摘要:

Abstract.Insulin‐like growth factor‐I (IGF‐I) is a single‐chain polypeptide which has multiple metabolic actions and effects on the differentiation and proliferation of a wide variety of cell types. IGF‐I has endocrine, paracrine and autocrine actions and is bound in the circulation to a complex system of binding proteins which alter its bioavailability and activity. Thus its physiology is complex and is altered in a number of pathological states. This review will discuss these states and the actual and proposed therapeutic applications of recombinant human IGF‐

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00958.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.Experimental studies demonstrate impaired regulation of the mesangial angiotensin II (AII) receptor in diabetes. This could contribute to the disturbance of glomerular blood flow and the development of diabetic nephropathy. The aim of this study was to determine whether a similar receptor abnormality occurs in patients with type I insulin‐dependent diabetes mellitus (IDDM) and if so whether this is more prevalent in patients with micro‐ or macro‐albumi‐nuria. The platelet AII receptor was chosen because of its availability from the circulation and its comparable regulatory properties to tissue‐based receptors. The interaction between plasma All and its platelet receptor was examined in 45 patients with TDDM and 36 age‐ and sex‐matched control subjects. Seven patients had clinical nephropathy and two had persistent micro‐albuminuria. The duration of diabetes varied from 1 month to 42 years.There was a significant inverse correlation between plasma AIT and the logarithm of receptor number in the control group (r= ‐0.555,P<0.001). This relationship was not observed in the diabetic patients irrespective of the duration of disease or the presence of nephropathy. Receptor expression in patients without nephropathy showed no correlation with either duration of disease or the degree of glycaemic control. However, a significant relationship between AII receptor number and duration of diabetes was noted in the group with nephropathy (r = 0.723,P<0.05). Patients without nephropathy had a significantly lower receptor number than control subjects (i.e. 3.9 ± 0.4 and 5.1±0.7 sites per cell respectively; P = 0.02), while comparable values to controls were observed in patients with renal disease (5.7 ±1.2 sites per cell). Plasma renin and AII levels for both groups of patients were comparable to those observed in the control subjects.If these findings are representative of tissue‐based AII receptors, then the loss of ligand/receptor relationship in the presence of higher receptor expression in patients with nephropathy could provide an explanation for the glomerular haemodynamic abnormalities obse

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00959.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.Deficiency of apolipoprotein C‐II (apo C‐II), the cofactor for lipoprotein lipase, results in the familial chylomicronaemia syndrome characterized by severe hypertriglyceridaemia and fasting chylomicronaemia. To investigate the biochemical features of the heterozygous state for apo C‐II deficiency, we characterized the lipid, lipoprotein and apolipoprotein profiles in 18 relatives of two affected individuals (brother and sister) homozygous for the apo C‐IIPadovagene defect which results in the synthesis of a truncated 36 amino acid apolipoprotein. Carrier status was established in first degree relatives as well as in seven non‐obligate heterozygotes by restriction enzyme analysis of amplified apo C‐II genomic DNA using RsaI.No significant differences in lipid, lipoprotein and apo C‐II levels were observed in heterozygotes when compared to unaffected family members. Thus, in this study, the carrier state was not associated with hypertriglyceridaemia or reduced plasma levels of apo C‐II.However, analysis of amplified DNA from members of the apo C‐IIPsdovakindred by digestion with the enzyme RsaI, which identifies the mutant apo C‐II, permitted the identification of heterozygous family members which could not be recognized by measuring either fasting triglycerides or plasma apo C‐II levels.This study provides further evidence that apo C‐II deficiency syndrome is a heterogeneous disease not only at the molecular level but also on the clinical ground with variable phenotypic expression in heterozygous individuals

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00960.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.Stimulation of cholecystokinin release by bombesin is augmented by cholecystokinin receptor blockade with loxiglumide. We hypothesize that this augmented cholecystokinin release results from inhibition of the pancreatico‐biliary response to bombesin during cholecystokinin receptor blockade. To test this hypothesis, we infused bombesin for 180 min in six healthy subjects Three bombesin‐infusion experiments were performed in each subject in random order on different days. In two of these experiments loxiglumide was co‐infused with bombesin, while in the third experiment saline was co‐infused with bombesin. In one of the loxiglumide experiments, duodenal juice, collected on the previous day during infusion of cholecystokinin‐GIH, was reperfused intraduodenally during the second hour of bombesin infusion.In the saline experiment, the integrated cholecystokinin response during the first hour of bombesin‐infusion (262 ± 63 pmol 60 min‐1) was significantly (P<0.01) higher than during the second (88 ± 26 pmol 60 min‐1) and third (87 ± 31 pmol 60 min‐l) hour of bombesin‐infusion. Loxiglumide augmented bombesin‐stimulated cholecystokinin secretion from 262 ± 63 pmol 60 min‐1to 453 ± 63 pmol 60 min‐1in the first hour of bombesin infusion (P

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00961.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.The concentrations of lipids, bile acids and proteins were evaluated in the ascitic fluid and plasma of 23 cirrhotics. Ascitic fluid density was highly correlated with its protein content, represented mostly by low molecular weight proteins. The ratio of plasma to ascitic fluid concentrations of nine examined proteins increased with molecular weight, indicating a selective ultrafiltration of the peritoneal transudate. Low density lipoproteins in ascitic fluid had modified electrophoretic mobility. Total cholesterol had a higher plasma to ascitic fluid ratio than high density lipoprotein cholesterol, whereas bile acids and proteins had similar plasma to ascitic fluid ratios. Indeed, bile acids strongly bind to circulating albumin: consequently ascitic fluid contains more cholic acid (less hydrophobic) than other bile acids. Analysis of both plasma and ascitic fluid composition in cirrhotics provides useful information on processes regulating passage of blood components into the peritoneal cavity.

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00962.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.Endotoxin was measured in over 1000 plasma samples from bone marrow transplant patients in a randomized trial of the IgM‐enriched intravenous immunoglobulin (IVIG) Pentaglobin. Peak endotox aemia was significantly reduced (P =0.02) in patients receiving Pentaglobin and 70% of all pyrexias of unknown origin were associated with endotoxaemia. Gut mucosal damage, assessed by lactulose/mannitol ratios, was significantly associated (P= 0.02) with endotoxaemia. Specific IgM antibody to endotoxin core‐glycolipid was significantly raised (P<0.01) in patients receiving the IVIG, and the IgM fraction of Pentaglobin was found to contain most of the antiendotoxin antibody activity of the IVIG. These results suggest a role for IgM‐enriched WIG as a prophylactic agent for the reduction of endotoxaemia and its consequences in bone marrow transplant pat

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00963.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.Objectives of the present study were to establish and investigate a standardized method for quantifying of intact parathyroid hormone secretion during sequential induction of hypo‐ and hypercalcaemia, and to explore the applicability to these data of a mathematical model derived fromin vitrostudies as presented in the literature.Twenty‐two healthy volunteers aged 20–80 years participated in one or more experiments. The experiments comprised three different protocols of sequential induction of a regular hypocalcaemic (citrate) clamp followed by increases in blood ionized calcium, ending in a regular hypercalcaemic (calcium) clamp.During protocol I, the induction of hypocalcaemia, blood ionized calcium 0.21 mmol 1‐‐1(SD0.01,n= 76) below baseline, the release of serum parathyroid hormone rapidly increased to a concentration of four to seven times above baseline. The serum parathyroid hormone declined gradually to a steady state of about two to three times above baseline. During stepwise increases in blood ionized calcium, the serum para thyroid hormone rapidly declined to new steady state concentrations. When a hypercalcaemia of 0.20 mmol I‐1(SD 0.02,n= 76) above baseline was reached, serum parathyroid hormone was suppressed to about one‐fourth of baseline concentration. Protocol II, the Cica‐clamp, and protocol III, are short versions of protocol I using a slow and gradual increase in blood ionized calcium from hypo‐ to hypercalcaemia. Proto col II reached a hypocalcaemia of blood ionized calcium 0.22 mmol l‐1(SD 0.03,n= 57) below baseline and a hypercalcaemia of 0.19 mmol l‐1(SD 0.04,n= 57) above baseline, whereas protocol III reached a hypocalcaemia of 0.38 mmol l‐1(SD 0.06,n= 57) below baseline and a hypercalcaemia of 0.34 mmol l‐1(SD 0.04,n= 57) above baseline blood ionized cal cium. During protocol II and III we obtained identical results of serum parathyroid hormone compared to protocol I (P>0.70), indicating that serum para thyroid hormone could neither be suppressed nor stimulated beyond what was observed applying the more tolerated protocol II (the standard procedure).Blood ionized calcium and serum parathyroid hormone demonstrate an inverse sigmoidal relationship with a blood ionized calcium concentration to the parathyroid hormone‐midpoint of 1.13 mmol l‐1(SD 0.04,n=19), distinctly different from mean baseline blood ionized calcium, 1.25 mmol I‐1(SD 0.04,n =38). Our data suggest an asymmetrical control of blood ionized calcium by serum Parathyroid hormone with a true calcium set‐point corresponding to about 85% inhibition of maximal parathyroid hormone secretion.In conclusion, the present data shows that it is possible to establish a standardized test for sequential induction of hypo‐ and hypercalcaemia suitably for quantifying of serum parathyroid hormone secretionin vivo. The Cica‐clamp test is short, easy to handle, reproducible and without discomfort to normocalcemic subjects. Its clinic

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00964.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.Aluminium is involved in the etiology of several complications of chronic renal failure and has been firmly established as having toxic effects on bone tissue. We have measured plasma aluminium together with serum osteocalcin, procollagen I C‐terminal peptide and total alkaline phosphatase activity in healthy subjects and in a group of subjects who consumed aluminium‐containing and non‐aluminium containing antacid preparations, with normal renal function. Age‐related healthy reference ranges for plasma aluminium are presented and the effects of chronic antacid consumption on plasma aluminium and biochemical markers of bone formation investi gated.In 172 healthy subjects the mean plasma aluminium concentration was 4.4 ± 2.9 μgL‐1, men having a significantly greater circulating aluminium load than women (5–4 ± 2.8 μg L‐1vs. 4.0 ± 2.8 μg L‐1respect ively (P =0.0039)). Older men were found to have significantly higher plasma aluminium levels than younger men. Increased plasma aluminium was seen in subjects taking antacids although this was not asso ciated with significant changes in most indi

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00965.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.In vivokinetics of lipoprotein(a) [Lp(a)] were investigated in homozygous Watanabe heritable hyperlipidaemic (WHHL) rabbits (an animal model of familial hypercholesterolemia (FH)), and in normo‐lipidemic Japanese White rabbits (controls).1251‐labelled Lp(a) and131I‐labelled LDL were simultaneously injected intravenously. Blood samples were then taken periodically. Kinetic parameters were cal culated from the plasma radioactivity decay curves. The fractional catabolic rates (FCRs) of both Lp(a) and LDL (1.355 ± 0.189 pools per day and 1.278 ± O.397 pools per day, respectively) in the WHHL rabbits were significantly (P<0.005) smaller than those in the control rabbits (2.008 ± 0.083 pools per day and 2.855 ± 0.759 pools per day, respectively). In WHHL rabbits, the FCRs of Lp(a) and LDL were similar. However, in control rabbits, the FCR of Lp(a) was significantly (P<0.01) smaller than that of LDL. In WHHL rabbit organs, the mean ratio of125I‐Lp(a):131I‐LDL, 48 h after injection, normalized to the corresponding isotope ratio in plasma, were 1.525, 1 020, 1.819 and 1.967, in liver, kidney, spleen and bile, respectively. These values were significantly higher than the corresponding values in control rabbits (0.590, 0.677, 0.862 and 0.766, respectively). Our data strongly suggest that Lp(a) clearance is not entirely dependent upon LDL receptors and may be mediated by some oth

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00966.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.Biochemical markers of bone turnover were measured in fasting urine and blood samples obtained from 38 postmenopausal women with previous surgi cal treatment of breast cancer combined with adjuvant chemotherapy, tamoxifen, or placebo. Significantly elevated urinary pyridinoline as nmol mmol‐1creatinine (47.5 and 42.5 in tamoxifen and placebo treated patients compared with 26.3 in normal controls, bothP<0.001) and deoxypyridinoline (11.9 and 10.5 com pared with 6.3,P<0.001 andP=0.002 respectively) were found with unchanged urinary hydroxyproline, serum alkaline phosphatase and procollagen I carboxyterminal peptide (PICP). These findings suggest enhanced bone resorption resulting from the humoral osteoclast activating effect of the previous breast cancer or underlying carcinoma recurrence. Alternatively the raised pyridinium excretion might indicate an altered cross linking composition of bone collagen. No specific effect on bone metabolism was found with tamoxifen treatment as all measured parameters were similar in both tamoxifen ex‐users and non‐users. This confirmed the safety of tamoxifen therapy with respect to

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb00967.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY