摘要:

Abstract.NIDDM is a heterogeneous disorder, characterized by defects in insulin secretion as well as in insulin action. Several pathophysiological mechanisms are involved in the development of disturbances in insulin secretion. One of the histological features of islets of NIDDM patients is the deposition of amyloid‐like material. Accumulation of amyloid over many years can lead to slowly progressive disruption of islet architecture and possibly to some of the abnormalities in insulin secretion, as found in NIDDM patients. Loss of pulsatility is the earliest detectable abnormality of insulin secretion in the disease, either as a specific early defect or as a disturbance caused by minimally elevated blood glucose levels. Although it has been shown that maximum insulin release is decreased by 50% in NIDDM, the B‐cell sensitivity to glucose appears to be normal. Coregulatory factors such as prostaglandins do not play a major role in the derangements of insulin secretion in NIDDM. An imbalance between stimulatory and inhibitory endorphins, or in sympathetic tone may be of more importance. Hyperglycaemia by itself has a deleterious effect on insulin release, and may perpetuate the disturbances of insulin secret

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00743.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.Patients with Bartter's syndrome exhibit an increased vascular resistance to the pressor effects of angiotensin II and noradrenaline. Further, an increased production of vasodilating renal prosta‐glandins, perhaps mediating the vascular unresponsi‐veness, has been hypothesized in this syndrome based on high urinary prostaglandins. To determine whether different peptides might contribute to blood pressure control in this syndrome, the basal immunoreactive plasma levels of an array of vasoactive peptides and catecholamines were analysed in six patients with Bartter's syndrome. Among the vasoconstrictors analyzed, the mean plasma levels of noradrenaline (NA), adrenaline (A) and neuropeptide Y‐like immunoreac‐tivity (NPY‐LI) were significantly increased as compared to healthy subjects (P= 0.030, 0.046 and 0.001, respectively). The plasma level of the vasodilator substance P (SP‐LI) was also higher in these patients (P = 0.057).These results indicate that in Bartter's syndrome the vasoconstrictive effect of catecholamines and angiotensin II may be enhanced by concomitant NPY release. Whether a release of the vasodilator substance P is an independent mechanism or represents a reflex response to the increased secretion of angiotensin II, catecholamines and/or NPY remains to be established. However, the significance of these biochemical findings for blood pressure maintenance in Bartter's syndrome remains to

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00744.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.The mechanism of diabetic macroangio‐pathy was studied from the view point of phenotypic change of aortic smooth muscle cells (SMC). The growth rates of cultured SMC of diabetic rats or rabbits were higher than those of non‐diabetic animals (controls). This difference of the growth responses was observed specifically with platelet‐derived growth factor (PDGF). Of the three PDGF dimers, PDGF‐AB heterodimer (PDGF‐AB) and PDGF‐BB homodimer (PDGF‐BB) stimulated growth of diabetic SMC more than that of control SMC but PDGF‐A A homodimer (PDGF‐AA) did not. The binding of ′251‐PDGF to the diabetic SMC was greater than that to control SMC. This was due to increase in the number of cell surface receptors for PDGF. Onin vitroculture, SMC from diabetic rats expressed more PDGFβ‐receptor mRNA than SMC from non‐diabetic rats. Moreover,in vivo, the aortic media of diabetic rabbits expressed PDGFβ‐receptor mRNA, but that from non‐diabetic rabbits did not. Thus diabetic SMC over‐react on PDGF stimulation through over‐expression of the PDGF P‐receptor gene. The significance of this fact in development of

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00745.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.The kinetics of13CO2have been investigated following oral administration at five doses between 12.5 and 100 mg of13C labelled sodium bicarbonate to 10 healthy subjects in a randomized study. Sodium bicarbonate in this study served as a model compound for carbon dioxide/bicarbonate generated in breath tests. Exhalation of13CO2into breath was monitored by stable isotope ratio mass spectrometry. The kinetics of13CO2were characterized by an apparent terminal elimination half‐life of 1 h and a mean recovery of 0.630 of the dose administered. The kinetics were not dose‐dependent. These results were in agreement with the findings reported previously after iv. application of sodium bicarbon

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00746.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.A sandwich enzyme‐linked immunosorbent assay was developed to assess Fc‐gamma receptor III (FcγRIII), based on a combination of two non‐competing monoclonal antibodies. This receptor was detectable in the serum of eight out of 23 patients with primary Sjögren's syndrome and two out of 23 normal controls. The proportion of FcγRIII‐carrying polymorphonuclear (PMN) cells was lower (P<0.05) in the patients with cell‐free FcγRIII (90·4 ± 7.5%) than in the remainder (84.8 ± 8.3%). The PMN cell functions were evaluated and the diminished adherence (71.7, geometric mean) and chemotaxis (1.23) paralleled the FcγRIII release. The relative inefficiency of PMN cells in SS might be due to phagocytosis of

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00747.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.Erythrocyte sodium‐lithium countertransport (SLC) activity, membrane fluidity, plasma trigly‐ceride and cholesterol were measured in hyperlipidaemic patients and normal subjects. Fluidity was assessed by the fluorescence anisotropy (inversely related to fluidity) of the probes 1,6‐diphenyl‐1,3,5‐hexatriene (DPH) and 1,4‐trimethylammonium‐3,5‐hexatriene (TMA‐DPH). In a second group of patients the maximum velocity (Vmax) and external sodium affinity constant (km) of SLC was also measured.In the first group of patients, SLC activity was increased compared with the controls (0.279 ± 0.019 vs. 0.213 ± 0.013,P= 0.006) as was membrane fluidity in the deep hydrophobic regions (DPH anisotropy 0.211 ± 0.0007 vs. 0.215 ± 0.0011,P= 0.007). There was a strong correlation between SLC and DPH anisotropy (Rs= ‐0.72,P=<0.001) which was due to the correlation between Vmax and DPH anisotropy (Rs=‐0.90,P=<0.001).Increases in Vmax of SLC in hyperlipidaemic patients may be due to differences in lipid organisation in the deep hydrophobic regions of the membrane which may affect the turnove

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00748.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.The aim of this study was to examine the relationships between oral contraceptive use and bone mineral density at the hip and spine.Community based women aged 41–76 years (n =841) were recruited from four general practices in Cambridge. Each subject completed a health questionnaire. Spine (L2‐L4,n= 841) and hip (n= 833) bone mineral density were measured by dual energy X‐ray absorptiometry using the Hologic QDR‐1000.After adjustment for age, there was no significant difference in regional bone mineral density between ever and never users of oral contraceptives. Similar results were obtained after stratifying for potential confounding factors including menopausal status, parity, smoking, hormone replacement therapy use, and body mass index. There was no relationship between duration of oral contraceptive use and bone mineral density.These results suggest that there is no relationship between oral contraceptive use and bone mineral density at the hip and spine in middle‐a

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00749.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.The effect of marine n‐3 polyunsaturated fatty acids on proliferation of human T‐cellsin vitrowas compared to other polyunsaturated, monounsa‐turated and saturated fatty acids. Monoenes and saturated fatty acids had little effect on T‐cell proliferation. Eicosapentaenoic acid and docosahexaenoic acid exerted a strong dose‐dependent inhibitory effect on proliferation of mitogen‐ or antigen‐stimulated T‐cells, similar to that observed for arachidonic acid. SixtyμMof albumin‐bound eicosapentaenoic acid or arachidonic acid promoted 25–40% inhibition of proliferation of T‐cells stimulated with mitogen, whereas the same concentration of albumin‐bound docosahexaenoic acid promoted 60% inhibition. When epidermal cells (Langerhans cells) were used as antigen‐presenting cells, 100μM of albumin‐bound eicosapentaenoic acid or arachidonic acid caused 40% inhibition on T‐cell proliferation. Low density lipo‐protein (LDL), isolated after four months of dietary intake of fish oil or corn oil, inhibited mitogen‐stimulated T‐cell proliferation in a dose‐dependent manner. Fish oil‐ and corn oil‐enriched LDL showed similar ability to inhibit T‐cell proliferation. Epidermal cells preincubated with docosahexaenoic acid, and extensively washed before adding purified T‐cells and antigen, resulted in a strong inhibition of T‐cell proliferation, whereas preincubation of purified T‐cells with docosahexaenoic acid did not cause any inhibitory effect. Cyclooxygenase and lipoxygenase inhibitors (indomethacin, acetylsalicyclic acid, nordi‐hydroguaertic acid) did not affect the antiproliferative effect of eicosapentaenoic acid and arachidonic acid, neither did the antioxidants butylated hydroxytoluene or alpha‐tocopherol. Eicosanoids, (PCE2, PGE3, LTB4, LTB5and lipoxin A or lipoxin B) added directly to mitogen‐stimulated peripheral blood mononuclear cells (PBMC) did not influence T‐cell proliferation significantly. Decreased viability was observed when mitogen‐stimulated lymphocytes were cultured with essential polyunsaturated fatty acids, whereas the viability of unstimulated lymphocytes was hardly influenced by the same fatty acids. We conclude that; (a) pharmacological albumin‐bound concentrations of the highly unsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid promote a strong antiproliferative effect on mitogen‐ and antigen‐stimulated human T‐cells: (b) docosahexaenoic acid can suppress accessory cell function and consequently suppress T‐cell activation; (c) physiologic concentration of LDL particles rich in n‐3 and n‐6 fatty acids, both promote a dose‐dependent antiproliferative effect on mitogen‐stimulated PBMC; (d) the inhibition is independent of eicosanoid metabolites: and (e) lipid

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00750.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.High density lipoproteins (HDL) are responsible for the Reverse Cholesterol Transport (RCT). The role of the composition of the HDL particle in RCT, involving free cholesterol (chol) uptake from cell membranes, is not completely understood. We have therefore studied the uptake capacity from subjects with a wide variety of plasma HDL cholesterol concentrations in an HDL‐receptor free model consisting of bovine heart mitochondrial membranes labeled with [14C]cholesterol. HDL were isolated by molecular sieve chromatography from fresh plasma samples of eight subjects with low plasma HDL chol concentrations (≤ 1.0 mmol L‐1) and 15 subjects with normal HDL chol concentrations. The latter were subdivided into an intermediate (HDL chol: 1.0–1.4 mmol L‐1;n= 9) and a high HDL chol group (>1.4 mmol L‐1;n= 6). In the HDL fractions isolated by chromatography (cHDL), total chol and apolipopro‐tein (apo) A1 were measured. Free chol uptake was significantly decreased by 32% in the tertile with the lowest plasma HDL chol (49 1 ± 15.8 arbitrary units; mean ± SD), compared to the tertile with high HDL chol (72.1 ± 16.6 au). Linear regression analysis showed a positive correlation between the free choi uptake and plasma HDL3 concentrations (r= 0.61;P<0.01), HDL chol (r= 0.56;P<0.01), HDL associated apo A1 (r = 0.46;P<0.05), cHDL apo AT (r = 0.56;P<0.05) and cHDL chol (r = 0.46;P<0.05) in all subjects combined. Stepwise multiple‐regression analysis confirmed the association of [14C]cholesterol uptake with plasma HDL3 concentrations (β, 061;P= 0.004). No correlations were found between free chol uptake and total plasma apoAI (r = 0.26; ns) or HDL2 (r = 0.27; ns). After an oral fat load in four FCH patients, free chol uptake parallelled the changes in plasma HDL3 chol concentrations. We conclude that HDL3 is involved in the early steps of RCT and low HDL3 levels may result in less efficient RCT in h

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00751.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.We have studied the iron metabolism in nine patients with erythropoietic protoporphyria (EPP) and three patients with sideroblastic anaemia (SA). All, except one EPP patient were iron deficient. The SA patients had a secondary haemochromatosis.The bone marrow aspirates of patients with SA and also three patients with EPP had a high incidence of ring sideroblasts. Ultrastructural examination of the bone marrow consistently showed finely dispersed electron‐dense deposits localized in mitochondria of erythroblasts in all patients with EPP and SA. Mito‐chondrial electron energy‐loss spectroscopy (EELS) indicated identical iron compounds in erythroblasts of all EPP and SA patients.These findings indicate that the mitochondrial iron utilization is disturbed in EPP and SA. The observation of mitochondrial iron deposition in erythroblasts in EPP and SA suggests that this feature is not of pathognomonic value for diagnosis of SA, but is apparently the result of an inefficient haem synthesis, in EPP due to a defective ferrochelatase. The mitochondrial iron deposition does not depend on the iron status (iron overload or iron deficiency) of the EPP pa

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00752.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY