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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review concerns the present state of accomplishments in the study of SEM of human and experimental renal disease. Critical techniques of specimen preparation reviewed include perfusion fixation, razor tissue sectioning, alcohol cryofracture, microtome sectioning of paraffin or styrene embedded tissue, ultraplaning with glass knives of hard carbowax embedded tissues and glomerular isolation. Gold-palladium coating and heavy metal impregnation with osmium, uranium, and silver are discussed. A compendium of SEM observations of human glomerular, vascular and tubular disease is presented. Techniques for SEM of experimental renal disease are reviewed. These include latex vascular injection, freeze drying, x-ray microanalysis and use of backscattered electron imaging. Experimental models previously investigated by SEM are puromycin aminonucleoside nephrosis, daunomycin nephrosis, and N,N1-Diacetylbenzedine glomerulopathy, nephrotoxic serum nephritis, and protamine perfusion glomerulopathy. Reviewed are acute tubular necrosis caused either by angiotensin, hypotension, norepinephrine, glycerol, mercury, and unilateral renal artery occlusion, also potassium depletion nephropathy, alloxan diabetes and diphenylamine-induced polycystic disease.
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PMID:SEM of human and experimental renal disease. 52 33

The blood levels of 25-hydroxyvitamin D (25-HCC) in 26 patients with nephrotic syndrome (proteinuria of 6.5 g/24 h +/- 0.8 SEM) ranged between 1 and 18.6 ng/ml (8.6 +/- 1.0 SEM). This value was significantly lower (P less than 0.01) than that in normal subjects (21.8 +/- 2.3 ng/ml) and patients with chronic renal failure (24.8 +/- 2.3 ng/ml). There was inverse correlation (P less than 0.01) between levels of 25-HCC and magnitude of proteinuria and a direct relation (P less than 0.01) with serum albumin. Reduction in proteinuria was rapidly followed by a rise in blood 25-HCC toward normal. Ionized calcium levels were low in 16 of 26 nephrotic patients irrespective of degree of renal failure. In four of seven nephrotic patients with normal renal function, ionized calcium levels were low and showed an inverse relation with levels of parathyroid hormone. These data show that patients with nephrotic syndrome have low blood levels of 25-HCC probably due to its loss in urine. This derangement is probably responsible for the disorders of calcium metabolism in nephrosis.
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PMID:Blood levels of 25-hydroxyvitamin D in nephrotic syndrome. Studies in 26 patients. 93 Dec 2

Samples of protein from the urine of 23 patients with lupus nephropathy and 15 patients with proteinuria who did not have systemic lupus erythematosus (SLE) were studied for the presence of cytokines, soluble interleukin 2 receptors (sIL-2R), and free light chain immunoglobulins. The patients with lupus nephropathy were divided into two groups with active (nephritis) and inactive inflammation (nephrosis) based on the results of the analysis of urine samples and renal histology. The crude urine proteins (5 mg/ml) after precipitation by 80% ammonium sulphate from 14 patients with lupus nephritis contained higher concentrations of sIL-2R (4.88 (SEM 1.27 ng/ml) than those from nine patients with nephrosis (1.11 (0.52) ng/ml) or 15 patients without SLE (1.31 (0.87) ng/ml). The concentration of sIL-2R in protein from urine samples was not correlated with the concentration in plasma and was inversely correlated with the excretion of protein in urine over 24 hours in patients with SLE. It is suggested that, in addition to leakage from the circulation, the local production of sIL-2R by inflamed kidneys is possible. The crude proteins in urine were further fractionated by gel filtration on Sephacryl S-200. Arbitrarily, four fractions could be obtained from urine from patients with SLE but only three fractions were found in the urine of patients without SLE. Fraction IV derived from patients with nephritis or nephrosis augmented the pokeweed mitogen induced [3H]thymidine uptake of mononuclear cells. In addition, the positive rates of free kappa (kappa) (35.7%) and lambda (lambda) (42.9%) chains in proteins in urine from nephritic patients were higher than those in the other two groups. These results suggest that the severity of inflammation in the kidneys of patients with lupus can be reflected by the increased excretion of sIL-2R, free light chain immunoglobulins, and cytokine-like molecules in urine.
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PMID:Increased excretion of soluble interleukin 2 receptors and free light chain immunoglobulins in the urine of patients with active lupus nephritis. 155 Mar 98

There are several early indicators of non-genotoxic bladder tumorigenicity. The non-invasive indications are polydipsia, diuresis, changes in urine pH and urinary cation concentrations, especially Na and Ca. The indicators requiring invasive techniques are increased bladder weight and increased cell replication assessed by DNA labeling or histologically as epithelial hyperplasia. SEM has been used to characterize bladder surface changes, and a reduction of bladder tissue Ca has been implicated in one mechanism leading to bladder cancer. Wherever multiple species have been tested, the non-genotoxic bladder carcinogens have induced bladder responses only in rats. This is true whether the criterion was complete carcinogenesis, promotion or short-term indicators. It is also evident that the response can vary greatly within rat strains and is dependent upon the diet being fed. These variables make the relevance of the results obtained in the rat bladder of questionable significance to man. In relation to chronic studies it is clear that as the male rat ages it loses the capacity to concentrate urine, probably because of the endemic, age-progressive loss of functional renal tissue. It is also clear that the bladder grows to accommodate the increase in urine output. Thus it is likely that any agent or treatment that causes bladder damage may be associated with increased neoplasia expression in aged male rats. No other species shows the degree of spontaneous nephrosis seen in the male rat, a condition which is both rat strain- and diet-dependent. Finally, it should be recognized that while there are some early indicators of bladder tumorigenesis that can be useful as warning signs, each compound is likely to yield unique responses when its mechanism is studied in detail. To facilitate discussion of the parameters that have been identified as early indicators of bladder tumorigenesis associated with non-genotoxic agents, the proposed mechanisms of cancer development, the information which led to these proposals and a critique of the mechanisms have been presented.
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PMID:Early indicators of bladder carcinogenesis produced by non-genotoxic agents. 204 84

Puromycin aminonucleoside (PAN)-induced nephrosis in rats provides a model for studying the pathogenesis of severe proteinuric conditions, such as minimal change disease. The present study used scanning (SEM) and transmission (TEM) electron microscopy to investigate the in vitro effects of PAN on rat glomerular podocytes. Slices of rat kidney were incubated for up to 3 days in Medium 199 with Hanks' salts (control) or in medium with PAN. Semiquantitative SEM analysis of glomeruli on the upper surface of kidney slices indicated that incubation with PAN (100 micrograms/ml and 500 micrograms/ml) decreased the number of microvilli on podocyte cell bodies (days 1, 2 and 3), increased the number of glomeruli showing flattening of podocyte cell bodies and major processes (days 2 and 3), and increased the number of glomeruli showing surface membrane blebbing on podocyte foot processes (day 3) (p less than 0.001 in all cases). TEM morphometry revealed that incubation with 500 micrograms/ml PAN retarded significantly (p less than 0.001 at days 2 and 3) the loss of podocyte foot processes observed in control cultures. Whilst the SEM changes to podocyte ultrastructure largely mimic those seen in PAN nephrosis in vivo, the retardation of foot process loss runs counter to the major TEM change observed in vivo.
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PMID:In vitro effects of puromycin aminonucleoside on the ultrastructure of rat glomerular podocytes. 237 13

Administration of puromycin aminonucleoside (PAN) to Wistar rats induces proteinuria and enhanced mesangial deposition of circulating macromolecules. After proteinuria of longer duration focal and segmental glomerular hyalinosis and sclerosis (FSGHS) develops. The present report analyzes these aspects of PAN nephrosis in PVG/c rats, a strain previously shown to be remarkably resistant to proteinuria and FSGHS with aging or after uninephrectomy. In Wistar rats multiple injections of PAN during five months resulted in sustained severe proteinuria and FSGHS lesions in 8.1 +/- 1.0% (mean +/- 1 SEM) of their glomeruli (N = 6). In PVG/c rats a 1.3-fold higher dose of PAN was needed to induce chronic proteinuria similar to the Wistar rats. After five months 3.3 +/- 0.9% of their glomeruli showed FSGHS (N = 6, P less than 0.01) and the glomerular lesions were considerably less advanced. In acute PAN nephrosis induced by a single intravenous injection of PAN the mesangium of Wistar rats contained large amounts of lipid in contrast to a few small mesangial lipid droplets in nephrotic PVG/c rats. After injection of colloidal carbon in nephrotic PVG/c rats no enhanced carbon accumulation was found in the mesangium when compared to nonproteinuric controls. This result clearly differs from the increased mesangial sequestration of circulating material in nephrotic Wistar, and most other rat strains. The unchanged mesangial traficking of macromolecules in nephrotic PVG/c rats and the low incidence of FSGHS lesions in the presence of sustained glomerular proteinuria may reflect a relative resistance to PAN-induced glomerular damage in this particular rat strain.
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PMID:Differences in puromycin aminonucleoside nephrosis in two rat strains. 336 53

Female Wistar strain rats injected intraperitoneally with 1 g of BSA per day for 5 days, a total of 5 g of BSA, developed heavy proteinuria. Characteristic morphological abnormalities were seen by both TEM and SEM in the large majority of glomeruli from these animals and were similar overall, but not identical to, those seen in puromycin aminonucleoside nephrosis. The heterologous protein overload model seems to present considerable opportunity for study of the basic mechanisms of glomerular visceral epithelial cell handling of protein.
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PMID:A scanning and transmission electron microscopic study of glomerular damage in the rat following heterologous serum albumin overload. 728 27

The nephrotic syndrome is associated with disturbances in plasma lipid pattern and metabolism. However, the reason for these perturbations is poorly understood. In the present study, we have investigated hepatic triglyceride metabolism in puromycin aminonucleoside-induced nephrotic syndrome in rats. Nephrotic rats displayed a 70% increase in hepatic triglyceride levels compared to controls (16.9 +/- 1.6 vs. 9.8 +/- 0.6 mumol/g liver; means +/- SEM, P < 0.01). The capacity for hepatic mitochondrial beta-oxidation of fatty acids was substantially elevated (80%). This was associated with a rise in the liver content of the fatty acid carrier carnitine (1.24 +/- 0.06 vs. 0.85 +/- 0.07 mumol/g dry weight, P < 0.05). A positive correlation between the levels of acetylcarnitine and acetyl-CoA was found in normal as well as in nephrotic rats, implying that carnitine plays an important role as an acetyl group acceptor in the liver under normo- and hyperlipidemic conditions. Changes in carnitine levels seem to be tightly coupled to the rate of fatty acid oxidation. There was a significant elevation in the activity of phosphatidate phosphohydrolase (E.C. 3.1.3.4) in liver microsomes from nephrotic rats (1.07 +/- 0.09 vs. 0.81 +/- 0.04 nmol/min.mg protein, P < 0.02). Hepatic very low density lipoprotein (VLDL)-triglyceride secretion rate was 18% higher in nephrotic rats than in controls. The results demonstrate a deranged hepatic triglyceride metabolism in nephrosis, with an increased hepatic triglyceride biosynthesis, a sizable accumulation of hepatic triglycerides, and only a modest increase in VLDL triglyceride secretion. In addition, mitochondrial beta-oxidation of fatty acids was enhanced, associated with an increased availability of carnitine.
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PMID:On the interrelationship between hepatic carnitine, fatty acid oxidation, and triglyceride biosynthesis in nephrosis. 927 Sep 76

Glomerular function and structure were serially evaluated in 15 patients with membranous nephropathy who exhibited relapsing nephrosis and chronic depression of GFR. GFR declined from 56+/-8 (mean+/-SEM) at onset to 31+/-4 ml/min per 1.73 m2 after a 2- to 5-yr period of observation (P < 0.05). An analysis of filtration dynamics suggested persistent elevation of net ultrafiltration pressure. To examine a possible role for declining intrinsic glomerular filtration capacity as the basis for the observed hypofiltration, glomeruli in the baseline and a repeat biopsy (performed after a median of 28 mo) were subjected to morphometric analysis and mathematical modeling. Analysis of the baseline biopsy revealed a reduction in filtration slit frequency and thickening of the glomerular basement membrane, lowering computed hydraulic permeability by 66% compared with normal kidney donors. In contrast, filtration surface area was increased by 37% as a result of glomerular hypertrophy. The repeat biopsy revealed persistent depression of hydraulic permeability, primarily owing to foot process broadening. An additional finding was a decrease in filtration surface area from baseline in patent glomeruli, possibly due to encroachment on the capillary lumen of an increasingly widened basement membrane. Also, a striking increase in the prevalence of global glomerulosclerosis from 7+/-2% to 23+/-4% was found between the two biopsies, suggesting a significant loss of functioning nephrons. It is concluded that hypofiltration in membranous nephropathy is the consequence of a biphasic loss of glomerular ultrafiltration capacity, initially owing to impaired hydraulic permeability that is later exacerbated by a superimposed loss of functioning glomeruli and of filtration surface area.
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PMID:Mechanisms of progressive glomerular injury in membranous nephropathy. 969 60

Human familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is characterized by low HDL, accumulation of an abnormal cholesterol-rich multilamellar particle called lipoprotein-X (LpX) in plasma, and renal disease. The aim of our study was to determine if LpX is nephrotoxic and to gain insight into the pathogenesis of FLD renal disease. We administered a synthetic LpX, nearly identical to endogenous LpX in its physical, chemical and biologic characteristics, to wild-type and Lcat-/- mice. Our in vitro and in vivo studies demonstrated an apoA-I and LCAT-dependent pathway for LpX conversion to HDL-like particles, which likely mediates normal plasma clearance of LpX. Plasma clearance of exogenous LpX was markedly delayed in Lcat-/- mice, which have low HDL, but only minimal amounts of endogenous LpX and do not spontaneously develop renal disease. Chronically administered exogenous LpX deposited in all renal glomerular cellular and matrical compartments of Lcat-/- mice, and induced proteinuria and nephrotoxic gene changes, as well as all of the hallmarks of FLD renal disease as assessed by histological, TEM, and SEM analyses. Extensive in vivo EM studies revealed LpX uptake by macropinocytosis into mouse glomerular endothelial cells, podocytes, and mesangial cells and delivery to lysosomes where it was degraded. Endocytosed LpX appeared to be degraded by both human podocyte and mesangial cell lysosomal PLA2 and induced podocyte secretion of pro-inflammatory IL-6 in vitro and renal Cxl10 expression in Lcat-/- mice. In conclusion, LpX is a nephrotoxic particle that in the absence of Lcat induces all of the histological and functional hallmarks of FLD and hence may serve as a biomarker for monitoring recombinant LCAT therapy. In addition, our studies suggest that LpX-induced loss of endothelial barrier function and release of cytokines by renal glomerular cells likely plays a role in the initiation and progression of FLD nephrosis.
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PMID:Lipoprotein X Causes Renal Disease in LCAT Deficiency. 2691 98


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