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Biomedical subjects

S Mann

Publications and source records attributed to S Mann.

At least 55 records · Page 3Linked to original sources
PubMed2000

A novel mutation, Ala315Ser, in FGFR2: a gene-environment interaction leading to craniosynostosis?

Mutations in the fibroblast growth factor receptor 1, 2 and 3 (FGFR1, -2 and -3) and TWIST genes have been identified in several syndromic forms of craniosynostosis. There remains, however, a significant number of patients with non-syndromic craniosynostosis in whom no genetic cause can be identified. We describe a novel heterozygous mutation of FGFR2 (943G --> T, encoding the amino acid substitution Ala315Ser) in a girl with non-syndromic unicoronal craniosynostosis. The mutation is also present in her mother and her maternal grandfather who have mild facial asymmetry but do not have craniosynostosis. None of these individuals has the Crouzonoid appearance typically associated with FGFR2 mutations. However, the obstetric history revealed that the proband was in persistent breech presentation in utero and was delivered by Caesarean section, at which time compression of the skull was apparent. We propose that this particular FGFR2 mutation only confers a predisposition to craniosynostosis and that an additional environmental insult (in this case foetal head constraint associated with breech position) is necessary for craniosynostosis to occur. To our knowledge, this is the first report of an interaction between a weakly pathogenic mutation and intrauterine constraint, leading to craniosynostosis.

Alanine↗
PubMed2000

Predictors of post-hospital employment status for psychiatric patients in Hong Kong: from perceptions of rehabilitation professionals to empirical evidence.

Fifty participants with mental illness and a concrete discharge plan were selected from two mental hospitals in Hong Kong and assessed on their Psychosocial support by the Chinese Version of the Significant Others Scale, social vocational competence using the Workshop Behavior Checklist and the Vocational Social Skills Scale, medical history, work history, and demographic variables. At three months after discharge, the employed participants (n = 12) were shown to have better psychosocial support and social vocational competence than the unemployed participants (n = 24) by univariate comparison. The employed and unemployed participants did not differ in their medical and work history, and demographic variables. Implications of the results for rehabilitation programming are discussed.

Adolescent↗
PubMed2000

Effects of differing durations of antecedent hypoglycemia on counterregulatory responses to subsequent hypoglycemia in normal humans.

The aim of this study was to determine whether the duration of antecedent hypoglycemia regulates the magnitude of subsequent counterregulatory failure. A total of 31 lean healthy overnight-fasted individuals (16 men/15 women) were studied. There were 15 subjects (8 men/7 women) who underwent two separate 2-day randomized experiments separated by at least 2 months. On day 1, 2-h hyperinsulinemic (9 pmol x kg(-1) x min(-1)) euglycemic (5.2 +/- 0.1 mmol/l) or hypoglycemic (2.9 +/- 0.1 mmol/l) glucose clamps (prolonged hypoglycemia) were carried out in the morning and afternoon. Of the other subjects, 16 participated in a 2-day study in which day 1 consisted of morning and afternoon short-duration hypoglycemia experiments (hypoglycemic nadir of 2.9 +/- 0.1 mmol for 5 min), and 10 of these individuals underwent an additional 2-day study in which day 1 consisted of morning and afternoon intermediate-duration hypoglycemia (hypoglycemic nadir of 2.9 +/- 0.1 mmol for 30 min). The next morning (day 2) all subjects underwent an additional 2-h hyperinsulinemic-hypoglycemic clamp (2.9 +/- 0.1 mmol/l). The rate of fall of glucose (0.07 mmol/min) was carefully controlled during all hypoglycemic studies so that the glucose nadir was reached at 30 min. Despite equivalent day 2 plasma glucose and insulin levels, there were significant differences in counterregulatory physiological responses. Steady-state epinephrine, glucagon, growth hormone, cortisol, and pancreatic polypeptide levels were similarly significantly blunted (P < 0.01) by the differing duration day 1 hypoglycemia compared with day 1 euglycemia. Muscle sympathetic nerve activity and endogenous glucose production were also similarly blunted (P < 0.01) by day 1 hypoglycemia (relative to day 1 euglycemia). Day 2 hypoglycemic symptoms were significantly reduced (P < 0.01) after day 1 prolonged intermediate- but not short-duration hypoglycemia. In summary, two episodes of short-duration moderate hypoglycemia can produce significant blunting of key neuroendocrine and metabolic counterregulatory responses. Hypoglycemic symptom scores are reduced by prolonged but not short-duration prior hypoglycemia. We conclude that in healthy overnight fasted humans, 1) neuroendocrine, autonomic nervous system, and metabolic counterregulatory responses are sensitive to the blunting effects of even short-duration prior hypoglycemia, and 2) the duration of antecedent hypoglycemia results in a hierarchy of blunted physiological responses with hypoglycemic symptom awareness less vulnerable than neuroendocrine responses.

Adult↗
PubMed2000

Quality of nucleic acids extracted from fresh prostatic tissue obtained from TURP procedures.

PURPOSE: The molecular genetic study of benign prostatic hyperplasia (BPH) requires high quality nucleic acids from BPH tissue. It has been generally assumed, but not experimentally proven, that the diathermy used in trans-urethral resection of the prostate (TURP) damages nucleic acids. MATERIALS AND METHODS: Total RNA, polyA+ RNA and genomic DNA isolated from fresh tissue obtained from TURP procedures were compared with those isolated from tissue obtained from open prostatectomy. RESULTS: On a formaldehyde agarose gel, there was an increase in low molecular weight RNA in the TURP derived samples, in comparison to that in the open prostatectomy derived samples. The 28S and 18S rRNA were present in all TURP specimens and although the two bands were reduced in some samples, there were samples in which the 2 bands were indistinguishable from the open prostatectomy derived samples. Low molecular weight fragments seen in total RNA were reduced greatly in polyA+ RNA and the difference in polyA+ RNA between the TURP and open prostatectomy derived samples was significantly diminished. RT-PCR of two ubiquitously expressed gene transcripts (Galpha11, 256 bp and HPRT, 847 bp) yielded products of similar size and intensity between TURP and open prostatectomy derived samples. Genomic DNA obtained from TURP derived specimens showed no difference in size or enzyme digestibility in comparison to that from open prostatectomy. CONCLUSIONS: Nucleic acids extracted from fresh prostatic tissue derived from TURP procedures can be used as readily as any other fresh tissue for RT-PCR based molecular genetic studies, although polyA+ RNA isolation is recommended if degradation-free RNA is required.

DNA↗
PubMed1999

Synthesis and characterization of hydrophobic ferritin proteins

Alkylated derivatives of the iron storage protein, ferritin, have been prepared by carbodiimide-activated coupling of long chain (C9, C12, C14) primary amines to surface carboxylic acid residues. In the case of a nonyl-derivatized protein, alkylation results in covalent modification of approximately 400 of the 520 amino acid carboxyl groups in the protein molecule. The hydrophobic proteins have a net positive charge in water and can be transferred from THF/water mixtures into dichloromethane, ethyl acetate and toluene by addition of small amounts of NaCl. Transmission electron microscopy, analytical ultracentrifugation, and polyacrylamide gel electrophoresis indicate that the hydrophobic proteins dissolve in the organic solvents as structurally intact, non-aggregated macromolecules which can be subsequently back-extracted into water.

Journal Article↗
PubMed1999

Coccolith ultrastructure and biomineralisation

The relationship between calcite biomineralisation and coccolith ultrastructure is analysed across the diversity of calcifying haptophytes. The emphasis is on integration of evidence from crystallographic and ultrastructural studies but additional relevant information from biochemical and phylogenetic work is reviewed. We attempt to identify aspects of ultrastructure which are most likely to be the product of self-organising processes. The principal topics reviewed are heterococcolith rim nucleation, including reassessment of the V/R model; crystal growth regulation in heterococcoliths; holococcolith biomineralisation; and the diversity of other biomineralisation modes in haptophytes. It is concluded that the diverse range of calcareous structures produced by haptophytes probably has a common phylogenetic origin and is produced via operation of a limited set of mainly shared genetic and biochemical pathways. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Structure of a voltage-dependent K+ channel beta subunit.

The integral membrane subunits of many voltage-dependent potassium channels are associated with an additional protein known as the beta subunit. One function of beta subunits is to modify K+ channel gating. We have determined the structure of the conserved core of mammalian beta subunits by X-ray crystallography at 2.8 A resolution. Like the integral membrane component of K+ channels, beta subunits form a four-fold symmetric structure. Each subunit is an oxidoreductase enzyme complete with a nicotinamide co-factor in its active site. Several structural features of the enzyme active site, including its location with respect to the four-fold axis, imply that it may interact directly or indirectly with the K+ channel's voltage sensor. This structure suggests a mechanism for coupling membrane electrical excitability directly to chemistry of the cell.

Amino Acid Sequence↗
PubMed1999

Impaired apoptotic deletion of myelin basic protein-reactive T cells in patients with multiple sclerosis.

T cell responses to myelin basic protein (MBP) may play an important role in the pathogenesis of multiple sclerosis (MS). If MBP-reactive T cells are involved in the disease processes and undergo clonal activation and expansion, their precursor frequency would be increased in patients with MS. The frequency of MBP-reactive T cells is also influenced by regulatory mechanisms in vivo, including apoptotic deletion. In this study, we examined changes in the frequency of MBP-reactive T cells in patients with MS as a function of the apoptotic deletional mechanism in vivo, using a cell culture-based assay. A significantly increased frequency of MBP-reactive T cells was found in patients with MS relative to healthy individuals only when Fas-ligand antibody was used to block apoptosis. This result indicates that a significant proportion of MBP-reactive T cells are sensitive to apoptosis and are not deleted in vivo in patients with MS, as opposed to healthy individuals, thus suggesting a functional deficit in apoptotic deletional mechanism. Surviving Fas-sensitive MBP-reactive T cell lines represent distinct subpopulations preferentially recognizing the 111-139 region of MBP and exhibiting a Th2 cytokine profile. The findings are relevant to our understanding of regulation of MBP-reactive T cells in vivo in MS.

Antibodies, Monoclonal↗
PubMed1999

Rhetoric to practice: the challenge of collaboration of academe and industry.

Community health nursing is a complex practice that encompasses nurses working in many diverse settings. This article discusses the development of a project which focused on better preparation of students for potential employment in community settings. The formation of the working team and the development of the curriculum is outlined. A focus is given to the linking of primary health care principles in the teaching and facilitation of students within hospital and community settings. Comprehensive conclusions cannot be made yet from the project's preliminary findings. However, the process of collaboration has demonstrated several issues. These will have an impact on everyone who has been part of this project, and the issues are discussed in this article. The article provides an overview of the first year of collaboration of a 4-year project.

Community Health Nursing↗