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Biomedical subjects

K Solez

Publications and source records attributed to K Solez.

125 records · Page 7Linked to original sources

Intrarenal urinary extravasation with formation of venous polyps containing Tamm-Horsfall protein.

Collections of periodic acid-Schiff-positive material are found in the intrarenal veins and in the renal interstitium in certain cases of hydronephrosis and unexplained unilateral hematuria. Using a fluorescent antibody to Tamm-Horsfall protein, a protein secreted by the ascending limbs and distal convoluted tubules, we have demonstrated that the venous and interstitial masses represent urinary filtrate, which probably enters the kidney parenchyma through forniceal or tubular ruptures.

Child, Preschool↗

Clonal characteristics in layers of human atherosclerotic plaques. A study of the selection hypothesis of monoclonality.

Two hypotheses have been proposed to explain the origin of monoclonal cell populations within human atherosclerotic plaques. The first of these proposes a mutational origin: the second suggests that the single clone of cells with the greatest proliferative advantage is selected following repetitive intimal injury. If the selection hypothesis is true, monoclonality should be observed more frequently in the layer of plaque most recently formed. Glucose-6-phosphate dehydrogenase (G-6-PD) isoenzymes were used as cellular markers in aortas of females heterozygous for the A and B isoenzymes. Ten plaques were divided into 45 portions, each of which was subdivided into upper layer, lower layer, and underlying media. No predominance of monoclonality was observed in the upper or lower layers of plaque, with 53% of samples from each layer being monoclonal. In all, 73% of portions of plaque contained at least one monoclonal layer. The layers tended to resemble each other in their clonal characteristics, with 60% of portions having layers with the same clonal characteristics. A significant correlation between isoenzyme distributions in upper and lower layers of the same portion was observed. No consistent trends in isoenzyme distribution in the three layers of each portion were observed. The results are interpreted as providing no evidence for clonal selection as the mechanism by which human atherosclerotic plaques become monoclonal.

Aorta↗

The human atherosclerotic plaque.

The fibrous plaque is regarded as the vascular lesion most characteristic of atherosclerosis. The notion that these lesions develop from mural thrombi has received considerable support, and there is also much support for the idea that plaques form as a reaction to mechanical or chemical damage to the endothelium. As an alternative to these two hypotheses, Benditt and Benditt have suggested that plaques represent monoclonal proliferation of altered smooth muscle cells similar to leiomyomas. Evidence in favor of this suggestion has been obtained using tissues from human black females who are heterozygous for the X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD). In such individuals, as a result of random inactivation of the X-chromosome during embryogenesis, all normal tissues contain both the A and B isoenzymes of G6PD, when assayed electrophoretically, whereas plaques and other lesions suspected of being of monoclonal origin contain predominantly one isoenzyme. A certain proportion of fatty streaks also show a single G6PD isoenzyme pattern, suggesting that some fatty streaks act as the foreunners of the fibrous plaque.

Aorta↗

Beneficial effect of propranolol in a histologically appropriate model of postischemic acute renal failure.

Acute renal failure caused in the rabbit by clamping one renal pedicle for 1 hour and removing the opposite kidney produced a histologic picture very similar to that observed in "hypotensive" acute renal failure in man. Intravenous infusion of propranolol, a drug which prevents renin release, at 1 mg/kg for 70 minutes beginning at time of pedicle clamping resulted in significantly lower serum creatinine in this model (2.8 +/- 0.2 mg% at 48 hours with propranolol versus 5.2 +/- 0.8 mg% without). Renin stimulation by dehydration or feeding a low-salt diet enhanced the difference between treated and untreated groups (2.6 +/- 0.4 mg% with propranolol versus 6.2 +/- 1.8 mg% without, after dehydration; 3.5 +/- 1.0 mg% with propranolol versus 7.6 +/- 1.4 mg% without, after low-salt diet).Suppression of renin production by saline feeding eliminated propranolol's beneficial effect (5.6 +/- 0.9 mg% with propranolol versus 4.0 +/- 0.6 mg% without). In rabbits with a normal food and water intake, renal denervation using phenol also eliminated propranolol's effect (creatinine 8.6 +/- 1.4 mg% with propranolol versus 8.6 +/- 1.8 mg% without). In rabbits with intact kidneys, flow probe recording of renal blood flow showed a significantly higher blood flow immediately after unclamping in the propranolol-treated animals, and renal angiograms showed less vasoconstriction in this group after unclamping. In this model of acute renal failure, renal vasoconstriction plays an important role following the initial ischemic insult. Propranolol lessens the severity of this vasoconstriction and the resulting acute renal failure. Its probable action is interference with neurogenically stimulated renin release.

Acute Kidney Injury↗

Inner medullary plasma flow in the kidney with ureteral obstruction.

To test the thesis that ureteral obstruction causes medullary ischemia, we determined inner medullary plasma flow (IMPF) in rats with bilateral or unilateral ureteral obstruction, and after relief of obstruction, by the intravenous 125I-albumin infusion technique. A progressive decline in IMPF was observed during obstruction of 18 h duration, greater in bilateral obstruction (7% of normal at 5h) than in unilateral obstruction (28% of normal at 5 h). The elevation in ureteral pressure was greater and more sustained in bilateral obstruction. After relief of obstruction, IMPF rose to 69-78% of normal in both groups within 2 h. Histologic studies showed tubular necrosis in portions of the inner and outer medulla immediately beneath the renal pelvic epithelium after bilateral or unilateral obstruction of 18 h duration, and India ink perfusion studies showed very poor filling of vasa recta in these areas. The concentrating defect in the postobstructive kidney may be related, at least in part, to damage inflicted by medullary ischemia during obstruction.

Albumins↗

The renal medulla and mechanisms of hypertension in the spontaneously hypertensive rat.

A significant number of offspring from brother-sister matings of NIH-Okamoto-Aoki spontaneously hypertensive rats (SHRs) were found to be normotensive at 20 weeks of age. Over 20% of the animals that were hypertensive at this age had mild-to-moderate unilateral hydronephrosis at the time of sacrifice. In over 90% of the rats that did not develop hypertension spontaneously, ligation of one ureter raised blood pressure above 150 mm Hg within 2 weeks. In those rats made hypertensive by obstructing one ureter and in those that developed hypertension with accompanying naturally occurring hydronephrosis, subcutaneous implants of fragmented renal medulla from unrelated normal rats decreased blood pressure to normotensive levels. In contrast, medullary implants had no significant effect in rats developing hypertension spontaneously without hydronephrosis. Renal inner medullary plasma flow was low in the obstructed kidneys of hydronephrotic hypertensive SHRs but was elevated in the kidneys of nonhydronephrotic hypertensive SHRs. The hypertension in hydronephrotic SHRs appears to be related to an impairment of the antihypertensive function of the renal medulla. Such an impairment of medullary antihypertensive function does not appear to play a significant role in the hypertension in SHRs without hydronephrosis.

Animals↗

Clonal characteristics of fibrous plaques and fatty streaks from human aortas.

Using isoenzymes of glucose-6-phosphate dehydrogenase (G-6-PD) as cellular markers, a study was made of atherosclerotic fibrous plaques and fatty streaks in aortas of black women heterozygous for G-6-PD. Of 29 fibrous plaques, 26 (89.7%) contained only one isoenzyme (17, A; 9, B), the other three containing both A and B. Of 28 fatty streaks, five (17.8%) contained only one isoenzyme (2, A; 3, B), the remaining 23 containing both A and B. Normal uninvolved aorta contained both A and B isoenzymes in 99 of 101 samples. These results confirm the monoclonal character of atherosclerotic fibrous plaques; this strands in contrast to the fatty streaks which most commonly contain the two isoenzymes. The studies on the fatty streaks are inconclusive at this stage in determining whether the streak is the forerunner of the fibrous plaque.

Adult↗

Testicular function in XYY men.

A previous survey of 48 subjects with XYY chromosome complement showed a wide scatter of values for plasma concentration of testosterone and luteinizing hormone (LH). To account for this scattering and in view of the impulsive behavior often attributed to XYY subjects, it was postulated that paroxysmal activity in the cerebral cortex produced paroxysmal stimulation at the level of the hypothalamus. To investigate this possibility, plasma concentrations of testosterone, dihydrotestosterone, follicle stimulating hormone (FSH), and LH were determined on seven consecutive days in four XYY subjects and five XY control men as well as bimonthly for four months in two XYY detainees and three XY control detainees. The variability of plasma androgen and gonadotropin levels in XYY subjects was similar to that of XY control men. The results thus do not support the above hypothesis as an explanation of the widely scattered plasma androgen values in XYY individuals. The "XYY syndrome" is probably heterogeneous and includes a number of patients with some degree of hypogonadism. Testicular biopsy, sperm count, and meiotic studies were carried out in eight XYY men. In one case the meiotic study showed two Y-chromatin bodies. Results of these various investigations support the diagnosis of maturation arrest of the germ cells with consequent oligospermia. Low fertility is therefore expected to be frequent among XYY subjects, although when fertilization does occur, it can result in normal XY or in XYY infants.

Adolescent↗

Experimental papillary necrosis of the kidney. IV. Medullary plasma flow.

To test the thesis that vasoconstriction plays a significant role in the pathogenesis of papillary necrosis caused by bromoethylamine hydrobromide (BEA), medullary plasma flow was determined in rats treated with BEA. Medullary blood flow was normal (1/2) to 1 hour after BEA treatment, and was actually elevated 6 hours after BEA. There was no increase in plasma levels of prostaglandins A and E, which would have been expected if there had been medullary ischemia. Pretreatment with reserpine, which inhibited the development of papillary necrosis, had little effect on medullary plasma flow. These observations do not support the notion that vasoconstriction is the mechanism by which BEA causes papillary necrosis.

Animals↗

Microembolic renal disease in rats induced with sephadex.

Sephadex particles (20-80 mu in size) were injected into the abdominal aorta of 134 male Sprague-Dawley rats near the renal arteries. In 31 rats, the right kidney was then removed. The Sephadex particles lodged in glomerular capillaries, afferent glomerular arterioles and interlobular arteries, creating renal infarcts, some of which were grossly visible. Shortly after injection, arterial blood pressure rose significantly in most animals. The hypertension in uninephrectomized rats was not demonstrably different from that in rats with two Kidneys. Severity and duration of hypertension (up to 8 months) were positively correlated with the number of Sephadex particles in renal vessels, and there was also a positive correlation between the degree of hypertension and serum urea nitrogen levels, and between degree of hypertension and degree of cardiac hypertrophy. The vascular permeability in acutely hypertensive rats was abnormal, as judged from penetration of iron-dextran into vessel walls. This experimental model resembles atheromatous microembolic renovascular disease, which may play a significant role in the pathogenesis of unexplained hypertension in patients with advanced aortic atherosclerosis.

Animals↗

Renal morphology and function and urine electrolytes in experimental acute renal failure produced by cyclosporine and ischemia.

It has been difficult to produce a good animal model for cyclosporine nephrotoxicity. It has been suggested that by following 20 minutes of renal ischemia with four daily doses of cyclosporine 60 mg/kg intraperitoneally, one can create a model of reproducible renal failure. We observed excessive mortality (65%), due in part to cyclosporine's CNS effects, with these combined insults in the Munich Wistar rat. In contrast, cyclosporine alone in this dosage produced only 17% mortality and resulted in a similar degree of renal failure. Pair-fed and pair-watered vehicle and saline controls were used. The morphologic changes brought about by the castor oil vehicle of the parenteral cyclosporine solution were qualitatively similar to those brought about by cyclosporine by light microscopy, although the severity of the changes was considerably less in the vehicle-treated groups. However, by electron microscopy, pale lipid vacuoles were seen only in the cyclosporine-treated groups, whereas dense alterations in lysosomes and dilated endoplasmic reticulum also were seen in other groups. Urine sodium determined by flame photometry and urine chloride determined by Saltex reagent strips tended to be high in the initiation phase of cyclosporine-induced acute renal failure and low in the maintenance phase. In animals that developed acute renal failure following the combination of ischemia and cyclosporine, the initial urine sodium and chloride were significantly correlated with the eventual degree of renal failure. The use of Saltex urine chloride sticks in clinical urine samples showed that the readings correlated well with urine sodium and chloride determined by conventional methods, suggesting that these strips may be useful in making a quick diagnosis in the setting of acute renal failure.

Acute Kidney Injury↗