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Biomedical subjects

B B Brown

Publications and source records attributed to B B Brown.

At least 19 recordsLinked to original sources

Functional analysis of six androgen receptor mutations identified in patients with partial androgen insensitivity syndrome.

Partial androgen insensitivity syndrome (PAIS) is caused by defects in the androgen receptor gene and presents with a wide range of undervirilization phenotypes. We studied the consequences of six androgen receptor ligand-binding domain mutations on receptor function in transfected cells. The mutations, Met742Ile, Met780Ile, Gln798Glu, Arg840Cys, Arg855His and Ile869Met, were identified in PAIS patients with phenotypes representing the full spectrum seen in this condition. In all cases the androgen receptor was found to be defective, suggesting that the mutation is the cause of the clinical phenotype. The Gln798Glu mutation is exceptional in that it did not cause an androgen-binding defect in our system, although the mutant receptor was defective in transactivation assays. This mutation may affect an aspect of binding not tested, or may be part of a functional subdomain of the ligand-binding domain involved in transactivation. Overall we found milder mutations to be associated with milder clinical phenotypes. There is also clear evidence that phenotype is not solely dependent on androgen receptor function. Some of the mutant receptors were able to respond to high doses of androgen in vitro, suggesting that patients carrying these mutations may be the best candidates for androgen therapy. One such mutation is Ile869Met. A patient carrying this mutation has virilized spontaneously at puberty, so in vivo evidence agrees with the experimental result. Thus a more complete understanding of the functional consequences of androgen receptor mutations may provide a more rational basis for gender assignment in PAIS.

Amino Acid Sequence↗

A single-bead decode strategy using electrospray ionization mass spectrometry and a new photolabile linker: 3-amino-3-(2-nitrophenyl)propionic acid.

A new linker that employs a photosensitive 3-amino-3-(2-nitrophenyl)propionyl functionality (ANP-resin) has been developed for the preparation of C-terminal carboxamides. A wide range of carboxamides were prepared and identified using the ANP-resin and electrospray ionization mass spectrometry. A single bead containing tripeptide Fmoc-Asp-Arg(Tos)-Val-NH2 was isolated, photocleaved and the peptide was characterized by tandem mass spectrometry, thereby verifying a library decode strategy that avoids complex tagging procedures.

Amino Acid Sequence↗

Parenting practices and peer group affiliation in adolescence.

Social scientists have often assumed that parental influence is sharply curtailed at adolescence because of the rising counterinfluence of peer groups, over which parents have little control. The present study tested a conceptual model that challenged this view by arguing that parents retain a notable but indirect influence over their teenage child's peer associates. Data from a sample of 3,781 high school students (ages 15-19) indicated that specific parenting practices (monitoring, encouragement of achievement, joint decision making) were significantly associated with specific adolescent behaviors (academic achievement, drug use, self-reliance), which in turn were significantly related to membership in common adolescent crowds (jocks, druggies, etc). Findings encourage investigators to assess more carefully parents' role in adolescents' peer group affiliations.

Adolescent↗

Ethnic differences in adolescent achievement. An ecological perspective.

Using data collected from a large sample of high school students, the authors challenge three widely held explanations for the superior school performance of Asian-American adolescents, and the inferior performance of African- and Hispanic-American adolescents: group differences in (a) parenting practices, (b) familial values about education, and (c) youngsters' beliefs about the occupational rewards of academic success. They found that White youngsters benefit from the combination of authoritative parenting and peer support for achievement, whereas Hispanic youngsters suffer from a combination of parental authoritarianism and low peer support. Among Asian-American students, peer support for academic excellence offsets the negative consequences of authoritarian parenting. Among African-American youngsters, the absence of peer support for achievement undermines the positive influence of authoritative parenting.

Achievement↗

The relationship between phoneme discrimination, speech production, and language comprehension in cerebral-palsied individuals.

Twenty-four individuals with impaired speech (anarthria or dysarthria) were compared on tests of receptive language to a control group with normal speech. All subjects were cerebral-palsied and groups were matched on age and nonverbal ability. The speech-impaired subjects performed less well than controls on a phoneme discrimination task in which they were required to judge whether pairs of nonwords were the same or different. They were also impaired relative to controls on a receptive vocabulary test, but not in understanding of grammatical structure. One year later, phoneme discrimination skills were reassessed in this sample, using another same-different task, plus a new task in which subjects were required to judge if the name of a picture was spoken correctly or altered by one sound. Speech-impaired subjects performed as well as controls on the word judgment task, indicating that they can discriminate phoneme contrasts adequately. However, the same-different task again resulted in highly significant differences between speech-impaired and control groups. It is concluded that poor performance on the same-different task reflects weak memory for novel phonological strings, rather than impaired phoneme perception. It is proposed that retention of unfamiliar words is facilitated by overt or covert repetition, so individuals who cannot speak fluently have difficulty remembering nonwords. This explanation can account both for the poor performance of speech-impaired subjects on the same-different task, and for their selective deficit in vocabulary acquisition.

Adolescent↗

Peer-group affiliation and adolescent self-esteem: an integration of ego-identity and symbolic-interaction theories.

To evaluate expectations derived from ego-identity theory and symbolic-interaction theories about the association between self-concept and peer-group affiliations in adolescence, we examined the self-esteem of 221 7th through 12th graders associated by peers with one of five major school crowds and 106 students relatively unknown by classmates and not associated with any school crowd. Among crowd members, self-esteem was directly related to the position of one's crowd in the peer-group status hierarchy (based on both peer-rated and self-perceived crowd affiliation). Outsiders' self-esteem differed in relation to the accuracy of their reflected appraisal of and the salience they attached to crowd affiliation. Crowd members as a whole exhibited higher self-esteem than outsiders as a whole. Differences, however, were mediated by crowd status, salience of crowd affiliation, and the accuracy of reflected appraisals. An adequate interpretation of the findings required an integration of Festinger's (1954, 1957) social comparisons and cognitive-dissonance theories, Cooley's (1902) notions of reflected appraisal, and Newman and Newman's (1976) extrapolations from ego-identity theory.

Adolescent↗

The importance of peer group ("crowd") affiliation in adolescence.

Many researchers have speculated about the role peer groups play in adolescent development, but few have examined teenagers' own perspective on the importance of group affiliations. The two studies reported here, involving 1,300 7th to 12th graders in three Midwestern U.S. communities, assessed teenagers' valuation of belonging to a "crowd" as well as the reasons they cited to support or oppose crowd affiliation. The importance of crowd affiliation declined across age. Younger adolescents generally favored membership, emphasizing the crowd's ability to provide emotional or instrumental support, foster friendships and facilitate social interaction. Older respondents expressed dissatisfaction with the conformity demands of crowds and felt their established friendship networks obviated the need for peer group ties. The importance of crowd affiliation was not related to the strength of respondents' sense of identity but did vary significantly with their willingness to conform to peers and the centrality of their position in peer groups or the type of crowd to which they belonged. Findings emphasized that adolescent peer groups can serve multiple functions, whose salience shifts with age.

Adolescent↗

The analysis of malignancy by cell fusion. IX. Re-examination and clarification of the cytogenetic problem.

Previous experiments with crosses between malignant and diploid mouse cells had shown that the reappearance of malignancy in hybrids in which it was initially suppressed was associated in some cases with the elimination of the chromosomes 4 derived from the diploid parent cell. In others, however, this did not appear to be so. In the present study, we have re-examined the role of the diploid chromosomes 4 in the suppression of malignancy using natural polymorphisms of the centromeric heterochromatin to identify the parental origin of the chromosomes 4 in the hybrid cells. We now find that the diploid chromosomes 4 are indeed involved in the suppression of malignancy in all the tumours that we have examined, which include a carcinoma, a melanoma, a sarcoma and a lymphoma. In all crosses between these malignant tumour cells and diploid fibroblasts, there is selective pressure in vivo against the chromosomes 4 derived from the diploid cell and in favour of the chromosomes 4 derived from the malignant cell. This indicates that the chromosomes 4 in all these tumours are in some way functionally different from the chromosomes 4 of the diploid fibroblast. Reappearance of malignancy in hybrids in which it was initially suppressed may result from a reduction in the number of diploid chromosomes 4, an increase in the number of malignant chromosomes 4, or both. The gene on the diploid chromosome 4 responsible for the suppression of malignancy acts in a dose-dependent manner.

Animals↗

Meiosis in Sxr male mice: II. Further absence of cytological evidence for a Y-autosome rearrangement in sex-reversed (Sxr) mice.

If the sex-reversal factor (Sxr) in mice is represented by a segment of the Y chromosome translocated on to an autosome, this segment might be expected to show some evidence of attempted pairing with the normal Y chromosome at the first meiotic division. Our failure to find such evidence in a light microscope study of the silver-stained pachytene spermatocytes from Sxr/4, XY males further supports existing cytological information that the factor is more likely to be represented by an autosomal dominant gene mutation.

Animals↗

Social and psychological correlates of help-seeking behavior among urban adults.

Drawing from a longitudinal survey of 1,106 urban adults aged 20 to 70, the present study investigated whether persons who sought help from informal and/or formal support systems for major troublesome life changes were distinguishable from those who handled problems without assistance in terms of demographic background, personal resources, social networks, or psychological barriers to help-seeking. Generally, nonseekers who felt self-reliant and respondents who sought assistance from informal associates exclusively seemed well prepared to manage bothersome transitions, crises, or role-related strains. Nonseekers who were reluctant to ask for assistance as well as help-seekers who only contacted professionals were comparatively more at risk.

Adaptation, Psychological↗

Active enzyme gel chromatography: II. Computer simulations.

The behavior of an enzyme undergoing reaction while on a gel chromatography column has been studied by computer simulation using the steady state assumtion for a system with a single enzyme-substrate complex. The profiles of the enzyme-substrate complex, product, and substrate were examined varying the parameters of kcat, flow rate, partition coefficient dispersion, and time. These investigations confirm that much information about both the active enzyme and the product may be obtained by examining the product profile alone, varying the power of applying scanning gel chromatography to active enzyme systems.

Binding Sites↗