摘要:

Abstract.Histamine 0–1 µM‐0.1 mM increased adenylate cyclase activity five‐ to ten‐fold in human fundic membranes, with a potency Ka = 3 µM. The histamine dose‐response curve was mimicked by the H3receptor agonist (R) α‐MeHA, but at 100 times lower potency, Ka = 0.3 mM. Histamine‐induced adenylate cyclase activation was abolished by H2, H1and H3receptor antagonists, according to the following order of potency IC50:famotidine (0.3 µM)>triprolidine (0.1 mM) thioperamide (2 mM), respectively. Famotidine has no action on membrane components activating the adenylate cyclase system, including the Gs subunit of the enzyme stimulated by forskolin and cell surface receptors sensitive to isoproterenol (β2‐type), PGE2and VIP. The Schild plot was linear for famotidine (P<0.01), with a regression coefficientr= 0.678. The slope of the regression line was 0.64 and differs from unity. Accordingly, famotidine showed a slow onset of inhibition and dissociation from the H2receptor in human cancerous HGT‐1 cells. The results demonstrate that famotidine is a potent and selective H2receptor antagonist with uncompetitive actions in human gastric mucosa. Consequently, famotidine might be a suitable drug with long‐lasting actions in the treatment of Zollinger‐Ellison syndrome. The results also confirm and extend the previous observations that (R) α‐MeHA and thioperamide are two selective ligands at histamine H3receptor sites. In the human gastric mucosa, these drugs are respectively 330 and 6700 times less potent than histamine and famotidine on the adenylate cyclase system. The possible involvement of histamine H3receptors in the regulation of

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1989.tb00299.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract.Because the syndrome of inappropriate antidiuretic hormone (SIADH) is a state of disturbed body fluid volume regulation and altered sodium balance we sought to determine if recently described volume regulatory factors were stimulated in SIADH. We measured atrial natriuretic peptide (ANP), endogenous digitalis‐like natriuretic factor (EDNF) and urinary free dopamine in SIADH (n= 27). We also determined fractional clearance of lithium (FCLi). The data obtained in SIADH were compared with similar measurements performed in sodium retaining hyponatremias, such as those of heart failure (n= 26), liver cirrhosis (n= 19) and volume contraction (n= 28). We observed:ANP was 19.5 ± 2.7 µM/ml in SIADH; it was significantly lower than ANP in cardiac failure, but no different from ANP in volume contraction. Urinary free dopamine was 2.2 ± 0.8 µM/24 h in SIADH; this was significantly higher than in volume contraction and liver cirrhosis. EDNF (259 ± 42 nM/24 h) and FCLi (21.4 ± 2%) were both numerically higher in SIADH than in other hyponatremic disorders; however, the differences did not achieve significance. In conclusion, our observations did not establish a specific role of ANP in chronic stable SIADH. As to the importance of EDNF, dopamine and proximal tubular fluid reabsorption (FCLi) additional work using acute volume changes may demonstrate their participation in the renal sodium handling of SIADH more clearly than our st

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1989.tb00300.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract.A previously unrecognized form of dual porphyria has been identified in four patients. One male and one female with acute symptoms were diagnosed as having acute intermittent porphyria (AIP), and two males with cutaneous and acute symptoms were diagnosed as having porphyria cutanea tarda (PCT). Biochemically, the excretion of haem precursors showed a complex constellation, with signs characteristic of both AIP and PCT. In one male, a clinical course with both overt PCT and acute manifestations of AIP was observed. Enzyme studies of haem biosynthesis in erythrocytes revealed a dual deficiency, with decreased activity of both porphobilinogen deaminase, as seen in AIP, and uroporphyrinogen decarboxylase, as seen in PCT. A family study showed that the two disorders do not consistently segregate together.These findings suggest that the dual porphyria reflects a double heterozygous condition of coexistent AIP and PCT genes in the same subject.

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1989.tb00301.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract.Alpha‐1‐antitrypsin (A‐1‐AT) and A‐1‐AT‐elastase complex levels in cerebrospinal fluid have been evaluated in 11 children with viral meningitis (VM), 14 with bacterial meningitis (BM), 10 with tuberculous meningitis (TBM) and 10 investigated for, but found not to have meningitis (NM). A‐1‐AT concentrations in the NM group were lower than in the BM group (P=0.0002) and the TBM group (P=0.0005) but did not differ from the concentrations in VM; those in the VM group were lower than in the BM group (P=0.0001) and the TBM group (P=0.003) but no difference was found between the BM and TBM groups. A‐1‐AT‐elastase complex concentrations in CSF were lower in the NM group than the BM group (P=0.0001) or the TBM group (P=0.0089), however those in the BM group were significantly higher than in the TBM group (P=0.0001). A significant correlation existed in CSF between the protein concentrations and neutrophil counts as well as the A‐1‐AT and A‐1‐AT

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1989.tb00302.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract.Heparin‐induced Extracorporeal LDL‐Pre‐cipitation (HELP) is an effective procedure for the elimination of both plasma LDL and fibrinogen.In 10 adult patients with severe type II hyperlipoproteinemia, a single HELP treatment of 3 1 plasma led to an acute decrease in the average plasma viscosity (PV) from 1.30 to 1.1 mPas. At the same time, an even more marked decrease in the mean erythrocyte aggregation rate from a pathological value of 7.9% to a value of 3.7% (normal range<5%) was observed. Long‐term studies on five patients demonstrated a lasting improvement in these two haemorheological variables. The acute rheological changes were also accompanied by an improvement in polarographically determined muscle oxygen tension. Mean oxygen tension values measured in both the m.biceps brachii and the m.tibia‐lis anterior in five patients before and after a single HELP treatment increased from 30±4 to 37±7 mmHg and from 27±2 to 31±3 mmHg respectively.These results may provide an explanation for the rapid improvement in patients' clinical symptoms such as angina pectoris and in stress electrocardiogram which have been observed during

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1989.tb00303.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract.In the present study, the hypothesis that the affinity of LDL to arterial proteoglycans might discriminate myocardial infarction patients from controls were tested. The patients were 52 men who had sustained a myocardial infarction at an age of 50 years or less and the controls, selected from a random population sample, were matched to the patients for age and sex. Serum cholesterol, triglycerides, LDL‐cholesterol, HDL‐cholesterol and apoB discriminated patients from controls. In addition, LDL reactivity with arterial proteoglycans was significantly higher in patients than in controls. In a multiple regression analysis, with patient or control as the dependent variable, apoB levels, LDL proteoglycan reactivity and serum triglycerides appeared as independent contributors to the regression. These observations indicate that LDL reactivity with arterial proteoglycans is a new, highly significant factor which discriminates between young myocardial infarction patients and contr

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1989.tb00304.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract.Monocytes of seven out of eight patients with type 1 C1‐inhibitor (C1‐inh) deficiency (HAE) produced 40% as much C1‐inh as monocytes from normal donors (controls). In contrast, monocytes from three patients with type 2 and three patients with acquired C1‐inh deficiency produced similar amounts of Cl‐inh as controls. Recombinant γ‐interferon (γ ‐interferon 10 ng/ml) stimulated C1‐inh production of C1‐inh (eight‐10‐fold) by control and patients' monocytes. Monocytes from patients with type 1 HAE contained 40% the level of C1‐inh messenger ribonucleic acid (mRNA) found in control monocytes, γ ‐interferon increased the abundance of Cl‐inh mRNA by the same extent in both control and patients' monocytes. C1‐inh protein and mRNA were undetectable in the monocytes of one patient, unless stimulated by γ‐interferon. Under these conditions, his monocytes produced comparable amounts of C1‐inh (protein and mRNA) as γ‐interferon‐stimulated monocytes of the other type 1 HAE patients.The data suggest that in most type 2 HAE patients there is a lesion in the C1‐inh gene such

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1989.tb00305.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract.The cysteinyl leukotrienes, comprising leuk‐otriene C4and its metabolites, are biologically most active mediators, eliminated from the blood circulation by the liver and the kidneys. The urine of normal subjects and of patients with hepatic and/or renal failure was analysed for endogenous cysteinyl leukotrienes. The leukotriene metabolites were separated by reversed‐phase high‐performance liquid chromatography and subsequently quantified by radioimmunoassay.Leukotreine E4was detected in all urine samples analysed. Its mean concentration increased from 0.3 nmol I‐1in healthy subjects to 0.8 nmol 1‐1in patients with liver cirrhosis. In patients with hepatorenal syndrome leukotriene E4averaged 7.8 nmol I‐1; in addition,N‐acetyl‐leukotriene E4was detected in an average amount of 1.5 nmol‐1. The mean leukotriene E4/creatinine ratio in urine increased from 0.02 in healthy subjects to 0.11 in patients with liver cirrhosis and to 1.2 µmol leukotriene E4mol‐1creatinine in patients with hepatorenal syndrome. These results indicate that cysteinyl leukotrienes may play an important role in the mediator network responsible for the development of the hepatorenal syndrome in patients with

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1989.tb00306.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract.Supernatants of faecal suspensions from patients with Crohn's disease (CD) showed much lower viscosity than those from healthy subjects. Material responsible for the viscosity could be precipitated with ethanol. Gel filtration indicated that the viscosity was not due to the glycoprotein fraction but to a fraction with higher molecular weight and relatively high contents of muramic acid suggesting a bacterial origin. The concentration and viscosity of this fraction are less in faeces from patients with CD than in that of healthy subjects.

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1989.tb00307.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract.We wanted to examine how adenosine stimulates ventilation in man. Bolus doses of adenosine were given i.v. in an antebrachial vein in multiples of 2.65 mg. The minute ventilation was increased by adenosine 5.3 to 15.9 mg (median values) from control 12.6 ± 1.9 1 min‐1to 42.5 ± 4.7 1 min‐1in a dose‐dependent manner. The adenosine receptor antagonist theophylline, 58.3 ± 3.3 (mean±SEM) µniol 1‐1plasma, inhibited the response by approximately 25%. Dipyridamole 10 mg, an adenosine uptake blocker, enhanced the effect of adenosine by approximately 60%. The ventilation was not affected by metoprolol, atropine, naloxone or cromolyn sodium but was attenuated by hyperventilation.The respiratory stimulation started before chest pain and cardiovascular effects such as AV‐block were encountered. It is concluded that this respiratory stimulation shows characteristics of adenosine receptor mediated responses but the location of such adenosine receptors is uncertain. The findings are compatible with a stimulatory or facilitating effect of adenosine on aff

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1989.tb00308.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY