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1. |
DNA polymorphisms of the α1‐antitrypsin gene region in patients with chronic obstructive pulmonary disease |
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European Journal of Clinical Investigation,
Volume 20,
Issue 1,
1990,
Page 1-7
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摘要:
Abstract.α1‐a α1‐antitrypsin (AAT) is an important part of the defence mechanism of the lung against proteolytic attack. The Z and Null mutants of the AAT gene are associated with very low or missing serum concentrations of AAT, so that for individuals with genotypes ZZ or Null there is a very high risk of developing chronic obstructive pulmonary disease (COPD). In more than 90% of the patients suffering from COPD, however, the common MM phenotype of AAT is expressed at normal AAT serum levels. The MM phenotype has a heterogeneous constitution and the alleles Ml, M2 and M3 are distinguished by isoelectric focusing. At the DNA level many mutants of the AAT gene may exist that cannot be recognized by IEF. In this paper we report DNA sequence heterogeneity of the AAT gene region among 137 patients with COPD and 130 healthy control subjects. All 267 individuals studied were MM phenotype. Several restriction fragment length polymorphisms (RFLPs) were observed using genomic probes of the AAT gene. One allele (T2) of a Taq I RFLP located 1 kb downstream of the AAT gene was significantly more frequent in patients (15.3%) than in controls (5.4%) (P<0.005). The relative incidence of COPD was 3.3 times higher for subjects carrying at least one T2 allele than for the common T1T1 genotype. The T2 allele may be in linkage disequilibrium with a functionally deficient variant of AAT or some gene in close neighbourhood, e.g. the α1‐antichymotrypsin gene. A deletion of 1.8 kb in the α1‐antitrypsin‐like gene (PIL gene) occurs at a frequency of 0.26 in patients and in control sub
ISSN:0014-2972
DOI:10.1111/j.1365-2362.1990.tb01784.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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2. |
Recent developments in the chemistry of gastrointestinal peptides |
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European Journal of Clinical Investigation,
Volume 20,
Issue 1,
1990,
Page 2-9
V. MUTT,
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摘要:
Abstract.Work carried out in different laboratories has shown that the peptide pattern of the intestinal tissue is very complex and that some of the peptides are identical to those found in the central nervous system. The best studied of the peptides are of a hormonal nature, but recently evidence has been obtained that others may primarily act as antibiotics. In addition, peptides have been isolated that are fragments of some well‐known proteins that have not been viewed as being prohormones. Whether the latter peptides only represent transient degradation products of the proteins or whether, at least some of them, have a physiologically meaningful selective function of their own is not yet clea
ISSN:0014-2972
DOI:10.1111/j.1365-2362.1990.tb01770.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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3. |
Altered collagen metabolism in osteogenesis imperfecta fibroblasts: a study on 33 patients with diverse forms |
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European Journal of Clinical Investigation,
Volume 20,
Issue 1,
1990,
Page 8-14
R. E. BRENNER,
U. VETTER,
A. NERLICH,
O. WÖRSDORFER,
W. M. TELLER,
P. K. MÜLLER,
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摘要:
Abstract.The pattern of collagen metabolism was analysed in fibroblast cultures from patients with diverse forms of osteogenesis imperfecta (OI). Generally, OI fibroblasts show an insufficient collagen synthesis which is most obvious in patients between 2 and 9 years of age during which period control fibroblasts have an elevated collagen synthesis. OI fibroblasts remain on a basal level except for fibroblasts from OI type IV patients which seem to approach normal levels. In addition, OI fibroblasts generally show a slightly increased degradation of newly synthesized collagen which again is most obvious between 2 and 9 years. These differences in collagen degradation, however, only contribute to a minor extent to the lack of net collagen synthesis during early childhood. No correlation could be found between the degree of overmodification of collagen and its degradation since fibroblasts of both OI type I and OI type II have an elevated degradation though only the latter ones produce overmodified collagen molecules. Pulse labelling of collagen with radioactivity labelled sugars was used to distinguish between normal collagen chains or CNBr‐derived peptides and those which were overmodified. In all three cases studied (OI II, OI III, OI IV) the entire triple helical domain of α 1(1) and α2(I) was overglycosylated. The amount of overmodification, however, was not uniform but rather unique for each patient studied. We assume that the molecular defects in the majority of OI cases may be located in the mechanisms operating on the control of both the age appropriate synthesis of collagen and its degree of post‐translational modific
ISSN:0014-2972
DOI:10.1111/j.1365-2362.1990.tb01785.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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4. |
The cytoplasmic Ca2+response to glucose as an indicator of impairment of the pancreatic β‐cell function |
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European Journal of Clinical Investigation,
Volume 20,
Issue 1,
1990,
Page 10-17
B. HELLMAN,
C. BERNE,
E. GRAPENGIESSER,
V. GRILL,
E. GYLFE,
P.‐E. LUND,
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摘要:
Abstract.The effects of glucose on the cytoplasmic Ca2+concentration (Ca2+i) regulating insulin release were investigated using pancreatic β‐cells representative for the normal and diabetic situations. Increase of the glucose concentration resulted in a slight lowering of Ca2+ifollowed by a rise, often manifested as high amplitude oscillations. The Ca2+i‐lowering component in the glucose action associated with suppression of insulin release became particularly prominent when the β‐cells were already depolarized by tolbutamide. Glucose‐induced inhibition of insulin release was observed also in experiments with rats made diabetic with streptozotocin or alloxan. Other studies indicated lowering of plasma insulin after intravenous glucose administration in patients with insulin‐ and noninsu‐lin‐dependent diabetes mellitus. Brief exposure of β‐cells to 2–2 mmol 1‐1streptozotocin resulted in impairment of the response to glucose, manifested as disappearance of the cyclic variation of Ca2+i. The results indicate that glucose‐induced depolarisation is a vulnerable process, the disturbance of which may contribute to insulin secretory defe
ISSN:0014-2972
DOI:10.1111/j.1365-2362.1990.tb01771.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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5. |
Evaluation of a euglycaemic clamp procedure as a diagnostic test in insulinoma patients |
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European Journal of Clinical Investigation,
Volume 20,
Issue 1,
1990,
Page 15-28
M. NAUCK,
F. STÖCKMANN,
W. CREUTZFELDT,
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摘要:
Abstract.In 15 patients with insulinoma, six patients after successful removal of this tumour, two patients with previous pancreas resection because of hypogly‐caemia elsewhere, and 10 control subjects, the diagnostic usefulness of euglycaemic clamp procedures (without exogenous insulin) was assessed in comparison with prolonged starvation. Only insulinoma patients developed sustained hypoglycaemia (≤2.3 mmol 1−1) within 2–44 h without caloric intake, because of inappropriately elevated immunoreactive insulin (IR‐insulin) concentrations. IR‐proinsulin values were elevated in most (7 out of 10), but not in all insulinoma patients. The steady‐state glucose infusion rate necessary to maintain a stable plasma glucose concentration of 4.4–5.0 mmol I−1was significantly (P≤0.001) higher in insulinoma patients (2.5 ±0.6 mg kg−1min−1) than in pancreas resected patients (0.6 ± 0.2 mg kg−1min−1), or in control subjects (0.5 ±0.1 mg kg−1min−1). Due to a considerable degree of ovelap, sensitivity (0.44) and specificity (0.95) were too low for such a procedure to qualify as a diagnostic test. There was no correlation of glucose infusion rates to IR‐insulin values (r= 0.024,p= 0.461). One reason for this was the development of insulin resistance in some, but not in all insulinoma patients. When, in analogy to insulin/glucose ratios, a diagnostic index was derived by multiplying the steady state glucose infusion rate by the steady state IR‐insulin concentration, the diagnostic accuracy was greatly increased (sensitivity and specificity 0.94, respectively), but still lower than that of ‘amended’ insulin/glucose ratios in fasting plasma or at the time of discontinuation of prolonged fasts (1.00). Somatostatin infusions inhibited insulin secretion (IR‐C‐peptide plasma concentrations) by 52–88% in subjects without insulinoma and in those insulinoma patients whose tumour cells ultrastructurally contained plenty of normal secretory granules, and to a lesser degree when only abnormal or virtually no secretory granules were present, i.e. in more de‐differentiated tumours. In contrast to this significant (P=0.036) association, malignancy, i.e. the presence of metastases, could not be predicted from whether or not insulin secretion was resistant to the inhibitory action of somatostatin. In conclusion, euglycaemic clamp experiments are less reliable for detecting or excluding a functioning insulinoma than the relation of glucose and insulin values during starvation. The inhibition of insulin secretion by somatostatin depends on the presence of normal β‐granul
ISSN:0014-2972
DOI:10.1111/j.1365-2362.1990.tb01786.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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6. |
Neuro‐humoral control of insulin secretion |
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European Journal of Clinical Investigation,
Volume 20,
Issue 1,
1990,
Page 18-19
E. BOBBIONI‐HARSCH,
B. JEANRENAUD,
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摘要:
Abstract.Hypothalamic extract from normal rats was shown to contain a principle able to stimulate insulin secretion bothin vivoandin vitro.This substance, whose peptidic nature was demonstrated by enzymatic digestion, has a molecular weight of about 1000 Daltons. An active release of this peptide was obtained when incubating hypothalamic fragments under appropriate stimulatory conditions (i.e. KC1 50 mmol 1‐1in the incubation medium) (i.e. molecular weight and insulin secretion stimulating activity) similar to the hypothalamic peptide was evidentiated in the plasma of normal rats. Since manipulations of hte hypothalamus (i.e. electrical lesions or stimulations) could respectively decrease or enhance the plasma concentration of this substance, the hypothalamic origin of the insulin secretion stimulating principle present in the plasma was strongly suggested. The possible participation of this hypothalamic peptide to the neural control of insulin secretion is suggeste
ISSN:0014-2972
DOI:10.1111/j.1365-2362.1990.tb01772.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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7. |
Gut signals for islet hormone release |
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European Journal of Clinical Investigation,
Volume 20,
Issue 1,
1990,
Page 20-26
R. EBERT,
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ISSN:0014-2972
DOI:10.1111/j.1365-2362.1990.tb01773.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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8. |
Hormones as regulators of pancreatic secretion in man |
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European Journal of Clinical Investigation,
Volume 20,
Issue 1,
1990,
Page 27-32
G. ADLER,
C. BEGLINGER,
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摘要:
SummaryAt the beginning of the century, Pavlov Suggested that the pancreas was exclusively controlled by the nervous reflex mechanisms. In 1902, Bayliss&Starling published their experiments on secretin and claimed that the nervous regulation is ‘superfluous and improbable’. In the following decades, especially after the discovery of CCK, it was generally held that exocrine pancreatic secretion is regulated mainly by hormones. The present summary clearly demonstrates the importance of the cholinergic system in regulating exocrine pancreatic secretion and the complexity of neurohormonal interactions. The question is no longer hormones or nerves, but rather a very complicated coordination of neural. hormonal and possible paracrine effects, resulting in the control of exocrine pancreatic activity. In this complex regulatory system, the cholinergic control is central with hormones such as CCK or secretin modulating the respo
ISSN:0014-2972
DOI:10.1111/j.1365-2362.1990.tb01774.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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9. |
Increased hepatic efficacy of urea synthesis from alanine in insulin‐dependent diabetes mellitus |
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European Journal of Clinical Investigation,
Volume 20,
Issue 1,
1990,
Page 29-34
T. P. ALMDAL,
T. JENSEN,
H. VILSTRUP,
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摘要:
Abstract.The relation of urea synthesis rate to blood alanine concentration was assessed in seven healthy controls and in 18 patients with insulin‐dependent diabetes mellitus (HbAlc = 8.4±1.0% (mean±SD)).Following an overnight fast alanine was infused at 2 mmol h−1kg−1body weight. The hourly rate of urea synthesis was determined as the urinary excretion of urea corrected for accumulation of urea in total body water and intestinal hydrolysis. The functional hepatic nitrogen clearance, i.e. the relation of urea synthesis rate to blood alanine concentration, was calculated as the slope of linear regression of urea synthesis rates on blood alanine concentrations.Fasting glucagon concentrations were 85 + 26 ng 1−1in controls and 161 ±35 ng 1−1(P<0.01) in patients.The functional hepatic nitrogen clearances were 21.8 ± 4.4 1 h−1in controls and 44.7±12.41 h−1(P<0.001) in patients.By multiple step‐wise linear regression analysis the functional hepatic nitrogen clearance was found to correlate independently to fasting glucagon concentration, duration of diabetes, change in blood glucose and insulin following alanine infusion (r2= 0.74). In a simple linear regression analysis the functional hepatic nitrogen clearance correlated strongly to fasting glucagon concentration (r2= 0.54).In conclusion the kinetics of urea synthesis in insulin‐dependent diabetes is changed in favour of increased conversion of alanine‐N to urea‐N at any blood amino acid concentration. The increased FHNC correlates strong
ISSN:0014-2972
DOI:10.1111/j.1365-2362.1990.tb01787.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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10. |
Neuronal control of pancreatic exocrine secretion |
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European Journal of Clinical Investigation,
Volume 20,
Issue 1,
1990,
Page 33-39
J. J. HOLST,
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ISSN:0014-2972
DOI:10.1111/j.1365-2362.1990.tb01775.x
出版商:Blackwell Publishing Ltd
年代:1990
数据来源: WILEY
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