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Biomedical subjects

S Wells

Publications and source records attributed to S Wells.

At least 91 records · Page 5Linked to original sources

Sequences contained within the promoter of the human thymidine kinase gene can direct cell-cycle regulation of heterologous fusion genes.

Recent evidence on the transcriptional regulation of the human thymidine kinase (TK) gene raises the possibility that cell-cycle regulatory sequences may be localized within its promoter. A hybrid gene that combines the TK 5' flanking sequence and the coding region of the bacterial neomycin-resistance gene (neo) has been constructed. Upon transfection into a hamster fibroblast cell line K12, the hybrid gene exhibits cell-cycle-dependent expression. Deletion analysis reveals that the region important for cell-cycle regulation is within -441 to -63 nucleotides from the transcriptional initiation site. This region (-441 to -63) also confers cell-cycle regulation to the herpes simplex virus thymidine kinase (HSVtk) promoter, which is not expressed in a cell-cycle manner. We conclude that the -441 to -63 sequence within the human TK promoter is important for cell-cycle-dependent expression.

Base Sequence↗

Primary mucinous adenocarcinoma developing in an ileostomy stoma.

We report a mucinous adenocarcinoma arising in an ileostomy stoma of a 60 year old woman after a subtotal colectomy done 28 years previously for ulcerative colitis. A study of the histochemical profiles of the mucin within the mucosa of the ileostomy and the carcinoma was undertaken. Previously documented cases are reviewed.

Adenocarcinoma, Mucinous↗

Pharmacokinetics of rimantadine hydrochloride in patients with chronic liver disease.

Six patients with chronic liver disease and six sex-, age (+/- 5 years)-, and weight (+/- 5 kg)-matched healthy control subjects received a single dose of two 100 mg tablets rimantadine HCl. Eight additional patients with chronic liver disease who were not matched to healthy subjects received a single dose of two 100 mg tablets of rimantadine HCl. Blood and urine samples were collected and rimantadine concentrations were determined by a GCMS method. The values for maximum plasma concentration, AUC, elimination half-life, and renal clearance were not significantly different between patients and control subjects, independent of the statistical analyses (parametric and nonparametric) used. The mean apparent elimination half-life, volume of distribution, and total clearance in the matched patients with liver disease were 32 hours, 24 L/kg, and 676 ml/min, respectively. Renal clearance and the amount excreted in the urine unchanged were 63 ml/min and 10%, respectively. In conclusion, rimantadine pharmacokinetics were not appreciably altered in patients with less severe chronic liver disease.

Adamantane↗

Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5'-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta.

The dependence of vascular relaxation on an intact endothelium and the relationship between relaxation and cyclic GMP accumulation were determined in coronary arteries isolated from cardiac transplantation patients with or without coronary atherosclerosis. In nonatherosclerotic arteries, the endothelium-dependent agent acetylcholine produced concentration-related relaxations. In atherosclerotic arteries, endothelium-dependent relaxations were abolished with acetylcholine, partly suppressed with substance P and histamine, and completely preserved with the ionophore A23187. In these arteries, the endothelium-independent agent nitroglycerin remained fully active. Accumulation of cyclic GMP in atherosclerotic strips was suppressed with acetylcholine but unattenuated with A23187 and nitroglycerin. In aortas from rabbits with diet-induced atherosclerosis, there was likewise an impaired cholinergic relaxation and cyclic GMP accumulation in the presence of preserved responses to A23187 and nitroglycerin. The results demonstrate that impaired cholinergic responses in atherosclerotic arteries reflect a muscarinic defect and not an inability of endothelium to release endothelial factor or smooth muscle to respond to it.

Acetylcholine↗

Do cardiorespiratory frequencies show entrainment with hopping in the tammar wallaby?

Breathing, heart and gait frequencies, tidal volume, cardiac output, and rates of oxygen consumption were measured in tammar wallabies (Macropus eugenii Desmarest) hopping on a treadmill. At speeds greater than 1.6 ms-1 the rate of metabolic power consumption was independent of hopping speeds. Blood lactate levels within the speed range where VO2 was independent of speed showed a mean increase of 4.8 mmol l-1. During bipedal hopping, the frequencies of breathing and limb movement are phase-locked in the ratio of 1:1. Inspiration begins as the animal leaves the ground and may be a passive process driven by a visceral piston. A relatively large central tendon in the diaphragm may correlate this function. Unlike breathing frequencies, cardiac frequencies show no entrainment with hopping. The site of dissipation of the presumed large arterial pressure excursion is unknown.

Animals↗

Eating and weight problems among women attending their general practitioner.

One hundred and fifty-seven women between the ages of 16 and 40, attending their general practitioners, were given a self-report questionnaire containing standard instruments measuring weight concerns and eating attitudes and behaviours. The majority (72%) of women wanted to weigh less, 46% were dissatisfied with their body shape, 48% dieted at least sometimes with 24% usually or always dieting, and 21% wanted help with their eating or weight problems. Increasing disparity between actual weight and desired weight was associated with higher scores on the eating problem scales.

Adolescent↗

The effect of divalent metal ions on the electrophoretic mobility of bovine prothrombin and bovine prothrombin fragment 1.

Examination of metal ion-dependent effects on the electrophoretic mobility of bovine prothrombin and fragment 1 provides a useful and sensitive method for investigation of conformational processes in these proteins. Utilization of this method reveals a conformational change in bovine prothrombin and fragment 1 which occurs at low metal ion concentrations. Equilibrium dialysis studies indicate that the metal ion-induced shape change occurs concomitant with binding of a single calcium ion/molecule of prothrombin or fragment 1. Mixed metal electrophoretic mobility studies with Mg2+ and Ca2+ have demonstrated the "synergistic" effect for fragment 1 observed by others. Mixed metal equilibrium dialysis has provided experimental support for this observation and allows us to conclude that two tight Ca2+ sites are not affected by low Mg2+ concentrations and that the third Ca2+ site is also a tight site for Mg2+. Thus, at low Mg2+ concentrations and upon the addition of Ca2+, there are effectively three tight sites; consequently more Ca2+ will bind to the protein at lower total Ca2+ ion concentrations.

Animals↗

Methylation analysis of a plasmid containing a mammalian cell cycle regulatory sequence after transient transfection into the host cell.

A hamster genomic sequence containing a cell cycle regulatory sequence derived from a histone H3.2 gene was transfected into K12 hamster fibroblasts in the form of plasmid DNA prepared from dam+ E. coli. Analysis of the plasmid DNA recovered 72 hr after the transfection revealed that it was resistant to Mbol but was sensitive to Dpn 1 enzyme digestion, suggesting that this plasmid had retained its dam E. coli methylated sites and was therefore unable to undergo replication following transfection into homologous host cells. These results were discussed with relation to a previously described yeast cell cycle regulatory sequence which was functionally linked to an autonomous replicating sequence and was located near a yeast H2B gene.

Animals↗

Enhanced synthesis of the glucose/calcium-regulated proteins in a hamster cell mutant deficient in transfer of oligosaccharide core to polypeptides.

The properties of two Chinese hamster temperature-sensitive mutants, K12 and H3.5, were examined. Both mutants originated from the same parental cell line, Wg1A, and were isolated as cell cycle mutants arrested in G1. Previously, we had been shown that the H3.5 ts mutation affected the transfer of the oligosaccharide from the lipid carrier to the nascent polypeptide and that the K12 ts mutation regulated the transcription of two glucose/calcium-regulated genes. We report here that these two mutants exhibit almost identical phenotypes at the biochemical level. Furthermore, a genetic complementation test demonstrates that the two ts lesions must be closely related, or even identical. Our results suggest that a specific defect in glycosylation may result in the overproduction of the glucose/calcium-regulated proteins and is capable of activating the promoter of the major glucose-regulated gene.

Animals↗

Preservation of endothelium-dependent vascular relaxation in cholesterol-fed rabbit by treatment with the calcium blocker PN 200110.

We tested the effects of low doses of a dihydropyridine calcium antagonist, PN 200110, on endothelium-dependent vascular relaxation in rabbits fed a 1% cholesterol diet. The drug was given orally, 1 mg/day, and control rabbits received placebo. Plasma total cholesterol after 10 weeks, was similar in the placebo- and PN 200110-treated groups. The respective values averaged 2140 +/- 116 (n = 14; mean +/- SEM) and 2012 +/- 115 mg/dl (n = 13). In placebo-treated rabbits, sudanophilic aortic lesions covered 52 +/- 5% of the intimal surface, and the aortic cholesterol concentration was 72 +/- 6 mg/g protein. Corresponding values in aortas from PN 200110-treated rabbits were significantly lower [36 +/- 5% (P less than 0.03) and 52 +/- 3 mg/g protein (P less than 0.03)]. Maximal endothelium-dependent cholinergic relaxation of aortic strips in untreated (n = 14) and treated cholesterol-fed rabbits (n = 13) differed significantly (P less than 0.01) and averaged 31 +/- 4% and 61 +/- 7% of the value in normocholesterolemic controls (n = 13). We conclude that cholesterol feeding suppresses endothelium-dependent relaxation evoked by acetylcholine, and that PN 200110 reduces the severity of atherosclerosis and impairment of endothelium-dependent relaxation.

Animals↗

Ischaemic dilatation of the colon.

The present paper describes the presentation and management of 9 patients who developed dilatation in the colon during the course of spontaneous ischaemic colitis. The length of history varied from 16 hours to 6 weeks. The patients usually had diarrhoea and abdominal pain but no bleeding and posed a difficult diagnostic problem. At laparotomy, three distinct types of colonic dilatation were recognised. Dilatation of non-diseased colon proximal to localised ischaemic segments occurred in 2 patients, 3 patients exhibited dilatation of obviously gangrenous colon, 4 patients showed dilatation of ischaemic but possibly viable colon, yet in 1 of these, multiple sealed perforations were present. Resection of the obvious or possibly gangrenous colon was the treatment used but in the 2 patients with dilatation due to stricture, transverse colostomy alone was employed.

Adult↗

Quantitation of pulmonary megakaryocytes and fibrin thrombi in patients dying from burns.

Pulmonary megakaryocytes and fibrin microthrombi were counted in lung sections from 22 patients dying from extensive burns. There was a significant correlation between numbers of megakaryocytes and fibrin microthrombi, supporting a relationship between disseminated intravascular coagulation (DIC) and numbers of pulmonary megakaryocytes. No correlation was found between antemortem platelet counts and either fibrin microthrombi or megakaryocytes. Possible explanations for this are forwarded and the nature of pulmonary megakaryocytes discussed.

Adult↗

Alimentary foreign body in an Amazon parrot.

An Amazon Parrot regurgitated and drooled and had blood in its droppings. Abdominal palpation revealed several small, spherical masses. Positive-contrast radiographs clearly delineated the objects. With the bird under halothane anesthesia and the beak held open, a sponge forceps was used to extract a string of 25 beads from the alimentary tract. Gentamicin and dexamethasone were given IM and recovery was uneventful.

Animals↗

Expression of receptors for tetanus toxin and monoclonal antibody A2B5 by pancreatic islet cells.

Studies of the reaction of antibody A2B5 and tetanus toxin with pancreatic islet cells, islet cell tumors, and other human amine precursor uptake and decarboxylation (APUD) tumors are described. By indirect immunofluorescence, antibody A2B5 and tetanus toxin were shown to specifically bind to the plasma membrane of human, rat, chicken, and mouse islet cells. The binding of antibody A2B5 to the cell surface of living islet cells has allowed isolation of these cells from a suspension of pancreatic cells by using a fluorescence-activated cell sorter. In studies designed to determine whether tetanus toxin and antibody A2B5 bound to the same surface antigen, A2B5 and tetanus toxin did not compete for binding to normal islet cells, a human islet cell tumor, or a rat islet cell tumor. In addition to binding to islet cell tumors, antibody A2B5 reacts with frozen sections, isolated cells, and cell lines of neural, neural crest, and APUD origin.

Animals↗

Malignant fibrous histiocytomas of salivary glands.

The light microscopic, immunohistological and ultrastructural findings in two cases of malignant fibrous histiocytoma arising in salivary glands are presented and the features of seven previously reported cases are reviewed. This neoplasm is extremely rare in this site and may pose problems in diagnosis. It has to be distinguished from other spindled cell tumours, in particular from epithelial tumours of predominantly spindled cell pattern; immunohistological markers for histiocytic cells may be of value. The histogenesis of this neoplasm is controversial but our electron microscopic findings support an origin from mesenchymal cells which differentiate along a broad fibrohistiocytic spectrum.

Adult↗