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R E Bulger

Publications and source records attributed to R E Bulger.

At least 55 records · Page 3Linked to original sources
PubMed1982

Proximal tubular necrosis associated with maleic acid administration to the rat.

Administration of maleic acid to the rat is used as an experimental model of Fanconi's syndrome. To determine the site and extent of morphologic injury within the kidney after maleic acid administration, we systematically examined renal tissue using light, transmission electron, and scanning electron microscopy. Tissue was studied either immediately or 24 hours after rats received maleic acid, 200 mg. or 400 mg. per kg. of body weight, and was compared with tissue from controls. In kidneys of maleic acid-treated rats, evidence of injury was observed only in cells of the late pars convoluta and the pars recta in the medullary rays of the cortex and in the outer stripe of the medulla. Injured cells were characterized by an increase in cytoplasmic density, accumulation of numerous small vesicles in the apical region of the cells, abnormal-appearing mitochondria with compressed cristal membranes and flocculent densities, and focal loss of microvilli. Injury was apparent immediately after maleic acid administration and progressed to extensive necrosis by 24 hours after either the 200- or 400-mg. per kg. dose. Except for the presence of granular and hyaline casts in the lumena, the loops of Henle and distal convoluted tubules were normal. Collecting ducts in the outer medulla, but not in the cortex, medullary rays, or inner medulla, had significantly increased numbers of dark cells per total cell population when compared with controls (p less than 0.005). This increase in dark cells may represent an adaptive response of the medullary collecting duct to the functional abnormalities of maleic acid-induced Fanconi's syndrome. Collecting ducts showed no evidence of cell injury or necrosis. These observations provide evidence that maleic acid, like many other renal toxins, produces tubular injury and necrosis only in the proximal tubules, primarily in the medullary rays, and outer stripe of the medulla, and not in the distal tubules.

Animals↗
PubMed1982

Effect of potassium depletion on tubular morphology in gentamicin-induced acute renal failure in dogs.

Potassium deprivation has recently been reported to potentiate the degree of functional impairment in a gentamicin-induced model of acute renal failure. The present study investigated the effects of two different states of potassium homeostasis on the development of cellular injury in the early stage of gentamicin nephrotoxicity in dogs. Gentamicin (15 mg. per kg. intramuscularly twice daily) was administered for 4 and 7 days to potassium-depleted or potassium-supplemented animals. The results show that potassium supplementation markedly lessens the severity of pathologic alterations induced by gentamicin. In both groups of animals, the S1 and S2 segments of the proximal tubule were the most consistently damaged regions of of the nephron. Potassium-supplemented dogs had a significantly higher number of normal proximal tubule cells than did the animals deprived of potassium and viewed 7 days after gentamicin treatment (77.3 versus 36.9 per cent; p less than 0.025). The degree of total injury to the proximal tubule was significantly higher in potassium-depleted animals than in those supplemented with potassium (59.9 versus 21.9 per cent; p less than 0.05). Only those dogs depleted of potassium prior to the administration of gentamicin had a markedly elevated plasma creatinine level of proximal tubular injury and functional impairment (r = 0.81; p less than 0.005). Potassium supplementation appears to lessen the extent of structural alterations seen in this model of gentamicin-induced acute renal failure in dogs.

Acute Kidney Injury↗
PubMed1981

The ultrastructure of the thin limbs of Henle in Kidneys of the desert heteromyid (Perognathus penicillatus).

The thin limbs of both long- and short-looped nephrons in Perognathus kidneys were studied with transmission and scanning electron microscopy. The superficial nephrons have a short thin limb located in the vascular bundles of the outer medulla and are characterized by a simple, low-lying epithelium (0.4 +/- 0.1 mu thickness). In contrast, the first descending part of the thin limb of the majority of midcortical and juxtamedullary nephrons has a relatively thick epithelium (1.7 +/- 0.6 mu in thickness) with marked lateral and basal interdigitation and a dense surface covering of microvilli. The remaining part of the long descending thin limb is relatively simple with a low-lying epithelium (0.6 +/- 0.1 mu in thickness), decorated on its surface by sparse microplicae. The bend of the loop and the ascending limb are covered by a very simple low-lying epithelium (0.6 +/- 0.2 mu in thickness) with relatively little surface modification. The extreme urine-concentrating ability of Perognathus does not appear to be due to the development of a unique thin loop epithelium but rather to the extensive length of the inner and outer medulla.

Animals↗
PubMed1981

Cell division in kidneys of rats fed a potassium-deficient diet.

Mitoses is stimulated in the kidneys of adult rats fed a potassium-deficient diet. A statistically significant increase in mitotic figures appears first in the collecting ducts of the inner strip of the outer medulla after two days on the K+ deficient diet (P less than 0.05). After six days, mitosis also increases in the collecting ducts in the outer stripe and in the inner medulla (P less than 0.01). After eight days there is a significant rise in mitotic activity in the cells of the proximal convoluted tubule (P less than 0.01). There is a questionable increase in mitosis found only on the fifth day in the distal convoluted tubule. In all other cell types there is no statistically significant increase in cell division over the normal low levels that are observed in the cells of the controls rats.

Animals↗
PubMed1981

Application of scanning electron microscopy to x-ray analysis of frozen-hydrated sections. III. Elemental content of cells in the rat renal papillary tip.

The electrolyte and water content of cellular and interstitial compartments in the renal papilla of the rat was determined by x-ray microanalysis of frozen-hydrated tissue sections. Papillae from rats on ad libitum water were rapidly frozen in a slush of Freon 12, and sectioned in a cryomicrotome at -30 to -40 degrees C. Frozen 0.5-micrometer sections were mounted on carbon-coated nylon film over a Be grid, transferred cold to the scanning microscope, and maintained at -175 degrees C during analysis. The scanning transmission mode was used for imaging. Structural preservation was of good quality and allowed identification of tissue compartments. Tissue mass (solutes + water) was determined by continuum radiation from regions of interest. After drying in the SEM, elemental composition of morphologically defined compartments (solutes) was determined by analysis of specific x-rays, and total dry mass by continuum. Na, K, Cl, and H2O contents in collecting-duct cells (CDC), papillary epithelial cells (PEC), and interstitial cells (IC) and space were measured. Cells had lower water content (mean 58.7%) than interstitium (77.5%). Intracellular K concentrations (millimoles per kilogram wet weight) were unremarkable (79-156 mm/kg wet weight); P was markedly higher in cells than in interstitium. S was the same in all compartments. Intracellular Na levels were extremely high (CDC, 344 +/- 127 SD mm/kg wet weight; PEC, 287 +/- 105; IC, 898 +/- 194). Mean interstitial Na was 590 +/- 119 mm/kg wet weight. CI values paralleled those for Na. If this Na is unbound, then these data suggest that renal papillary interstitial cells adapt to their hyperosmotic environment by a Na-uptake process.

Animals↗
PubMed1981

Cyst formation in rat kidney induced by cis-platinum administration.

The long-term pathologic effects of the antitumor drug, cis-diamminedichloroplatinum II (CP) on the structure of the rat kidney were investigated. Light microscopy and transmission and scanning electron microscopy were used to characterize the morphologic changes 2 weeks, 4 weeks, and 6 months after the intraperitoneal injection of CP to rats. At all time intervals examined, the S3 segment of the proximal tubule located in the outer stripe of the medulla showed the most consistent pattern of injury. Two weeks after CP, the proximal tubules located in the outer stripe region as well as in the medullary rays were widely dilated and lined by low-lying epithelial cells, many of which contained large atypical nuclei. Many tubules still showed evidence of necrosis, whereas other tubules appeared to be undergoing atrophic changes. After 4 weeks, proximal tubular dilation continued resulting in the formation of numerous microcysts in the region of the outer stripe. These changes appeared to progress, and after 6 months large cysts (mean diameter 2152 +/- 1241 micrometer) were identified which involved the entire outer stripe, with many of these cysts extending to the subcapsular cortex. The kidneys at this time period showed a pattern of chronic renal injury in the outer stripe, and this damage was now also observed in the cortex. In several animals, small foci of abnormal foam cells surrounded by a basal lamina could be identified. We conclude that CP has a pronounced long-term effect and causes cyst formation in the rat kidney.

Animals↗
PubMed1980

Glomerular architectural changes after a two-hour infusion of norepinephrine.

Alterations in glomerular architecture have been suggested to play a role in the pathogenesis of several models of acute renal failure. In this study, mongrel dogs were subjected to an intrarenal infusion of norepinephrine for 2 hours. Light microscopy and scanning and transmission electron microscopy were used to describe glomerular architecture 2 days after the initial norepinephrine infusion. In addition, scanning electron microscopy was used to quantitate the percentage of "abnormal areas" in glomerular capillary-loop morphology in both norepinephrine-infused kidneys and the contralateral control kidneys. Alterations in glomerular structure in these experiments appeared to be much less extensive than previously reported. A variable amount of glomerular pedical shape simplification was seen, which involved about 15% of the capillary loop. Quantitative evaluation revealed abnormal morphology of 15.2% +/- 0.6% of the glomerular capillary loop in the norepinephrine-infused kidneys, compared to 2.9% +/- 0.4 abnormal loop structure in the contralateral control kidneys (P less than 0.001). It is concluded that alterations in glomerular structure are not extensive in this model.

Acute Kidney Injury↗
PubMed1980

A rapid method of cryofixation of tissues in situ for ultracryomicrotomy.

A device is described for the rapid freezing of tissue in situ by a punch biopsy approach using a specially designed cryogun with a highly thermal conductive specimen holder. The cryogun consists of a sampling device using a double, spring-loaded gun mechanism and a system of cryochambers. Ultrathin freeze-dried sections cut from samples obtained with this cryogun are relatively free of artifacts and have few ice crystals. Organelles are seen by natural contrast when cryosections of approximately 1000 A are observed with a transmission electron microscope or in the transmission mode of a scanning electron microscope. The construction of the cryogun is described along with a method of obtaining improved, ultrafast cryofixation of tissue specimens. The reliability of obtaining x-ray microanalysis measurements of diffusible ions where movement within cell compartments has been retained is discussed.

Basement Membrane↗
PubMed1980

X-ray microanalysis of the kidney.

The use of x-ray microanalysis for the localization of insoluble deposits in kidney tissue, the quantitation of micropuncture samples from tubular lumens, and the localization and quantitation of histochemical reaction products are becoming standard procedures in a variety of laboratories involved in renal research. The validity of these procedures has been established and exploitation of them should lead to new research insights. Even more exciting are the new analytical procedures for quantitative analysis of soluble substances in tissue sections. Shock frozen kidney can be analyzed in the frozen hydrated, frozen dried, or freeze substituted state. The promise of applying these technical achievements to renal research is a more precise understanding of the ion concentrations in lumens, intersititium, cells, and their organelles from various regions of the kidney in documented physiological and pathological states.

Animals↗
PubMed1980

Natural history of aminoglycoside nephrotoxicity in the dog.

The natural history of aminoglycoside nephrotoxicity is not well described. This study investigated in the dog renal functional and electrolyte abnormalities during and for 20 days following a 10-day course of low-dose gentamicin (7 mg/kg/day), high-dose gentamicin (30 mg/kg/day), and netilmicin (30 mg/kg/day). Renal histology was examined at the end of the study. Renal functional abnormalities occurred only in animals receiving high-dose gentamicin. A fall in maximal urinary osmolality (1579 +/- 347 mOsm/kg/H2O to 450 +/- 118, p less than 0.05) was followed by renal glycosuria and a fall in GFR (66.9 +/- 11.9 ml/min to 21.3 +/- 8.6, p less than 0.05). These three functional indices had recovered by day 30 in the survivors. Plasma potassium fell in animals receiving high-dose gentamicin (3.8 +/- 0.02 mEq/L to 3.3 +/- 0.4, p less than 0.05) and reached the lowest values (2.7 and 2.9 mEq/L) just prior to death in two animals dying in uremia. Netilmicin also caused a significant fall in plasma potassium (4.3 +/- 0.1 mEq/L to 3.9 +/- 0.1, p less than 0.05). Hypocalcemia (10.0 +/- 1.3 mg/dl to 7.8 +/- 1.4, p less than 0.05) but not hypomagnesemia developed following high-dose gentamicin. Peak serum aminoglycoside levels after high-dose gentamicin and netilmicin were comparable, but trough levels rose only in high-dose gentamicin animals and paralleled the fall in GFR. Light microscopy of the kidney 3 weeks after high-dose gentamicin demonstrated no proximal tubular necrosis but extensive focal tubulointerstitial nephritis, especially in the juxtamedullary cortex. Similar but less extensive derangements were noted in animals receiving low-dose gentamicin, despite the absence of functional abnormalities. Minor histological abnormalities were noted in animals receiving netilmicin. To summarize: 1) major renal functional and electrolyte abnormalities developed only following high-dose gentamicin and included impaired urinary concentration, glycosuria, reduced GFR, hypokalemia, and hypocalcemia (except for a fall in plasma potassium, similar doses of netilmicin were not nephrotoxic); (2) tubulointerstitial nephritis, particularly in the juxtamedullary cortex, occurred with low-dose gentamicin as well as high-dose gentamicin and may be a factor in delayed or incomplete recovery from gentamicin nephrotoxicity; (3) in this model, netilmicin at comparable doses was substantially less nephrotoxic than gentamicin; (4) renal postassium wasting may be a heretofore unrecognized consequence of aminoglycoside administration.

Animals↗
PubMed1979

Survey of the morphology of the dog kidney.

Dogs are frequent subjects in experimental studies of renal physiology and pathology in spite of the paucity of information on their normal renal morphology. In this study, gross morphology, light microscopy, and scanning and transmission electron microscopy were used to describe dog renal anatomy. The dog has a multilobed kidney with the medulla fused into an elongate crest and a renal pelvis of elaborate shape. The outer zone of the medulla lacks a definitive outer stripe. The proximal tubule consists of four distinct anatomical segments. Dark cells are abundant in the collecting duct of the inner medulla. The majority of the nephron segments demonstrate remarkable similarities to those of the human kidney and less to those of the kidney of the laboratory rat.

Animals↗
PubMed1978

Pathogenic mechanisms in early norepinephrine-induced acute renal failure: functional and histological correlates of protection.

The present study investigated the protective effect of acute volume expansion (25%) with isotonic saline, isotonic mannitol, and hypertonic mannitol in a model of unilateral norepinephrine-induced acute renal failure (ARF). Three hours following a 40-min intrarenal infusion of norepinephrine (NE) (0.75 microgram/kg/min), inulin clearance had fallen from a control value of 54.1 +/- 6.5 to 1.3 +/- 1.3 ml/min in untreated dogs and fell similarly (P = NS) to 3.3 +/- 1.5 ml/min in animals preexpanded with 0.9% saline (0.75 ml/kg/min). In contrast, as compared to the untreated animals, inulin clearance 3 hr post NE infusion was significantly greater in dogs preexpanded with 5% mannitol (9.2 +/- 2.5 ml/min, P less than 0.01), or 20% mannitol (16.6 +/- 3.9 ml/min, P less than 0.01). The protective effects of 5% and 20% mannitol were not statistically different from each other. Recovery of renal excretory function in all groups, expressed as 3-hr post NE inulin clearance, correlated with the magnitude of pre NE solute excretion rate (r = 0.612, P less than 0.001) and osmolar clearance rate (r=0.593, P less than 0.001), but not with pre insult inulin clearance (r = 0.233, P = NS) or renal blood flow (r = 0.249, P = NS). In the presence of a profound fall in inulin clearance, proximal tubular (PT) pressures in untreated dogs 3 hr post NE infusion achieved a value equal to control (26 +/- 11 vs. 25 +/- 2 mm Hg). In contrast, pretreatment with isotonic mannitol produced a rise in PT pressure both before (45 +/- 4 mm Hg, P less than 0.05) and 3 hr post NE infusion (38 +/- 5 mm Hg, P less than 0.05). In all groups of animals, at both 3 and 24 hr post NE, tubular injury was observed but glomerular architecture remained normal by light and electron microscopy. Conclusion. the protective effect of mannitol in this reversible model of ARF did not correlate with inulin clearance, renal blood flow, extracellular fluid (ECF) volume, ECF hypertonicity, or renal histologic changes but did correlate with the solute excretion rate. The increased PT pressures with mannitol both before and after the NE insult could contribute to the protective effect of attenuating any relative intratubular obstruction.

Acute Kidney Injury↗