摘要:

Abstract.Antibodies against haemopoietic differentiation antigens are widely used for the identification and classification of leukaemic cells. Mast cells are distinct haemopoietic cells and express a unique composition of antigens. They can be differentiated from basophils and all other lymphohaemopoietic cells by using antibodies to cell surface receptors and granular mediator molecules. This paper provides evidence that antibodies against mast cell antigens can be used to identify and classify malignant cell populations in patients with mastocytosis.

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01948.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01949.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Haemolytic anaemia induced by phenylhy‐drazine (PZ) promotes iron absorption across rat small intestine. This present study investigates the role of the brush border potential difference (Vm) and mucosal reducing activity in the response. In addition, quantitative autoradiography was used to assess PZ‐induced changes in the villus localization of brush border iron uptake. Iron transfer from duodenum to blood was increased significantly 5 days after treatment with PZ. Autoradiography showed that most brush border iron uptake occurred at the upper villus region and the maximal rate was increased fourfold by PZ. Duodenal villus length was increased in PZ‐treated rats. PZ treatment did not influence mucosal reducing activity butVm, measured using duodenal sheets, increased from ‐50 to ‐57mV {P<0.001) and this was due to a reduced brush border sodium permeability. Thus, an expanded absorptive surface and an enhanced electrical driving force for iron uptake across the duodenal brush border are important adaptations for increased iron absorption in PZ‐induced haemoly

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01950.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Atrial natriuretic peptide (CDD/ANP‐99–126) has been identified as a bronchodilator in various species including humans. We investigated the effect of urodilatin (CDD/ANP‐95–126) in 18 clinically stable asthmatics showing an increase of the FEV1by ≥15% after salbutamol inhalation. Prior to the study inhaled β2‐agonists were withheld for 8 h. After baseline measurements of lung function parameters (FEV1, VC, PEF, MEF75, MEF50, MEF25), blood pressure, and heart rate in intravenous infusion of 20, 40 or 60 ng kg‐1min‐1urodilatin was administered for 40min in the morning. All measurements were repeated every 10 min during the infusion, for 30 min thereafter, and after the inhalation of l.25 mg salbutamol. Forty and 60 ng kg‐1min‐1urodilatin showed a significant effect on the central (FEVl, PEF, MEF75) and peripheral airways (MEF50, MEF25) after 10 min infusion (P<0.05). A broncho‐dilation not significantly different from l.25 mg salbutamol was induced by 40 ng kg‐1min‐1in the central airways only, while 60 ng kg‐1min‐1led to a similar effect at all levels of the bronchial tree. Lung function parameters returned to baseline within 30 min after cessation of the urodilatin infusion. Heart rate showed a tendency to increase after 40min infusion (P<0.05), but blood pressure did not change significantly. In conclusion, the maximal bronchodilating effect of intravenous urodilatin in clinically stable asthmatics was co

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01951.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Although in therapeutic use for more than a century, the mode of cellular action of organic nitrates remains incompletely understood. Despite ample experimental evidence from animal studies to show that nitrates are metabolized to NO in the vascular smooth muscle, direct demonstration of such an activity in human vascular cells is still lacking. Moreover, the role of the endothelium in modulating the pharmacodynamic action of nitrates is far from clear. We therefore aimed to investigate whether or not human endothelial cells are capable of bioactivating these drugs to NO and whether the amounts generated are sufficient to elicit any biological effects. Using cultured human umbilical vein endothelial cells (HUVECs) as an established model system a combination of three different methods was used to address this issue: (1) quantification of NO formation upon endothelial nitrate metabolism using the oxyhaemo‐globin technique; (2) evaluation of the second messenger response using radioimmunoassay for cGMP; and (3) assessment of mechanism and extent of potentiation of the anti‐aggregatory effect of nitrates in the presence of endothelial cells as a relevant bioassay. We now show that superfusion of cultured human endothelial cells on microcarrier beads with either glyceryl trinitrate (GTN) or isosorbide dinitrate (ISDN; both at 01.100 μmol L‐1) results in a concentration‐dependent formation of NO. NO generation from isosorbide 5‐mononitrate (IS‐5‐N) was below the detection limit. The amounts of NO produced (maximally 2–97 ± 0.98 pmoles NO min‐1x mg protein with 100μmol L‐1GTN;n= 8) were similar to those elicited upon challenge of the cells with 100nM bradykinin. NO formation from either organic nitrate was accompanied, in a concentration‐dependent and methylene blue‐inhibitable manner, by stimulation of endothelial soluble guany‐lyl cyclase with consequent increases in the intracel‐lular level of cGMP (maximally 32‐fold over basal levels with ISDN), a significant portion of which was released into the extracellular space. Upon continuous 30 min superfusion or repeated application of high concentrations of GTN (100μmol L‐1) nitrate bioac‐tivation to NO was subject to partial tachyphylaxis. Co‐incubation of washed human platelets with HUVECs potentiated the anti‐aggregatory action of nitrates in a cell number dependent and oxyhaemo‐globin‐sensitive manner and this effect, too, was accompanied by increases in intraplatelet cGMP levels. The potentiating effect was largely inhibited after blockade of sulfhydryl groups by pre‐incubadon of HUVECs with N‐ethylmaleimide and completely abrogated after pretreatment of cells with the tissue fixative glutaraldehyde. These results demonstrate that human endothelial cells are capable of bioactivating organic nitrates to NO by an enzymatic, apparently thiol‐sensitive pathway, in quantities sufficient to influence endothelial and platelet function. Besides the well known vasorelaxant action of organic nitrates, which is mainly due to their metabolism in the smooth muscle compartment, these drugs may therefore be endowed with a hitherto underestimated potential to directly influence endothelial functions via the NO/ cGMP pathway. Through specific bioactivation in the endothelium itself organic nitrates can thus mimic and reinforce protective functions normally served by a functional endothelium such as the modulation of blood cell/vessel wal

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01952.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Gallbladder stasis is frequent in obese subjects and may contribute to their increased risk for gallstone formation. The bile salt sequestrant cholestyramine acutely enhances postprandial gallbladder emptying in lean subjects, through dis‐inhibition of a negative feedback between intraluminal bile salts and CCK release. In this study the effect of cholestyramine on both gallbladder and gastric antrum dynamics were studied by realtime ultrasonography in 12 obese and 15 lean subjects. For the acute study, on different days, subjects ingested a liquid meal (two egg yolks plus water 200 mL, 50 kJ) or a meal with 4g cholestyramine. Gallbladder emptying was impaired in obese patients who had significantly larger fasting gallbladder volume (39.4 ± 6.9 vs. 21.6 ± l.7mL,P<0.02), larger residual volume (12.3 ± 1.8 vs. 4.0 ± 0.5ml,P<0.0006) and slower emptying time (T/2: 33 ± 2 vs. 21 ± 2 min,P<0.05) than lean subjects. Integrated antral emptying was also less in obese than lean subjects (5521 ± 578 vs. 7908 ± 491 % 120min‐1,P<0.02). Cholestyramine enhanced postprandial gallbladder emptying in both obese and lean subjects. Gastric emptying was delayed with cholestyramine in lean but not obese subjects. For the chronic study, after 1 month therapy with cholestyramine (4 g every 2 days), the motility tests were repeated in nine obese subjects. Gallbladder and gastric responses to a test meal, with or without cholestyramine, were preserved. We conclude that both gallbladder and antral emptying of a liquid test meal are impaired in obese subjects. Gallbladder emptying improves after acute administration of a low dose cholestyramine with test meal. This effect is sustained after 1 month treatment with a low dose of cholestyramine and does not interfere with gastric emptying of obese patients. Cholestyramine may improve gallbladder hypomotility in o

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01953.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Vasodepressor (vasovagal) syncope, the most common cause of acute loss of consciousness, can occur in otherwise vigorously healthy people during exposure to stimuli decreasing cardiac filling. Antecedent physiological or neuroendocrine conditions for this dramatic syndrome are poorly understood. This study compared neurocirculatory responses to non‐hypotensive lower body negative pressure (LBNP) in subjects who subsequently developed vasodepressor reactions during hypotensive LBNP with responses in subjects who did not. In 26 healthy subjects, LBNP at ‐15 and ‐40mmHg was applied to inhibit cardiopulmonary and arterial baroreceptors. All the subjects tolerated 30min of LBNP at ‐15 mmHg, but during subsequent LBNP at ‐40 mmHg 11 subjects had vasodepressor reactions, with sudden hypotension, nausea, and dizziness. In these subjects, arterial plasma adrenaline responses to LBNP both at ‐15 and at ‐40 mmHg exceeded those in subjects who did not experience these reactions. In 16 of the 26 subjects, forearm noradrenaline spillover was measured; in the eight subjects with a vasodepressor reaction, mean forearm noradrenaline spillover failed to increase during LBNP at ‐15mmHg (Δ= ‐0.06±(SEM) 0.04pmol min‐1100mL‐1), whereas in the eight subjects without a vasodepressor reaction, mean forearm noradrenaline spillover increased significantly (Δ=0.31±0.13pmolmin‐1100mL‐1). Plasma levels of β‐endorphin during LBNP at ‐15 mmHg increased in some subjects who subsequently had a vasodepressor reaction during LBNP at ‐40 mmHg. The findings suggest that a neuroendocrine pattern including adre‐nomedullary stimulation, skeletal sympathoinhibition, and release of endogenous opi

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01954.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.This study examines the role of uraemia and the effect of different dialysis treatments on red cell cation transport. We evaluated the main cation transport systems in erythrocytes of non‐dialysed end‐stage renal disease (ESRD) subjects, of patients undergoing haemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD), as well as the changes induced by human recombinant erythropoietin (r‐HuEPO) administration. In uraemic undialysed and dialysed patients, we observed an increase in K/Cl co‐transport activity and in shrinkage‐induced amiloride‐sensitive (HMA‐sensitive) Na efflux (Na/H exchange) and a decrease in Na/K pump and Na/K/Cl co‐transport activity, while Na/Li exchange was increased only in dialysed patients. In uraemic erythrocytes, we showed for the first time an increased K/Cl co‐transport activity, which was cell age independent. Generally, the different method of dialysis (CAPD or HD) did not modify the cation transport abnormalities observed. During the treatment with r‐HuEPO, all the systems, with the exception of the Na/K pump and Na/K/Cl co‐transport, increased their activities following the increase of circulating young red cells. The changes produced under r‐HuEPO administration were transient and cation transports returned to the baseline values within 100 days of treatment, indicating a primary and prominent pathogenetic role of uraemia in modulating the red cell membrane cati

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01955.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Hypertriglyceridaemia, insulin resistance and glucose intolerance are conditions associated with an increased risk of coronary heart disease. In this study we have examined randomly selected non‐diabetic hypertriglyceridaemic (HTG) males, 40–50 years (n= 65) and age‐matched normotriglyceridae‐mic (NTG) controls (n= 61). The (mean ± SD) insulin sensitivity index, as assessed by the Minimal Model method, was significantly lower in the HTG compared with the NTG group (3.69 ±2.96 vs. 6.29 ± 3.38 times 10‐4min‐1per mUL‐1;P<0.001). Thirty‐eight per cent of the HTG group was glucose intolerant, compared with 8% in the NTG group (X2= 13.16;P<0.001). The glucose intolerant HTG sub‐group had, when compared with the glucose tolerant one, significantly higher serum concentrations of apoB (1318±284 vs. 1094±312mgL‐1;P<0.01) and glycerol (84 ±26 vs. 65±22 nmolL‐1;P<0.01). Serum FFA concentrations were, irrespective of glucose tolerance/intolerance, higher in the HTG than in the NTG group. By logistic regression analysis with the HTG/NTG state as the dichotomous variable, it was found that neither a low insulin sensitivity, nor glucose intolerance were independently linked with the HTG state. Instead, the lower insulin sensitivity of the HTG group was related to their higher body mass index. The higher frequency of glucose intolerance in the HTG group was explained by their higher mean serum apoB concentration, when compared with the NTG group. In conclusion, this study of a randomly selected HTG group has confirmed the frequent coexistence of HTG, insulin resistance and glucose intolerance. The new important finding was that neither of these two latter conditions appear to be of direct pat

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01956.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Peroxidation by peripheral blood leucocytes was measured in 15 patients in acute septic shock and 15 uninfected controls, using the probe dichloroflor‐escein. Mortality in septic subjects was 40%. In 14 of 15 patients from whom serial samples were analysed, periods of increased oxidative activity were detected. Increased peroxidation occurred early in the sequence of clinical changes, at the same time as increases in temperature, blood pressure and C‐reactive protein. Peak peroxide production preceded increases in acute phase reactants and changes in leucocyte distribution. Mean peroxide production in leucocytes from patients who died was significantly higher (P<0.001) than paired controls, and greater (P<0.05) than peroxide production in patients who survived. Thein vitrooxidative response to endotoxin was upregulated in infected patients. This supports the hypothesis that systemic mediators and leucocyte‐derived reactive oxygen are involved in the vascular and organ damage associated with fatal septic

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1995.tb01957.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY