摘要:

Abstract.Polyploidization is a distinctive feature of megakaryocyte differentiation. The physiological meaning and the regulation of this process are obscure. Megakaryocyte ploidy varies in normal biology and in disease. Here we review the evidence suggesting that ploidy changes may have a role in the determination of platelet reactivity and in the aetiology of coronary artery occlusion. We also present a hypothesis that may serve as a framework to explore the regulation of megakaryocyte polyploidization at the molecular level and also may provide a rational basis to explain the occurrence of ploidy changes in ischaemic heart disease.

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00711.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.Paracrine interactions between fibroblasts residing in the retro‐ocular space and infiltrating lymphocytes/macrophages are thought to be of central importance in the pathogenesis of Graves' opthalmopathy (GO). Although various roles have been suggested for interferon‐γ (IFNγ), tumour necrosis factor‐αTNFα) and interleukin‐lα (IL‐lα) in GO, their actual presence in Graves' retro‐ocular connective tissue has not been demonstrated. We examined surgical specimens obtained during orbital decompression from patients with severe GO (n= 6), and from normal individuals (n= 5), for the presence of IFNγ, TNFα and IL‐1α. We used immunohistochemical methods on frozen tissue sections and primary fibroblast cultures, and sodium dodecylsulfate polyacryl‐amide‐gel electrophoresis of tissue extracts and tissue culture supernatants. In addition, immunohistochemical staining of tissues for characterization of the mononuclear cell infiltrates was performed. Aggregates of mononuclear cells in retro‐ocular connective and fatty tissue were found in five of six GO tissue specimens, but in none of the control specimens. We detected immunoreactivity for the three cytokines (IFNγ, TNFα and IL‐lα) in the five GO tissue specimens that contained mononuclear cell aggregates. In addition, IL‐la immunoreactivity was demonstrable in primary and subsequent GO fibroblast cultures and in their supernatants. In contrast, no immunoreactivity for any of these cytokines was detected in tissue specimens, primary cultures or culture supernatants derived from normal individuals. The presence of mononuclear cell infiltrates and associated immunoreactivity for IFNγ, TNFα, IL‐1α in retro‐ocular connective tissue derived from patients with GO suggests that the previously demonstratedin vitrofunctions of these cytokines may indeed be operativein vivo. Our results further support the concept that IFNγ, TNFα and IL

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00712.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.Among the various immune abnormalities which characterize active sarcoidosis, a low proliferative response of peripheral blood lymphocytes to mitogenic lectins has long been observed. Since membrane‐associated G‐proteins are very likely to be crucial elements in lectin signal transduction, we investigated the binding of 5′‐guanylylimidodiphosphate (GppNHp), a non hydrolyzable GTP analogue, to blood total lymphocyte membranes and to blood T‐lymphocyte membranes from patients with active sarcoidosis, and from healthy control subjects. GppNHp binding was markedly decreased in peripheral cells from patients with sarcoidosis as compared to controls, suggesting the occurence of a detect at the level of G‐protein(s). A further characterization of G‐proteins in these cells by means of ADP‐riboselabelling in the presence of bacterial toxins brought forward a significant decrease in the labelling of a 40 kDa protein, the major pertussis toxin substrate, in membranes from sarcoid patients, while the labelling of the major 44 kDa cholera toxin substrate proved to be unchanged with respect to control membranes. It is hypothesized that, in sarcoid lymphocytes, a detect in the negative control of adenylate cyclase mediated by the inhibitory G‐protein Gi, prevents the lowering of cAMP necessary to normal mitogenic response of blood lymphocytes to stimulation. cAMP degradation by the specialized enzyme phosphodiesterase constitutes another critical step in the control of cAMP levels. Both CAMP and cGMP phosphodiesterase activities were found decreased in blood total lymphocyte preparations from sarcoid patients. With purified T‐cells, although the mean cAMP and cGMP phosphodiesterase activities from sarcoid patients were found more markedly decreased with respect to healthy donors, only the decrease in cGMP phosphodiesterase was found statistically significant. The role these detects in cyclic nucleotide degradation potentially play in the disturbance of blood lymphocytes response associated with sarc

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00713.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.The aim of this study was to evaluate the biotransformation of orally administered ursodeoxycholic acid in man. The distribution of ursodeoxycholic acid and its metabolites in gallbladder bile, in serum and in urine with emphasis on separation of their unconjugated, amidated and sulfated species in particular, was investigated. Seven gallstone patients were given 750 mg of ursodeoxycholic acid daily for 2–3 weeks. Six gallstone patients who did not receive ursodeoxycholic acid served as controls. Ursodeoxycholic acid became the major bile acid in gallbladder bile contributing 43% to total bile acids. 2% of biliary ursodeoxycholic acids were in the unconjugated form, 87% in the amidated form and 11% in the sulfated form. Iso‐ursodeoxycholic acid was found in bile in small amounts and was present only as the sulfated species and not as the amidated one. Other metabolites of ursodeoxycholic acid tentatively identified in bile were 1β, 12β, 6α‐ and 21,22‐hydroxylated derivatives of ursodeoxycholic acid. Lithocholic acid in bile tended to increase under ursodeoxycholic acid treatment and was positively correlated to ursodeoxycholic acid. The concentration of cholic acid in bile decreased significantly whereas the levels of deoxycholic acid and chenodeoxycholic acid did not change. Total bile acid concentration in serum and excretion of bile acids in urine increased from 5.4 ± 1.1 to 18.4 ± 9.5 μmol l‐1(mean ± SD,P<0.005) and from 5.6 ± 1.3 to 13.1 ± 7.9 μmol g‐1creatinine (mean ± SD,P<0.05) after ursodeoxycholic acid ingestion mainly due to spillover and excretion of ursodeoxycholic acid. Ursodeoxycholic acid became the major bile acid in serum and urine contributing 46% and 50% to total bile acids. 14% ursodeoxycholic acid in serum were in the unconjugated form, 42% in the amidated form and 45% in the sulfated form; the percentages in urine were 11%, 23% and 66%. Iso‐ursodeoxycholic acid was higher in serum and urine than in bile and contributed 16% and 8% to total bile acids. Iso‐ursodeoxycholic acid was present in serum and urine only as the unconjugated and sulfated species. Other iso‐bile acids and 3β‐hydroxy‐5‐cholenoic acid were found in bile only in traces, but contributed 8% to total bile acids in serum and 10% in urine. In serum and urine the sulfated form of lithocholic acid prevailed and was significantly enhanced after ursodeoxycholic acid ingestion. Further metabolites of ursodeoxycholic acid in urine were tentatively identified to be hydroxylated at postitions 1β, 5α, 6α and 22 and co

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00714.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.The effects of human atrial natriuretic peptide (ANP) on glomerular filtration rate (GFR), renal plasma flow (RPF), urinary flow rate, urinary sodium excretion, tubular function estimated by lithium clearance, and plasma levels of sodium and water homeostatic hormones were studied in a dose‐response study with 50 healthy subjects. Placebo or ANP 0.5, 1.0, 1.5, or 2.0 μg kg‐1bwt was given as an intravenous bolus injection to five different groups. GFR rose after ANP, whereas no immediate change in RPF was observed. Significant increases with no distinct additional effect of ANP doses higher than 1.0 μg kg‐1were detected in filtration fraction, urinary flow rate and urinary excretion rate of sodium. Both proximal and distal fractional reabsorption of sodium was reduced and the effect seemed to flatten out at doses higher than 1 0 μgkg‐1. Dose‐dependent increases in cyclic guano‐sine monophosphate in urine and plasma were found after ANP bolus injection, and the rise in both was correlated with the increase in urinary sodium excretion. ANP caused a dose‐dependent decrease in blood pressure and an increase in pulse rate. Plasma concentrations of angiotensin II and arginine vasopressin did not change after ANP.In summary, we found that ANP bolus injection caused a natriuresis and diuresis in healthy man with a threshold at a dose of 1.0 μg kg‐1. No distinct further renal effects were observed with higher doses despite dose‐dependent increases in urinary cGMP excretion and plasma cGMP. Inhibition of both proximal and distal tubular fractional sodium reabsorption by ANP contributed to the natriuretic effect. The correlation between the rise in cGMP and the increase in urinary sodium excretion is concordant with cGMP being a secondary mes

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00715.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.The aim of this study was to demonstrate significant factors behind elevated resting energy expenditure in weight‐losing cancer patients. There tore, weight‐losing cancer patients (n= 60), with normal liver and kidney function tests, were randomized to receive one of four drug treatments for 5 days: (a) Propranolol 80 mg × 2 (β‐adreneceptor blockade); (b) Indomethacin 50 mg × 2 (prostaglandin synthesis inhibition); (c) Morphine 5 mg × 3 (pain reliet) or (d) Placebo x 2. A reterence group of healthy well‐nourished individuals were examined outside the formal randomization protocol and they received Propranolol 80 mg × 2. The cancer patients were randomized by a computer based algorithm stratifying for measured resting energy expenditure (REE), body composition, biochemical tests, previous therapy, tumour type and tumour stage. Resting energy expenditure was measured by indirect calorimetry in the morning after an overnight fast betore and after drug treatment. β‐blockade reduced REE significantly in cancer patients from 1416 ± 95 kcal day‐1to 1160 ± 63 kcal day‐1(P<0.02) and from 1472 ± 69 vs. 1398 ± 62 kcal day‐1, (P<0.01) in the well‐nourished reterence individuals. The reduction found in cancer patients (10%) was significantly larger than that in the group of reterence patients (5%), (P<0.01). Indomethacin, morphine or placebo did not induce any significant alteration in energy expenditure in our cancer patients. Propranolol treatment was associated with a significant reduction in plasma concentrations of free fatty acids (FFA), but not in plasma glycerol. Our results support the suggestion that adrenergic factors are the most important mediators behind elevated resting energy expenditure in weight‐losing cancer patients. Such factors were more important than inflammation and cytokine production related to pro

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00716.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.Pharmacological suppression of lipolysis is being increasingly used in the treatment of diabetic hyperlipidaemia. Although theoretical hazard of such treatment is that recovery from hypoglycaemia might be impaired. Seven normal subjects were theretore studied on two occasions, following treatment with a single dose of either acipimox 250 mg or placebo. Hypoglycaemic recovery was unaffected, despite effective suppression of plasma non‐esterified fatty acid levels with acipimox. The results suggest that under these conditions activation of lipolysis may not be essential to recovery from hypoglycaemi

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00717.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.It has recently been demonstrated that the infusion of a high caloric load (3.3 kcal min‐1≙ 14.0 kJ min‐1) into human upper jejunum inhibited pancreatic enzyme and bile salt secretion. The aim of the present study was to investigate whether this phenomenon was mediated by gastrointestinal hormones which interfere with pancreatic secretion. In six healthy volunteers, jejunal infusion of 1.3 kcal min‐1(5.5 kJ min‐1) did not modify secretion of lipase and chymotrypsin to any significant extent compared with saline infusion, but the rate of 3.3 kcal min‐1(14.0 kJ min‐1) resulted in an inhibition. Somatostatin and pancreatic polypeptide, which are known to inhibit exocrine pancreatic secretion, remained unchanged during jejunal nutrient infusion. The inhibition of pancreatic enzyme secretion was observed in temporal relationship with an increase of the stimulators of pancreatic exocrine secretion such as secretin, neurotensin, and CCK. The existence of an hitherto undetined inhibitor and a feedback mechanism

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00718.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.Calcium has been proposed to prevent colon cancer in subjects at risk for this tumour. This effect is supposed to be due at least in part to binding the bile acids to calcium, making them insoluble and harmless. To evaluate the effects of oral calcium supplementation on intestinal bile acids, 19 patients with adenomatous colonic polyps were supplemented with 35.5 mmol Ca2+daily for 12 weeks. Duodenal bile, 24‐h feces and 24‐h urine were collected betore and at the end of the 12‐week period. In duodenal bile proportional concentration of cholic acid increased (38 ± 4 vs. 51 ± 3%,P<0.001), whereas that of chenodeoxycholic acid decreased (35 ± 3 vs. 25 ± 2%,P<0.01). Total fecal bile acid excretion increased (950 ± 126 vs. 1218 ± 137 μmol 24 h‐1P<0.01), with proportional concentrations of the main primary and secondary bile acids remaining the same. Cytolytic activity of fecal water, measured by the degree of lysis of erythrocytes by the water, decreased (45 ± 8 vs. 30 ± 7%,P<0.05). Total excretion of calcium increased as expected from the supplementary dose. It is concluded that calcium supplementation markedly affects intestinal bile acids and lytic activity of fecal water and that, in view of similar results during 1‐week calcium supplementation in young healthy subjects, these effects remain constant over at least 3 months and occur both in healthy persons and in patients at increased ris

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00719.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00710.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY