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Biomedical subjects

R B Nagle

Publications and source records attributed to R B Nagle.

At least 145 records · Page 8Linked to original sources
PubMed1978

Unilateral obstructive nephropathy in the rabbit. II. Late morphologic changes.

The late histologic and ultrastructural effects of complete unilateral ureteral obstruction in the rabbit kidney were studied from 7 to 32 days postobstruction. Papillary necrosis occurred in all animals by the 7th day. There was progressive widening of the cortical interstitial space with proliferation of fibroblasts. Increased interstitial collagen fibers first became apparent on the 7th day and showed a progressive increase with time. The fibroblasts underwent myofibroblast transformation beginning on the 7th day. All segments of the nephron showed ultrastructural evidence of sublethal cell injury with loss of cell specialization. The dedifferentiation of the tubular cells was associated with a repetitive formation of new lamellae of basement membrane on the luminal side of the original basement membranes beginning on the 16th day of obstruction. These morphologic changes are discussed in terms of the physiologic changes previously reported in this model and the known clinical abnormalities found in obstructive uropathy.

Animals↗
PubMed1977

Hypovolemic models of acute tubular necrosis in the rat kidney.

Studies were undertaken to determine whether a hypotensive episode under variable conditions is capable of inducing experimental acute renal failure in rats. Animals were subjected to hypovolemic shock by withdrawing volumes of blood necessary to maintain a systolic pressure of 30-40 mm Hg for 105-110 min. The blood was then reinfused and the animal was allowed to recover for 48 h prior to sacrifice. In an attempt to increase the injury, a second group of animals was salt-depleted prior to injury, a third group was volume-depleted by being deprived of H2O for 72 h prior of injury, a fourth group received 7.5 mg/kg indomethacin 30 min prior to injury, and a fifth group had 30% of the blood which was removed to produce shock hemolyzed and returned following the injury. In all groups examined, light microscopy revealed a moderate to severe acute tubular necrosis localized mainly in the outer stripe of the outer zone as defined by Peter (1909). Tubular damage was confined to the medullary pars recta of the proximal tubule and only in the most severe cases did injury involve the cortical pars recta and pars convoluta. Casts were present in the distal tubules and collecting ducts. Despite these significant histologic alterations, BUN values from all experimental groups remained within control levels. These studies clearly show that extensive necrosis of the medullary pars recta can be dissociated from the development of acute renal failure.

Acute Kidney Injury↗
PubMed1977

Localization of receptors for activated complement on visceral epithelial cells of the human renal glomerulus.

Receptors for activated C3 have recently been demonstrated to be present in glomeruli of normal human kidneys. In the present communication, the precise location of these receptors within the renal corpuscle was studied with scanning electron microscopy. By this technique, the glomerular complement receptor (GCR) was found to be located on the visceral epithelial cell of the renal corpusle. This epithelial cell location was confirmed by comparison of in vitro GCR activity with the location of immunoglobulin and C3 deposited in vivo. Renal tissues in which Ig and C3 had been deposited in vivo diffusely in subepithelial loci had no in vitro GCR activity. Renal biopsies not showing Ig or C3 deposition or biopsies with Ig and C3 in the mesangium retained GCR activity. These results further confirm an important role for GCR in the trapping and deposition of C3 in some forms of immunologically mediated renal disease.

Binding Sites↗
PubMed1976

Studies on the pathophysiology of acute renal failure. I. Correlation of ultrastructure and function in the proximal tubule of the rat following administration of mercuric chloride.

Acute renal failure was induced in male rats by the subcutaneous injection of 4 mg HgC12 per kg body weight. Changes in the proximal tubule were studied by light and electron microscopy at six time intervals from 15 min to 24 h. Renal function was monitored at 6 and 24 h. Between 15 min and 3 h changes were similar in all regions of the proximal tubule (pars convoluta and pars recta). Dispersion of cytoplasmic polysome groups was widespread and mitochondrial matrices were condensed in some cells. No changes were noted in the brush border but increased endocytotic activity occurred in some convoluted tubules at 1 and 3 h. At 6 h severe changes had occurred in the pars recta in the medullary rays. Microvilli of the brush border were focally absent, the mitochondria were swollen and the endoplasmic reticulum was dilated. At this time only subtle changes occurred in the pars recta in the outer stripe of the outer medulla. However by 24 h necrosis was widespread throughout the pars recta, yet changes in the proximal convoluted portion were minimal. A significant azotemia, decreased GFR and increased FENa+ and FEK+ occurred at 6 and 24 h after HgC12 injection. Thus HgC12 at 4 mg per kg body weight produced reproducible renal failure and necrosis involving the pars recta of every nephron but necrosis did not begin in the pars recta until after 6 h while acute renal failure was probably initiated much earlier. The following hypothesis is presented. HgC12 initially interacts with the entire proximal tubule. Although injury is sublethal in the pars convoluta it is responsible for greatly diminished sodium reabsorption and is related to the pathogenesis of the renal failure through feedback mechanisms involving the macula densa and release of renin. This results in renal hemodynamic alterations, decreased GFR and other functional disturbances associated with renal failure. The development of necrosis in the pars recta appears to be a relatively late event, possibly due to further accumulation of Hg++ in this region. In any case, the necrosis appears pathogenetically dissociable from the mechanism of acute renal failure.

Acute Kidney Injury↗
PubMed1976

Studies on the pathophysiology of acute renal failure. II. A histochemical study of the proximal tubule of the rat following administration of mercuric chloride.

Acute renal failure was induced in male rats by the subcutaneous injectioon of 4 mg HgC12 per kg body weight. Enzyme activities of the proximal tubule were studied histochemically at six time intervals from 15 min to 24 h. The enzyme studied were alkaline phosphatase, 5'-nucleotidase, acid phosphatase, alpha-glycerophosphate dehydrogenase (NAD-independent), malic dehydrogenase, succinic dehydrogenase, latic dehydrogenase, glucose-6-phosphate dehydrogenase and glucose-6-phosphatase. Decreases in activity were observed for alkaline phosphatase and 5'-nucleotidase after 15 min. Acid phosphatase was decreased after 30 min. These three enzymes returned to control levels after 3 h, but malic dehydrogenase and alpha-glycerophosphate dehydrogenase were decreased at this time interval. Succinic dehydrogenase was first decreased after 6 h. The earliest morphological changes detectable by light microscopy were observed in pars recta tubules in the medullary rays after 6 h, a time when all enzymes studied showed widespread decreased activity throughout the proximal tubule. After 24 h, the pars convoluta appeared morphologically normal but the pars recta was necrotic and exhibited calcification, whereas enzyme activity was decreased (absent in some cases) in both pars convoluta and pars recta. These results support the hypothesis that Hg++, when given in a sublethal dose, is associated with early histochemical changes in the brush border of the proximal tubule, which may be related to early changes in sodium reabsorption and to the subsequent development of acute renal failure. The observation that changes in plasma membrane-associated enzymes occur early and prior to alterations in enzymes of mitochondria and the endoplasmic reticulum suggests that Hg++ interacts initially with the plasma membrane.

Acute Kidney Injury↗
PubMed1976

Effects of transient hypotension on the structure and function of rat kidney.

The immediate effects of renal structure and function of 60 or 90 min of hypotension and the effects of one to four days of recovery were studied in the rat. An initial diuresis occurred during the first day after hypotension, followed by decreased urine volumes. Along with the diuresis, the animals secreted a hypo-osmolar urine for two days following hypotension, which returned to a normal concentration at three days. Twenty four hour urine sodium excretion was depressed during the first and second days after hypotension while potassium excretion was no different from that of control animals. The morphologic alterations of tissue fixed immediately following 60 and 90 min of hypotension were greatest in the pars recta of the proximal tubule but were also seen focally in the pars convoluta. The cellular changes included dilated endoplasmic reticulum clumped nuclear chromatin, swollen mitochondria with small flocculent densities, and the formation of multivesicular bodies. One day after the hypotension, death cell and necrosis were observed extensively in the pars recta. This study describes an experimental model for the study of the renal effects of hypovolemic shock in rats.

Animals↗
PubMed1976

The glomerular complement receptor in immunologically mediated renal glomerular injury.

We examined 25 renal-biopsy specimens to determine whether there is a relation between immunologically mediated renal diseases and the activity of complement receptors that selectively bind antigen-antibody complexes containing activated third component of complement (C3b). These receptors have been termed glomerular complement receptors. Renal lesions associated with in vivo deposition were associated with a loss of receptor sites as demonstrated by reduced or absent in vitro binding of C3b-coated test reagents by glomerular complement receptor. These findings suggest that binding of complement containing immune complexes to glomerular complement receptors in human subjects may participate in the immunopathologic processes of certain immune-complex-mediated renal diseases.

Antibody Specificity↗
PubMed1976

Scanning electron microscopy of renal vascular casts.

The use of Cementex to form casts of the renal vascular system is described. These casts are useful in delineating the vascular microarchitecture of the kidney including that of the glomerular capillaries, but do not appear to reproducibly reflect physiological vascular tone. The postglomerular vascular system is often incompletely filled using this technique. The amount of filling can be altered by the techniques used in cast preparation. The effect of perfusion pressure, concentration of Cementex, fixation, and type of colour additive are compared with respect to the cast structure.

Animals↗
PubMed1976

Proliferation of renal interstitial cells following injury induced by ureteral obstruction.

The proliferation of renal interstitial cells was studied by the use of tritiated thymidine incorporation following unilateral ureteral obstruction in the rabbit. There was a nonuniform response with significant increase in nuclear labeling in the obstructed kidney in all zones at 24, 48, and 72 hours following obstruction with the exception of the inner medulla where the counts at 24 and 48 hours were not significantly different from sham-operated controls. The major labeling occurred in interstitial fibroblasts. Within the zones of high labeling (cortex and outer medulla) these cells were separated by widening of the intersittial space. In the zone of low labeling (inner medulla) the interstitial cells maintained their normal spatial relationships.

Animals↗
PubMed1975

Contractility of renal cortex following complete ureteral obstruction.

Contractility of strips of renal cortex obtained from rabbit kidneys obstructed by complete ureteral ligation for 8 and 32 days was tested and compared with control tissue. Concentration-response data were obtained for norepinephrine, angiotensin, and 5-hydroxytrypamine, and were expressed as mg tension/cm of tissue. Control tissue tested simultaneously revealed minimal responses, but obstructed tissue containing modified interstital cells revealed statistically significant evidence of contraction in response to all three drugs studied. The response to norepinephrine could be blocked by the alpha adrenergic antagonist, phenoxybenzamine, but this drug did not significantly affect the response to angiotensin or 5-hydroxytryptamine. The findings are related to similar observations reported in stimulated fibroblasts of granulation tissue and are discussed in terms of the possible role this phenomenon may play in the pathogenesis of renal interstitial injury.

Angiotensin II↗