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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↗
PubMed1992

A comparison of workloads of physician-gastroenterologists and other consultant physicians. Prepared on behalf of the Clinical Services Committee, British Society of Gastroenterology.

In response to a workload questionnaire, carried out as part of an enquiry into manpower needs in gastroenterology, replies were received from 17 health regions, relating to 86 hospitals and 135 consultant gastroenterologists. The average yearly number of deaths and discharges of patients under the care of gastroenterologists was 992, while that of patients cared for by consultant physicians in other specialties was 679. When daycase admissions were also included, there were 1,553 annual discharges per gastroenterologist as compared with 871 for other physicians. These 682 extra cases per gastroenterologist largely represent the additional workload of gastrointestinal endoscopy.

Endoscopy↗
PubMed1991

Cloning and sequencing of Lol pI, the major allergenic protein of rye-grass pollen.

We have isolated a full length cDNA clone encoding the major glycoprotein allergen Lol pI. The clone was selected using a combination of immunological screening of a cDNA expression library and PCR amplification of Lol pI-specific transcripts. Lol pI expressed in bacteria as a fusion protein shows recognition by specific IgE antibodies present in sera of grass pollen-allergic subjects. Northern analysis has shown that the Lol pI transcripts are expressed only in pollen of rye-grass. Molecular cloning of Lol pI provides a molecular genetic approach to study the structure-function relationship of allergens.

Allergens↗
PubMed1991

Isolation of cDNA encoding a newly identified major allergenic protein of rye-grass pollen: intracellular targeting to the amyloplast.

We have identified a major allergenic protein from rye-grass pollen, tentatively designated Lol pIb of 31kDa and with pI 9.0. A cDNA clone encoding Lol pIb has been isolated, sequenced, and characterized. Lol pIb is located mainly in the starch granules. This is a distinct allergen from Lol pI, which is located in the cytosol. Lol pIb is synthesized in pollen as a pre-allergen with a transit peptide targeting the allergen to amyloplasts. Epitope mapping of the fusion protein localized the IgE binding determinant in the C-terminal domain.

Allergens↗
PubMed1991

CD4-positive T lymphocytes are required for the generation of the primary but not the secondary CD8-positive cytolytic T lymphocyte response to herpes simplex virus in C57BL/6 mice.

To understand the cellular basis for recovery from HSV infection, it is critical to identify functional interactions between HSV-specific T lymphocyte subpopulations involved in the generation of the optimal response. To this end, the requirement for CD4+ (L3T4+) T lymphocytes in the development of the primary and secondary CD8+ (Lyt-2+) cytolytic T lymphocyte (CTL) response following HSV infection in C57BL/6 mice was investigated. It was found that chronic depletion of CD4+ cells in vivo by treatment with the mAb GK1.5, which resulted in greater than 95% depletion of peripheral CD4+ T lymphocytes in treated animals, caused a profound decrease in the levels of cytolytic activity obtained during the primary response in the draining popliteal lymph nodes of mice responding to infection in the hind footpads. However, treatment did not affect the levels of in vivo secondary CTL activity in the popliteal lymph nodes, nor the in vitro secondary response in the spleen. The decreased CTL activity observed during the primary response was not due to an inability to prime HSV-specific CTL precursors (CTLp), as full cytolytic activity was obtained following culture of lymphocytes in the presence of exogenous IL-2 and antigen, and the response could be reconstituted by treatment with recombinant IL-2 in vivo. Analysis of the secondary CTL response in the spleen indicated that CD4+ cells were not required for either the generation or maintenance of this aspect of the response. However, blockade of IL-2 utilization by CTL using anti-IL-2R antibodies indicated that this lymphokine was absolutely essential for secondary CTL expansion in vitro. Finally, mice that had been infected 12 months previously exhibited a decreased ability to generate secondary HSV-specific CTL in vitro following CD4-depletion in vivo. Taken together, these results suggest two distinct stages of CTL development during the response: an early primary stage dependent upon the presence of CD4+ cells, and a later, CD4-independent stage operative during the secondary response, which decays with time postinfection.

Animals↗
PubMed1991

The management of variceal bleeding.

Variceal bleeding has a high mortality, as the majority of patients have cirrhosis, with hepatic coma, renal failure, ascites and clotting deficiencies as complicating factors. Bleeding varices must therefore be treated as an emergency. Resuscitation, endoscopic diagnosis and haemostasis are the cornerstones of treatment. Once bleeding varices have been identified, attempts to stop the bleeding must be made at once as this will lessen the chances of hepatic failure developing. Endoscopic sclerotherapy at the time of diagnosis is the best available treatment at present, although profusely bleeding varices can be difficult to see and inject. In these circumstances the passage of a Sengstaken tube should stop the bleeding, allowing later sclerotherapy to be successful. If rebleeding recurs and cannot be controlled, oesophageal transection with a stapling gun may be life-saving, although the varices may later recur and long-term endoscopic follow-up will be necessary. Portacaval shunting and the distal splenorenal shunt involve arduous surgery and are followed by a significant incidence of hepatic encephalopathy; they should be reserved for those few cases when simpler measures have failed, although shunts do lead to permanent decompression of the portal system. The acute variceal bleed may also be dealt with pharmacologically. Vasopressin, used in combination with nitroglycerin to lessen the harmful side-effects, is cheaper and as effective as terlipressin or somatostatin and its synthetic analogue octreotide. Several courses of injection sclerotherapy will be required to eliminate oesophageal varices. Thereafter, long-term follow-up will be necessary to deal with any recurrence. The place of non-selective beta-blockers is still contentious, but they do reduce portal pressure and may lessen the chance of rebleeding. There is also a growing role for hepatic transplantation, which not only eliminates the varices but also restores liver function to normal and greatly reduces the risk of subsequent hepatoma development.

Catheterization↗
PubMed1991

The effect of dietary taurine content on the plasma taurine concentration of the cat.

The essential role of taurine in the diet of the cat has been well documented and a deficiency of this nutrient is known to be responsible for a number of clinical conditions. At present, the National Research Council (1986) recommendation for the minimum dietary requirement of the kitten is 400 mg/kg dry matter and for a pregnant cat is 500 mg/kg dry matter. However, these minima were established by feeding the animals on semi-purified diets and, therefore, may be inappropriate for other dietary regimens. The aim of the present study was to investigate the effect of feeding a series of specially prepared diets containing different concentrations of taurine (canned diets 1475-5750 mg/kg dry matter, dry diets 811-1240 mg/kg dry matter) on the plasma taurine concentration of the cat. All diets were fed solus for 6 weeks and plasma taurine concentration was measured every 2 weeks. The results showed that to maintain plasma taurine values in the 'normal' range (less than 60 mumol/l), a canned diet must supply at least 39 mg taurine/kg body-weight per d and a dry diet at least 19 mg/kg body-weight per d; a cat fed on a semi-purified diet need only achieve a daily intake of at least 10 mg taurine/kg body-weight to maintain an adequate circulating level of taurine. The cause of the reduced availability of taurine from these diets is not yet known. Furthermore, repletion of plasma concentration above 60 mumol/l can be achieved within 2 weeks of feeding an adequate diet.

Animal Nutritional Physiological Phenomena↗
PubMed1991

Morphogenetic and regulatory effects of mutations in the envelope proteins of an avian hepadnavirus.

The envelope gene of the avian hepadnavirus, duck hepatitis B virus, was mutated in order to dissect the functions of the two major envelope proteins pre-S/S and S. Both envelope proteins were found to be required for virus particle assembly and secretion. The placement of stop codons after each of the first three AUG codons in the pre-S region allowed efficient translational initiation at downstream AUG codons to produce novel N-terminally truncated pre-S/S proteins. These proteins could substitute for pre-S/S protein in the production of enveloped virus production, but not in the production infectious virus. A mutant defective in myristylation of the pre-S/S protein produced reduced amounts of enveloped virus, and this virus was not infectious. Mutants defective in the pre-S/S protein accumulated high levels of covalently closed circular viral DNA (cccDNA) compared with the wild type or with a mutant defective in only the S protein. Hyperamplification of cccDNA resulted in high levels of viral RNA, consistent with the proposed role of cccDNA as the transcriptional template. Myristylation of the pre-S/S protein was not required for control of cccDNA amplification, and mutants that produced N-terminally truncated pre-S/S proteins displayed higher levels of cccDNA. We concluded that the pre-S/S protein, but not the S protein, is required for control of cccDNA amplification and persistent infection.

Animals↗
PubMed1991

Poisoning with oxybutynin.

A case of poisoning with 100 mg of oxybutynin in a 34-year-old female is reported. The main features were anticholinergic effects, including stupor, followed by disorientation and agitation on awakening, dilated pupils, dry skin and retention of urine. She had a sinus tachycardia which resolved 3 h after admission, and in addition ventricular ectopics and bigeminy which continued for a further 30 h. She recovered fully on symptomatic treatment alone.

Adult↗
PubMed1991

Nonoperative management of blunt splenic trauma in adults.

The management of isolated blunt splenic trauma in adults is controversial. The authors present a series of 17 patients with blunt splenic trauma who were selected for nonoperative management. Only one patient eventually required surgery, for a ruptured spleen. Complications included pneumonia (two cases) and pleural effusion, atelectasis and ileus (one case each). There were no deaths. Five patients required transfusion, for a total of 17 units of blood. The mean length of hospital stay was 9.4 days. Comparison with a group of 17 patients treated operatively during the same period showed that those treated nonoperatively had fewer complications, required less blood and had a similar length of hospital stay. The authors conclude that nonoperative management of selected patients with isolated blunt splenic trauma is safe, if the patient's condition is closely monitored.

Adolescent↗