ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1977.tb01602.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

Abstract.Experiments were performed to elucidate the mechanisms involved in the enhanced conversion of amino acids to glucose in acute uraemic rats. Increased gluconeogenesis from a mixture of serine, threonine, lysine, glutamate, ornithine and citrulline was confirmed using a non‐recirculating perfusion system. Stimulation was concentration dependent, being most pronounced at physiological amino acid concentrations. Stimulation of glucose and urea formation could be mimicked by using serine alone whereas with lactate and pyruvate inhibition of gluconeogenesis was observed. Serine dehydratase activity was significantly elevated following nephrectomy. Further, the uptake of the non‐metabolizable amino acid α‐aminoisobutyrate was considerably increased. It is concluded that serine may play a special role as substrate for the additional glucose formation in acute uraemic rats, probably mediated by an activation of serine dehydratase. Acceleration of amino acid transport seems to represent an additional component of stimulation of amino acid utilization in acute u

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1977.tb01603.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

Abstract.Drug metabolizing capacity was investigated in sixteen patients with cancer in the liver by comparingin vivo(antipyrine disappearance rate from plasma) andin vitro(cytochrome P‐450, benzpyrene hydroxylase, and 7‐ethoxycoumarin O‐deethylase activities in liver biopsies) indices of drug metabolism with the condition of tumour‐free liver parenchyma and with biochemical liver function tests. Drug metabolism was impaired as antipyrine hydroxylation was significantly lower than in matched controls. Impairment of antipyrine metabolism was related to the pathological changes in the liver; patients with metastatic liver cancer or with tumour and cirrhosis metabolized antipyrine at a reduced rate, whereas those with a hepatoma occupying from 20 to 80% of the liver volume had normal antipyrine metabolism. Liver enzyme activities were related to the site of the biopsy; values were low in and around the tumour tissue and high in normal parenchyma. The antipyrine half‐life was related to serum albumin concentration but not to other liver function tests. The results demonstrate that in liver cancer patients the drug‐hydroxylating capacity is dependent on the ability of the tumour‐free parenchyma to metabolize drugs. Hence quantitative evaluation of liver changes together with tests measuring liver synthetic capacity might be of significance when predicting drug metabolism in patients with hepat

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1977.tb01604.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

Abstract.The incorporation rate of leucine into albumin and the incorporation rate of leucine into hepatic proteins were determined in human liver tissue slices.Leucine was linearly incorporated into hepatic tissue albumin, into albumin released into the incubation medium, and into hepatic proteins during 4 h incubation. Amino acids stimulated the albumin and hepatic protein synthesisin vitroandin vivo. The incorporation rate of leucine into hepatic albumin and tissue proteins was correlated to hepatic RNA concentration.In twenty‐one experiments the mean incorporation rate of leucine into hepatic tissue immunoreactive albumin was 5.1±0.6 μmol leucine h‐1g albumin‐1(mean±; SEM), and 0.87±;0.17 μmol leucine h‐1g albumin‐1into albumin released to the incubation medium. By crossed immunoelectrophoresis, the hepatic immunoreactive albumin could be partly resolved into two components one of which migrated at the same rate and the other at a lower rate than serum albumin. Treatment of the slowly migrating component with a low concentration of trypsin changed its mobility to that of serum albumin. Gel filtration through Sephadex G‐100 of the slowly migrating fraction showed that it had similar molecular size as that of serum albumin. The results support the hypothesis that human hepatic albumin biosynthesis involves a polypeptide precursor similar to that described f

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1977.tb01605.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

Abstract.Serum 25‐hydroxyvitamin D (25‐OH‐D) was measured by means of a sensitive competitive protein binding assay in forty‐five patients with conservatively treated renal disease and in fifteen patients on chronic dialysis. The mean concentration of 25‐hydroxyvitamin D in twenty‐five normal subjects was 41.4 nmol/l with a range from 19.2 to 90 nmol/l. Fourteen patients with chronic pyelonephritis (creatinine clearance over 25 ml/min) had normal serum 25‐OH‐D. Low values were found in twelve patients with nephrotic syndrome (mean 11.2 nmol/l, range 1–19 nmol/l) and in these subjects the serum 25‐OH‐D levels were inversely correlated with the 24 h urinary protein loss. In thirteen conservatively treated uraemic subjects without significant proteinuria, the mean 25‐OH‐D was 29.4 nmol/l (range 18.2–41.4 nmol/l), whereas in six uraemics losing more than 3 g protein in 24 h urine the mean was 14.2 nmol/l, range 5.2–23.2 nmol/l.Fifteen patients on chronic dialysis were routinely given a multi‐vitamin preparation providing 125 nmol (2000 i.u.) vitamin D3daily, and their mean 25‐OH‐D concentration in March 1975 was 51.4 nmol/l. In August 1975, 25‐OH‐D averaged 89.1 nmol/l suggesting seasonal variation and possible role of endogenous vitamin D production in the prevention of

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1977.tb01606.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

Abstract.Total serum haemolytic complement activity, plasma fibrinogen, erythrocyte sedimentation rate and other biological values in forty‐three patients with Hodgkin's disease were correlated with results of staging.A highly significant increase (P = 10‐5) of the mean total serum haemolytic complement activity was found in stages IIIA and IVA and in all stages with systemic symptoms. The complement activity in patients with less extensive disease without systemic symptoms (stages IA and IIA) did not show a significant increase over the controls.The best initial parameters correlating well with disease activity were complement activity, ESR and fibrinogen level. It is concluded that total serum haemolytic complement activity gives additional information and can be helpful in differentiating between favourable and unfavourable forms of Hodgkin's dise

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1977.tb01607.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

Abstract.The concentration of immunoreactive prolyl hydroxylase was measured in human skin, serum and synovial fluid. In skin concentrations of the immunoreactive enzyme protein and the enzyme activity were highest in foetuses, at an intermediate level in 0–1‐year‐old children and lowest in adults. About 13–19% of the enzyme protein in foetal skin was in the active form compared with 2–4% in the adult. Concentrations of immunoreactive prolyl hydroxylase in serum were lower than in skin and no changes were found with age. The concentration of immunoreactive prolyl hydroxylase in synovial fluid of the knee joint in patients with traumatic effusion was about half that found in serum.The ratio of enzyme tetramer, which is the active form of the enzyme, to the total immunoreactive protein was studied by gel filtration. In foetal skin, about 15–20% of the total immunoreactive protein was present in tetramer form, and a good correlation was found between the ratio of enzyme tetramer to the total immunoreactive protein and the ratio of enzymic activity to the concentration of total immunoreactive enzyme. Small amounts of enzyme tetramer were found in the serum and synovial fluid. The data suggest that the activity of prolyl hydroxylase in human tissues may be partly controlled by a mechanism involving changes in the ratio of the active enzyme tetramer to total enz

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1977.tb01608.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

Abstract.The regulation of sterol synthesis and 3‐hydroxy‐3‐methylglutaryl CoA reductase (HMG‐CoA reductase) activity in leucocytes has been studied in seventy‐five subjects of whom thirteen had familial hypercholesterolaemia (heterozygous). The activity of HMG‐CoA reductase in leucocytes was closely parallel to the incorporation of14C‐acetate into sterols over a wide range of activities, suggesting that the enzyme is ratedetermining for the pathway. When six obese subjects were placed on an acaloric diet for 7 days sterol synthesis declined by 75% in adipocytes but was unaffected in leucocytes. A low cholesterol diet (<250 mg/day) for 7 days did not affect sterol synthesis in either cell type.In subjects with familial hypercholesterolaemia (heterozygous) the enzyme tended to increase to higher levels than controls when leucocytes were incubated in a lipid‐deficient medium; but a more marked abnormality was a failure of suppression of the enzyme when leucocytes from affected subjects were returned for 8 h to a medium containing low‐density lipoprotein. In one kindred the index patient with severe heterozygous familial hypercholesterolaemia had a normally regulated enzyme whereas his affected siblings (brother and sister) showed incomplete suppression of the enzyme by low‐density lipoprotein.It is concluded that loss of regulation of HMG‐CoA reductase may be phenotypically linked to the origin of familial hypercholesterolaemia and in most cases provides a useful genetic m

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1977.tb01609.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

Abstract.The effect of vitamin A, a membrane surface‐active agent, on parathyroid hormone secretion was studiedin vitro, using bovine parathyroid tissue, andin vivoin man. Parathyroid tissues were incubated with vitamin A (retinol), retinoic acid, and calcium, and with hydrocortisone and vitamin E, agents that antagonize the membrane effects of vitamin A. The stimulation of parathyroid hormone release by vitamin A, 10‐6to 10‐9mol/lin vitro, was dose and time dependent. Retinoic acid did not stimulate secretion. High calcium concentration, hydrocortisone, 10‐5mol/l and 10‐6mol/l, and vitamin E, 10‐5mol/l, antagonized vitamin A‐induced parathyroid hormone secretion. Vitamin A increased the lysosomal cathepsin D activity of parathyroid tissues.In human studies, eleven healthy men received two intramuscular injections of vitamin A palmitate, 25 000 units each, within 24 h. In every subject, serum parathyroid hormone increased after vitamin A administration.Our studies indicate that: (1) vitamin A stimulates parathyroid hormone secretionin vitro, possibly through modification of the cell or secretion granule membrane, or through stimulation of lysosomal proteolytic activity, and (2) vitamin A increases serum parathyroid hormonein vivo, and this effect may be important in clinical states of vit

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1977.tb01610.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY

摘要:

Abstract.In this study the effect of calcium infusion over 3 h without gastric aspiration on serum gastrin was determined in fifteen normal subjects, ten patients with duodenal ulcer, nine with stomal ulcer, five with total gastrectomy, six with achlorhydria and sixteen with proved or presumed Zollinger‐Ellison (ZE) syndrome. Serum gastrin only rose significantly in the patients with ZE‐syndrome or achlorhydria. An increase of above or below 50% of basal value seems to be a valuable criterion by which to differentiate between patients with and without ZE‐syndrome. Serum gastrin levels in forty‐four patients with chronic hypercalcaemia (72±24 pg/ml, mean± SD) were not significantly different from the levels in 100 normal subjects (66±18 pg/ml;p>0.10). However, in one patient with ZE‐syndrome and in two patients with achlorhydria serum gastrin values were markedly higher during chronic hypercalcaemia than during normocalcaemia.It is concluded that acute or chronic hypercalcaemia without gastric aspiration does not lead to hypergastrinaemia in the absence of ZE‐syndrome o

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1977.tb01611.x

出版商:Blackwell Publishing Ltd    

年代:1977

数据来源: WILEY