Tetsuo Shimamura

Mechanisms of renal tissue destruction in an experimental acute pyelonephritis

Abstract To find out the mechanism of renal tissue destruction in Escherichia coli -induced acute pyelonephritis, the relationship between the infiltration of polymorphonuclear leukocytes into the kidney and the renal tissue damage has been investigated. An acute pyelonephritis was produced by administration of E. coli into the kidneysof the leukocyte-depleted and the leukocyte-nondepleted rats, and the sequence of morphologic events in the kidneys has been studied by light and electron microscopy. There was little infiltration of leukocytes into the E. coli -infected kidneys of the leukocyte-depleted rats despite formation of prominent bacterial colonies. Associated with this suppressed leukocytic infiltration into the kidney was a good structural preservation of those kidneys of leukocyte-depleted rats. On the contrary, a massive infiltration of polymorphonuclear luekocytes into the E. coli -infected kidneys was present in the leukocyte-nondepleted rats. Associated with this massive infiltration of leukocytes was a destruction of tubular basement membrane and tubular epithelia. The data appear to indicate that the polymorphonuclear leukocytes infiltrated into the kidney plays a role in renal tissue destruction in the early phase of E. coli -induced acute pyelonephritis.

Relationship of dietary intake to the development of glomerulosclerosis in obese Zucker rats

Abstract Obese Zucker rats are hyperphagic and develop premature glomerulosclerosis. The purpose of this study was to find out the effects of restriction of dietary intake on this glomerulosclerosis. The obese and lean male Zucker rats were fed with restricted amounts of balanced diet for periods of 40 and 50 weeks, sacrificed, and the body weight, the light and ultrastructural alterations of glomeruli, and the serum levels of blood urea nitrogen, triglyceride, and cholesterol were examined. Obese and lean male rats of identical ages were fed ad libitum with the diet and studied similarly. The dietary restriction significantly lessened the development of the glomerulosclerosis in obese rats, while those on the nonrestricted diet manifested an advanced glomerulosclerosis. The dietary restriction, however, did not normalize the obesity nor correct the elevated serum lipid level to the range of lean control rats. The spontaneous glomerular lesions of the obese rats were characterized by segmental mesangial expansion, disappearance of podocytes and endothelia, and obliteration of capillary lumina. The lean rats maintained essentially normal renal morphology. A similar study on the renal morphology done in female Zucker rats also revealed a preventive effect of dietary restriction on the development of glomerulosclerosis. In conclusion, there is a strong association between the glomerulosclerosis and the hyperphagia of the obese Zucker rats, both in males and females, and the emergence of this lesion is preventable to a significant degree.

Secondary hyperparathyroidism in rats with an experimental chronic renal disease

Abstract Benign secondary hyperparathyroidism was induced in rats by experimental chronic renal disease. A gross parathyroid gland enlargement was present in 6 out of 11 rats. The cells of the enlarged parathyroid glands had increased tortuosity of the cytoplasmic membranes, enlarged mitochondria with increased electron lucency of their mitochondrial matrix, and an apparently increased number of ribosomes. The Golgi apparatuses were prominent and had numerous Golgi vesicles. It is suggested that the formation of secretory material of parathyroid glands takes place at rough endoplasmic reticula. A similarity of morphologic changes of the enlarged parathyroid glands of the 5 6 nephrectomized rats to those seen by others in stimulated glands in vivo and in vitro appears to indicate that the mechanism of control of parathyroid hormone synthesis and secretion is similar in both in vivo and in vitro systems and is not interfered with by uremia.

Drug-induced renal medullary necrosis: III. Increased Salt Intake and Enlargement of the Adrenal Cortex

Abstract Renal medullary necrosis has been produced in rats with the injection of 2-bromo-ethylamine hydrobromide, and the amount of daily urinary output and fluid intake has been measured. In addition, the enlarged adrenal glands that develop in these rats have been quantitatively analyzed, and examined by light microscopy. The rats with renal medullary necrosis develop a prominent degree of polyuria and polydipsia, and drink a large amount of 0.9% sodium chloride solution. The enlarged adrenal glands show an increase in width of the zona fasciculata, and their weight progressively increases until the sixth day of the experiment. In conclusion, the renal medullary necrosis induces a profound derangement of the homeostatic function.

Ultrastructural studies of the medial aortic sclerosis in rats with experimentally induced chronic renal disease

Abstract Ultrastructure of rat aortic medial sclerosis developing after experimental production of chronic renal disease is described. The calcium deposit in the medial layer of the aortic wall occurs with a predilection for the elastic fibers and more precisely the microfibrils of the elastic fibers. The calcification occurs in variable ultrastructural configurations. It appears that microfibrils and collagen fibers can act as a core of calcification. Ultrastructural modifications of smooth muscle cells such as increased cytoplasmic organelles, cytoplasmic cysternae, or vacuoles, and extension of many cytoplasmic processes are present without any atheromatous change of the wall.

Drug-induced renal medullary necrosis. IV. Effects on the urinary sodium output and systemic blood pressure.

Abstract Renal medullary necrosis was produced in rats by administration of 2-bromo-ethylamine hydrobromide and the resulting functional alterations of the kidneys, such as renal handling of sodium and potassium, response to salt-loading and glomerular filtration rate, and the effects of necrosis on the systolic blood pressure were investigated. The pair-fed rats drinking either distilled water or 0.9% NaCl solution had exaggerated natriuresis during the period examined. Glomerular filtration rate measured on day 2 and week 16 was significantly reduced. In addition, experimental rats consumed a large amount of 0.9% NaCl solution. Elevation of systolic blood pressure was seen in some of the experimental rats that drank 0.9% NaCl solution. In conclusion, the renal medullary necrosis in rats either primarily or secondarily influences the function of the kidneys. The renal medullary necrosis per se appears to have little effect on the systolic blood pressure unless it is coupled with NaCl loading.

Drug-induced renal medullary necrosis: II mode of calcification in the kidney

Abstract Necrosis of the papillary portion of the renal medulla was produced by administration of 2-bromoethylamine hydrobromide in rats. Following the necrosis, calcification develops in the renal medulla adjacent to the necrosed tissue. The calcium deposit is seen in the vesicular bodies about the basement membranes of the tubules and capillaries and in the collagen fibers of the interstitium. These structures such as the vesicular bodies and collagen fibers appear to serve as nucleation sites for dystrophic calcification.

Partial characterization of apoptotic factor in Alzheimer plasma

We have previously demonstrated that a plasma natriuretic factor is present in Alzheimers disease (AD), but not in multi-infarct dementia (MID) or normal controls (C). We postulated that the natriuretic factor might induce the increased cytosolic calcium reported in AD by inhibiting the sodium-calcium antiporter, thereby activating the apoptotic pathway. To test for a factor in AD plasma that induces apoptosis, we exposed nonconfluent cultured LLC-PK1 cells to plasma from AD, MID, and C for 2 h and performed a terminal transferase-dUTP-nick-end labeling (TUNEL) assay. The plasma from AD increased apoptosis nearly fourfold compared with MID and C. The effect was dose dependent and the peak effect was attained after a 2-h exposure. Additionally, apoptotic morphology was detected by electron microscopy, and internucleosomal DNA cleavage was found. We inhibited apoptosis by removing calcium from the medium, inhibiting protein synthesis with cycloheximide, alternately boiling or freezing and thawing the plasma, and digesting a partially purified fraction with trypsin. Heating AD plasma to 56°C did not deactivate the apoptotic factor. These results demonstrate the presence of an apoptotic factor in the plasma of patients with AD.

GROWTH PROMOTION OF UROTHELIAL CELLS BY A SILK SUTURE IN THE BLADDER WALLS OF RATS

This study is to describe the reaction of urothelial cells to a silk suture placed surgically in the urinary bladder. Experimental rats have a single silk suture transmurally inserted in the wall and lumen of the bladder. The controls received sham operations. At various time intervals up to the 54th week, the sequence of morphologic events which took place in the bladder wall has been studied by gross and by light and electron microscopic examinations. The mucosal hyperplasia was the major finding for those sacrificed at weeks 2, 4, and 8. A single growth or multiple polypoid growths composed of well differentiated urothelial cells were found at weeks 16, 24, and 54. None of these growths were invasive. They exhibited little evidence of progressive morphologic change with time. Ultrastructurally, the tumor cells essentially showed characteristics of urothelial cells. None of the controls developed a similar urothelial growth. In conclusion, presence of a silk suture in the urinary bladder resulted in mucosal hyperplasia followed by noninvasive tumorous growth of well differentiated transitional cells. Exact mechanisms of this growth promotion by a silk suture and the potential of the growths becoming invasive neoplasms remain to be determined.

A Method to Identify Microinjected Nephrons of Rat

This paper describes a technique for identifying individual nephrons that have been subjected to micropuncture. The general location of the nephron is marked on the surface of the kidney by implanting two micropipette tips on opposite sides of it two or three tubule diameters away. The tubule itself is marked by the injection into the lumen of a tracer material, for purposes of this account, a suspension of E. coli. After perfusion fixation the kidneys are removed and a block of tissue containing the extrapapillary portion of the nephron is excised. This block is cut into thin slices parallel to the surface of the kidney; these are embedded in plastic for subsequent sectioning. On sectioning, the marker material makes the nephron in question readily discernible under the microscope. A major advantage of this technique is that it allows the tubule of interest to be located as much as 48 hours later.