ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1996.tb02126.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract.We tested the hypothesis that long‐term smoking is responsible for increased plasma noradrenaline (NA) in elderly healthy subjects. Thirty‐nine subjects were studied both at rest and during exercise: 10 young non‐smokers (median age 24 years, range 21–33), 10 young smokers (30.5 years, 27–36), 10 elderly non‐smokers (64 years, 52–75) and nine elderly smokers (62 years, 56–68). The young and elderly subjects had smoked for an average of 15 years and 46.8 years respectively. Plasma NA was significantly elevated in elderly long‐term smokers compared with elderly non‐smokers, young non‐smokers and young smokers in both supine and sitting positions (supine: 1.06 ± 0.24 vs. 0.71 ± 0.22, 0.53 ± 0.12, and 0.70 ± 0.29 nmolL‐1respectively; sitting: 3.01 ± 0.83 vs. 2.07 ± 0.77, 1.89 ± 0.52 and 2.25 ± 0.47 nmol L‐1respectively). Plasma adrenaline did not differ among the groups. At submaximal exercise (60 W), plasma NA was significantly elevated in the elderly smokers compared with the other groups, owing to the elevated basal values. Increments in plasma NA at 60, 100 and 140 W were correlated with the relative exertion and not influenced by smoking. Plasma NA increased more in young subjects than in the elderly during maximal work load (21.7 ± 8.0 vs. 13.4 ± 5.4 nmol L‐1) and correlated with the peak O2uptake. Total blood volume was not different among the four groups and correlated inversely with basal plasma NA. It is concluded that long‐term smoking may contribute to increased basal plasma NA concentrations and probably also increased sympathetic nerve activity in elderly healthy subjects, whereas smoking has little if any effect on plasma NA responses induced by exercise. Interindividual variability in basal plasma NA concentrations may in part be e

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1996.tb02127.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract.In addition to the major genetic determinants of insulin‐dependent diabetes mellitus (IDDM) in the major histocompatibility complex (MHC) on chromosome 6, there are also minor genetic risk markers, e.g. in the insulin gene region on chromosome 11p15.5 (IDDM2). We studied the significance of the ‐23HphI polymorphism in the insulin gene region (‐23HphI INS) in the Finnish population in combination with HLA genotyping data. The frequency of the ‐23HphI INS +/+ genotype was higher in diabetic subjects with a low risk HLA DQBI genotype than in control subjects (P= 0.05). Diabetic children in multiple‐case families also had a higher frequency of the INS risk genotype than the controls (P<0.05), and this difference was independent of the HLA genotype. Furthermore, we studied siblings positive for islet cell antibodies (ICAs) and/or insulin autoantibodies (IAAs) to evaluate the impact of the ‐23HphI INS +/+ genotype on their beta‐cell function assessed by sequential intravenous glucose tolerance tests and on their progression to IDDM. When analysing siblings with a low‐risk HLA DQBI genotype, those with the ‐23HphI INS +/+ genotype had lower first phase insulin responses (P<0.02) on several occasions than the remaining sibling. Six siblings (26.1%) in the former group progressed to clinical disease during the observation period, whereas none in the latter group presented with IDDM (P= 0.01). These observations suggest that the ‐23HphI INS +/+ polymorphism is associated with an increased risk of IDDM in subjects without predisposing genes in the MHC region. The enhanced susceptibility may be related to a reduced insulin

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1996.tb02128.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract.Plasma homocysteine concentration is a sensitive marker for cobalamin and folate deficiency. The previously reported high incidence of increased plasma homocysteine in psychogeriatric patients and the association between reduced concentrations of cobalamin, folate and neuropsychiatric symptoms led to the present study on 741 consecutive psychogeriatric patients. The concentrations of plasma homocysteine correlated significantly with blood folate, serum cobalamin and serum creatinine both in demented (n= 295) and in non‐demented patients with other psychiatric disorders (n= 215). Plasma homocysteine concentrations were significantly increased in both the demented and the non‐demented patients, whereas only the demented patients had lower blood folate and serum creatinine concentrations than 163 control subjects. Almost all of the different diagnostic groups of demented and non‐demented patients exhibited significantly increased plasma homocysteine concentrations compared with control subjects. Significantly decreased blood folate concentrations were mainly found in the different diagnosis groups of demented patients. Plasma homocysteine concentrations in both demented and non‐demented patients with serum cobalamin and blood folate above the lower 20th percentile of these vitamins in the control subjects were also studied. Despite these vitamin concentrations, both groups of patients still exhibited significantly higher plasma homocysteine concentrations than the control subjects, which may indicate an increased frequency of impaired genetic capacity to metabolize homocysteine in these patients. Patients with either dementia of vascular cause or a history of other occlusive arterial disease had a significantly higher plasma homocysteine concentration than those without a history of vascular

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1996.tb02129.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract.This study has been designed to demonstrate thein vivoeffects of iloprost therapy on expression of adhesion molecules on phagocytes. Sixty patients suffering from peripheral arterial occlusive disease (PAOD) and/or from skin ulcers due to secondary progressive systemic sclerosis (PSS) were enrolled in a double‐blind controlled parallel study. Thirty patients (group I) underwent iloprost infusion and 30 patients (group II) were treated with aspirin. Clinical assessment and measurement of phagocyte activationin vivo, using quantitative flow cytometry, were performed on entry and after 6 h on the first day of therapy. After 3 months of therapy, complete healing of all cutaneous lesions was observed in 84% of the patients treated with iloprost compared with the control patients (P<0.001). Neutrophils and monocytes of PAOD and PSS patients showed a significant decrease in the expression of the αMβ2integrin adhesion receptor after 6 h of iloprost infusion. Neutrophils and monocytes released a lower amount of anion superoxide (O2‐) after 6 h of iloprost treatment. These data confirm other clinical observations but demonstrate thatin vivothis drug modifies the expression of the αMβ2integrin of phagocytes that has a key role in leukocyte‐endothelium interactions in cases of inflammation and t

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1996.tb02130.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract.Nitric oxide (NO) is generated from L‐arginine by a family of enzymes called the NO synthases. Previous investigators have proposed that the expression of this inducible enzyme (iNOS) may account for the characteristic vasodilatation, oedema and impairment of gut motility seen in active ulcerative colitis. Using a specific antibody to iNOS, we have investigated the distribution of this enzyme in colonic tissue from patients with histologically proven ulcerative colitis. Eight patients with ulcerative colitis expressed calcium‐independent citrulline activity (9.96±2.34 pmol citrulline mg‐1protein min‐1) and showed immunoreactivity to the iNOS antibody within the inflammatory infiltrate of the lamina propria, and also within the cytoplasm of the epithelial cells lining the colon. Five age‐matched controls showed no calcium‐independent citrulline activity (0.2 ±0.08 pmol citrulline mg‐1protein min‐1) and no immunoreaction to the antibody. We conclude that this enzyme is present in colonic tissue including the epithelium from patients with active colitis. Inhibition of this enzyme may provide a novel therapeutic option for patients with active u

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1996.tb02131.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract.Administration of the murine IgG2a CD3 monoclonal antibody OKT3 exerts a transient nephro‐toxic effect. Increased levels of group II secretory phospholipase A2(sPLA2‐II) might account for this nephrotoxicity as sPLA2‐II induces the biosynthesis of prostaglandins, vasoactive lipid mediators that influence glomerular haemodynamics and renal function. Furthermore, extracellular phospholipases seem to be involved in proximal tubular cell injury. We studied plasma sPLA2‐II levels in relation to circulating creatinine, tumour necrosis factor α, interleukin 6 and C‐reactive protein levels in 15 renal allograft recipients receiving rejection treatment with OKT3. As a control group, we studied 15 renal allograft recipients receiving rejection treatment with methyl‐prednisolone. A maximal fourfold increase in sPLA2‐II levels was observed 48 h after the first OKT3 administration, preceded by increased tumour necrosis factor α and interleukin 6 levels and accompanied by increased C‐reactive protein levels. Creatinine levels reached a maximal increase 72 h after initiation of treatment. During methylprednisolone treatment no increase in any of the studied parameters was observed. Thus, administration of OKT3 induces increased sPLA2‐II levels, presumably via generation of cytokines. We hypothesize that sPLA2‐II may contribute to the nephrotoxic effect of OKT3 by inducing vasoconstrictive prostaglandins and rena

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1996.tb02132.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract.Both arginine vasopressin (AVP) and corticotropin‐releasing hormone (CRH) are involved in the release of ACTH in man. Desmopressin (DDAVP), a synthetic analogue of AVP, has been shown to have a CRH‐like action (able to promote ACTH and cortisol release) in animals but not in normal man. Nevertheless, DDAVP is able to release ACTH and cortisol in ACTH‐dependent Cushing's disease. We studied eight anorexia nervosa (AN) patients [as AN is a condition in which chronic activation of the hypothalamic‐pituitary‐adrenal (HPA) axis is commonly reported] in a refeeding phase of the disease, to evaluate whether, after weight gain, ACTH and cortisol response to ovine corticotropin‐releasing hormone (oCRH) [1 μg kg‐1body weight (BW) i.v.] is restored. We also wanted to ascertain the effect on the HPA axis of 10 μg i.v. DDAVP alone and as pretreatment to oCRH (1 μg kg‐1BW i.v.)‐induced secretion of ACTH and cortisol. We studied six normal women as control subjects. No significant differences in ACTH and cortisol responses to oCRH were found between AN patients and control subjects. DDAVP was not able to stimulate ACTH or cortisol release in AN patients or in control subjects, but in the latter it was able to significantly enhance (P<0.05) ACTH [area under curve (AUC): 590.0± 104.4 pmol L‐1120 min‐1and cortisol (AUC: 28899.0 ± 6935.2nmol L‐1120 min‐1) responses to oCRH (ACTH AUC: 325.7 ± 101.7 pmol L‐1120 min‐1, cortisol AUC: 14197.4 ± 2930.0 nmol L‐1120 min‐1). The present data show that DDAVP does not stimulate ACTH and cortisol in AN patients or, as previously reported, in normal subjects. However, DDAVP is able to enhance ACTH and cortisol release after oCRH administration in normal subjects but not in AN patients. This finding could be due to a down‐regulation of hypophyseal DDAVP V3 receptors in AN as a direct consequence of the

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1996.tb02133.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract.The aim of this study was to investigate whether the oxygen radical scavengerN‐acetylcysteine (N‐AC) impairs bacterial clearance, thus predisposing the host to increased risk of disease. Blood clearance ofEscherichia coliand organ colonization were investigated in anaesthetized rabbits after pretreatment withN‐AC (250 mg kg‐1body weight,n= 16) and in sham‐operated animals (n= 12). To enable quantification of the clearance process, defined numbers of exogenousE. coli[1.3 times 108 colony‐forming units (CFUs)] were injected intravenously. Parameters monitored were kinetics of bacterial elimination from the blood, and polymorphonuclear leucocyte (PMN) oxidative burst activity. Samples of liver, kidney, spleen and lung were collected for bacterial counts. Compared with controls, pretreatment withN‐AC resulted in delayed bacterial elimination from blood and higher organ colonization with increased numbers ofE. coliin liver, lung and kidney (P<0.05).N‐AC treatment was associated with a suppressed PMN oxidative burst activity. Impaired bacterial clearance and enhanced organ colonization inN‐AC‐treated animals correlated with reduced oxidative burst activity, suggesting impaired granulocyte‐dependent bacterial killing d

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1996.tb02134.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract.Previous studies have failed to explain the link between copper accumulation and abnormal caeruloplasmin expression in Wilson's disease. Furthermore, despite the isolation of a candidate gene for Wilson's disease, which predicts a defective copper transport protein, the localization of this putative protein and its relationship to the pathway involved in copper excretion and to caeruloplasmin remain unknown. We now present evidence that caeruloplasmin, the major plasma copper‐carrying protein, is present in the liver in Wilson's disease, and thus that reduced circulating levels of the protein result from a post‐translational defect in the secretory pathway. We have also identified a novel form of caeruloplasmin, molecular weight 125 kD, which we propose may act as the carrier for excretory copper into bile, since it is normally present in both liver and bile, although largely absent from serum, and undetectable in bile from Wilson's disease patients. The presence of this form of caeruloplasmin in Wilson's disease liver suggests that a related post‐translational defect may also be responsible for its absence from bile in Wilson's disease. This study thus provides the first plausible explanation of a link between the defective copper excretion and the reduced plasma caeruloplasmin, which characterize Wilson's di

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1996.tb02135.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY