Increased expression of Ia (HLA-DR) antigens in rejecting kidneys.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J F Moorhead.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The relative roles of hepatic lipase and lipoprotein lipase in the pathogenesis of uremic lipid abnormalities were studied in 92 hemodialysis patients. Fasting serum cholesterol, triglyceride, and HDL-cholesterol concentrations were measured. Plasma lipoprotein electrophoretic patterns were determined in all patients. Hepatic lipase and lipoprotein lipase activities were selectively measured in post-heparin plasma in 59 patients. Hemodialysis patients had higher serum triglyceride and lower HDL-cholesterol concentrations than did their age and sex-matched control subjects. Both hepatic and lipoprotein lipase activities were reduced in hemodialysis patients. An inverse relation between lipoprotein lipase activities and serum triglyceride concentrations emerged. Lipoprotein lipase activities correlated with in vivo post-heparin fractional clearance rates of Intralipid. A positive correlation between lipoprotein lipase activities and HDL-cholesterol concentrations probably reflected impaired catabolism of triglyceride-rich lipoproteins being responsible for the low HDL-cholesterol concentrations. Hemodialysis patients (41.3%) had an abnormal lipoprotein (the 'mid-band'). While hepatic lipase activities did not correlate with any parameters of lipid metabolism, patients with 'low' hepatic lipase activities had a significantly higher prevalence of 'mid-bands' than did those with 'normal' activities. No evidence was developed to prove that the 'mid-band' lipoproteins were remnant particles.
In the DA-to-Lewis renal allograft model, donor whole blood enhanced renal allograft survival (14.5 +/- 7.6 days versus 6.9 +/- 0.6 days in controls [P less than 0.01]). The effect of individual cell components given in numbers equivalent to those present in the enhancing volumes of donor whole blood was studied. Immunization with donor red cells alone produced greater enhancement than that produced by whole blood (36.14 +/- 19.5 days [P less than 0.01]). B lymphocytes also enhanced allograft survival (16.0 +/- 3.9 days [P less than 0.01]). Although slight enhancement was observed with platelets (8.5 +/- 0.6 days) and 10(5) dendritic cells (8.4 +/- 0.5 days), in terms of allograft function dendritic cell immunization produced evidence of dose-dependent accelerated rejection. A similar finding was obtained with donor T cell immunization. Donor plasma had no effect. We conclude that, although donor blood has an overall enhancing effect on renal allograft survival in this model, the sensitizing and enhancing effects can be ascribed to individual types of cells.
Lipid metabolism was studied in 18 patients with nephrotic syndrome due to various glomerulonephritides. Nephrotic patients had hypercholesterolemia with or without hypertriglyceridemia. The mean serum high-density lipoprotein cholesterol concentration was not significantly reduced in nephrotic patients. Hepatic lipase and lipoprotein lipase activities were measured selectively in post-heparin plasma from all 18 patients using a substrate-specific method. The mean lipoprotein lipase activity in nephrotic patients was markedly reduced while the mean hepatic lipase activity was not significantly different from that of controls. Lipoprotein lipase activities correlated inversely with serum triglyceride concentrations, but positively with in vivo post-heparin fractional clearance rates of Intralipid and with serum high-density lipoprotein concentrations. Nephrotic serum inhibited lipoprotein lipase activity in normal subjects. The percentage inhibition, however, did not correlate with the degree of hypertriglyceridemia. A relatively weak inverse correlation was shown to exist between plasma albumin concentration and hepatic lipase activities.
Eight hypertensive renal allograft recipients who had received captopril are presented. Captopril in a maximal daily dose of 250 mg enabled the withdrawal of large doses of beta-blocking agents and vasodilators. Blood pressure was satisfactorily controlled in all except one. No adverse side effects were observed other than the 'first dose' effect which resulted in transient anuria in one patient. Captopril appears to be a useful agent in the management of severe hypertension after renal transplantation.
Explore the source record for details and available documents.
Sixty-five renal transplant recipients underwent digital vascular imaging of the graft and simultaneous selective venous sampling for plasma renin activity. Renal artery stenosis was found in seven patients but did not appear to be functionally important. Diffuse intrarenal arterial attenuation was found in seven patients and was associated with impaired graft function and perfusion; it may indicate chronic rejection. Lower pole hypoperfusion was found in nine patients without impaired graft function or perfusion; its clinical relevance is uncertain. Aneurysmal dilatation of the main renal artery was found in two patients. Severe hypertension was common in patients with these three major abnormalities, but a causal association between the abnormality and hypertension could rarely be inferred. It may be the abnormalities on digital vascular imaging, especially diffuse intrarenal arterial attenuation and lower pole hypoperfusion, are secondary to severe hypertension. Digital vascular imaging with simultaneous selective venous sampling for plasma renin activity is useful in evaluating the vascular anatomy of the grafted kidney and in assessing any abnormality found. The combined procedure was well tolerated by all patients with no complications and no incidence of acute tubular dysfunction or proteinuria after the investigation.
Explore the source record for details and available documents.
Intestinal calcium and phosphate absorption have been measured in nine patients with nephrotic syndrome and normal renal function, by a combined radioisotope technique which allows simultaneous measurement of both quantities. The values obtained were compared with those obtained in 20 normal controls. Calcium absorption in the nephrotic group was significantly lower than in the control group (P less than 0.01), but phosphate absorption in the nephrotic group did not differ from controls. This dissociation between calcium and phosphate absorption provides further evidence for independent mechanisms governing the two absorption processes.
Biopsies of normal kidneys taken at time of transplantation were studied using a variety of immunofluorescent and cytochemical techniques. A heterogeneous population of HLA-DR+ cells was found, mainly confined to the intertubular interstitium. The majority of these cells (80%) were positive when stained with a rabbit anti-factor VIII antiserum suggesting that they were endothelial cells. A minority however (20%) were factor VIII- but were positively stained with FMC17, a monoclonal antibody (McAb) directed against human monocyte/macrophage antigens. Positive staining of this subpopulation was also noted with RFD1, a McAb which reacts with an antigen on human interdigitating cells (ID cells). Cytochemical reactions revealed that these cells contain adenosine triphosphatase (ATPase) and acid phosphatase (ACP) and thus do not conform to the phenotype of tissue histiocytes. The phenotype of this latter population is identical with that of the ID cells found in tonsil, thymus and spleen and it is suggested that they play a major role in initiating the process of renal allograft rejection.
We assessed the nephrotoxicity of ionic and non-ionic radiocontrast material (CM) in two groups of patients in a prospective study. One group of 25 potential live kidney donors was studied following conventional renal angiography, carried out as part of the routine pre-operative assessment. The other group of 49 renal transplant patients with varying degrees of renal impairment was studied following digital vascular imaging carried out for investigation of hypertension. Plasma creatine, urinary N-acetyl-D-glucosaminidase (NAG), urinary microglobulin (B2M) and urinary protein excretion were measured before and after the imaging procedure. There were no significant changes in these parameters following digital vascular imaging, but there were increases in plasma creatinine (p less than 0.005) and urinary NAG creatinine ratio (p less than 0.002) in the conventional angiography group following the procedure. Substantial proteinuria developed in 35% of patients following conventional angiography. The differences in nephrotoxicity of radiocontrast agents during the two procedures could not be accounted for by the dose of material used, but probably reflect the effect of differences in the route of administration on the maximal concentration of the material reaching the kidney. Non-ionic radiocontrast material proved less toxic than ionic and may be preferable in conventional angiography.
Explore the source record for details and available documents.
Forty-four hypertensive transplant patients were investigated by digital vascular imaging of the graft and simultaneous selective venous sampling for plasma renin activity to attempt to identify those patients whose hypertension may be amenable to surgical treatment. Localization of renin hypersecretion was possible in 12 patients. In ten of these, hypersecretion originated from the native kidney and in two from the graft. Localization was possible in a significantly higher proportion of patients with severe hypertension (8 of 17), and all of these had native kidney hypersecretion. Bilateral nephrectomy may be indicated in these patients. No cases of functionally significant renal artery stenosis were identified. The other major types of abnormal vascular pattern found on digital vascular imaging, diffuse intra-renal arterial attenuation and lower pole hypoperfusion may be secondary to hypertension. This combined technique may be useful in the evaluation of post-transplant hypertension, especially when hypertension is severe.
It is hypothesised that chronic progressive kidney disease may be mediated by abnormalities of lipid metabolism. A series of self-perpetuating secondary events follows an initial glomerular injury. Increased glomerular basement membrane permeability leads to loss of lipoprotein lipase activators, resulting in hyperlipidaemia. Circulating low-density lipoprotein binds with glycosaminoglycans in the glomerular basement membrane and increases its permeability. Filtered lipoprotein accumulates in mesangial cells and stimulates them to proliferate and produce excess basement membrane material. The proximal tubular cells metabolise some of the filtered lipoprotein and the remainder are altered on passage down the nephron. Luminal apoprotein precipitates, initiating or aggravating tubulo-interstitial disease, if the intraluminal pH is close to the isoelectric point of the apoprotein. The hypothesis offers new approaches to the study of chronic progressive kidney disease by proposing a major pathogenetic role for lipid abnormalities.
Explore the source record for details and available documents.