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Biomedical subjects

P Bennett

Publications and source records attributed to P Bennett.

At least 55 records · Page 3Linked to original sources

Growth control in the ontogenetic and regenerating zebrafish fin.

The growth and regeneration of the zebrafish fin provide yet another opportunity to exploit genetics to study important vertebrate problems. Mutants have been identified in zebrafish that affect the development of the embryonic fin, disrupt the normal growth relationship of fin and body, or disrupt the regeneration of the fin. Analysis of a regeneration mutation suggests that the developmental checkpoints that ensure developmental integrity in normal growth are absent in the early stages of regeneration. These stages correspond to the only time in fish developmental when differentiated bone cells divide.

Animals↗

Word learning in the context of referential and salience cues.

Adult referential behavior (gaze direction) and salience (target activation) were independently manipulated in a study of novel word learning. Children (seventy-five 18-month-olds and seventy-two 24-month-olds) were trained in different conditions with a novel word in the context of 2 remote-controlled toys. In response to the novel word at test, 24-month-olds tended to pick out the toy to which the adult referred in all conditions. They also tended to use the novel word appropriately. Comprehension by 18-month-olds was good when the salience of the toy did not conflict with the adult's referential intent, but it was disrupted when referential and salience cues conflicted and when referential cues were not available. Results imply that, at 24 months, children use the referential intent of the speaker to learn new words, but when first learning words, children may have a less secure grasp on the meaning of speakers' referential cues.

Age Factors↗

Reduced androgen levels in adult turner syndrome: influence of female sex steroids and growth hormone status.

BACKGROUND AND OBJECTIVES: In girls with Turner syndrome androgen levels are reduced. In order to assess androgen status in women with Turner syndrome, we compared untreated adult women with Turner syndrome with a group of normal women. In addition, the effects of female sex hormone replacement therapy and GH status on the levels of circulating androgens in Turner syndrome was examined. DESIGN: All patients were receiving female hormone replacement therapy (HRT), which was discontinued four months prior to the initial examination. Patients were studied before and during HRT. Following the initial evaluation, patients were given cyclical HRT for six months consisting of either oral substitution (17beta-oestradiol with norethisterone from day 13-22), or transdermal oestrogen substitution (17beta-oestradiol) with 1 mg norethisterone administered orally from day 13-22. Control subjects were studied once in the early follicular stage of the menstrual cycle. SUBJECTS: The study group consisted of 27 (33.2 +/- 7.9 years) patients with Turner syndrome and an age matched control group of 24 (32.7 +/- 7.6 years) normal women. MEASUREMENTS: Body composition measures, SHBG, testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), alpha-4-androstendione (A), dehydroepiandrosterone sulphate (DHEAS), 17beta-oestradiol (E2), oestrone (E1), oestrone sulphate (ES), 24 h integrated GH concentration (ICGH), insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein (IGFBP-3) were determined at baseline and after six months in women with Turner syndrome, and at baseline in control women. RESULTS: Circulating levels of A, T, FT, DHT, and SHBG were reduced by 25-40% in comparison with age matched normal women. The level of DHEAS was normal. The level of E2 was undetectable and levels of E1 and ES were very low in untreated Turner women. Treatment with 17beta-oestradiol and norethisterone increased oestrogen to levels comparable to those of normal women, while further decreasing FT (P = 0.02), DHT (P = 0.04), and T (P = 0.1). In untreated women with Turner syndrome IGF-I correlated significantly with DHEAS (R = 0.503, P < 0.01), while in normal women IGF-I correlated with A (R = 0.637, P < 0.01), T (R = 0.536, P < 0.01), and FT (R = 0.700, P < 0.01). During hormonal replacement in women with Turner syndrome IGF-I correlated significantly with DHEAS (R = 0.547, P < 0.01). Employing multiple regression analysis IGFBP-3, ICGH, DHEAS and fat free mass explained 85% (adjusted R = 0.92, P < 0.0005) of the variation in the level of IGF-I in untreated Turner syndrome. In treated Turners IGFBP-3, ICGH, SHBG, T, and FT explained 78% (adjusted R = 0.88, P < 0.0005). In controls IGFBP-3, SHBG, BMI and age explained 74% (adjusted R = 0.86, P < 0.0005) of the variation in IGF-I, while GH status did not contribute at all. CONCLUSION: The present study shows that many adults with Turner syndrome have reduced levels of circulating androgens, compared with an age-matched group of normal women. Conditions associated with Turner syndrome such as increased prevalence of sexual problems, reduced bone mineral content, osteoporosis, and an increased incidence of fractures and alterations in body composition could perhaps be alleviated or abolished by substitution with a low dose of androgens. Treatment with female hormonal replacement therapy is associated with a decrease in testosterone, free testosterone and dihydrotestosterone, possibly mediated by the androgenic effect of norethisterone. Furthermore significant differences in sex steroid levels, GH status and indices of body composition can be compatible with comparable levels of IGF-I in two very different groups of individuals.

Adult↗

Opinion of New Zealand physicians on management of acute ischaemic stroke: results of a national survey.

BACKGROUND: Randomised trials have evaluated various treatments for acute ischaemic stroke, but it is unclear how the results of these studies are used in everyday practice. AIMS: To obtain the opinions of physicians on the management of acute ischaemic stroke. METHODS: A questionnaire was sent to 368 New Zealand Fellows of the Royal Australasian College of Physicians. The survey included questions about the availability of hospital services for stroke patients, management of acute ischaemic stroke and opinion on the efficacy of treatments used in acute ischaemic stroke. RESULTS: Of the 293 physicians who responded to the questionnaire, 171 managed patients in the first week after stroke. Forty-seven per cent of these physicians were general physicians. Ninety-five per cent usually managed these patients in a general medical ward. Only five physicians admitted patients to an acute stroke unit and only 57% considered acute stroke units were beneficial. Aspirin was usually or sometimes used for patients with acute ischaemic stroke by 92% of physicians, intravenous heparin by 43%, low-dose subcutaneous heparin by 41%, low-molecular-weight heparin by 25% and tissue-plasminogen activator (t-PA) by 3%. Two thirds considered that aspirin was definitely beneficial, but most were uncertain about the efficacy of intravenous heparin, low-dose subcutaneous heparin, low-molecular-weight heparin and t-PA. Sixty-two per cent were prepared to begin aspirin and 21% subcutaneous heparin before computerised tomography (CT). Twenty-three per cent used anti-hypertensive treatment in the first few hours after an ischaemic stroke. CONCLUSIONS: Several common deficiencies in the management of acute ischaemic stroke were identified. The widespread lack of stroke units, use of aspirin and heparin before CT, and lowering of blood pressure after an acute ischaemic stroke differed from accepted guidelines. Many physicians used heparin despite lack of evidence from randomised trials that it is beneficial. The development of stroke units and the appointment of physicians with a special interest in the management of stroke may improve the management of patients with acute stroke.

Anticoagulants↗

Intrusive memories, post-traumatic stress disorder and myocardial infarction.

OBJECTIVES: To identify the associations between two personality variables (alexithymia, negative affect), social support, awareness of myocardial infarction, and the severity of post-traumatic stress symptoms. DESIGN: A cross sectional design was adopted with simultaneous measures of both dependent and independent variables. METHOD: A random sample of 69 patients who had an MI between 6 and 12 months previously were sent postal questionnaires measuring alexithymia, negative affect, social support, awareness of myocardial infarction, the severity of post-traumatic stress symptoms and a number of demographic details. RESULTS: Forty-four individuals completed and returned all the questionnaires. A 10% prevalence of post-traumatic stress symptoms was found. Regression analyses were conducted to identify independent associates of the dependent variables with and without the inclusion of the measure of negative affect. Alexithymia, age, social support and awareness at the time of having a myocardial infarction, were each strongly predictive of one or all measures of symptoms. CONCLUSIONS: Evidence supporting the impact of each of the variables on the course of post-traumatic stress disorder was supported in a population of myocardial infarction patients. If these variables were found predictive in a longitudinal study, they would indicate possible risk factors for post-traumatic stress disorder in this population.

Aged↗

Expression of cyclo-oxygenase types-1 and -2 in human fetal membranes throughout pregnancy.

Human labour is associated with increased prostaglandin synthesis within the fetal membranes. We have studied the expression of the two isoforms of the central prostaglandin synthetic enzyme, cyclo-oxygenase (COX-1 and COX-2), in human fetal membranes throughout pregnancy, at mRNA, protein and activity levels. COX-1 mRNA expression was low in human amnion and chorion-decidua and did not change with gestational age. COX-2 mRNA expression in fetal membranes increased with gestational age, with significant up-regulation prior to the onset of labour and in association with labour. Protein concentrations of COX-1 did not change, whilst concentrations of COX-2 increased from the first to the third trimester. COX activity increased with gestational age and in association with labour, although prostaglandin production in fetal membranes collected after labour was reduced, suggesting reduced substrate supply. These data suggest that it is up-regulation of COX-2, rather than of COX-1, which mediates increased prostaglandin synthesis within the fetal membranes at term. Much of the increase in COX-2 expression precedes the onset of labour, suggesting that it is a cause, rather than a consequence, of labour.

Amnion↗

A direct correlation between nicotinamide N-methyltransferase activity and protein levels in human liver cytosol.

Phenotypic differences in nicotinamide N-methyltransferase (NNMT, E. C. 2.1.1.1) activity may be due to a genetic polymorphism. We report the characterisation of the hepatic NNMT activity in cytosol from normal human livers, enzyme protein levels determined by Western blotting and ELISA and mRNA levels determined by SDS-PAGE/Northern blotting. Subjects with high NNMT activity had high levels of NNMT protein and NNMT mRNA levels in hepatic cytosol and the converse was true for individuals with low NNMT activity. No differences in sequences were seen when cDNAs of individuals with high and low NNMT activity were compared. Thus phenotypic differences in the general population are due to differences in steady-state mRNA levels and not because of a polymorphism in the coding region of the NNMT gene.

Adolescent↗

Expression of the insulin-like growth factors and their receptors in term placentas: a comparison between normal and IUGR births.

Intrauterine growth retardation (IUGR) is defined as growth retarded to be below the tenth centile. The insulin-like growth factors and their receptors are implicated in pre- and postnatal growth and development, and it is believed that alteration in their activity may contribute to IUGR. In this study nine normal and nine intrauterine growth retarded births were followed and term placentas examined for expression of the insulin-like growth factors and their receptors. It was found that the expression of insulin-like growth factor 1 (IGF1), insulin-like growth factor 2 (IGF2), and the insulin, IGF1 and IGF2 receptor transcripts (IGF1R and IGF2R, respectively) was present in all term placentas examined. Expression of insulin was not detected. Quantitative polymerase chain reaction (PCR) was used to compare transcription levels in term placentas from normal with IUGR births. There was no significant difference in the levels of transcripts for IGF1, insulin receptor, or IGF2R between normal and IUGR term placentas. However, the IUGR term placentas had significantly higher levels of IGF2 and IGF1R expression compared with the normal term placentas. The increase in the transcription of IGF2 and IGF1R in IUGR term placentas may represent a counter regulatory mechanism in response to the growth retardation.

Adult↗

Detection of fetal messenger ribonucleic acid in maternal blood to determine fetal RhD status as a strategy for noninvasive prenatal diagnosis.

OBJECTIVES: Our purpose was to test the hypothesis that reverse transcriptase-polymerase chain reaction for fetal messenger ribonucleic acid in maternal blood is more sensitive than polymerase chain reaction from genomic deoxyribonucleic acid in prenatal determination of fetal RhD blood type. STUDY DESIGN: Fetal nucleated erythrocytes in peripheral blood from 35 RhD-negative women were enriched by triple-density gradient centrifugation, anti-CD71 magnetic sorted, and deoxyribonucleic acid and ribonucleic acid extracted. Sensitivities of reverse transcriptase-polymerase chain reaction and polymerase chain reaction were compared to predict definitive fetal RhD blood type determined in fetal tissues. RESULTS: Reverse transcriptase-polymerase chain reaction was significantly more accurate (P = .03) than genomic-polymerase chain reaction in predicting fetal RhD blood type, both overall (28 of 35 vs 22 of 35) and when the fetus was RhD-positive (12 of 19 vs 6 of 19). CONCLUSIONS: Reverse transcriptase-polymerase chain reaction is more sensitive than genomic-polymerase chain reaction in detection of fetal RhD sequences in maternal blood.

Female↗

Absence of expression of RhD by human trophoblast cells.

OBJECTIVE: Our purpose was to determine whether the RhD gene is expressed in trophoblast at any stage of gestation. STUDY DESIGN: Trophoblast and fetal tissue were obtained from 18 pregnancies at 8 to 40 weeks' gestation. Deoxyribonucleic acid and ribonucleic acid were extracted from trophoblast. Complementary deoxyribonucleic acid was synthesized from ribonucleic acid, and reverse transcriptase-polymerase chain reaction was performed using primers specific for the RhD gene. Deoxyribonucleic acid was extracted from fetal tissue to determine the fetal RhD status by means of polymerase chain reaction. Antigen expression was also sought by analytic cytometric analysis (flow cytometry and immunocytochemistry) using a monoclonal anti-D antibody. RESULTS: Trophoblast was studied from various combinations of RhD-positive and RhD-negative fetuses (on deoxyribonucleic acid) from mothers to find no RhD gene expression in any sample. Flow cytometry and immunocytochemistry confirmed this by demonstrating no RhD antigen sites on trophoblast cells. CONCLUSION: Contrary to a previous report, we conclude that the RhD gene is not expressed in human trophoblast in any trimester.

DNA↗

Evidence for a chromosome 2p13-14 schizophrenia susceptibility locus in families from Palau, Micronesia.

A large multiplex schizophrenia pedigree ascertained from the Micronesian nation of Palau was genotyped with 406 microsatellite DNA markers evenly distributed throughout the genome. Assuming autosomal dominant inheritance, the highest genome-wide lod scores were found for DNA loci mapping to 2p13-14; the maximum lod score was 2.17 (theta = 0.05) at D2S441. A nonparametric APM analysis was also suggestive at D2S441 (APM score = 2.96, P = 0.011). Of the 14 affected cases in this extended family, eight share a large haplotype in this region spanning approximately 11 cM. When 16 other families containing 65 schizophrenic cases were typed in a follow-up study of this region, the maximum lod score remained positive (maximum at D2S441 1.69, theta = 0.20). APM results also remained positive at D2S441 for all 17 families (APM score = 4.87, P = 0.0006). The linkage and haplotype sharing results provide suggestive evidence for a 2p locus predisposing to schizophrenia in a subset of families in the Palauan population.

Adult↗

Understanding binge drinking among young people: an application of the Theory of Planned Behaviour.

Binge drinking (i.e. consuming half the recommended weekly consumption of alcohol in a single session) is a common activity among young people. Using the Theory of Planned Behaviour as its theoretical framework, this paper reports a study exploring the motivational and attitudinal factors underlying binge drinking in a sample of undergraduate students. Questionnaires were completed by 136 undergraduates which focused on their drinking behaviour and their beliefs about binge drinking. Binge drinking was found to be more prevalent among male respondents, and a number of significant differences in the beliefs of male and female respondents were found which supported this difference in drinking behaviour. A regression analysis identified two key predictors of the frequency of binge drinking; these being positive control beliefs and perceived behavioural control. Frequent binge drinkers were more likely to recognize the influence of a range of factors which may serve to encourage binge drinking (e.g. celebrating an event) and less likely to believe that the decision to engage in binge drinking is under their control. The results are discussed in relation to measures which may help to reduce the incidence of binge drinking through changes in the social environment.

Adolescent↗

Changes in the expression of the type-2 but not the type-1 cyclo-oxygenase enzyme in chorion-decidua with the onset of labour.

OBJECTIVE: To determine the relative expression of cyclo-oxygenase (COX)-1 and COX-2 in the chorion-decidual part of human fetal membranes following delivery at term and to identify any changes in expression associated with labour. METHODS: Fetal membranes were collected from 12 term pregnancies before labour following elective caesarean section and from 12 spontaneous vaginal deliveries. Expression of COX-1 and COX-2 mRNA was measured using a previously validated quantitative RT-PCR assay. RESULTS: COX-2 expression exceeded that of COX-1 by approximately eight-fold. COX-1 expression did not change but COX-2 expression was found to increase four-fold with labour. CONCLUSIONS: Chorion-decidua has the capacity to contribute to the increase in prostaglandin synthesis within the uterus associated with labour. As in the amnion, it is COX-2 and not COX-1 which is upregulated with labour. COX-2 selective anti-prostaglandins should therefore be as effective as nonselective drugs in inhibition of fetal membrane prostaglandin synthesis.

Cesarean Section↗