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Biomedical subjects

A Clark

Publications and source records attributed to A Clark.

At least 91 records · Page 5Linked to original sources
PubMed1999

Estimating European admixture in African Americans by using microsatellites and a microsatellite haplotype (CD4/Alu).

We have analyzed 10 unlinked microsatellites and a linked Alu deletion polymorphism at the CD4 locus in an African American population sample from Chicago (USA). Heterozygosity estimates at the microsatellite loci range from 0.727+/-0.025 (D3S1358) to 0.873+/-0.017 (D18S51), with an average of 0.794+/-0.016. These values are comparable to or higher than those reported for Europeans, with only one exception (D3S1358). The CD4/Alu haplotypic diversity (0.887+/-0.012) is comparable to diversity levels observed in sub-Saharan African populations and is higher than the diversity levels reported in European populations. No consistent pattern of within, between, or multi-locus deviations from Hardy-Weinberg expectations is observed, suggesting a low sub-heterogeneity within the sampled population. We have applied a maximum likelihood method and estimated the proportion of European admixture to the African American gene pool to be 0.26+/-0.02. The narrow confidence interval indicates that allele frequency data from multiple microsatellite loci, whether analyzed independently or as haplotypes, are particularly useful for estimating genetic admixture.

Black or African American↗
PubMed1999

Expression of the mouse Delta1 gene during organogenesis and fetal development.

Cell-to-cell communication mediated by the evolutionary conserved Notch signalling pathway regulates cell fate decisions and patterning in various tissues in diverse organisms (Artavanis-Tsakonas et al., 1995, Science 268, 225-232). Signalling between neighboring cells is transduced by binding of DSL and Notch proteins which interact as ligand (DSL) and receptor (Notch). Mouse Delta1 (delta-like 1; Dll1) encodes one of the four known mammalian DSL proteins and is essential for normal somitogenesis and neuronal differentiation. Here, we describe Delta1 expression during organogenesis and fetal development using the highly sensitive histochemical detection of the lacZ gene product expressed from a targeted Delta1:lacZ knock-in allele (Dll1(lacZ)). We find that Delta1 is expressed in epithelial ducts of several organs, skeletal and smooth muscles, the central nervous system, as well as some sensory epithelia.

Animals↗
PubMed1999

Insulin-like growth factor-I deficiency caused by a partial deletion of the IGF-I gene: effects of rhIGF-I therapy.

Insulin-like growth factor-I (IGF-I) is one of the most important regulator of growth. IGF-I deficiency is associated with prenatal and post-natal growth failure and may arise primarily as a result of GH receptor/post-receptor abnormalities or defects in the synthesis and transport of IGF-I. We have previously reported a 17.2-year-old boy with severe growth retardation and undetectable serum levels of IGF-I caused by a partial deletion of the IGF-I gene. This short review will concentrate on results of a recent study which examined the effects of rhIGF-I therapy on the GH-IGF system of this patient. Similar to healthy individuals, this patient had normal IGFBP-3 but elevated ALS levels. IGF-I treatment has improved linear growth and insulin sensitivity in this patient by restoring IGF-I levels and by normalizing circulating GH, IGFBPs and insulin levels.

Adolescent↗
PubMed1999

An embodied cognitive science?

The last ten years have seen an increasing interest, within cognitive science, in issues concerning the physical body, the local environment, and the complex interplay between neural systems and the wider world in which they function. Yet many unanswered questions remain, and the shape of a genuinely physically embodied, environmentally embedded science of the mind is still unclear. In this article I will raise a number of critical questions concerning the nature and scope of this approach, drawing a distinction between two kinds of appeal to embodiment: (1) 'Simple' cases, in which bodily and environmental properties merely constrain accounts that retain the focus on inner organization and processing; and (2) More radical appeals, in which attention to bodily and environmental features is meant to transform both the subject matter and the theoretical framework of cognitive science.

Journal Article↗
PubMed1999

Nurse education: a skill mix for the future.

The requirement to support students in the clinical environment during their preparation has recently been given renewed attention. Many practitioners, managers and students are concerned that preregistration nurses are emerging from nursing education programmes without essential clinical skills. The decision to discontinue the clinical teaching role was made against a background in which low priority was ascribed to the clinical teaching role by nurse teachers when compared with a classroom role. The last few years has also been marked by far-reaching and rapid change in the environment within which the education of nurses is carried out. Against the above background, this paper explores the changing nature of the role of nurse teachers in placement areas and outlines a variety of potential new models. These include: link teacher role, the clinical teacher role, the lecturer/practitioner role and Clinical Research Fellowships. The paper proposes a radical scenario and outlines a skill mix for the future for nurse education.

Clinical Competence↗
PubMed1999

The effects of B-sitosterol (BSS) and B-sitosterol glucoside (BSSG) mixture on selected immune parameters of marathon runners: inhibition of post marathon immune suppression and inflammation.

A pilot study was undertaken to investigate the effects of the intake of capsules containing the plant sterols and sterolins (BSS:BSSG mixture) on selected immune parameters of volunteers participating in an ultra-marathon in Cape Town, South Africa. Those runners having received active capsules (n=9) showed less neutrophilia, lymphopenia and leukocytosis when compared to their counterparts having received placebo capsules (n=8): the placebo treated individuals showed significant increases in their total white blood cell numbers as well as in their neutrophils (p=0.03 and 0.03 respectively). Furthermore, statistically significant increases within lymphocyte subsets were observed in the runners having received the active capsules: CD3+ cells increased (p=0.02) as did CD4+ cells (p=0.03). In parallel, the BSS:BSSG capsules decreased the plasma level of IL6 in the runners using the active capsules (p=0.08) and significantly decreased the cortisol: DHEAs ratio (p=0.03), suggesting that these volunteers had less of an inflammatory response and were less immune suppressed during the post-marathon recovery period. These findings justify further investigations into the use of the phytosterols to prevent the subtle immunosuppression associated with excessive physical stress.

Adult↗
PubMed1999

Formation of amyloid fibrils by peptides derived from the bacterial cold shock protein CspB.

Three peptides covering the sequence regions corresponding to the first two (CspB-1), the first three (CspB-2), and the last two (CspB-3) beta-strands of CspB, the major cold shock protein of Bacillus subtilis, have been synthesized and analyzed for their conformations in solution and for their precipitation behavior. The peptides are nearly insoluble in water, but highly soluble in aqueous solutions containing 50% acetonitrile (pH 4.0). Upon shifts of the solvent condition toward lower or higher acetonitrile concentrations, the peptides all form fibrils resembling those observed in amyloid associated diseases. These fibrils have been identified and characterized by electron microscopy, binding of the dye congo red, and X-ray fiber diffraction. Characterization of the peptides in solution by circular dichroism and NMR spectroscopy shows that the formation of these fibrils does not require specific preformed secondary structure in the solution state species. While the majority of the soluble fraction of each peptide is monomeric and unstructured, different types of structures including alpha-helical, beta-sheet, and random coil conformations are observed under conditions that eventually lead to fibril formation. We conclude that the absence of tertiary contacts under solution conditions where binding interactions between peptide units are still favorable is a crucial requirement for amyloid formation. Thus, fragmentation of a sequence, like partial chemical denaturation or mutation, can enhance the capacity of specific protein sequences to form such fibrils.

Amino Acid Sequence↗
PubMed1999

Assessment of chronic heart failure using gas exchange: which variable and when to correct for body mass.

We investigated whether correction for body mass is appropriate when using variables derived from gas exchange measurements in the assessment of chronic heart failure. Patients with heart failure were studied either on a bicycle ergometer (22 subjects) or on a treadmill (28 subjects). For bicycle exercise testing either peak V(O2) or peak V(CO2) uncorrected for body mass reflected exercise capacity. However, for treadmill exercise, body mass correction was necessary to relate exercise capacity to peak V(O2) or peak V(CO2). Mass correction is therefore appropriate for treadmill but not for bicycle exercise.

Body Mass Index↗
PubMed1999

Braincutting for psychiatrists: the time is ripe.

In the past two decades, neuroscientific investigations such as postmortem and neuroimaging studies have revealed a variety of regional brain disturbances in major mental illnesses. These emerging findings are difficult to appreciate fully without a sufficient grasp of the neuroanatomy of the regions identified in these studies. The authors have developed, for psychiatrists-in-training, a braincutting exercise designed to highlight the neuroanatomical features of specific regions; namely, regions with behavioral affiliations relevant to contemporary hypotheses about the brain bases of major mental disorders. The focus of the braincutting is markedly different from the traditional braincuttings that have been available to trainees in neurology, neurosurgery, and neuropathology. This article describes the authors' approach to braincutting and the behavioral neuroanatomy seminar of which it is a part.

Brain↗
PubMed1999

Localisation of presenilin 2 in human and rodent pancreatic islet beta-cells; Met239Val presenilin 2 variant is not associated with diabetes in man.

Mutations in presenilin 1 and 2 are causative factors for early onset familial Alzheimer's disease and possible roles for presenilins include protein trafficking, regulation of apoptosis and/or calcium homeostasis. Presenilin 2 mRNA is expressed in brain, muscle and pancreas but the role of pancreatic presenilin 2 and its relationship to diabetes are unknown. Presenilin 2 immunoreactivity was localised in human and rodent pancreas to islet cells and found in granules of beta-cells. Presenilin 2 was identified in primitive islet and duct cells of human foetal pancreas and in proliferating exocrine duct cells in human pancreatitis but not found in islet amyloid deposits in Type 2 diabetic subjects. Full length, approximately 50 kDa, and the approximately 30 kDa N-terminal fragment of presenilin 2 were identified by western blotting in extracted rodent pancreas but only the 30 kDa fragment was detected in mouse islets and human insulinoma. Post-mortem pancreatic morphology was normal in a subject with the presenilin 2 Met239Val variant and early onset familial Alzheimer's disease. Oral glucose tolerance tests on subjects with the presenilin 2 Met239Val mutation unaffected by early onset familial Alzheimer's disease (mean age 35 years) and on their first-degree relatives without the mutation demonstrated no evidence of glucose intolerance or increased proinsulin secretion. PS2 is a novel &bgr;-cell protein with potential roles in development or protein processing but pancreatic islet structure and function appear to be unaffected by the Met239Val mutation.

Adult↗
PubMed1999

Mutations of CTSK result in pycnodysostosis via a reduction in cathepsin K protein.

Pycnodyostosis, an autosomal recessive osteosclerosing skeletal disorder, has recently been shown to result from mutations in the cathepsin K gene. Cathepsin K, a lysosomal cysteine protease with an abundant expression in osteoclasts, has been implicated in osteoclast-mediated bone resorption and remodeling. DNA sequence analysis of the cathepsin K gene in a nonconsanguineous family demonstrated compound heterozygozity for mutations in two affected siblings. We have identified a missense mutation with a single base G-->A transition at cDNA nucleotide 236, resulting in conversion of a conserved glycine to a glutamine residue (G79E). The other mutation is an A-->T transition at nucleotide 154, leading to the substitution of a lysine residue by a STOP codon (K52X) predicting premature termination of the precursor cathepsin K polypeptide. Sequencing of genomic and cDNAs from the parents demonstrated that the missense mutation was inherited from the father and the nonsense mutation from the mother. Protein expression in both affected children was virtually absent, while in the parents was reduced by 50-80% compared with controls. The protein studies demonstrate that even significantly reduced cathepsin K levels do not have any phenotypic effect, whereas absent cathepsin K results in pycnodysostosis.

Cathepsin K↗
PubMed1999

On diagnosing rare disorders rarely: appropriate use of screening instruments.

The main aim of this study was to determine whether child mental health professionals who regularly use questionnaires to screen for mental disorders know that these questionnaires have a low predictive value when the base rate of a disorder is low. The study was based on a representative sample of professionals who used questionnaires regularly to screen for mental disorders. They were set a problem in which a clinic sample was screened with a questionnaire that, at a certain cut-point, had 80 % sensitivity and 80 % specificity, and in which the true base rate of disorder was 10%. Only 10% (5/48) of respondents answered correctly that just 30 % of individuals who scored above this cut-point would actually have the disorder and more than half of respondents believed that 80 % would have the disorder. Both users and designers of questionnaires need to be more aware of and explicit about their drawbacks as screens for mental disorders.

Child↗
PubMed1999

Measles, mumps, and rubella vaccine coverage in 2 year old children in East Lancashire--better than it looks.

A study population of 1850 children resident in East Lancashire born between 2 July and 1 October 1994 was obtained from local child health information systems (CHIS) and family health service (FHS) general practitioner registration data in March 1997 to determine the accuracy of reported measles, mumps, and rubella (MMR) vaccine coverage in 2 year old children registered with East Lancashire general practitioners. The reported MMR immunisation coverage was 89.7%, but the observed coverage was higher at 95.5% (95% confidence interval (CI) 93.9-97.3%). Small practices (3 Pounds GPs) achieved significantly higher MMR coverage (97.1%; 95% CI 95.8-98.0%) than large practices (93.5%; 95% CI 91.5-95.1%). Significantly higher MMR coverage was found in practices that used CHIS recall systems (96.2%; 95% CI 95.1-97.1%) than those using their own recall methods (91.2%; 95% CI 87.0-94.4%). Logistic regression showed that MMR vaccine coverage was independently predicted by practice size (odds ratio (OR) 2.5; 95% CI 1.5-4.0), recall method (OR 2.3; 95% CI 1.4-3.8), and relative deprivation (OR 1.7; 95% CI 1.0-2.6). Actual MMR coverage in 2 year old children in East Lancashire was significantly higher than reported, mainly because of inaccuracies in the CHIS database. Methods to improve the transfer of data on immunisation from practices to population databases should be explored.

Child Health Services↗
PubMed1998

Effect of smaller droplet size of dornase alfa on lung function in mild cystic fibrosis. Dornase Alfa Nebulizer Group.

Aerosolized recombinant human DNase (dornase alfa) reduces mucus viscoelasticity in vitro and improves pulmonary function in patients with cystic fibrosis (CF). We postulated that if dornase alfa could be delivered more peripherally to small airways in the lung in the form of smaller aerosol droplets in patients with early airway obstruction, the increase in pulmonary function from baseline might be improved. CF patients (n = 749) with mild lung disease (baseline forced vital capacity > or = 70% predicted) were randomly assigned to receive dornase alfa 2.5 mg daily for 2 weeks by one of two nebulizer systems: 1) the Medic-Aid Durable SideStream nebulizer powered by the MobilAire Compressor (SS/MA) producing a droplet size with a mass median aerodynamic diameter (MMAD) of 2.1 microm; or 2) the Hudson T Up-draft nebulizer with a DeVilbiss Pulmo-Aide compressor (HT/PA) with an MMAD of 4.9 microm. Spirometry was performed at baseline and following 14 days of treatment. Dornase alfa delivered by both nebulizer systems produced small but statistically significant improvements in pulmonary function compared with baseline. There was a trend (P = 0.06) toward greater improvement in forced expiratory flow in 1 s in the SS/MA group (4.3%) compared with the HT/PA group (2.5%). These results indicate that the short-term spirometric response to dornase alfa is influenced in part by the physical characteristics of the aerosol in patients with mild lung disease. We speculate that this may be true for other therapeutic aerosols, and it appears that localization of disease in the lung plays a role in the response to inhaled agents.

Adolescent↗
PubMed1998

Successful recovery of motility and fertility of cryopreserved cane toad (Bufo marinus) sperm

The recent decline and extinction of amphibian species is a worldwide phenomenon without an identified cause or solution. Assisted reproductive technologies, including sperm cryopreservation, are required to manage endangered amphibian species and preserve their genetic diversity. This study on the Anuran amphibian (Bufo marinus) was undertaken to determine the feasibility of cryopreservation of amphibian sperm. Sperm suspensions for cryopreservation were prepared by macerating testes in cryoprotective additives of 10% (w/v) sucrose or 10% (w/v) sucrose containing either 10, 15, or 20% (v/v) glycerol or 10, 15, or 20% (v/v) dimethyl sulfoxide (Me2SO). Suspensions were then cooled to -85 degreesC using a controlled rate cooler, stored in LN2, and thawed in air. The motility and fertilization rate of cryopreserved suspensions and unfrozen control suspensions in Simplified Amphibian Ringer were compared. Sucrose alone had no cryoprotective effect. All other treatments showed varying degrees of recovery of motility and fertilizing capacity. High rates of recovery of motility and fertilizing capacity were observed with 15% Me2SO (68.9 +/- 3.8 and 60.5 +/- 4.7%) and 20% glycerol (58.0 +/- 5.9 and 81.4 +/- 4.3%), respectively. Motility and fertilization rates were similar with Me2SO but diverged with glycerol as cryoprotectant. The data demonstrate the feasibility of using sperm cryopreservation with amphibian species. Copyright 1998 Academic Press.

Journal Article↗