摘要:

Abstract.Porphobilinogen deaminase, the third enzyme of the haem biosynthetic pathway, is encoded by two distinct mRNA species expressed in a tissue‐specific manner from a single gene. These two mRNAs are transcribed from two promoters and only differ in their first exon. An inherited deficiency or porphobilinogen deaminase in man is responsible for the autosomal dominant disease acute intermittent porphyria. Different classes of mutations have been described at the protein level suggesting that this is a heterogeneous disease.In the present report, we describe the molecular abnormality responsible for a variant form of acute intermittent porphyria where the enzyme defect is restricted to non‐erythroid cells. Upon cloning and sequencing the mutant allele of a patient from a large Finnish kindred, a single‐base substitution within the 5′‐splice donor sequence of intron 1 was found at the last position of exon 1 (CGCT).The identification of this mutation allowed us to detect asymptomatic gene carriers among family members usingin vitroamplification of DNA and hybridization of the target sequence to allele‐specific oligo

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1989.tb00252.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract.Fifty‐two male patients undergoing coronary angiography were allocated to four groups each consisting of 13 subjects: group I had normal coronary arteries and patients in groups II‐IV exhibited coronary artery disease. In group II, plasma cholesterol was below 250 mg dl‐1and triglycerides below 160 mg dl‐1; in group III, cholesterol was above 270 mg dl‐1and triglycerides under 160 mg dl‐1; and in group IV, cholesterol was under 270 mg dl‐1and triglycerides above 180mgdl‐1.The hypertriglyceridaemic group IV had the highest coronary score. In addition, it had lowest lipoprotein lipase activity, lowest HDL‐cholesterol and lowest high‐density lipoproteins‐2 (HDL‐2) levels, suggesting that this type of hypertriglyceridaemia is caused—at least, in part—by lipoprotein lipase deficiency with impaired removal of the triglyceride‐rich lipoproteins and increased catabolism of HDL‐2. Our findings point towards a type of hypertriglyceridaemia strongly associated with coronary artery disease which should t

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1989.tb00253.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract.Defective lipoprotein lipase (LpL) was found in the postheparin plasma (PHP) of a patient with severe hypertriglyceridaemia. The patient was a 14‐year‐old girl with a maximum plasma triglyceride (TG) level of 3600 mg d‐1who had been suffering from recurrent pancreatitis. The patient's LpL purified from the PHP by heparin‐Sepharose and phenyl‐Sepharose chromatographies hydrolysed tributryrin, but not triolein emulsified with Triton X‐100 and phosphatidylcholine (PC), or in chylomicrons, whereas normal LpL hydrolysed these substrates. Moreover, unlike normal LpL, LpL from the patient did not associate with VLDL, as shown by Sepharose 4B column chromatography. The patient's LpL hydrolysed triolein emulsified with lysophospholipid at a normal rate in the presence of apolipoprotein CII. These findings suggest that this patient has LpL with a normal catalytic site for tributyrin but with a defect in lipid interface recognition resulting in loss of ability to recognize VLDL or chylomicrons, but not of triolein emulsified with lysop

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1989.tb00254.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract.A monoclonal antibody to lipoprotein lipase (LPL) has been used in an enzyme‐linked immunosorbent assay (ELISA) for LPL protein mass. Measurement of LPL immunoreactive mass in pre‐ and postheparin plasma distinguished three classes of abnormalities in patients with classical deficiency of lipoprotein lipase activity. The class I defect consisted of the absence of LPL immunoreactive homodimer in pre‐ and postheparin plasma compatible with a potential ‘null allele’. Patients with a class II defect had almost no LPL immunoreactive mass in preheparin plasma but showed an increase in their LPL mass of 68 ± 23 ng ml‐1(mean ± SD) after heparin. Patients with the class III defect had considerable amounts of LPL immunoreactive material in preheparin plasma (159 ± 190 ng ml‐1). Heparin administration, however, caused very little additional release of LPL into the plasma (16 ± 51 ng ml‐1). Thus although both class II and class III patients had an LPL protein with abnormal catalytic activity, class III patients also appeared to have a defect in heparin binding of LPL. To test this hypothesis, postheparin plasma of classes II and III patients was analysed by heparin‐Sepharose chromatography. In contrast to class II patients, the LPL immunoreactive mass of class III patients did not show affinity for the heparin and eluted in the column void volume, suggesting the class III defect is also associated with a defe

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1989.tb00255.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract.Ten men with Klinefelter's syndrome were studied to assess the effect of testosterone replacement on plasma lipids and apolipoproteins. Measurements taken before the insertion of a testosterone ester implant were compared with those obtained 1 week and 4 weeks later.Mean plasma testosterone, androstenedione, total cholesterol and calculated LDL‐cholesterol increased significantly after 1 and 4 weeks. No significant changes were seen in total plasma concentrations of HDL‐cholesterol, HDL‐cholesterol subfractions 2 and 3 or in apoplipoproteins A‐I, A‐II or B.A significant correlation was seen between total cholesterol and plasma oestradiol concentrations (Rs=0.61;P<0.001). A significant negative correlation was seen between the concentrations of total testosterone and total triglyceride (Rs= ‐0.56;P<0.005) but not with the other lipid parameters.Testosterone replacement is associated with slight but potentially adverse changes in plasma cholest

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1989.tb00256.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract.The present study was undertaken to investigate the role of the gastric phase of fat‐induced gallbladder contraction and endogenous cholecystokinin (CCK) secretion in humans. Gallbladder emptying, measured by cholescintigraphy, and endogenous CCK secretion, measured by radioimmunoassay, were studied in healthy subjects after both intragastric and intra‐intestinal administration of corn oil. In addition, patients with partial gastrectomy were investigated to study the effect of accelerated gastric emptying. In the healthy subjects, intragastric administration of fat resulted in a significantly (P<0.05) later increase in plasma CCK levels (20 ± 2 min) compared to intraintestinal fat (5 ± 1 min). Similarly, the onset of gallbladder emptying was significantly (P<0.05) delayed after intragastric fat (20±2 min) compared to intestinal fat (10±1 min). In the healthy subjects the integrated plasma CCK response to intragastric fat was significantly (P<0.005‐P<0.01) reduced from 10 to 30 min. In the patients with partial gastrectomy the rise in plasma CCK (10 ± 1 min) and the onset of gallbladder emptying (15 ± 2 min) were in the same range after intra‐intestinal and intragastric fat. No significant differences in plasma CCK levels, integrated CCK response or gallbladder emptying were found in the patients according to the site of fat application. It is concluded that endogenous CCK secretion and gallbladder emptying in response to intragastric fat are significantly delayed in healthy subjects but not in patients with partial gastrectomy, in whom gastric emptying is accelerated. The main role of the stomach in the regulation of gallbladder contraction is by regulating the delivery of the stimulus to

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1989.tb00257.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract.Acute and long‐term changes of ornithine decarboxylase and polyamines during pancreatic adaptation in response to cholecystokinin administration (1 μg kg‐1body wt every 8 h) were studied in rats. α‐difluoromethylornithine, an irreversible and specific inhibitor of ornithine decarboxylase, was applied simultaneously to elucidate the essential role of polyamines in pancreatic growth. In the cholecystokinin‐treated animals ornithine decarboxylase activity was increased after 2 h, reached a maximum after 8 h (444.6 pmol14CO2h.‐1mg‐1DNA, about 65‐fold greater than controls,P<0.001) followed by a significant increase of putrescine after 6 h and spermidine after 24 h while spermine remained unchanged. The trophic parameters increased in the following time sequence: thymidine kinase (12 h), DNA polymerase (24 h), pancreatic weight (2 days), protein (2 days) and DNA (5 days), α‐difluoromethylornithine significantly delayed the increase in ornithine decarboxylase, putrescine and spermidine as well as all trophic parameters. Increases in ornithine decarboxylase, polyamines and all trophic parameters were completely inhibited by simultaneous application of the CCK receptor antagonist L‐364,718. These data indicate an important role for ornithine decarboxylase and polyamines in cholecystokinin‐induced pan

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1989.tb00258.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract.The expression of six antigenic epitopes on plasma Tg and tissue‐derived Tg was investigated using mouse mabs in immunoradiometric assays. The sensitivity of the assays ranged between 0.5 and 1.5 μg 1‐1. Plasma thyroglobulin of 15 normal individuals and 18 patients with metastatic, differentiated thyroid cancer was analysed. Whereas five monoclonals produced values comparable to the conventional RIA system, the monoclonal antibody Tg 158 did not detect any Tg in the normal individuals and only low levels in two of the cancer patients with the highest Tg levels.In contrast, dilutions of extracts of three different euthyroid goitre samples and three different samples of differentiated thyroid cancer revealed no difference in the antigenic expression of all six epitopes, including the Tg 158 epitope. Papain digestion of purified Tg resulted in a 76 kD fragment which showed immuno‐reactivity for Tg 158 as well as for Tg 11. No interference of the binding of Tg 158 by T3, T4or DIT could be detected.We conclude that the monoclonal antibody Tg 158 detects an epitope which is present in thyroid tissue‐derived Tg but not in circulating thyroglobulin. This antibody might be useful for the investigation of the secretory process of thyroglobulin from the thyrocytes into the cir

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1989.tb00259.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract.IgE antibodies to peptide hormones or their fragments were investigated using specific radioaller‐gosorbent tests. Ninety‐six sera were obtained from otherwise healthy individuals with a positive RAST to at least one common allergen and without previous contact to exogenous hormones. Total serum IgE was normal (8 times background) were observed frequently: hGH 9.1%, GHRH1–445.5%, GHRH1–2912.7%, erythropoietin 10.9%, human calcitonin 14.6%, salmon calcitonin 1.8%, ACTH 5.5%, insulin 14.6%, proinsulin 7.3%, insulin A chain 1.8%, insulin B chain 18.2%, C‐peptide 9.1%, and IGF 9.1%.The data show natural occurrence of reagins to peptide hormones in atopic persons. A risk at exposure to these peptides may exist in about 1% of the general

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1989.tb00260.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract.Due to a longer plasma half‐life and half‐time of action on glucose metabolism biosynthetic human proinsulin was thought to be an alternative to long‐acting insulin preparations. To test this hypothesis we studied 23 type 2 diabetic patients who could no longer be treated sufficiently with oral hypoglycaemic agents. After an initial 1 week phase during which all patients received protamine bound insulin twice daily, the patients either continued on NPH insulin (Group A,n= 11) or were randomly switched to human proinsulin (Group B,n= 12). Glucose profiles and peripheral and hepatic insulin sensitivity (euglycaemic clamp: 120 mU m‐2min‐1) were measured at the end of the initial period (Time 1) and 1 week later (Time 2).The insulin‐mediated glucose disposal (RD) was not changed after either treatment (group A: 176±18 vs. 192±19 mg m‐2min‐1; group B: 175 ± 15 vs.174±12 mg m‐2min‐1for times 1 and 2, respectively, NS). Suppression of hepatic glucose output (HGO) was complete in both groups at both times. Fasting blood glucose levels (FBG) and basal HGO were equally low at times 1 and 2 (group A: FBG 118 vs. 123 mg dl‐1, BHGO 81 vs. 79 mg m‐2min‐1; group B: FBG 118 vs. 106 mg dl‐1, BHGO 87 vs. 84 mg m‐2min‐1; NS). Mean blood glucose levels (MBG) were unchanged in the group receiving NPH insulin (164 vs. 162 mg dl‐1; NS) but improved in group B (182 vs. 142 mg dl‐1;P<0.001). Blood glucose levels were lower in group B, expecially during the afternoon (from 12.00 to 19.00 h). Insulin requirement was the same in group A at times 1 and 2; in group B the proinsulin dosage was reduced significantly to 33 U day‐1at time 2 as compared to an insulin dose of 41 U day‐1at time 1 (P<0.01). In summary, equal metabolic control can be achieved with proinsulin compared to protamine bound insulin with a lower dose on a unit base for proinsulin. Peripheral and hepatic insulin sensitivity remain unchanged during proinsuli

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1989.tb00261.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY