Heat shock protein 72/73 in normal and diseased kidneys.

The induction of heat shock (stress) proteins (HSP) is a response by cells due to a variety of physical, chemical, and infectious agents. They have a significant role as cytoprotectants, in the regulation of cellular functions, and in the recovery after sublethal injury. Using antibody to mammalian HSP 72/73, we have performed as immunohistological study of human renal tissue in normal and diseased states, including idiopathic nephrotic syndrome, proliferative and crescentic glomerulonephritis, and interstitial nephritis. A significant increase of HSP expression was noted in certain segments of the tubule in acute interstitial nephritis and in glomerulonephritis accompanied by active interstitial inflammation. A possible role by the inflammatory mediators in the induction of HSP in those cases is suggested.

Renal disease in Marfan syndrome.

We encountered 4 individuals with Marfan syndrome who presented with microhematuria and proteinuria. In 2 of them, a renal biopsy was performed. The predominant glomerular change by light microscopy was a focal segmental increase in mesangial matrix with early sclerotic lesions. Ultrastructurally, there was variable subendothelial widening containing haphazardly arranged microfibrils, 10-13 nm in diameter. Changes in small arteries present in the biopsies were mild in case 1 and more striking in case 2 which consisted of elastolysis and fragmentation and focal disruption of internal elastic lamina, and focal degenerative changes in the media. In light of observations on the abnormalities of microfibrillar protein (fibrillin) in the microfibrillar-fiber system and the presence of abnormal type IV collagen in the connective tissues in Marfan syndrome, the glomerular basement membrane alterations may be related to these defects and lead to microhematuria and proteinuria.

Renal failure due to tubular obstruction by large protein casts in patients with massive proteinuria.

We describe two patients with nephrotic syndrome whose histologic findings on renal biopsy and at autopsy are characterized by numerous large protein casts in dilated cortical tubules, as well as podocyte swelling with effacement of foot processes in the glomeruli. Both patients progressed rapidly to renal failure. The casts and the protein precipitate in the Bowman's capsule were found to be composed of varying proportions of albumin and globulin but contained no Tamm-Horsfall protein. This suggests a glomerular rather than tubular origin of proteins. Light and electron microscopic examination of tubules revealed changes mainly due to compression by the casts. We propose that tubular obstruction due to the large casts was the main cause of renal failure.

Alkaptonuria and renal failure: a case report and review of the literature.

In alkaptonuric ochronosis, the absence of homogentisic acid oxidase results in the accumulation of homogentisic acid in the body. Associated renal failure is rare and usually occurs in the later stages of the disease. We report a 19-yr-old girl who presented initially with severe renal failure, without family or past history of illness. There was no significant proteinuria or hematuria. No clinical evidence of pigmentation such as skin and subcutaneous cartilages was noted. However, pigment deposits were identified in the renal biopsy specimens obtained within a week after admission and another after a month. Two months later the peritoneal dialysis fluid and skin progressively darkened, suggesting ochronosis. This was confirmed by the detection of homogentisic acid in the serum and urine. The patient expired in renal failure. Renal biopsy tissues showed diffuse chronic tubulo-interstitial disease characterized by widespread tubular atrophy, interstitial fibrosis, and a moderate degree of inflammation. Many tubular cells contained brown, coarsely granular ochronotic pigment (OP) and a few pigment casts were in the lumina. Similar deposits were also in the interstitium and within histiocytes. Ultrastructural studies of the glomeruli revealed small sparse OP deposits in the visceral and parietal epithelial cells, mesangial cells, and rare extracellular and basement membrane deposits. The tubulointerstitial changes were varied: atrophy and dilatation of tubules, varying degrees of lysosomal OP and degeneration of tubular cells, casts containing OP with crystalline material, histiocytes distended with OP, and free interstitial pigment deposition.(ABSTRACT TRUNCATED AT 250 WORDS)

Significance of cytoplasmic inclusions in lupus nephritis.

The report describes 22 cases of lupus nephritis (20 diffuse and 2 mesangial) showing frequent tubuloreticular inclusions (TRI) in the glomerular and peritubular capillary endothelial cells as well as cylindric confronting cisternae (CCC) mainly in interstitial infiltrating cells. Ten other cases of lupus nephritis that were actively treated or were in the sclerosing stage and did not show CCC were also studied. The presence of cytoplasmic inclusions correlated with various clinical and histologic parameters. Cytoplasmic inclusions, especially CCC, are associated with clinically active, minimally treated renal disease of recent onset and histologically with active diffuse glomerular and acute interstitial lupus nephritis with many immune deposits.

Dietary obesity and neonatal sympathectomy. I. Effects on body composition and brown adipose.

The effect of neonatal sympathectomy with guanethidine (50 mg/kg for 3 wk) on the development of diet-induced obesity (DIO) was assessed by raising guanethidine-(G) or saline-treated (S) Sprague-Dawley rats in small litters (4-5 pups/dam) and feeding a high-calorie diet from weaning (n = 29-30) or by raising similarly treated rats in normal litters (10 pups/dam) and feeding chow from weaning (n = 29-30). Sympathectomy depleted norepinephrine (NE) levels 65-98% in all organs except the adrenals and brain but had no statistically significant effect on weight gain, food intake, food efficiency, body composition, plasma glycerol, insulin, or glucose, or on basal rectal temperatures in either diet group; there was a tendency toward increased adiposity in sympathectomized rats. Despite 95-98% depletion of NE in interscapular brown adipose tissue (IBAT), sympathectomy affected only the percentage of multilocular cells that was decreased 46-69%. Rats from small litters in both treatment groups (S and G) became obese without increased food intake (increased food efficiency), had heavier IBAT pads with bigger cells and more lipid, and were also hyperlipidemic, hyperinsulinemic, and hyperglycemic compared with controls. Therefore neonatal sympathectomy was not as significant in the subsequent development of DIO as were diet and litter size.

Defective brown adipose oxygen consumption in obese Zucker rats.

The thermogenic capacity and morphologic characteristics of interscapular brown adipose tissue (IBAT) were assessed in 3- to 4-mo-old male, lean and obese Zucker rats. Pads from obese rats were threefold heavier and contained similar numbers of cells but an average of 50% fewer multilocular cells than pads from lean rats and 40% less mitochondrial protein per pad. The maximal number of beta-adrenoreceptor binding sites, as assessed by [125I]iodocyanopindolol binding to isolated brown adipocytes from obese rats was 50% of that in lean rats on a per cell and per pad basis. Basal and norepinephrine (NE)-stimulated in vitro oxygen consumption in isolated brown adipocytes from lean rats correlated directly with the proportion of mutilocular cells present. This correlation was not seen in cells from obese rats that had a 50% decrease in their basal respiratory rates and could not be further stimulated by excess NE or fatty acid. Electron micrographs of IBAT from obese rats revealed distorted mitochondrial shapes and cristae patterns and the presence of numerous inclusion bodies. Because NE-stimulated lipolysis had previously been shown to be normal in the obese Zucker rat, these data suggest that defective BAT thermogenesis in the obese rat is due to an inability of mitochondria to utilize free fatty acids for the production of enhanced oxygen consumption.

Effects of diet and obesity on brown adipose metabolism.

The effect of diet-induced obesity on interscapular brown adipose tissue (IBAT) was assessed after feeding male Sprague-Dawley rats a high-fat diet for 3-5 mo beginning at 3 mo of age. IBAT pads in 6-mo-old obese rats were heavier (22%), had more lipid (71%), and larger unilocular cells (38%) than chow-fed controls. Mitochondrial morphology, beta-adrenergic receptor binding ([ 125I]iodocyanopindolol), and norepinephrine-stimulated lipolysis were similar in IBAT from obese and control rats. When 8-mo-old chow-fed rats were switched to the high-fat diet for 7-14 days, IBAT pads became hypercellular without cell hypertrophy and with a 70% increase in norepinephrine-induced lipolysis. However, when 8-mo-old obese rats that had been on the high-fat diet for 5 mo were switched to chow for 3 days, IBAT cellularity was unchanged, but norepinephrine-induced lipolysis was increased 70%. Therefore, in lean and obese 6- to 8-mo-old rats, short-term dietary manipulation led to metabolic activation, whereas chronic diet-induced obesity on a stable diet was associated with a return of IBAT metabolism to control levels.

Optically clear endometrial nuclei.

The ultrastructure of optically clear endometrial nuclei is presented. These nuclear alterations have been found in spontaneous abortion, term pregnancy, endometriosis, and uterine choriocarcinoma.

Pre-elastofibroma and elastofibroma (the continuum of elastic-producing fibrous tumors). A light and ultrastructural study.

A fibroproliferative lesion arising anterior to the lower end of the scapula and containing polymorphic often fiberlike deposits of weakly elastinophilic fibrillary material is described. It is compared on the light and ultrastructural level to a typical elastofibroma. The fibrillary material seen in this tumor strongly resembles that which surrounds the strongly elastinophilic deposits in the typical elastofibroma and from which the elastin is thought to be derived. It is concluded that elastin-producing tumors form a continuum; at one end of which lies the tumor we have designated pre-elastofibroma and at the other, the typical elastofibroma.

Transport of gentamicin in rat proximal tubule.

The intrarenal distribution of tritiated gentamicin (GM) was determined in rat by combined immunofluorescence and section freeze-dry autoradiography, techniques that permit subcellular localization before and after diffusional redistribution. Tissue from these kidneys was also examined by electron microscopy. After parenteral administration of 4 to 100 mg/kg, GM accumulates in S1 and S2 but not S3 segments of proximal tubules. Within 10 minutes, autoradiography demonstrates 3H-GM in the lumina of proximal and distal tubules; a subapical distribution consistent with pinocytotic uptake is prominent in many proximal cells. After 1 hour, 3H-GM is diffusely distributed within the cytoplasm in section freeze-dry autoradiographs with minimal evidence of intracellular sequestration. At this time, 3H-GM is presumably within endocytotic vacuoles, and electron microscopy reveals only rare vacuoles containing single myeloid bodies. Subsequently, section freeze-dry autoradiography shows sequestration of the aminoglycoside, but this intracellular localization is lost during tissue processing for fluorescent microscopy up to 6 hours after injection. At 6 hours large cytoplasmic vacuoles containing multiple well-organized myelin figures first appear in S1 and S2 segments. By 48 hours, 3H-GM is firmly bound in these vacuoles and is maintained in situ in both section freeze-dry autoradiographs and immunofluorescent preparations in association with increased numbers of vacuoles containing multiple myeloid bodies by electron microscopy. These studies thus demonstrate diffusible 3H-Gm within the cell which is available to initiate nephrotoxicity 1 to 6 hours after administration.

Role of Ca++, CaATPase and alkaline protease in cardiac contraction band formation.

Cardiac cells' total homogenates and subcellular components Ca++, CaATPase and alkaline protease levels were matched with their respective microscopic samples in order to ascertain their role in the formation of contraction bands. It was seen that those samples having contraction bands also had a high incidence of intracellular Ca++, low CaATPase and high alkaline protease levels. This study confirms reports that contraction bands are not limited to pathological hearts (Adomian et al., 1977), but neither are they limited to artifacts related to autopsy procedures. They were seen in varying degrees of severity in hearts of healthy rats sacrificed by decapitation and less frequently with only sarcomeric involvement to absence of in animals sacrificed by diethyl ether overdose. It is postulated that the elevated Ca++ activated alkaline protease (pH 8.5) by inhibiting its inhibitor (Waxman and Krebs, 1978). It may have inhibited total CaATPase activity (Hasselbach, 1974) as well. We believe that the activated alkaline protease produced irreversible contraction bands by lysing the microhinge between light and heavy meromyosin.