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Biomedical subjects

M White

Publications and source records attributed to M White.

At least 217 records · Page 12Linked to original sources
PubMed1995

Adapter function of protein-tyrosine phosphatase 1D in insulin receptor/insulin receptor substrate-1 interaction.

Insulin signal transduction involves the multisite docking protein insulin receptor substrate-1 (IRS-1) and a number of Src homology-2 (SH2) domain factors, including p85/p110 phosphatidylinositol 3-kinase, p110 GTPase-activating protein, and the phosphotyrosine-specific phosphatase PTP1D. In transfected baby hamster kidney cells, Rat1 fibroblasts, and normal IM9 lymphoblasts, PTP1D directly binds activated insulin receptor. This interaction is mediated by catalytic domain-proximal SH2 determinants of the phosphatase and phosphotyrosine 1146 of the activated insulin receptor. While the receptor and the phosphatase do not serve as substrates for each other, their interaction promotes IRS-1 binding to the receptor, indicating that PTP1D functions as an adapter for insulin receptor and IRS-1. The formation of a multiprotein signaling complex involving the insulin receptor, PTP1D, and IRS-1 enhances cellular glucose uptake, a critical process in the physiological action of insulin.

Amino Acid Sequence↗
PubMed1995

Right to choose.

Explore the source record for details and available documents.

Abortion, Legal↗
PubMed1995

The electronic medical-student exchange: a low-cost alternative to overseas electives.

The authors report on an international collaboration that uses the Internet for medical education. In addition to introducing the students to electronic communication, the project aims to further international collaboration and understanding and to emphasize the importance of a population perspective for health and disease. Students and professors in Canada, England and Hungary participated.

Canada↗
PubMed1995

Cardiac beta-adrenergic neuroeffector systems in acute myocardial dysfunction related to brain injury. Evidence for catecholamine-mediated myocardial damage.

BACKGROUND: Ten percent to 20% of potential cardiac donors with brain injury and no previous cardiac history have myocardial dysfunction. We assessed components of the beta-receptor-G-protein-adenylyl cyclase complex as well as the contractile response in 10 explanted acutely failing human hearts (donor heart dysfunction [DHD]) and compared the results with 13 age-matched nonfailing (NF) organ donor controls. METHODS AND RESULTS: As measured by echocardiography, all DHD hearts exhibited a decreased shortening fraction (16 +/- 2%, mean +/- SEM). Although total and subpopulation beta-receptor densities measured by [125I]iodocyanopindolol (ICYP) were similar in the DHD and NF groups, DHD hearts exhibited a 30% decrease in maximum isoproterenol-stimulated adenylyl cyclase activity and a 50% decrease in the maximal response to zinterol. DHD hearts also exhibited decreases in adenylyl cyclase maximal stimulation by forskolin (211 +/- 25 [DHD] versus 295 +/- 23 [NF] pmol cAMP.min-1.mg-1, P < .05) and 5'-guanylylimidodiphosphate (12.5 +/- 1.8 [DHD] versus 19.6 +/- 3.2 [NF] pmol cAMP.min-1.mg-1, P < .05), but there was no significant decrease in adenylyl cyclase stimulation by Mn2+, a direct activator of adenylyl cyclase. Right ventricular trabeculae removed from DHD hearts exhibited a profound decrease in the contractile response to isoproterenol (8.7 +/- 1 [DHD] versus 22 +/- 2 [NF] mN, P < .001) as well as reduced calcium responses (7.2 +/- 1.6 [DHD] versus 14 +/- 3 [NF] mN, P = .03). Morphological examination of two hearts revealed some ultrastructural evidence suggestive of catecholamine-mediated injury, but there was no difference in tissue creatine kinase activity between the two groups. CONCLUSIONS: Compared with NF hearts, DHD hearts exhibit marked uncoupling of beta 1- and beta 2-adrenergic receptors from adenylyl cyclase and contractile response stimulation as well as decreased intrinsic systolic function. Thus, acute myocardial dysfunction accompanying brain injury is characterized by marked alterations in beta-adrenergic signal transduction as well as changes in the contractile apparatus, and this profile is markedly different from what occurs in the chronically failing human heart.

Adenylyl Cyclases↗
PubMed1995

Bacterial production and characterization of ATP11, a yeast protein required for mitochondrial F1-ATPase assembly.

ATP11 is a nuclear gene product that is required for assembly of mitochondrial F1-ATPase in the yeast Saccharomyces cerevisiae. ATP11 is synthesized in the yeast cytoplasm with an N-terminal targeting sequence. Following import into mitochondria, the leader sequence is cleaved, generating the functional form of the protein. ATP11 is present in small amounts in yeast mitochondria, which has made it difficult to study its role in F1 assembly. We have developed a bacterial expression system for the overproduction of the mature form of ATP11 and its biotinated derivative, BTATP11. Yeast complementation assays showed that the DNA fragments used to produce ATP11 and BTATP11 in bacteria encode biologically active proteins. The recombinant proteins produced in bacteria were purified to homogeneity and their physical characteristics were shown to be similar to those of the mitochondrial ATP11 protein synthesized in yeast.

Base Sequence↗
PubMed1995

Pathologic human vitreous promotes contraction by fibroblasts. Implications for proliferative vitreoretinopathy.

OBJECTIVE: To establish and quantify the presence of contraction-stimulating activity in pathologic vitreous and correlate this activity with clinical presentation and outcome, especially with proliferative vitreoretinopathy. METHODS: Contraction-stimulating activity of vitreous collected during surgery was quantified with a tissue culture assay using fibroblasts as target cells. The activity of each sample was correlated with patient history, clinical presentation, risk factors, proliferative disease, and postoperative proliferation. RESULTS: Pathologic vitreous contained measurable quantities of contraction-stimulating activity and stimulated contraction in vitro, with elevated activities in samples from patients with proliferative vitreoretinopathy, epimacular proliferation, retinal detachment, retinal defects, pigmented cells in the vitreous, hemorrhage, or uveitis. Patients with postoperative proliferation had significantly elevated mean activities. CONCLUSIONS: Levels of contraction-stimulating activity in pathologic vitreous correlate with some risk factors for the development of proliferative vitreoretinopathy and may ultimately be useful in the assessment of disease severity and the prediction of postoperative proliferation.

Adolescent↗
PubMed1995

Cross-hybridization of the chromosome 13/21 alpha satellite DNA probe to chromosome 22 in the prenatal screening of common chromosomal aneuploidies by FISH.

In a routine application of commercially available centromeric DNA probes for the prenatal screening of common trisomies involving the autosomes 13, 18, and 21, and sex chromosomes, four cases of discrepancy between fluorescence in situ hybridization (FISH) results and follow-up cytogenetic analysis were observed from a total of 516 cases of amniocentesis. In three of these cases, the results were false negative, and in one false positive. In this case, amniocentesis was performed because of a positive triple test in a 34-year-old woman with previous infertility treatment. The alpha satellite DNA probe for chromosomes 13/21 revealed five signals in 50 per cent of uncultured amniocytes, while standard cytogenetic analysis showed a normal karyotype. FISH analysis on metaphase chromosomes demonstrated the location of the additional signal in the centromeric region of chromosome 22. This additional signal was also present in the centromeric region of chromosome 22 of the mother, providing evidence for a possible inherited polymorphism in chromosome 22 responsible for unspecific hybridization with the alpha satellite probe for chromosomes 13/21 in this case. The observed polymorphism in centromeric regions may contribute to unreliability of the use of the 13/21 alpha satellite probe for prenatal screening by FISH.

Adult↗
PubMed1995

Antithymocyte globulin and methotrexate therapy of severe or persistent cardiac allograft rejection.

BACKGROUND: The treatment of severe or persistent acute rejection remains difficult despite newer immunosuppressive agents available. METHODS: To evaluate the effectiveness of rabbit antithymocyte globulin and methotrexate as therapy for severe or persistent acute cardiac allograft rejection, we conducted a retrospective analysis of clinical and laboratory data from 150 consecutive heart transplant recipients between 1983 and 1994. RESULTS: Thirteen episodes of severe or refractory acute rejection were treated with rabbit antithymocyte globulin in 10 patients. Rabbit antithymocyte globulin (125 mg/day for 3 consecutive days) was effective in 90% of patients. Therapy was well tolerated, and contributed to one infectious complication, no malignancy, and long-term survival in 8 of 10 patients. Recurrent rejection developed in 60% of patients. Methotrexate (7.5 to 15 mg/wk for 16 weeks) was administered to 8 patients with persistent rejection documented on three consecutive endomyocardial biopsies. Therapy was effective in 6 of the 8 patients, with one infectious complication and no malignancy on follow-up. White blood cell count decreased significantly during therapy (p = 0.008). Seven of the 8 patients in the methotrexate group are long-term survivors. CONCLUSIONS: Rabbit antithymocyte globulin is a valuable alternative in patients with severe or refractory acute rejection. Methotrexate is an important adjunct in patients with persistent rejection unresponsive to conventional immunosuppressive regimens.

Adult↗
PubMed1995

Flow cytometric crossmatching in renal transplantation--the long-term outcome.

The association of a positive flow cytometric crossmatch between recipient IgG directed against donor T lymphocytes and poor outcome is well described in renal transplantation. Until now no long-term follow-up on such patients has been available. In this study, 117 renal transplant patients were followed up for a period of 5 years. Of these 21 were known to have donor T cell directed IgG and five had B lymphocyte directed IgG. Both groups of patients with these antibodies had a significantly poorer outcome at 5 years than did the group of patients without IgG (p < 0.0001, Handel Maenzel test). Patients with antibody detected preoperatively were tested again either at the time of graft failure or at 5 years post-transplantation. The sera were tested against stored donor cells and the intensity of surface IgG compared with the preoperative levels. In those recipients who lost their grafts the levels increased in 60% of cases, but those who retained their grafts also had an increase in levels of donor directed antibody in 50% of cases. The changing levels of antibody therefore appeared to have little relevance to outcome. However when IgG isotypes were considered, in those who experienced graft failure and also had a gamma 3 isotype, a rise in IgG was demonstrated in all cases. Conversely, successful grafts with gamma 3 had a decline in levels between preoperative and 5-year samples in three of the four cases (not significant).

Flow Cytometry↗
PubMed1995

Living on the margin: a salutogenic model for socio-economic differentials in health.

Research into health inequalities shows that socio-economic position (SEP) is strongly associated with differentials in health. Yet at present there is no adequate model to explain the causal link between the social and the biological variables: in particular why the association between SEP and health is found in all societies; and why inequalities are not simply a reflection of poverty causing sickness, but are also seen among the wealthiest classes in the wealthiest societies. In this paper we propose a model which brings together many diverse strands of research, and helps to explain how stratification by socio-economic position may be seen in terms of differentials in the margin of resources. Resource differentials lead to stratified health outcomes owing to the differential capacity of individuals and groups to realise 'universal' psychological aspirations of a broadly 'health promoting' nature. The margin model builds upon a previously described salutogenic theory of health. On average, the relative size of the margin will predict differential health outcome. This prediction is empirically testable and opens up a new agenda for research on health differentials; it also provides a framework for understanding, planning and evaluating health promotion.

Health Policy↗
PubMed1995

Unattended words need to be primed to be recognized.

The categorical relation between a target word and a flanking, to-be-ignored, nontarget word can influence target response. Although usually taken as evidence of a full and automatic analysis of stimuli whether or not they have been attended, this flanker effect may only point to the failure of focused attention when nontarget stimuli have been primed and made task-relevant. The present study examined the role of priming in the flanker task. In one condition, schematic and semantic priming of nontargets was potentiated by having subjects categorize the target as an instance of a living or nonliving thing. In a second condition, priming was minimized by requiring only a shallow analysis of the target for a response; subjects searched the target for the presence of the letter R. A flanker effect was found only in the categorization condition, and then only when the target was the name of an animal. There was no evidence that unattended nontargets had been fully and automatically encoded to a semantic level.

Attention↗
PubMed1995

Severe controlled cortical impact in rats: assessment of cerebral edema, blood flow, and contusion volume.

Controlled cortical impact (CCI) is a contemporary model of experimental cerebral contusion. We examined the cerebrovascular and neuropathologic effects of a severe CCI in rats. The utility of magnetic resonance imaging (MRI) for the assessment of contusion volume after severe CCI was also established. Severe CCI (3.0 mm depth, 4 m/sec velocity) to the left (L) parietal cortex was produced in anesthetized (isoflurane/N2O/O2), intubated, and mechanically ventilated male Sprague-Dawley rats (n = 58). Physiologic parameters were controlled. The time course of alterations in edema [L-R% brain water (% BW) in 3-mm coronal sections through injured and contralateral hemispheres, wet-dry weight] was evaluated at 2 h, 24 h, 48 h, and 7 days posttrauma. Local cerebral blood flow (ICBF, measured in 8 structures in each hemisphere by autoradiography) was evaluated at 2 h, 24 h, and 7 days. Contusion volume (measured by histology and image analysis) was assessed at 14 days and measured in 6 rats by both MRI and histology. The survival rate after severe CCI was 96.2%. The L-R difference in % BW increased to 1.69 +/- 0.18% at 2 h, 3.00 +/- 0.08% at 24 h, 2.69 +/- 0.09% at 48 h, and 0.94 +/- 0.21% at 7 days. These values all differed from the control (p < 0.05). The % BW was greater at 24 h and 48 h than at 2 h and 7 days (p < 0.05). Marked reductions in ICBF were limited to structures in the injured hemisphere and were observed in the parietal cortex (2 and 24 h), subcortical white matter (2 and 24 h), and hippocampus (2 h), (p < 0.05) vs control rats. In the contusion core, ICBF was 19.4 +/- 8.8 mL 100 g-1 min-1 at 24 h (p = 0.011 vs normal). Necrosis was seen in large portions of the parietal cortex and subcortical white matter, and portions of the hippocampus and thalamus. Contusion volume was 47.8 +/- 9.2 mm3, which represented 14.4 +/- 2.1% of the traumatized hemisphere. Estimates of contusion volume by MRI and histology were closely correlated (r = 0.941, p < 0.017). Severe CCI in rats is accompanied by contusion, reproducible edema, and marked hypoperfusion, involving over 14% of the injured hemisphere, and can be produced with minimal mortality. T2-weighted MRI successfully and noninvasively identifies contusion volume in this model.

Animals↗
PubMed1995

The haemodynamic effect of prophylactic peri-operative dopexamine in coronary artery bypass patients.

Twenty-three low risk coronary artery bypass graft patients underwent a controlled study of the effects of prophylactic perioperative dopexamine hydrochloride on haemodynamic indices and peripheral perfusion. The infusion commenced following induction of anaesthesia and continued for 24 h postoperatively. The study demonstrated that dopexamine significantly increased cardiac index compared with the control group (P < 0.05) and that this effect was mediated through an increase in both left ventricular stroke volume index and heart rate (P < 0.05). This was associated with a significantly lower systemic vascular resistance (P < 0.05), without an increase in left ventricular stroke work index in the dopexamine group. Despite normal pre-operative left ventricular function, both groups exhibited a fall in pH (P < 0.05) relative to baseline levels. This fall in pH began prior to cardiopulmonary bypass and persisted in the early postoperative period in both groups, suggestive of tissue hypoperfusion and oxygen deficiency. These indices normalized more rapidly in the dopexamine group, suggesting a more rapid reversal of an intra-operative oxygen debt in this group. The study demonstrates the mechanism of action of dopexamine on cardiac function and peripheral perfusion during cardiac surgery and shows that the inodilator properties during cardiac surgery are useful haemodynamically and facilitate early reversal of tissue hypoperfusion and oxygen debt in this environment.

Adult↗
PubMed1995

Pregnancies following pre-conception diagnosis of common aneuploidies by fluorescent in-situ hybridization.

Chromosomal aneuploidies contribute considerably to the low pregnancy rate in in-vitro fertilization (IVF). The objective of this experimental work was to explore the possibility of detecting common aneuploidies in oocytes by polar body sampling. The study included 45 infertile patients of advanced maternal age participating in an IVF programme. The first polar body was removed prior to fertilization or both the first and second polar bodies were removed after fertilization and studied by fluorescent in-situ hybridization (FISH) using chromosome-specific probes for chromosomes X, 18 and/or 13/21. Of 155 oocytes with FISH results, 36 demonstrated chromosomal abnormalities. Of 119 oocytes predicted to be free from aneuploidy of chromosomes X, 18 and/or 13/21, 72 were normally fertilized, cleaved and transferred in 23 treatment cycles, which resulted in two healthy deliveries and three ongoing pregnancies confirmed to be unaffected by chorionic villous sampling. The method may appear useful for the detection of oocytes with common chromosomal aneuploidies in IVF patients of advanced maternal age.

Adult↗