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Biomedical subjects

J E Gardiner

Publications and source records attributed to J E Gardiner.

At least 19 recordsLinked to original sources
PubMed1984

Studies on human protein C inhibitor in normal and Factor V/VIII deficient plasmas.

Activated protein C is a potent anticoagulant which inactivates Factors V and VIII in plasma. Normal plasma contains an inhibitor of activated protein C. A previous report from our laboratory hypothesized that the absence of this inhibitor in plasmas from patients with combined Factor V/VIII deficiency could be the molecular basis for this disease. This report demonstrates the presence of protein C inhibitor in those Factor V/VIII deficient plasmas originally studied. Freezing and thawing significantly reduced the ability of normal and Factor V/VIII deficient plasmas to inhibit activated protein C. It is suggested that this explains the conflicting literature reports describing functional assays of protein C inhibitor in Factor V/VIII deficient plasma. This observation also emphasizes that extreme care must be used in handling and storing plasma samples that are to be assayed for protein C inhibitor.

Factor V Deficiency↗
PubMed1984

Treatment of pyoderma gangrenosum with disodium cromoglycate.

The case of a 35-year-old black woman with a 10-year history of ulcerative colitis and a 3-year history of pyoderma gangrenosum is presented. The pyoderma gangrenosum was treated successfully with topical application of disodium cromoglycate.

Administration, Topical↗
PubMed1984

Proteolytic inactivation of human factor VIII procoagulant protein by activated human protein C and its analogy with factor V.

Purified human factor VIII procoagulant protein (VIII:C) was treated with purified human activated protein C (APC) and the loss of VIII:C activity correlated with proteolysis of the VIII:C polypeptides. APC proteolyzed all VIII:C polypeptides with mol wt = 92,000 or greater, but not the doublet at mol wt = 79-80,000. These results and our previous thrombin activation studies of purified VIII:C, are analogous with similar studies of factor V and form the basis for the following hypothesis: activated VIII:C consists of heavy and light chain polypeptides [mol wt = 92,000 and mol wt = 79-80,000 (or 71-72,000), respectively] which are similar in Mr to the heavy and light chains of activated factor V. Thrombin activates VIII:C and V by generating these polypeptide chains from larger precursors and APC inactivates both molecules by cleavage at a site located in the heavy chain region of activated VIII:C and V.

Antigens↗
PubMed1977

Effect of two hemicholiniums on the disposition and distribution of endogenous free choline in anaesthetized rabbits.

1 The effects of hemicholinium no. 3 (HC-3) and its p-terphenyl analogue (TPHC-3) on the disposition and distribution of free choline were studied in rabbits under pentobarbitone anaesthesia. Free choline was determined by bioassay. 2 The respiration of animals given 0.35 mumol/kg of HC-3 was hardly affected; however, 4 out of 6 rabbits given the same dose of TPHC-3 exhibited varying degrees of respiratory impairment. All animals that received 2 injections (1 h apart) of either HC-3 (1.4 mumol/kg) or TPHC-3 (0.7 mumol/kg) developed respiratory difficulty about 1 h after the second injection. 3 The respiratory distress was accompanied by a 2 to 15-fold rise in plasma choline concentration. This rise has been attributed to hypoxia. 4 In experiments in which choline has been infused it was observed that HC-3 could impair the animal's ability to dispose of exogenous choline. In control rabbits neither HC-3 nor TPHC-3 produced changes in plasma choline concentrations unless the respiration was depressed. 5 Either HC-3 or TPHC-3 (both at 0.35 mumol/kg) significantly (P less than 0.05) reduced the kidney choline concentration by 40% and 30% respectively; both hemicholiniums raised the lung choline concentration by about 35%. Only TPHC-3 caused a significant rise (40%) in liver choline. The choline concentrations in other tissues were unaffected by the hemicholiniums.

Animals↗
PubMed1974

The distribution in the rabbit of choline administered by injection or infusion.

1. The concentration of choline in plasma, erythrocytes, skeletal muscle, heart, lung, liver, small intestine and kidneys and the changes that follow the injection or infusion of choline have been measured in rabbits anaesthetized with pentobarbitone.2. The concentration of choline in the plasma of arterial blood was 11.8 +/- 0.6 n-mole/ml. and in the erythrocytes 28.4 +/- 1.3 n-mole/ml. blood.3. All tissues contained a higher concentration of free choline than did plasma. The values range from 19.1 +/- 2.2 n-mole/g in skeletal muscle to 500 +/- 25 n-mole/g in the kidney.4. In order of their choline concentrations the tissues were intestine (duodenal end) > kidney > intestine (caecal end) > liver > lung > brain > heart > erythrocytes > (blood) > skeletal muscle > plasma, while in order of the contribution to the total body choline they were liver > intestine > skeletal muscle > (blood) > kidney > erythrocytes > lung > brain > plasma > heart. The total free choline determined by these analyses was between 30-40 mumole/kg body weight, about one third being present in the liver.5. The choline content of the small intestine varied along its length. The lowest amount being present in the portion adjoining the caecum.6. Within 1 min of the injection of choline 100 or 300 mumole/kg, 70-90% had left the circulation. The proportionate loss was higher after 100 mumole/kg than after 300 mumole/kg.7. The loss following 300 mumole/kg was increased if that dose were preceded by a dose of 100 mumole/kg 40 min earlier; this suggests some additional disposal mechanism(s) had been activated by the first dose.8. Three minutes after the injection of choline 300 mumole/kg, about 60% was present as free choline in the tissues studied. The order of the concentration increases was kidneys > liver > muscle > lung > small intestine (caecal end) > heart > intestine > small intestine (duodenal end) > brain.9. Forty minutes after the injection of choline 300 mumole/kg, only 11% could be accounted for as free choline. Only the levels in the kidney, liver, muscle and lung were significantly above normal at this time.10. Infusion of choline 0.8 mumole/kg. min or greater produced rises in plasma choline that corresponded to a clearance of 32 ml. plasma/kg. min.11. After the infusion of 300 mumole/kg over a period of 1 hr, raised levels of choline were detected in all tissues assayed, but the amount found accounted for only 14% of the choline administered. The concentrations in the kidney, liver and lung were similar to those found 40 min after the injection of 300 mumole/kg.12. There was no change in the concentration of choline in the erythrocytes after the injection of choline 100 or 300 mumole/kg, nor during the infusion of choline at the rate of 5 mumole/kg. min for 1 hr.13. The plasma volume appeared to be affected by the injection of the large doses of choline; after choline 300 mumole/kg the plasma volume was reduced. No effect on the plasma volume was observed during the infusion of the same dose.

Animals↗
PubMed1972

The control of the plasma choline concentration in the cat.

1. Changes in choline concentration of the blood after injections or infusions of choline were studied in cats anaesthetized with chloralose.2. Single I.V. injections of choline 10-100 mumole/kg produced arterial plasma levels 1 min later corresponding to an apparent volume of initial distribution of 430 ml./kg. The concentration then declined rapidly (half-time, 1-2 min), with a later slower decline after large doses.3. Infusions of choline at a rate of 0.8 mumole/kg.min or greater produced steady rises in plasma level, corresponding to a clearance of 28.6 ml. plasma/kg.min. The half time of rate of approach to steady state was 7 min or less. Infusions at rates of 0.40 mumole/kg.min or less produced much smaller or negligible rises, suggesting mechanisms for disposal which were saturated at higher concentration. At low rates, little infused choline appeared in urine. At the end of an infusion, the plasma choline level usually fell without delay.4. Portal blood contained about 50% of the arterial level, renal venous blood 15-70%, caval blood 30-60%, and amniotic fluid 2.5%. Occlusion of renal coeliac or mesenteric arteries raised plasma choline, but relatively rapid choline removal still occurred in the eviscerate animal.5. After infusions of [methyl-(14)C]choline, the level of radioactivity retained in the circulation amounted to only a few per cent of the total dose infused. At low rates of infusion (0.0125-0.1 mumole/kg.min) the radioactivity represented only a small fraction of bio-assayable choline; but at 0.40 mumole/kg.min it came to exceed the concentration of free choline, indicating metabolic conversion. Only traces of (14)C were found in expired air, and only 1-1.5% of total infused radioactivity in the urine. After infusion of 150 mumole over 3 hr, high levels of radioactivity were found in liver, kidney, lung, brain and heart, but levels in muscle and spleen were comparable to that of blood.6. It was concluded that choline is rapidly lost from the blood, that the abdominal viscera, liver, kidney and lung are important extraction sites, that some partial metabolism occurs, the metabolites also being rapidly lost from blood, and that it is probable that choline lost to the tissues becomes bound in some form.

Animals↗