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Biomedical subjects

V Robinson

Publications and source records attributed to V Robinson.

At least 55 records · Page 3Linked to original sources

The Nuclear Receptor Resource Project.

We have expanded the original Glucocorticoid Receptor Resource (GRR) database to include several individual resources as part of a larger project called the Nuclear Receptor Resource (NRR). In addition to the GRR, the NRR currently features the Thyroid Hormone Receptor Resource, the Androgen Receptor Resource, the Mineralocorticoid Receptor Resource, the Vitamin D Receptor Resource, and the Steroid Receptor Associated Proteins Resource. The goal of the NRR project is to provide a comprehensive resource for information on the nuclear receptor superfamily, and to provide a forum for the dissemination and discussion of both published and unpublished material on these proteins. Although the individual resources are managed from different servers, all the files are integrated and can be accessed through the project's Home Page, housed at http://nrr. georgetown.edu/nrr.html. In the near future, we hope to expand the project to contain information on other nuclear receptors and to better our electronic publication system. To accomplish this, we encourage the involvement of nuclear receptor investigators in the NRR.

Amino Acid Sequence↗

Roles of Eph receptors and ephrins in neural crest pathfinding.

Neural crest cells migrate along specific pathways to their destinations and, like neuronal growth cones, must be guided by extracellular cues. One example of neural crest pathfinding is the segmental migration of branchial and trunk neural crest; this is associated with the patterning of the skeletal components of the branchial arches and of the peripheral nervous system. In this review, we discuss recent work that has implicated Eph receptors and their ephrin ligands in mediating repulsive interactions that restrict neural crest cell migration. We relate these findings to the roles of these receptors and ligands in growth cone guidance and the segmental restriction of cell movement in the hindbrain.

Animals↗

A marker of terminal stalk cell terminal differentiation in Dictyostelium.

We describe the isolation of staB, a Dictyostelium gene that is selectively expressed in stalk cells. If an aggregate enters culmination immediately staB is expressed in the bottom half of the stalk and in the basal disc but if a migratory slug is formed it is also expressed in the top of the stalk and in a disc of cells that surmounts the spore head. The latter two populations of cells derive from the rear part of the prestalk region, the pstO cells, which would therefore seem to change their transcriptional competency during slug migration. The staB promoter contains a distal region that is required for expression within both the stalk and the basal disc and a proximal region that is required only for expression within the basal disc. This uncoupling of transcriptional specificities suggests that the signalling mechanisms that direct terminal differentiation in these two tissues differ in some way.

Amino Acid Sequence↗

The duration of infection modifies mitochondrial oxidative capacity in rat skeletal muscle.

Sepsis increases phosphocreatine (PCr) breakdown and reduces PCr stores in skeletal muscle. To determine if systemic infection impairs mitochondrial function, in vivo 13P magnetic resonance spectroscopy (31P MRS) studies of the gastrocnemius muscle were performed in virus-free male Wistar rats 24 or 48 hr after cecal ligation and 18-gauge needle single puncture (24 degrees CLP, n = 16; 48 degrees CLP, n = 15) or sham operation (24 degrees SHAM, n = 18; 48 degrees SHAM, n = 13). Physiologic saline (6 ml/100 g body wt) was injected intraperitoneally for fluid resuscitation. Water but no food was allowed in all animals. High resolution (8.45 Tesla) 31P MRS spectra, obtained at rest and during exercise using a 1.4-cm surface coil, were used to calculate PCr/ATP, PCr/P(i) ratios, and intracellular pH. Steady-state muscle exercise was induced by supramaximal sciatic nerve stimulation at 10 Hz for 10 min. Recovery of PCr/(PCr + P(i)) ratios after exercise was fitted to a monoexponential curve. The resultant function was used to calculate the half time for PCr recovery, the initial PCr resynthesis rate, and the maximal oxidative ATP synthesis rate, which reflect the rephosphorylation of ADP and are therefore measures of mitochondrial oxidative capacity. PCr/ATP ratios decreased by 12 and 11%, 24 and 48 hr after CLP, respectively. The PCr/P(i) ratios decreased incrementally (7% in 24 degrees CLP vs 23% in 48 degrees CLP animals). Twenty-four hours after operation the half time for PCr recovery was shortened while the initial PCr resynthesis rate and maximal oxidative ATP synthesis rate were accelerated in CLP animals compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗

Solid-state 13C NMR study of a transglutaminase-inhibitor adduct.

We have used solid-state 13C NMR to study the structure of the adduct resulting from the inactivation of the enzyme transglutaminase by 3-halo-4,5-dihydroisoxazoles. These inhibitors were conceived on the assumption that they would inhibit transglutaminase by attack of an enzyme active site cysteine thiol on the imine carbon of the dihydroisoxazole ring. The tetrahedral intermediate formed could then break down with the loss of the halide group and the subsequent formation of a stable imino thioether adduct. We have compared the 13C CPMAS spectra of the chloro-, bromo-, and (ethylthio)dihydroisozazole inhibitors, and the results indicate that the chemical shift of the C-3 carbon is sensitive to the nature of the heteroatom. Subtraction of the natural-abundance 13C solid-state NMR spectrum of the enzyme from that of the enzyme inactivated by C-3-labeled chlorodihydroisoxazole reveals a broad peak at 156 ppm. The chemical shift of this peak is very close to that observed for a model 3-ethylthio compound and suggests the formation of a stable imino thioether enzyme adduct. Similar results were obtained for lyophilized enzyme adducts and for frozen solutions of the enzyme adduct in the absence and presence of Ca2+. We have also compared these results with those obtained by solution NMR on an aqueous solution of the enzyme-inhibitor complex. The 13C-labeled C-3 resonance was not observed in this case.

Animals↗

Glutathione depletion alters hepatocellular high-energy phosphate metabolism.

Oxygen free radicals have recently been implicated as a major cause of tissue injury in critically ill patients. Glutathione (GSH) is a potent endogenous antioxidant that may be important in minimizing oxidant-induced organ damage. However, this tripeptide is depleted during severe illness. In order to determine the effect of GSH depletion on hepatic high-energy phosphate metabolism, in vivo 31P magnetic resonance spectroscopy was used to measure phosphate ratios in male Wistar rats given 1 ml/kg of diethylmaleate (DEM), an agent that binds and thus depletes tissue GSH, or corn oil vehicle intraperitoneally. Spectra of the liver were obtained in noninjected animals (baseline, n = 15) and in rats 2 and 24 hr after the intraperitoneal injection of DEM (n = 20) or corn oil (control, n = 20). These spectra were used to measure hepatocellular pH, phosphomonoester to ATP (PME/ATP), and phosphodiester to ATP ratios, measures of hepatocellular damage; and the inorganic phosphate (Pi)/ATP ratio, a measure of energy status. In addition, tissue GSH, phosphofructokinase, citrate synthase, and beta-OH-acyl-Co-A dehydrogenase activities as well as hepatocellular ATP were measured in vitro in representative liver samples. Hepatic GSH levels were maximally depressed by 85% 2 hr after the injection of DEM (6.94 +/- 0.34 vs 0.94 +/- 0.22 microM/g wet wt, baseline vs 2 degrees DEM). This was associated with a marked increase in the PME/ATP and Pi/ATP ratios by 25 and 33%, respectively, and both ratios were significantly correlated with the severity of hepatic GSH depletion (r = 0.63, P < 0.001 and r = 0.42, P < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxyacyl CoA Dehydrogenases↗

"Race", gender, and internal migration within England and Wales.

"First, the propensity of men and women to engage in interregional migration within the Pakistani and West Indian populations in England and Wales is examined for differentials, and these propensities are compared with those derived from a white, control population. Second, the main spatial flows of long-distance gender-specific migration are described. Third, the rewards which different groups derive from internal migration are considered and any gender discrepancies are highlighted. Last, the conjunction of 'race', gender, marital status, and migration is investigated to see whether certain subgroups suffer a treble jeopardy and whether this is exacerbated or alleviated by different gender roles within the Afro-Caribbean and Pakistani populations."

Culture↗

Monoclonal antibodies recognising stage and region specific epitopes in embryonic mouse palatal epithelial cells.

Four monoclonal antibodies raised against murine embryonic palatal epithelium were used to stain frontal cryosections of embryonic mouse heads (d 11-15). One antibody (6A11) recognised the nasal epithelium at the angle of the palate prior to shelf elevation (embryonic d 11-d 13) and the epithelia at the tips of the approximated shelves (embryonic d 14.5). Two further antibodies (2H6 and 3H2) recognised epitopes on the entire palatal epithelium until shelf elevation (embryonic d 14.5) when their expression ceased. The epitope recognised by antibody 6D3 was absent from the palatal epithelium until embryonic d 13 when it displayed region specific expression, being present on the nasal aspect in the midpalate and the tip of the palate posteriorly. On embryonic d 14.5 staining of the medial edge epithelia was present in all regions. Whilst the nasal palatal epithelium stained in the anterior and mid regions, only patchy staining of the oral epithelium was detected. By embryonic d 15 staining was present throughout the palatal epithelia. These antibodies are directed against intracellular epitopes, possibly keratins. Indeed, immunoblotting assays revealed that antibody 2H6 recognised keratin 18. The developmental regulation of the epitopes recognised by the antibodies corresponds with differentiative events occurring during murine palatogenesis.

Animals↗

A study of human respiratory tract chlamydial infections in Cambridgeshire 1986-88.

Human respiratory tract chlamydial infections have been studied in Cambridgeshire for many years, but until recently we have been unable to distinguish between infection with Chlamydia psittaci or Chlamydia pneumoniae (TWAR). In this study, we have employed the micro-immunofluorescence (micro-IF) test for this purpose and to look for the relative incidence of C. psittaci and C. pneumoniae infections in Cambridgeshire. Among 50 patients with community-acquired respiratory tract symptoms whose serum samples had Chlamydia complement fixation test titres greater than or equal to 64, 25 had evidence of recent C. psittaci or C. pneumoniae infection. Nineteen (76%) of the 25 patients had evidence of recent C. psittaci infection and of these 16 (84%) had recently had contact with birds. Six patients (24%) had evidence of recent C. pneumoniae infection, and of these, only two (33%) had recently had contact with birds. While C. psittaci was grown from several of the birds associated with human C. psittaci infection, it was not cultured from any of the birds in contact with the two human C. pneumoniae cases.

Adult↗

Acute changes in forearm venous volume and tone using radionuclide plethysmography.

In this investigation blood pool scintigraphy was validated as a method to study acute changes in human forearm veins. Changes in regional forearm vascular volume (capacity) and the occluding pressure-volume (P-V) relationship induced by sublingual nifedipine (NIF) and nitroglycerin (GTN) were recorded in 16 patients with simultaneous data collection by the radionuclide and the mercury-in-rubber strain-gauge techniques. The standard error of estimate (Syx) between successive control measurements using the radionuclide method was 3.1% compared with 3.2% for the strain-gauge method. The venous P-V curves were highly reproducible using both techniques. Strain gauge and radionuclide measurements of acute changes in forearm venous volume correlated well (r = 0.86; Syx = 7%, n = 156). After 20 mg of NIF or 0.6 mg of GTN, mean heart rate increased from 71 +/- 10 to 77 +/- 9 and from 68 +/- 10 to 75 +/- 11 beats/min, respectively, and group systolic blood pressure decreased from 128 +/- 22 to 120 +/- 19 and from 136 +/- 18 to 126 +/- 23 mmHg, respectively (P less than 0.05). At venous occluding pressures of 0 and 30 mmHg, the forearm vascular volume did not change after NIF (2 +/- 4 and -1 +/- 4%; P greater than 0.05), whereas it increased after GTN (8 +/- 5 and 12 +/- 7%; P less than 0.001). The forearm venous P-V relationship did not change after NIF, whereas a significant rightward shift (venodilation, with an increase in unstressed volume) occurred after GTN.(ABSTRACT TRUNCATED AT 250 WORDS)

Forearm↗

In vitro biologic toxicity of native and surface-modified silica and kaolin.

An in vitro study of the biologic responses of surface-modified and native silica and kaolin was made to provide comparative information on the suppression of cytotoxicity by pulmonary surfactant. The release of alveolar macrophage cytoplasmic enzyme, lactate dehydrogenase (LDH), and lysosomal enzymes beta-N-acetylglucosaminidase (beta-NAG) and beta-glucuronidase (beta-GLUC) and sheep blood-cell hemolysis were monitored as indicators of cell membrane damage and cytotoxicity. Surface modification of silica and kaolin with dipalmitoyl lecithin (DPL) resulted in complete abrogation of cytotoxicity of both minerals. These findings indicate that surface modification of minerals with different adsorption properties by pulmonary surfactant generally lessens their prompt adverse effects.

Acetylglucosaminidase↗

Comparative in vitro cytotoxicity of volcanic ashes from Mount St. Helens, El Chichon, and Galunggung.

Dry sedimented volcanic ash samples from each of three widely separated volcanoes of the "Circum Pacific" region have been subjected to mineralogic analysis and in vitro tests for cytotoxicity. The ash samples from the three different volcanoes varied in particle size, surface area, and concentration of silica. Total crystalline silica in the respirable fraction of ashes was 1.5% (Mount St. Helens, Moses Lake); 1.36% (Galunggung, Bandung-1); 1.95% (Gallunggung, Bandung-2); and 1.72% (El Chichon, Tuxtla). Hemolysis as an index of cytotoxicity was measured by in vitro tests on sheep blood erythrocytes and indicated wide differences in hemolytic activity among ash samples. Alveolar macrophage cytosolic (lactate dehydrogenase) and lysosomal (beta-glucuronidase and beta-N-acetyl glucosaminidase) enzymes were measured as an index of cellular integrity following dust exposure. Hemolysis and release of enzymes from alveolar macrophages were greater with volcanic ash from Galunggung (Bandung-1) and El Chichon (Tuxtla) than the other ashes. Although crystalline silica induced an effect similar to volcanic ash from Galunggung (Bandung-1) on the release of enzymes from alveolar macrophages, the hemolytic potency of silica was much greater. Light and electron microscopic observations of dust-exposed alveolar macrophages indicated that the ash particles were readily phagocytized. These results indicate that volcanic ash is moderately cytotoxic and that exposure may lead to overt reactions and the exacerbation of preexisting chronic inflammatory processes.

Air Pollutants↗

Control of osteitis deformans using glucagon, calcitonin, and mithramycin.

Glucagon, porcine calcitonin, and mithramycin were given to patients with Paget's disease of bone. There was rapid complete relief of bone pain accompanied by biochemical improvement or normalization in all cases. Calcitonin and glucagon appear to have additive properties in Paget's disease and the use of the 3 drugs in combination may reduce the incidence of side effects and the development of "drug resistance". The cost of treatment might also be reduced if periodic treatment as demonstrated in Case 1 is used.

Aged↗

An experimental study of pictures produced by acute schizophrenic subjects.

The purpose of this study was to examine the validity of assessing pictures produced by acute schizophrenic subjects as a technique in differential diagnosis. It was hypothesized that art productions by schizophrenics differ from those both by other acute psychiatric patients and by 'normals'. Coloured slides were made from pictures produced in standardized conditions by three samples of each of thirty subjects. It was found that repetition of abstract forms was the only factor studied to be associated specifically with schizophrenia; whereas the presence of pictorial imbalance, overelaboration, childlike features, uncovered space, detail and colour variety were found to be associated with psychiatric admission irregardless of diagnosis. Doubt is cast on the use of art as a technique in differential psychiatric diagnosis.

Acute Disease↗

The cause and treatment of postvagotomy diarrhoea.

Six patients with watery postvagotomy diarrhoea and 4 patients with intractable diabetic diarrhoea were treated with cholestyramine. The diarrhoea responded completely to therapy, during which the stool content of water, sodium, postassium and magnesium fell. Two of the patients, while receiving cholestyramine, had a rise in faecal fat, but this was not accompanied by diarrhoea, the stools being well formed. Evidence is presented which suggests that the mechanism of diarrhoea is similar in both disorders and is due to division or neuropathy of the hepatic fibres of the vagus nerve. This results is distension of the gallbladder, contraction of which expels increased quantities of bile salts, which swamp the reabsorptive capacity of the small intestine and induce diarrhoea by direct action on the colon. If this theory is valid, cholecystectomy, by preventing large quantities of concentrated bile salts from suddenly entering the gut, may result in improvement of postvagotomy and diabetic diarrhoea.

Adult↗