation between parent- and teacher-reported shyness decreased with age. The overall pattern of findings was partially consistent with the conclusion that parent-rated shyness reflected primarily social wariness with unfamiliar people (i.e., temperamental shyness), whereas teacher-rated shyness tapped social inhibition due to social evaluative concerns.

Adaptation, Psychological↗

PubMed1997

The relations of regulation and emotionality to resiliency and competent social functioning in elementary school children.

The relations of regulation and emotionality to elementary school children's social functioning were examined. Teachers and peers reported on children's social functioning; 1 parent and teacher rated children on various measures of regulation, resiliency, and emotionality; and a behavioral index of regulation was obtained. The effects of individual differences in attentional regulation on social status and socially appropriate behavior were mediated by resiliency, and dispositional negative emotionality moderated the positive relation between attentional control and resiliency (with this path being stronger for children high in negative emotionality). The effects of behavioral regulation were not mediated by resiliency; however, the relation of behavioral regulation to socially appropriate behavior (but not social status) was moderated by negative emotionality, with effects being significant and higher for children high in negative emotionality.

Adaptation, Psychological↗

PubMed1997

Contemporaneous and longitudinal prediction of children's social functioning from regulation and emotionality.

Relations of regulation and emotionality to social functioning were examined for 77 children followed from early to middle school age. Parents and teachers reported on children's social behavior, emotionality, and regulation, and children engaged in analogue peer conflict situations (i.e., with puppets). High-quality social functioning was predicted by high regulation and low levels of nonconstructive coping, negative emotionality, and general emotional intensity. Prediction often was obtained across reporters and time, although prediction was strongest within context (home versus school). Moreover, measures of regulation and emotionality frequently contributed unique variance to the prediction of social functioning. Contemporaneous correlations at age 8-10 were similar to those obtained at age 6-8, and prediction of later social functioning from emotionality and regulation at age 4-6 was similar at ages 6-8 and 8-10.

Adaptation, Psychological↗

PubMed1996

Getting angry at peers: associations with linking of the provocateur.

We examined how preschoolers coped with anger in interactions with well liked and not well liked peers. The free-play interactions of preschool-aged children (M age = 66.27 months) were observed for 6 months. The frequency, causes, and intensity of children's anger, as well as their anger-related reactions, were compared for incidents provoked by peers who were "really liked" to those provoked by peers who were liked only " a little bit." Although there were no differences in the intensity of anger provocations by well liked and not well liked provocateurs, children's responses to provocations by well liked peers were more controlled than was the case for anger provoked by peers who were not well liked. In general, boys were more responsive to how they felt about the provocateur than were girls. These findings suggest that anger episodes with well liked children were less stressful than those with peers who were not well liked.

Adaptation, Psychological↗

PubMed1996

The relations of children's dispositional prosocial behavior to emotionality, regulation, and social functioning.

The purpose of this study was to examine the relations of a measure of children's dispositional prosocial behavior (i.e., peer nominations) to individual differences in children's negative emotionality, regulation, and social functioning. Children with prosocial reputations tended to be high in constructive social skills (i.e., socially appropriate behavior and constructive coping) and attentional regulation, and low in negative emotionality. The relations of children's negative emotionality to prosocial reputation were moderated by level of dispositional attentional regulation. In addition, the relations of prosocial reputation to constructive social skills and parent-reported negative emotionality (for girls) increased with age. Vagal tone, a marker of physiological regulation, was negatively related to girls' prosocial reputation.

Adaptation, Psychological↗

PubMed1996

Parents' reactions to children's negative emotions: relations to children's social competence and comforting behavior.

The purpose of this study was to examine the relations of mothers' and fathers' reported emotion-related practices to parents' and teachers' reports of third- to sixth-grade children's social skills, popularity, and coping, as well as the quantity and quality of children's comforting of an infant. Mothers' problem-focused reactions tended to be positively associated with children's social functioning and coping, whereas maternal minimizing reactions tended to be linked to lower levels of social competence and high levels of avoidant coping. There were few findings for fathers' reactions, although fathers reported fewer problem-focused reactions with socially competent, in contrast to less competent, daughters. Emotion-focused and problem-focused maternal reactions, as well as encouragement of the expression of emotion, were associated with boys' children's comforting behavior, although a moderate level of maternal encouragement of the expression of emotion was associated with quality of girls' comforting.

Adaptation, Psychological↗

PubMed1995

Relations of shyness and low sociability to regulation and emotionality.

The relations of shyness and low sociability (i.e., the nonfearful preference to be alone) to measures of regulation and emotionality were examined. College students and (for some variables) friends reported on their relevant dispositional characteristics. In general, shyness was associated with low regulation and high negative emotionality (including intensity, negative affectivity, and personal distress), low positive affect, and low constructive coping. In contrast, low sociability was unrelated to negative emotionality; associated with low positive emotional intensity, low physiological reactivity, and high inhibition control; and correlated with low seeking of social support as a means of coping. The findings are considered within a heuristic model in which emotional reactivity and regulation are proposed as predictors of social responding.

Adaptation, Psychological↗

PubMed1992

Effects of extracellular matrix components and dihydrotestosterone on the structure and function of human prostate cancer cells.

The extracellular matrix (ECM) has been shown to play a major role in cell structure and function. Several studies have demonstrated that the ECM can alter cell morphology and effect DNA synthesis and gene expression. The ECM also interacts with growth hormones which have been shown to be located in or near the ECM where they are believed to effect cell structure and function. In the nontransformed cell, these ECM and hormone-mediated effects appear to be tightly regulated and this is believed to be accomplished through cell receptor-tissue matrix interactions. We, therefore, undertook a study to determine the effects of a variety of ECM components and the adrogenic hormone dihydrotestosterone (DHT) on the structure and function of the human prostate cancer cell line, LNCaP. The effects of individual matrix components in the presence and absence of 1 nM DHT on the static and dynamic morphology, growth rate, and PSA production of the LNCaP cell line were studied. We determine that the ECM and DHT interact in complex ways to effect cell structure and function. DHT produced alterations in cytoplasmic structure that increased cell size and decreased the nuclear area/cytoplasmic area ratio. Dynamic cell structure as measured by cell motility was very sensitive to the ECM components and the presence of DHT. PSA and growth could be regulated by substratum and DHT and there was an inverse relationship between PSA production and growth rate. These data exemplify the complex interactions which occur between prostate cancer cells, ECM components, and exogenous DHT that are reflected in cell structure and function.

Antigens, Neoplasm↗

PubMed1992

Effect of pentosan, a novel cancer chemotherapeutic agent, on prostate cancer cell growth and motility.

Pentosan is a new chemotherapeutic drug which is currently in Phase I clinical trials. In our experimental systems, in vivo, pentosan inhibits the growth of the highly metastatic MAT-LyLu (MLL) Dunning R3327 prostate cancer cell line only at toxic doses and has no apparent effect on growth in vitro. The mechanism of tumor inhibition of this drug is unknown; however, in vitro, pentosan exhibits a potent inhibition of cell motility. Cell motility is essential for tumor cell metastasis and angiogenesis. By blocking cell motility, pentosan has the potential to inhibit both tumor growth and metastasis. We have characterized the mechanism of motility inhibition by pentosan and believe it alters cell-extracellular matrix interactions. The mechanism of motility inhibition by pentosan appears to be independent of cytoskeletal structural alterations, including changes in microfilament and microtubule networks. Pentosan acts through a different mechanism than suramin, a drug which inhibits motility through inhibition of growth factor effects. In vitro, pentosan alters cellular contacts with the extravascular matrix and inhibits cell motility. In vivo, pentosan prolongs survival of rats injected with MLL cells by 25%, but did not appear to decrease the rate of primary tumor growth or the number of metastatic lesions in the treated animals. These data suggest that, in vivo, pentosan acts through an as yet undefined mechanism.

Animals↗

PubMed1992

Environmentally contaminated families: therapeutic considerations.

The unique stress for families of exposure to environmental toxins is discussed in terms of the physical characteristics of such contaminants and resultant adaptational dilemmas, the agent or cause of the injury, and institutional responses to the contamination. Recommendations for mental health professionals working with contaminated families are presented.

Adaptation, Psychological↗

PubMed1992

Educating mental health professionals about gay and lesbian issues.

Despite the large number of clients with gay and lesbian concerns, many mental health professionals remain biased and unqualified to serve them. Mental health professionals are poorly prepared to deal with sexuality in general and with gay and lesbian issues specifically. Education and training about gay and lesbian topics is needed both in graduate schools and in the field. This training should focus on three components: (1) information about sexual orientation, gay and lesbian lifestyles, and community resources; (2) the interface between the gay or lesbian client, his or her sexuality, and the effects of living in a heterosexist and homophobic society; and (3) the interaction between the attitudes, feelings, and sexual orientation of the clinician and of the client.

Adult↗

PubMed1991

The effect of extracellular matrix interactions on morphologic transformation in vitro.

There is emerging evidence that the structure and function of a cell is dependent in part on the contacts that cells make with the extracellular matrix. We report here the effect of extracellular matrices secreted from both normal and tumor cells have on the structure of normal rat kidney epithelial cells. Normal rat kidney cells plated on the basement membrane secreted by tumor cells adopt a morphology and phenotype which closely resembles a Kirsten-ras transformed normal rat kidney cell. This morphologic transformation was not observed for cells plated on individual extracellular matrix components or on basement membrane secreted by normal placenta cells. This suggests that tumor derived basement membrane has unique characteristics which may cause morphologic transformation of normal rat kidney cells.

Animals↗

PubMed1991

Modifications of the intermediate filament and nuclear matrix networks by the extracellular matrix.

The tissue matrix system is a dynamic, interacting structural network directly linking the nuclear matrix, cytoskeleton and the extracellular matrix. We report here that interaction of normal rat kidney epithelial cells (NRK) and Kirsten-ras transformed rat kidney cells, with an extracellular matrix secreted by tumor cells, causes modifications to the protein composition of the intermediate filament and nuclear matrix networks. The matrix networks are different between normal and transformed cells; however, these alterations by the tumor extracellular matrix are similar in both cell types. These data represent the first report that modification of the extracellular matrix environment can have an effect on the protein composition of the nuclear matrix.

Animals↗

PubMed1990

Atomic veterans and their families: responses to radiation exposure.

In-depth interviews with seven atomic veterans and their families indicated powerful psychological effects on all family members from exposure to low-level ionizing radiation. Four themes emerged: the invalidation of their experiences by government and other authority figures; family concerns about genetic effects on future generations; family members' desire to protect each other from fears of physical consequences; and desire to leave a record of their experiences to help prevent future suffering.

Abnormalities, Radiation-Induced↗