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Biomedical subjects

P M Smith

Publications and source records attributed to P M Smith.

At least 19 recordsLinked to original sources
PubMed1992

Ins(1,3,4,5)P4 promotes sustained activation of the Ca(2+(-dependent Cl- current in isolated mouse lacrimal cells.

Infusion of 50 microM-Ins(1,3,4,5)P4 in addition to 500 microM-Ins(1,4,5)P3 into mouse lacrimal cells via a patch-clamp pipette promoted sustained activation of the Ca(2+)-dependent Cl- current, which could not be achieved with 500 microM-Ins(1,4,5)P3 alone. It has been proposed that Ins(1,3,4,5)P4 facilitates Ca2+ influx in the presence of Ins(1,4,5)P3 [Morris, Gallacher, Irvine & Petersen (1987) Nature (London) 330, 653-655], but a subsequent study in mouse lacrimal cells [Bird, Rossier, Hughes, Shears, Armstrong & Putney (1991) Nature (London) 352, 162-165] showed that a high concentration of Ins(1,4,5)P3 could mobilize both intra- and extra-cellular Ca2+ in the absence of Ins(1,3,4,5)P4. My data confirm these findings, but also show that Ins(1,3,4,5)P4 can stimulate additional Ca2+ influx even when the Ins(1,4,5)P3-dependent intracellular Ca2+ pools have been depleted.

Animals↗
PubMed1992

The effect of dietary supplementation with cysteic acid on the plasma taurine concentration of cats maintained on a taurine-restricted diet.

The biochemical impairment in the taurine anabolic pathway of the cat has not yet been fully elucidated; however, a number of key enzymes are known to have reduced activity in the cat compared to the rat. There are a series of possible routes resulting in the formation of taurine, one of which is the decarboxylation of cysteic acid. The aim of this study was to investigate the effect of cysteic acid, as a precursor, on the circulating concentration of taurine. A group of twelve adult cats was fed a basal, canned diet containing 0.22 g taurine/kg fresh weight for a period of eighty-four days. The diet was supplemented with 2.0 g/kg fresh weight L-cysteic acid on day fifteen through fifty six and plasma taurine concentration was measured every two weeks throughout the study. The results showed that when the dietary intake of taurine was inadequate to maintain the plasma concentration above 40 mumol/L, the addition of L-cysteic acid to the diet gave rise to an increase in plasma taurine concentration in some cats. Eight of the twelve cats showed a significant rise in plasma taurine after dietary supplementation for six weeks (52.0 +/- 22.3 vs 212.4 +/- 97.9 mumol/L, p less than 0.01) and a subsequent decrease in plasma levels when the cysteic acid was withdrawn (65.6 +/- 37.1 mumol/L). The other four cats showed no significant rise in plasma taurine after six weeks supplementation (13.5 +/- 4.2 vs 35.5 +/- 19.4 mumol/L, ns). However, withdrawal of the cysteic acid resulted in a subsequent decrease in circulating levels of taurine (11.8 +/- 1.5 mumol/L, ns). These data indicate that the addition of cysteic acid to a taurine-restricted, canned diet will, in some cats, result in the biosynthesis of taurine. The plasma taurine concentration of the remaining cats, although not apparently increasing significantly, was maintained at a slightly higher constant level until the cysteic acid was withdrawn. These results suggest that cats are able to synthesise taurine via an alternative pathway utilising L-cysteic acid as a precursor, although the efficiency of this process differs considerably among individual animals.

Animal Nutritional Physiological Phenomena↗
PubMed1992

Acetylcholine- and caffeine-evoked repetitive transient Ca(2+)-activated K+ and C1- currents in mouse submandibular cells.

1. Resting and acetylcholine-induced membrane currents were measured in single mouse submandibular acinar cells using the patch-clamp whole-cell current recording technique. 2. Micromolar ACh activated a large, sustained outward, Ca(2+)-dependent K+ current and a single transient inward Ca(2+)-dependent C1-current. 3. Nanomolar ACh induced a series of transients in both the K+ and C1- currents; C1- current activation was now observed throughout the period of agonist application. We consider this repetitive transient current activation better able to support sustained fluid and electrolyte secretion than the response elicited by a high dose of agonist. 4. Repetitive K+ and C1- current transients were also induced by 1 mM-caffeine, consistent with caffeine-induced Ca2+ release from the Ca(2+)-sensitive Ca2+ stores which are thought to comprise part of the pathway for activation of secretion. 5. The ACh-induced current transients were inhibited by 10 mM-caffeine, 100 microM-IBMX and 10 microM membrane-permeable cyclic AMP. Therefore, it seems likely that caffeine is able to inhibit agonist-induced calcium mobilization via a cyclic AMP-dependent pathway.

Acetylcholine↗
PubMed1992

Incidence of ulcerative colitis in Cardiff over 20 years: 1968-87.

The annual incidence of ulcerative colitis in the city of Cardiff was examined over a 20 year period. In the decade 1968-77, the mean annual incidence was 6.4 per 10(5) of the population compared with 6.3 for the period 1978-87. There was no difference in the distribution or extent of the disease between decades or between sexes. This contrasts with the increased incidence of Crohn's disease during the same period. The study included a survey of family practitioners which identified a further 19 patients (11% of the total).

Adolescent↗
PubMed1979

Abnormal blood vessels in the gastric antrum: a cause of upper-gastrointestinal bleeding.

Three patients who bled from curious vascular lesions of the gastric antrum are described. Each presented with an iron-deficiency anemia. Histological examination in two of the patients demonstrated numerous ectatic submucosal vessels in the antrum, the appearances being somewhat similar to angiodysplasia of the colon. The gastric lesions were not shown by barium meal examination or angiography but gave characteristic appearances on endoscopy. We believe that Billroth I partial gastrectomy is the treatment of choice for this condition.

Aged↗
PubMed1979

Identification of differences between the surface proteins and glycoproteins of normal mouse (Balb/c) and human erythrocytes.

The topography of the external surface of the Balb/c mouse erythrocyte has been investigated and compared to the human erythrocyte by using a series of protein radiolabeling probes. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the pattern of Coomassie Blue stained proteins was very similar for mouse and human erythrocyte ghosts, as was the distribution of radioactivity in protein bands after lactoperoxidase catalyzed radioiodination. The mouse erythrocyte glycoproteins identified by periodic-acid-Schiff and 'Stains-All' reagents, sialic acid analysis of gel slices, binding of 125I-wheat germ agglutinin and 125I-concanavalin A to the gels, and glycoprotein radiolabeling techniques, differed markedly from the sets of proteins labeled by radioiodination, and also differed from the human erythrocyte glycoproteins. Instead of the PAS I to PAS IV series of sialoglycoproteins characteristic of human erythrocytes, the mouse erythrocyte possesses a broad band of sialoglycoproteins with several peaks ranging in mol wt from 65,000 to 32,000. The same group of sialoglycoproteins were labeled by the periodate/B3H4-technique specific for terminal sialic acid, and the galactose oxidase/B3H4-method (plus neuraminidase) specific for galactosyl/N-acetylgalactosaminyl residues penultimate to sialic acid. These results emphasize the necessity to employ a variety of protein radiolabeling probes based on different labeling specificities, to study the membrane topography of cells which are poorly understood compared to the human erythrocyte membrane.

Animals↗
PubMed1979

Optimal conditions for lactoperoxidase catalyzed radioiodination of external proteins on mouse erythrocytes.

Optimal conditions were established for specific labelling of the surface proteins of mouse erythrocytes using lactoperoxidase-catalyzed radioiodination. The levels of H2O2 and I-, and cell concentrations required for restriction of haemoglobin labelling to less than 5% of the total 125I-protein, were different for radioiodination employing direct H2O2 addition or generation of H2O2 with glucose oxidase plus glucose. Preparation of mouse erythrocyte ghosts by hypotonic lysis caused loss of some minor labelled proteins present on intact cells and shifts to lower molecular weights of others. It is therefore important to solubilize labelled cells directly in electrophoresis buffer to avoid artifactual degradation of labelled proteins. The extent of labelling internal cell proteins was measured by a procedure suitable for the comparison of a large number of samples: solubilized radioiodinated erythrocytes were electrophoresed on 14% acrylamide gels and the radioactivity determined in the haemoglobin band which migrates separately from other proteins. The major labelled protein on the mouse erythrocytes had an apparent molecular weight of 92,000, and may be analogous to Band 3 of the human erythrocyte.

Animals↗
PubMed1979

Controlled trial of cimetidine in upper gastrointestinal haemorrhage.

One hundred and one patients were studied in a double-blind controlled trial to assess the role of oral cimetidine in preventing the continuation or recurrence of acute upper gastrointestinal haemorrhage from various sources, chiefly peptic ulcer. The dose of cimetidine was 800 mg on entering the study followed by 400 mg six hourly. The source of bleeding was identified endoscopically in 96% of patients, peptic ulcer comprising 70%. Bleeding continued or recurred in 11 of 51 (21.5%) of patients on cimetidine and in 12 of 50 (24%) of patients on placebo. Analysis of the effect of cimetidine according to age or severity of bleeding showed no significant advantage for the drug.

Adult↗
PubMed1979

Double-blind comparison of cimetidine and placebo in the maintenance of healing of chronic duodenal ulceration.

Patients suffering from chronic duodenal ulceration were allocated at random to treatment with either cimetidine (400 mg twice daily) or matching placebo for six months. Before entry to the trial all patients were shown to have healed ulcers on endoscopy. Most of the patients had participated in a one-month trial of cimetidine during which their ulcers healed. The trial showed that four of 29 patients relapsed on maintenance treatment with cimetidine, which therefore did not confer complete immunity from relapse. However, cimetidine treatment was very much better than placebo treatment, on which 18 of 31 patients relapsed. Of the 22 patients who relapsed clinically, 20 were submitted to endoscopy and 19 of these were shown to have ulcerated again. Endoscopy at the end of the trial showed that ulcers had also redeveloped in five of 28 asymptomatic patients. Length of previous dyspeptic history had no bearing on the results of the trial but there was evidence that relapse on placebo was less likely if the ulcer had originally healed on a high dose of cimetidine. Clinical relapse was associated with worsening duodenitis. Symptoms, clinical observation, and laboratory tests showed no important abnormalities in the patients.

Chronic Disease↗
PubMed1979

Naturally occurring antibodies to liposomes. I. Rabbit antibodies to sphingomyelin-containing liposomes before and after immunization with unrelated antigens.

Liposomes were prepared from a mixture of sphingomyelin, cholesterol, and dicetylphosphate or L-alpha-dimyristoyl phosphatidylcholine, cholesterol, and dicetylphosphate, in the presence of glucose. The amount of trapped glucose released from these liposomes was monitored after incubation with a variety of normal and immune sera in the presence of guinea pig complement. All normal rabbit sera tested were found to release, in the presence of complement, detectable amounts of trapped glucose from sphingomyelin-containing liposomes. After immunization with a variety of unrelated antigens, the anti-sphingomyelin liposome activity increased signficantly and in direct proportion to the number of injections, despite the fact that the liposomes used in the assay did not contain the relevant antigen used for immunization. Liposomes prepared from dimyristoyl phosphatidylcholine showed only marginal release of their trapped marker when assayed with the same rabbit sera and complement. These liposomes, however, were fully reactive when the appropriate antigen was inserted in their bilayer structure. The antiliposome activity was associated mainly with the IgM antibody class. These results raise the interesting possibility that antigenic stimulation may trigger the activation of lymphocyte clones directed against autologous cell-membrane components that cross-react with artificial model membranes containing sphingomyelin.

Animals↗
PubMed1978

Portal hypertension in vinyl chloride monomer workers. A hemodynamic study.

Hemodynamic studies were performed in 5 vinyl chloride monomer workers in whom splenomegaly or thrombocytopenia was detected during a screening program at major chemical plant. Three patients had portal hypertension and collateral venous circulations, with intrasplenic pressures between 20 and 29 mm Hg and normal wedged hepatic venous pressures, but the gradient between the wedged and free hepatic vein pressures was also increased. Splenic blood flows were increased in both hypertensive and normotensive patients. There was no correlation between the splenic blood flow and the portal pressure or the presence of portal fibrosis. The portal hypertension associated with vinyl chloride exposure is mainly presinusoidal in type, and may be attributed to an abnormality of the portal vein radicles, or hepatic sinusoids.

Adult↗