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Biomedical subjects

P Bennett

Publications and source records attributed to P Bennett.

At least 91 records · Page 5Linked to original sources
PubMed1996

Post traumatic stress disorder.

Post traumatic stress disorder (PTSD) occurs after a person has been exposed to a traumatic event involving actual or threatened death, and has responded with intense fear or helplessness. The event is then persistently re-experienced. The person avoids stimuli associated with the trauma and experiences a numbing of general responsiveness. Symptoms of increased arousal can occur as well as depression and anxiety. PTSD causes clinically significant distress or impairment in social, occupational, or other important areas of functioning. The general practitioner is uniquely placed to identify PTSD and can have a key role in treatment. Cognitive behavioural treatment is a central therapeutic approach and can be carried out in general practice. The issues are to counteract the physiological components, expose the patient to the feared situation and help the patient to relearn that the stimuli are not necessarily associated with danger or threat. Repeated brief consultations over time can facilitate this process.

Antidepressive Agents↗
PubMed1995

WT1 suppresses synthesis of the epidermal growth factor receptor and induces apoptosis.

The Wilms tumor suppressor gene WT1 encodes a developmentally regulated transcription factor that is mutated in a subset of embryonal tumors. To test its functional properties, we developed osteosarcoma cell lines expressing WT1 under an inducible tetracycline-regulated promoter. Induction of WT1 resulted in programmed cell death. This effect, which was differentially mediated by the alternative splicing variants of WT1, was independent of p53. WT1-mediated apoptosis was associated with reduced synthesis of the epidermal growth factor receptor (EGFR), but not of other postulated WT1-target genes, and it was abrogated by constitutive expression of EGFR. WT1 repressed transcription from the EGFR promoter, binding to two TC-rich repeat sequences. In the developing kidney, EGFR expression in renal precursor cells declined with the onset of WT1 expression. Repression of EGFR and induction of apoptosis by mechanism that may contribute to its critical role in normal kidney development and to the immortalization of tumor cells with inactivated WT1 alleles.

Alternative Splicing↗
PubMed1995

The WT1 gene product stabilizes p53 and inhibits p53-mediated apoptosis.

The Wilms' tumor-suppressor gene product WT1 coimmunoprecipitates with p53 from baby rat kidney (BRK) cells and Wilms' tumor specimens, and expression of WT1 in BRK cells is associated with increased levels of endogenous wild-type p53 protein. To study the effect of WT1 on p53 function, we cotransfected expression constructs into Saos-2 cells, an osteosarcoma cell line without endogenous expression of either gene. Expression of WT1 resulted in increased steady-state levels of p53, attributable to a prolongation in protein half-life, and associated with protection against papillomavirus E6-mediated degradation of p53. This effect mapped to zinc fingers 1 and 2 of WT1 and was not observed with the closely related EGR1 protein. The stabilized p53 demonstrated enhanced binding to its target DNA sequence and increased trans-activation of a promoter containing this RGC site, but reduced transcriptional repression of a TATA-containing promoter lacking this site. Expression of WT1 inhibited p53-mediated apoptosis triggered by UV irradiation or by expression of temperature-sensitive p53 in the wild-type conformation, but did not affect p53-mediated cell cycle arrest. We conclude that WT1 protein can stabilize p53, modulate its trans-activational properties, and inhibit its ability to induce apoptosis. This effect may contribute to the elevated levels of wild-type p53 protein that are observed in Wilms' tumors.

Animals↗
PubMed1995

Molecular analysis of the expression of transthyretin in intestine and liver from trisomy 18 fetuses.

Human trisomy 18 (Edwards syndrome) provides a model for the role that genes on chromosome 18 play in fetal development. Trisomy 18 occurs in approximately 1 in 3000 live births. Despite its compatibility with life in 5% of cases, prolonged survival is rare. Anomalies involve the urogenital, cardiac, craniofacial and central nervous systems. The abnormalities could be caused by the abnormal expression of developmentally important genes on chromosome 18. We have investigated the quantity and localisation of the expression of a candidate gene, transthyretin (TTR), on chromosome 18 at the RNA level in intestine and liver tissues from trisomic fetuses and have compared the expression with normal age-matched fetal tissues. The mRNA level of TTR in 10 to 14-week intestine was the same in trisomy 18 and control tissues. However, overexpression was seen for both trisomy 18 liver and intestine at 20-23 weeks. TTR transports both thyroxine and retinol and is therefore important for normal fetal development.

Adult↗
PubMed1995

Psychology, health promotion and aesthemiology. Paper one: Social cognition models as a framework for health promotion: necessary, but not sufficient.

Much of health promotion is premised on the notion that health-related behaviours are under individual control, and strongly influenced by intra-psychic factors, including knowledge and attitudes. The emphasis placed on such factors has led to a neglect of the social and material context in which the individual is situated. This paper describes a number of psychological theories which have influenced health promotion, and suggests ways in which a wider set of psychological theories and methods, which take into account social and material factors, may more usefully inform health promotion initiatives.

Cognition↗
PubMed1995

Ovarian carcinoma serum markers and ovarian steroid activity--is there a link in ovarian cancer? A correlation of inhibin, tetranectin and CA-125 to ovarian activity and the gonadotropin levels.

In a previous study, we have demonstrated that inhibin-production may be associated with improved survival and, also, that tetranectin (TN) is a valuable prognostic marker in ovarian epithelial cancer. We investigated the possible correlation between inhibin, tetranectin, CA-125, ovarian steroid activity and the gonadotropin levels. Preoperative serum levels of the tumor markers inhibin, tetranectin (TN) and CA-125 were measured and related to ovarian steroid function and the pituitary-gonadal axis (gonadotropin levels) in 28 postmenopausal ovarian cancer patients. The following median levels and 95% confidence limits were demonstrated for the tumor markers: Inhibin 0.4 U/l (0.2-0.9), TN 8.9 mg/l (6.8-9.2), CA-125 160 kU/l (75-687). A significant inverse correlation was demonstrated between inhibin and the gonadotropins. The Spearman correlation coefficients showed a highly significant correlation of inhibin with the examined ovarian steroid hormones except DHEAS which also has a suprarenal component. This indicates a synthesis of inhibin and the steroid hormones from the same cell compartment as known from the normal ovary and an apparently intact negative feed back mechanism. Inhibin may be produced in the normal ovary as a defense mechanism against an elevated gonadotropin level and inhibin acts by lowering the gonadotropins or by altering their biological activity. Elevated values of the tumor markers TN and CA-125 due to gonadotropin stimulation could not be demonstrated but a significant inverse correlation between TN and CA-125 was confirmed.

Adenocarcinoma↗
PubMed1995

The impairment of long-term memory formation by the phosphatase inhibitor okadaic acid.

While there is considerable evidence that protein kinase activity is involved in memory formation, there has been, as yet, no direct investigation of a role for protein phosphatases. However, phosphatases have been implicated in the effects of the activation of glutamate receptors of the NMDA type, in long-term depression, and in the regulation of transmitter release and membrane ion channel activities, phenomena which have been shown to be possibly involved in cellular memorial processes. In the present paper, inhibition of protein phosphatase by 0.5 nM okadaic acid, a selective inhibitor of phosphatases 1 and 2A, is demonstrated to prevent memory consolidation in day-old chicks trained on a single trial passive avoidance task. Retention losses first occurred after 30 min post-learning, at an intermediate stage of memory formation preceding a protein synthesis-dependent long-term stage. It is suggested that protein phosphatase activity is involved in precursor processes to long-term memory consolidation.

Animals↗
PubMed1995

GcvA, a LysR-type transcriptional regulator protein, activates expression of the cloned Citrobacter freundii ampC beta-lactamase gene in Escherichia coli: cross-talk between DNA-binding proteins.

Escherichia coli JRG582 is an ampD ampE deletion derivative of strain HfrH and accordingly it is derepressed for expression of the cloned inducible beta-lactamase gene of Citrobacter freundii, carried on plasmid pNU305. Following chemical mutagenesis of JRG582(pNU305) a cefotaxime sensitive mutant was isolated, CS51(pNU305), which produced low levels of beta-lactamase due to a mutation in the host chromosome. Two recombinant plasmids containing genomic DNA from E. coli HfrH, namely pUB5608 and pUB5611, were isolated as a consequence of their ability to restore the beta-lactam resistant phenotype to CS51(pNU305). This ability was due to direct transcriptional activation of the beta-lactamase gene, ampC, rather than complementation of the CS51 mutation. Transposon mutagenesis and subcloning showed that restoration of ampicillin resistance to CS51(pNU305) was the function of a single gene, which maps at 60.3 min on the E. coli chromosome. The gene encodes a 33 kDa protein with significant homology to members of the LysR family of bacterial activator proteins, in particular the AmpR protein from C. freundii. Homology is especially strong over the N-terminal region which includes the helix-turn-helix DNA-binding motif. This gene was shown to complement the gcvA1 mutation at 60.3 min on the E. coli chromosome, and the DNA sequence agrees exactly with the published sequence of gcvA which encodes the transcriptional activator of the inducible glycine cleavage enzyme system. It is suggested that GcvA can activate transcription of ampC by binding to the AmpR binding region upstream of ampC so as to mimic the activated state of AmpR and hence provides an example of cross-talk between DNA-binding proteins of different inducible enzyme systems.

Amino Acid Sequence↗
PubMed1995

Why university?

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Attitude of Health Personnel↗
PubMed1995

Prognostic markers for diet-induced weight loss in obese women.

OBJECTIVE: To identify prognostic metabolic and hormonal markers for long-term weight loss outcome in obese women. DESIGN: Dietary intervention consisting of 36 weeks treatment by a 4.2 MJ/d low-fat high carbohydrate diet, and follow-up 2 1/2 years after termination of treatment. SETTING: Outpatient clinic in Copenhagen. SUBJECTS: Forty consecutive female obese patients aged 15 to 62 years. MAIN OUTCOME MEASURE: Weight loss. RESULTS: The maximum weight loss (mean 16.2 kg, 95% CI 14.2-18.2) was positively associated to pre-treatment 24-h energy expenditure (P < 0.01), fat oxidation (%) (P < 0.02), plasma dihydrotestosterone (DHT) (P < 0.01), and to postprandial noradrenaline concentration (P < 0.04). Together these factors could explain 41% of the variation in maximum weight loss. Only 24-h EE and DHT had predictive power on weight loss after 36 weeks. Weight losses in upper and lower tertiles of DHT concentrations were 17.7 kg (14.1-21.4) and 9.8 kg (6.2-13.3) (P < 0.02). The adjusted relative risk of losing < 10 kg in the upper compared to the lower DHT tertile was 12% (4-32%). At 2 1/2 y follow-up 21 patients had maintained some of the weight loss (54%), while 14 patients had maintained > 5 kg weight loss (36%). High levels of pre-treatment DHT were also associated with better weight loss at 2 1/2 y follow-up. CONCLUSION: The study suggests that in particular DHT, but also 24-h EE, fat oxidation, and plasma noradrenaline, may be prognostic markers for weight loss outcome in obese women.

Adolescent↗
PubMed1995

Pre-eclampsia. IV: The midwife's role after diagnosis.

Once a woman with pre-eclampsia has been referred for obstetric care, the midwife's role is to: Provide continuity of midwifery care. Advise the woman and her partner on what to expect, without frightening them. Interpret the doctor's information where necessary. Arrange a visit to the special care baby unit if appropriate. Monitor both the woman and the fetus and act on any signs that show a deterioration in their condition.

Female↗
PubMed1994

Implication of mRNA binding proteins in the regulation of cyclo-oxygenase in human amnion at term.

The onset of labour is associated with an increase in prostaglandin synthesis in amnion which appears to be mediated at least in part by an increase in cyclo-oxygenase (COX) expression. We have tested the hypothesis that COX expression is controlled in amnion by the binding of a protein to the COX mRNA which may inhibits its translation, as has been seen in vascular smooth muscle cells. Using differential RNA extraction protocols which extract either total mRNA or only mRNA which is not protein bound, we have found that, in amnion, the increase in COX-2 expression seen after the onset of labour is entirely in the protein bound fraction. Unlike in vascular smooth muscle, increased expression of COX-2 in amnion cells is therefore associated with increased rather than decreased protein binding to the mRNA. This protein may be involved in translation initiation or elongation or in mRNA stability. There does not appear to be a protein bound COX-1 mRNA fraction.

Amnion↗
PubMed1994

Methods for the analysis of the new vinca alkaloid derivative, S 12363, in plasma by high-performance liquid chromatography with fluorescence detection.

Two sensitive analytical methods for the analysis of S 12363 in plasma are described. A highly sensitive procedure for human and dog plasma using cyanopropyl solid-phase extraction with ion pairing chromatography and fluorescence detection, has a limit of quantification of 0.1 ng ml-1. The technique has an overall precision and accuracy of 4.8 and 5.4% respectively over the concentration range 0.1-20 ng ml-1. A second, less sensitive, assay specifically adapted for rodent plasma, uses benzene sulphonyl cation-exchange solid-phase extraction followed by reversed-phase chromatography, with post-column fluorescence enhancement. This method has a limit of quantitation of 1.0 ng ml-1, with overall accuracy and precision of 7.2 and 11.6% respectively, over the concentration range 1.0-20.0 ng ml-1. Both assays have been successfully applied to dog and mouse toxicokinetic studies.

Animals↗
PubMed1994

An SH3 domain and proline-rich sequence mediate an interaction between two components of the phagocyte NADPH oxidase complex.

Neutrophils possess a multicomponent NADPH oxidase system capable of producing large quantities of superoxide in a process known as the respiratory burst (1). Upon stimulation of a phagocytic cell, two cytosolic components of the oxidase, p67phox and p47phox, associate with a membrane-bound flavocytochrome b and a small GTP-binding protein to form a functional enzyme complex. Each of the Phox proteins contains two src homology 3 (SH3) domains, which are of unknown function but are potential mediators of protein-protein interactions between components of the activated oxidase. We have isolated a 47-kDa protein from lysates of differentiated HL60 cells that specifically bound to the carboxyl-terminal SH3 domain of p67phox and not to any other SH3 domain tested. This protein was identified as p47phox, and the putative SH3 domain binding site was located to a carboxyl-terminal proline-rich region. Proline-rich synthetic peptides based on this carboxyl-terminal region specifically inhibited the binding of p47phox to the carboxyl-terminal SH3 domain of p67phox, and sequential truncation defined a unique minimal sequence, which, although similar, does not match the consensus sequence defined for other SH3-binding proteins.

Amino Acid Sequence↗