摘要:

The Jak–STAT pathway is a newly discovered intracellular signal transduction pathway that is used by a growing number of extracellular signalling proteins (ESPs) for transciptional activation of target genes. Binding of ligands to their transmembrane receptors leads to activation of members of the Jak tyrosine kinase family. The activated receptor–kinase complexes recruit members of the STAT family and activate them by phosphorylation. As a consequence, the phosphorylated STAT proteins dimerize, translocate into the nucleus, bind response elements in the promoter of target genes and stimulate the transcription of these genes. Their dual role as signalling molecules and transcription factors is reflected in the name: STAT stands for signal transducers and activators of transcription. Different ligands specifically activate different members of the Jak and STAT families. Signal transduction through the Jak–STAT pathway contributes to the specificity and diversity of cellular responses to peptide hormones, growth factors, cytokines and interle

ISSN:0014-2972    

DOI:10.1046/j.1365-2362.1996.103248.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Type III hyperlipoproteinaemia (HLP) is usually associated with homozygosity for apolipoprotein (apo) E2 (Arg‐158→Cys). We identified a 46‐year‐old white female with severe hyperlipidaemia and the heterozygous apo E3/2* phenotype. Typical clinical characteristics of type III HLP, i.e. palmar xanthomas (orange–yellowish discolorations of the palmar creases) and tuberoeruptive xanthomas, were present in the patient. Without therapy the patient's serum triglycerides (1.098 mg dL−1), cholesterol (546 mg dL–1), very low‐density lipoprotein (VLDL) cholesterol (372 mg dL−1) and the apo E concentration (25.0 mg dL−1) were distinctly elevated as well as her VLDL cholesterol to serum triglyceride (TG) ratio at 0.34 (normal ratio about 0.2). Direct sequencing of polymerase chain reaction (PCR)‐amplified segments of the apo ε gene identified a thymine for cytosine (C→T) exchange in the first base of codon 136 that is predictive for a Cys (TGC) for Arg (CGC) substitution in the encoded amino acid sequence. Two children, an 18‐year‐old female with the heterozygous apo E4/2* phenotype, a 25‐year‐old female with the heterozygous apo E3/2* phenotype and the 73‐year‐old father of the proband with the heterozygous apo E3/2* phenotype are also carriers of the rare mutant. The father has severe atherosclerosis and lipid values compatible with the diagnosis of type III HLP. The affected children have hyper/dyslipidaemia but as yet no clinical expression of the disease. We propose that in the analysed family this rare apo E2 (Arg‐136→Cys) variant

ISSN:0014-2972    

DOI:10.1046/j.1365-2362.1996.83232.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract.Serum vitamin K1concentrations were measured at presentation (just before surgery) and then at weekly intervals for 3 weeks in two groups of elderly patients requiring either hemiarthroplasty for fractured neck of femur (FON,n= 13) or total hip replacement for osteoarthritis of the hip (OA,n= 16). In comparison with healthy elderly volunteers (n= 25), serum vitamin K1concentrations were significantly lower in both groups at presentation, and fell significantly within 24 h after surgery to concentrations approaching non‐detectable, subsequently returning to pre‐operative values within 3 weeks. Serum vitamin K1tended to be lower in the fracture group both before and after operation, although calculation of a vitamin K1–triglyceride ratio reduced the apparent difference as triglyceride concentrations were lower in the fracture group. Osteocalcin concentrations were similar and fell significantly after operation in both groups, returning to pre‐operative levels within 7 days. No differences in the two forms of osteocalcin (carboxylated and undercarboxylated) were observed either before or after operation in either group. 25‐Hydroxyvitamin D3concentrations were not significantly different between the two groups at any time. Vitamin K1status may be lower than desirable in certain groups of the elderly population, and supplementation should be considered as prophylacti

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1996.tb02382.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

The aim of the study was to investigate whether pre‐eclampsia is associated with an altered release of vasoactive substances from trophoblastic cellsin vitro. Trophoblastic cells from 15 uncomplicated control pregnancies and 18 pre‐eclamptic pregnancies at preterm (weeks 31–36;n = 12) and term (weeks 37–40;n = 21) were cultured for 5 days. The concentrations of angiotensin II (AII), endothelin‐1,2 (ET‐1,2), thromboxane B2(TXB2), 6‐keto‐prostaglandin F1α(6‐keto‐PGF1α) and leukotriene B4(LTB4) were measured daily in culture media for 5 days by radioimmunoassay. In pre‐eclampsia, concentrations of ET‐1,2 were decreased (P<0.01) at both preterm and term, TXB2concentrations were increasedP<0.05) only at preterm and the TXB2–6‐keto‐PGF1αratio was increased at both preterm and term (P<0.01) as compared with the controls. Concentrations of AII, 6‐keto‐PGF1αand LTB4were similar to the controls. The data suggest that pre‐eclampsia is associated with a decreased release of ET‐1 and an incre

ISSN:0014-2972    

DOI:10.1046/j.1365-2362.1996.87238.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Low glutathione (GSH) in patients with HIV infection could contribute to their immune deficiency since GSH plays an important role in the function of lymphocytes and sulphydryls decrease the expression of HIVin vitro.In order to gain more insight into the mechanisms responsible for the deranged sulphydryl homeostasis in HIV infection, the release of GSH into the circulation, an estimate of the systemic production of GSH, was determined using a pharmacokinetic approach. The basal plasma concentrations of free GSH (3.3±1.3 vs. 5.3±1.9 μmol L‐1) and cysteine (7.7±2.6 vs. 13.4±4.9 μmol L‐1) were significantly lower in eight HIV‐infected patients than in eight controls. Upon infusion of GSH at a constant rate of 1 μmol min‐1 kg‐1, GSH in plasma reached a new plateau. The increment in plasma GSH was significantly larger in the HIV‐infected patients than in the controls. The input of GSH into the circulation (12.9±5.7 vs. 30.1±11.7 μmol min‐1P<0.01) and the clearance of GSH (25±7 vs. 35±7 mL min‐1 kg‐1) were significantly lower in patients with HIV‐infection. During infusion of GSH the concentration of cysteine in peripheral blood mononuclear cells of the HIV‐infected patients increased significantly. Nevertheless, intracellular GSH did not increase. Thus, the consumption of GSH is not increased in HIV infection. Rather, the present data suggest that GSH in patients with HIV infectio

ISSN:0014-2972    

DOI:10.1046/j.1365-2362.1996.88237.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Cell‐mediated immunity is impaired during cholestasis. The aim of this study was to evaluatein vivothe effects on this immune defect of high serum levels of endotoxin and bile acids. Heterotopic cardiac allotransplantations were performed in the DA/Lewis rat combination. Cholestasis, induced by ligation/section of the common bile duct, was responsible for a significant delay in the rejection time (16 ± 0.5 vs. 7.1 ± 0.4 days in controls,P<0.01). Elimination of Gram‐negative intestinal bacteria from cholestatic rats by a vancocin/colimycin/tobramycin (VCT) mixture induced a significant reduction in endotoxin levels and a reduction in rejection times (9.5 ± 1.0 days,P<0.01) that remained, however, significantly longer than those of controls (P<0.05). Oral administration of chenodeoxycholic acid in non‐cholestatic rats significantly enhanced the serum concentration of total bile acids (60.6 ± 15.3 μmol L−1vs. 17.4 ± 1.9 μmol L−1in controls,P<0.01) and postponed allograft rejection (10.7 ± 0.6 days,P<0.01 vs. controls). These data suggest that increased endotoxin level and serum bile acid concentration may play a role

ISSN:0014-2972    

DOI:10.1046/j.1365-2362.1996.95240.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

In this study the authors examine whether smoking further heightens platelet activity and reduces fibrinolysis above that already present in mild hypertension. Ten smokers and 11 non‐smokers, all with mild hypertension (defined as a diastolic pressure between 90 and 110 mm Hg) were compared for their platelet activityin vitroandin vivoand for their fibrinolytic activity. Successive measurements were made with the patients lying at rest after they had assumed the erect posture for 10 min and at the end of a 5‐min moderately strenuous exercise test. The threshold for platelet aggregation by ADPin vitrowas significantly lower in samples taken from the smokers at rest (1.4 ± 0.9 μmol L−1) than in the non‐smokers (3.5 ± 2.5 μmol L−1), and the difference persisted both in the upright posture and after exercise. The level of platelet release of β‐thromboglobulin was, likewise, higher in the smokers in the upright posture. Neither standing up nor physical exercise had any significant influence on either of these two indices of platelet activity. The euglobulin clot lysis time was slightly longer in the smokers than in the non‐smokers in all three experimental situations, but the differences were not significant. Inhibitor of tissue plasminogen activator was not materially different in the two groups (Table 2). The results indicate that smoking adds a further element of heightened platelet activity to t

ISSN:0014-2972    

DOI:10.1046/j.1365-2362.1996.00096.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

The authors have previously reported that platelet‐activating factor (PAF), a phospholipid mediator with potent proinflammatory activities, is produced in the gastric mucosa and stimulates gastric acid secretion in humans and animals. In the present study they used the human gastric tumour cells HGT1 (clone 6) to examine whether PAF production is regulated by neuromediators. PAF was extracted by ethanol and assayed by the washed platelet aggregation test. HGT1 cells produced PAF spontaneously (110 ± 20 pg 106cells). The addition of vasoactive intestinal peptide (VIP; 10−9to 10−7 mol L−1) or of histamine (10−5to 10−3 mol L−1) increased PAF production by three‐ to fivefold, while the addition of carbachol (10−7to 10−4 mol L−1) increased PAF production up to sevenfold. PAF production was also increased up to 10‐ to 13‐fold, in a dose‐ and time‐dependent manner, by the addition of calcium and two‐ to threefold by the addition of phorbol myristate acetate (PMA; 10−7to 10−5 mol L−1). However, the addition of dibutyryl cyclic AMP (dBcAMP; 10−6to 10−4 mol L−1) was without any effect. This is the first report showing PAF production by gastric epithelial cells in response to histamine, VIP and carbachol. Furthermore, the findings are consistent with a central role of calcium in this production. The results of this study, together with those of previous studies from the authors’ laboratory, support the

ISSN:0014-2972    

DOI:10.1046/j.1365-2362.1996.00097.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

The reduction in thyroid size in 92 patients treated with radioiodine for Graves' thyrotoxicosis was monitored by ultrasound volumetry. The patients were randomly treated with either a standard131I activity of 555 MBq or an activity calculated to deliver a thyroid dose of 100 Gy. Within 1 year after radioiodine treatment, a remarkable volume reduction of about 71% (median) (quantile 25% (Q 25) = 49%, Q 75 = 82%,n = 67) was observed. The bulk of this reduction (median 57%, Q 25 = 21%, Q 75 = 74%,n = 92) was found within the first 6 months. Statistical analysis reveals that the effect was clearly related to the thyroid dose actually achieved during therapy. The median reduction obtained 6 months after radioiodine application was 45% for 25 mL in men) was reduced from 73% to only 16% 1 year after radioiodine treatment. In patients with a thyroid volume of more than 60 mL, the median pretherapeutic thyroid volume of 102 mL was reduced to 29 mL. In conclusion, radioiodine treatment in Graves' hyperthyroidism sufficiently reduces thyroid volume in a dose‐dependent manner. The findings of this study demonstrate that radioiodine is also an attractive mode of

ISSN:0014-2972    

DOI:10.1046/j.1365-2362.1996.98243.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

The authors measured Na+–H+exchanger kinetics together with Na+–Li+countertransportVmaxin the erythrocytes of 21 subjects with essential hypertension and 16 normotensive control subjects. Na+–H+exchangerVmaxappeared to be increased in patients with essential hypertension, while the Na+–H+exchanger affinity for intracellular proton sites (K50%) proved to be unchanged and the index of cooperativity among intracellular proton binding sites as measured by Hill's coefficient (Hill'sn) decreased as compared with normotensive control subjects. Na+–Li+countertransportVmaxappeared to be higher in patients with essential hypertension than in control subjects. The authors were unable to find any correlations between Na+–H+exchanger kinetic parameters and metabolic variables such as parameters of insulin resistance and plasma lipids. On the basis of the data obtained, erythrocyte Na+–H+exchanger activity was found to be abnormal in two kinetic variables in essential hypertensive patients and showed no simple linear correlations with the main variables of glucose metabolism, plasma lipids, renin o

ISSN:0014-2972    

DOI:10.1046/j.1365-2362.1996.99244.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY