摘要:

Abstract.Genetic haemochromatosis is an autosomal recessive inherited iron overload disease. The genetic defect and the underlying metabolic error are not known. Several observations indicate that the 2–4‐fold increase of iron absorption is due to a regulatory defect of a membrane iron transport system in duodenal mucosal cells. The key pathophysiologic factor may be the increase of gut‐derived non‐transferrin bound iron liganded to low‐molecular mass organic molecules. A putative membrane carrier protein for nontransferrin bound iron was identified and preliminary data suggest its enrichment in plasma membranes of human mucosal cells as well as in liver and other organs which are affected in genetic haemochromatosis. Cellular accumulation of ionic iron leads to peroxidative decomposition of organelle membrane phospholipids with the consequence of cell degeneration and cell death. Impairment of organ function and structural alterations such as cirrhosis of the liver are clinical manif

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb02031.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.The evidence is reviewed for the hypothesis that clubbing and hypertrophic osteoarthropathy are due to the peripheral impaction of megakaryocytes and platelet clumps in the fingers and toes, to which this particulate matter has passed in an axial stream. The normal pulmonary vascular bed retains these large particles, which fragment before entering the systemic circulation. A right‐to‐left shunt allows them to bypass the pulmonary vascular bed. A preliminary histological report of platelet clumps seen at necropsy in nail bed capillaries of clubbed fingers supports the hypothesis. Platelets contain and release platelet‐derived growth factor, whose known effects could explain all the pathological changes in clubbing. In addition to explaining why clubbing should occur in cyanotic congenital heart disease, clubbing in sub‐acute bacterial endocarditis and distal to infected arterial grafts and aneurysms can be understood in terms of platelet clumps breaking off valves or arterial walls, and passing distally. Clubbing in liver disease is associated with multiple small pulmonary arteriovenous anastomoses which allow large particles through. Hypertrophic osteoarthropathy probably shares the same mechanism, and is mainly attributable to PDGF release; but there may also be altered platelet function and an additional growth factor derived from the lungs.SUMMARYIn 1987 John Martin and I proposed that clubbing was due to the peripheral impaction of megakaryocytes and platelet clumps in the fingers and toes, to which this particulate matter has passed in an axial stream. A preliminary histological report of platelet clumps or microthrombi seen at necropsy in nail bed capillaries of clubbed fingers is compatible with our hypothesis. We suggested that at the site of impaction platelet‐derived growth factor (PDGF) is released. This material is a general growth promoter. It is known to have effects which include all the pathological changes recognized to occur in clubbed digits, including increased vascular permeability, increased vascularity, and stimulation of smooth muscle cells and fibro‐blasts.In cyanotic congenital heart disease with a macroscopic right‐to‐left shunt large particles can pass directly from bone marrow to the systemic arterial circulation without fragmenting in the lungs, as they normally do. In sub‐acute bacterial endocarditis, and in arterial aneurysms or infected arterial grafts, platelet clumps form locally on heart valves or on the damaged arterial wall, then detach themselves and pass peripherally. This mechanism accounts well for localized clubbing. In those lung diseases in which clubbing is common, there may be not only local shunting of blood through multiple small arteriove‐nous anastomotic channels, but also local platelet aggregation and in some cases altered platelet function. In severe liver disease, clubbing can be accounted for by multiple small arteriovenous shunts in the lungs. These have been demonstrated histologically and radiologically, and by tests with particulate matter of different sizes.Clubbing might be expected in the newborn, because blood largely bypasses the lungs during fetal life; but it has not been noted. The likeliest explanation is that fetal platelet PDGF release is undeveloped or inhibited, as are many other fetal platelet release functions: but this matter has not so far been investigated.Hypertrophic osteoarthropathy (HOA) in mild form can often be found in cyanotic congenital heart disease; but its special occurrence and severity in certain diseases (especially carcinoma of the bronchus) suggests that some additional factor may be operating, perhaps associated with the tumour itself. In most respects, however, HOA can be regarded as a more advanced stage of the same process that results

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb02032.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb02033.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.The measurement of the 3–OH pyridinium compounds, pyridinoline (Pyr) and deoxypyridinoline (Dpyr), in urine by high performance liquid chromato‐graphy is potentially useful in clinical studies, since they are specific biochemical markers of bone resorption. The aims of the present study were to improve assay performance and optimize sample collection. An isocratic high performance liquid chromatogram (HPLC) separation with baseline resolution was accomplished within 4 min using heptafluorobutyric acid as an ion‐pair. The sample preparation for HPLC, using CFl cellulose, produced uncontami‐nated samples with a recovery higher than 90% for both crosslinks. An elastin‐derived material, tentatively identified as isodesmosine (Ides), was also tested and proved to be a suitable internal standard. Use of this standard improved assay precision. The effect of an oral gelatin load on the excretion of Pyr and Dyr was investigated. The creatinine corrected excretion of Pyr and Dpyr was unchanged over a 6 h period, in contrast to the 10–fold increase in the excretion of urinary hydroxyproline with a peak 2–4 h after ingestion. In 20 postmenopausal women, 2 h fasting morning urine results correlated with results from 24–h urine collections Dpyr/Cr (r = 0.70,n= 20). There was a day‐to‐day variation of 26% in adults

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb02034.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.To test if different leucine tracers behave in an indistinguishable manner and, by implication, that their metabolism is identical to that of natural leucine, we measured whole body leucine turnover in dogs and humans and fibrinogen synthesis in dogs by simultaneously infusing either [1–14C]leucine or [4,5–3H]leucine or [I‐14C]α‐ketoisocaproate (KIC) and [4,5–3H]KIC. Whole body leucine fluxes calculated from the plasma specific activity of the transaminated product of the infused tracer (reciprocal pool model) were lower (dogs by 5.7%; humans by 6.4%, both P<0.02) when the plasma 'H specific activity compared to14C specific activity were used with leucine tracers and were also lower (dogs by 4.4%,P<0.02;humans by 86%,P<0.06) using the KIC tracers. Using leucine or KIC tracers in dogs, the fractional rate of fibrinogen synthesis was 6.7% or 9.4% lower, respectively, (P<0.02) using the3H versus the14C tracer. The apparently lower incorporation of3H into protein was only in part accounted for by detritiation (2.1%, P = 0.05) of [3H]leucine during acid hydrolysis of proteins. These results suggest thatin vivoand/orin vitrodifferential isotope effects are small (˜5%), but should be considered when dual isotopes infusions are employed to partition amino acid

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb02035.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.In view of the importance of short‐chain fatty acids (SCFA) for the colonic epithelial function and their possible relation with the reported spontaneous regression of rectal polyps after subtotal colectomy with ileorectal anastomosis, we compared the SCFA concentrations in faeces of five familial adenomatous polyposis (FAP) patients before, and in 10 FAP patients after operation to each other and to those of 10 healthy controls. Anaerobe cultural counts and concentrations of organic acids were also investigated in the same faecal samples from FAP patients and controls.The preoperative cultural counts were not significantly different from those of the controls. After colectomy, theBacteroides(P<0.002; P<0.02), and bifidobacteria counts (P<0.02;P<0.005) were decreased compared to controls and untreated FAP patients. The ratio of acetic acid to total SCFA significantly increased, which coincided with a proportional decrease of the other SCFA.The frequently observed regression of rectal polyps after colectomy cannot be explained from these results. One would rather expect a possible stimulation of polyp growth and dedifferentiation of colonic epithelial cell

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb02036.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.Platelet size has been shown to reflect platelet activity. We prospectively measured the mean platelet volume (MPV) in 47 patients undergoing single vessel angioplasty for symptomatic angina. The patients underwent repeat angiography 4–8 months later irrespective of symptomatic status. Restenosis was assessed quantitatively by hand held calliper measurements of the lesion and qualitatively by a return of angina, ST segment changes on an exercise test and visual analysis of the lesion severity by two experienced angiogra‐phers. Twenty‐four patients developed recurrent angina during the follow‐up period, the MPV in the group with chest pain was 8.54 ± 0.60 fl compared to 8.1±0.69 fl in the asymptomatic group (P = 0.04). Twenty two patients had significant ST segment changes at exercise. In this group the MPV was 8.6 ± 0.56 fl compared to 8.0 ±0.70 fl for the group with a negative test (P =0.002). Similarly visually assessed angiographic stenosis showed a significant increase in the restenotic group (8.6 ± 0.56 vs. 8.0 ± 0.61 fl, P=0.001). The relative odds for developing clinically defined restenosis were 10.2 times greater if the pre‐procedural MPV lay in the upper compared to the lowest quartile.There was a positive correlation between MPV and change in minimal luminal diameter between post angioplasty and follow‐up angiography, assessed quantitatively, r=+0.56, P = 0.016. There was no association between clinical or angiographic definitions of restenosis and haemoglobin, red cell count, mean corpuscular volume, white cell count or platelet count. Platelet size may influence the development of restenosis after succeesful cor

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb02037.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.The major lipid disturbance in children with congenital nephrosis of the Finnish type (CNF) is hypertriglyceridaemia. To determine whether or not hypertriglyceridaemia is caused by defective triglycer‐ide catabolism, we measured lipoprotein lipase (LPL) activities and masses at various stages of the disease. At age 3 months in CNF both LPL activity and mass were decreased, but a close positive correlation between these parameters similar to that in controls was observed. At age 9 months both LPL activity and mass were even lower. At that time a significant positive correlation (r = 0.72, P<0.05) between LPL activities and albumin concentrations and significant negative correlations between plasma free fatty acid (FFA) concentrations and LPL activities (r= ‐0.72, P<0.05) and between plasma FFA concentrations and serum albumin concentrations (r= ‐0.73,P<0.05) were observed, suggesting that low albumin concentrations result in increase of FFA levels, which could interfere with a normal LPL function at the endothelial surface. On dialysis after nephrectomy, LPL activities and masses increased. At age 3 and 9 months apoprotein C‐II (apo C‐II) and apoprotein C‐III (apo C‐III) levels were not decreased although apoproteins were being lost into the urine. On dialysis the mean ratio of apo C‐II/C‐III was significantly lower than the mean in controls (P<0.001). We conclude that impaired function of LPL seems to be the major cause of hypertriglyceridaemia and disinte‐grity of the VLDL‐IDL‐LDL delipidation casca

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb02038.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.A 90–min intravenous infusion of the direct vasodilator sodium nitroprusside (SNP) was compared with a placebo infusion in 32 healthy control subjects in order to study the acute effects of SNP on renal haemodynamics, tubular function evaluated by the lithium clearance technique, the plasma levels of atrial natriuretic peptide (ANP), angiotensin II (Ang II), aldosterone (Aldo) and arginine vasopressin (AVP) and the tubular transport of cGMP (TcGMP). SNP infusion induced a significant reduction in mean arterial blood pressure (from 89.5 to 81.5 mmHg), urinary output (from 7.7 to 4.5 ml min‐1), free water clearance (from 4.0 to 1.3 ml min‐I) and ANP (from 3.3 to 2.5 pmoll‐1) and a significant increase in heart rate (from 57 to 64 beats min‐l), Ang II (from 11 to 18 pmoll‐1), Aldo (from 189 to 308 pmol L‐1) and in the tubular secretion of cGMP (TcgmPfrom 28.8 to 214.4 pmol min‐1), (all values are medians and changes from baseline to 90 min after infusion start). Glomerular filtration rate, renal plasma flow, urinary sodium excretion, lithium clearance and plasma level of AVP were not significantly changed. It is concluded that SNP infusion in healthy subjects decreases urinary output and free water clearance without any change in sodium excretion, indicating a dissociation between the salt and water retaining effects of SNP in the early phase of treatment, probably due to an enhanced distal tubular water reabsorption of water. It is suggested that this increase in reabsorption of water in the distal parts of the nephron during SNP infusion may be mediated by an increase of cGMP production in the kidney, as indicated by the increase in TcGMPduring t

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb02039.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Abstract.The change of subspecies of protein kinase C (PKC) was studied in 3T3—L1 cells in terms of their differentiation to adipocytes. 3T3—L1 cells feasible to differentiate to adipocytes by exposure to 3–isobutyl‐1–methylxanthine (IBMX) and dexamethasone had both α‐ and β‐PKC. However, 3T3–Ll cells unfurnished with such feasibility had only α‐PKC. α‐PKC, therefore, seems to be more deeply involved in differentiation of 3T3–LI cells

ISSN:0014-2972    

DOI:10.1111/j.1365-2362.1993.tb02040.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY