Bystanders or active players: the role of extra centrosomes as signaling hubs.

Centrosomes serve as microtubule-organizing organelles that function in spindle pole organization, cell cycle progression, and cilia formation. A non-canonical role of centrosomes that has gained traction in recent years is the ability to act as signal transduction centers. Centrosome amplification, which includes numerical and structural aberrations of centrosomes, is a candidate hallmark of cancer.

Gordon Murray: heparin, hemodialysis and hubris.

Gordon Murray (1894-1976), a brilliant and innovative surgeon who spent the majority of his professional career at the University of Toronto, Ont., Canada, is properly credited with having performed the first successful hemodialyses in humans in North America. Neither he nor Kolff, working in the Netherlands, were aware of each other's work during the middle 1940s when wartime hampered communication.

Renal physiology between two wars: the contributions of Dr. Harvey Lester White.

Harvey Lester White (1896-1977) graduated from Washington University (St. Louis) School of Medicine and subsequently spent his entire professional career in the School's Department of Physiology. White's interest in the function of the kidney was evident early in his academic career when he pioneered research related to renal physiology.

A history of eclampsia, toxemia and the kidney in pregnancy.

Eclampsia, accompanied by convulsions, is one of the most dangerous complications of pregnant women. This condition was known to the ancient Greeks, who named it eclampsia. Prior to the 18th century, the term eclampsia was used only to refer to the visual phenomena which accompanied the neurologic aspects of the malady.

History of women in nephrology (1918 to 1960).

Little has been written concerning the role of women in nephrology in America during the first half of the twentieth century. However, the records show that women scientists made substantial contributions to nephrology and definitely were involved in research efforts at a number of prestigious academic institutions that had interests focused on kidney function in health and disease. Here, we describe the contributions of some of these pioneering women scientists to whom nephrology shall always be indebted.

Depictions of the kidney through the ages.

Recent publications [American Journal of Nephrology (1985-1995)] have contributed much to our understanding of the history of nephrology. Whether the earliest medical knowledge of the kidney was kindled in Egypt, by the Hindus in India, in ancient China, or by Assyro-Babylonians we cannot determine with certainty. What is known is that the invention of the printing press (circa 1450 AD), with the subsequent availability of translations of earlier writings plus new text editions, contributed in prodigious measure to the development of the critical and questioning character of medicine.

Effects of probucol in renal function and structure in rats with subtotal kidney ablation.

Probucol is a bisphenolic compound that lowers serum cholesterol and also has potent antioxidant properties. The present studies examined the effects of probucol administration on renal function and structure in a rat model of subtotal renal ablation. After subtotal nephrectomy, rats were fed an isocaloric rat chow diet containing 22.

Dietary supplementation with L-arginine ameliorates the progression of renal disease in rats with subtotal nephrectomy.

We studied the effect of dietary supplementation with L-arginine for 6 weeks on the progression of renal disease in female Sprague-Dawley rats subjected to sham-operation (groups 1 and 2) or surgical ablation of 85% to 90% of the total renal mass (groups 3 and 4). All rats were fed a standard rat chow containing 22.8% protein.

The recovery of renal function in rats after release of unilateral ureteral obstruction: the effects of moderate isotonic saline loading.

Following 24 h of ureteral obstruction in the rat, renal blood flow and glomerular filtration rate are markedly depressed. The effect of saline loading on post-obstructive glomerular filtration (GFR) was studied in 15 female Sprague-Dawley rats in the awake state, 4 h following the release of 24 h of unilateral ureteral obstruction. Group I (n = 8) received 39 microliters min-1 of 0.

Lovastatin ameliorates the development of glomerulosclerosis and uremia in experimental nephrotic syndrome.

The nephrotic syndrome was induced in uninephrectomized Sprague-Dawley rats using repeated injections of puromycin and protamine sulfate. Preliminary studies demonstrated that the administration of lovastatin (4 mg/kg body weight [BW] subcutaneously [SC] daily) was effective at lowering plasma cholesterol over a 63-day period, although not to normal values. Subsequently, two groups of rats that had been made nephrotic were studied; one group (n = 8) received lovastatin, the other (n = 9) received the vehicle alone.

Role of ANG II in eicosanoid production by isolated glomeruli from rats with bilateral ureteral obstruction.

The production of prostaglandin (PG) E2, 6-keto-PGF1 alpha, and thromboxane B2 (TxB2) under basal conditions and after exposure to angiotensin II (ANG II) or arginine vasopressin (AVP) was examined in vitro in isolated glomeruli. The glomeruli were obtained from control rats and rats with bilateral ureteral obstruction (BUO) of 24-h duration that were pretreated or not with an inhibitor of the angiotensin I converting enzyme (ACE). Basal prostanoid production was greater in isolated glomeruli from BUO rats than in controls.

Prior inhibition of vasoconstrictors normalizes GFR in postobstructed kidneys.

The present studies were designed to analyze the potential contribution of angiotensin II and thromboxane A2 to the remarkable decrease in glomerular filtration rate (GFR) and renal plasma flow observed after unilateral release of 24-hour bilateral ureteral obstruction. Pretreatment of the animals with inhibitors of either thromboxane or angiotensin synthesis for 48 hours prior to and during obstruction eliminated the contribution of these vasoconstrictors. Inhibition of these vasoconstrictors during the period of obstruction results in a greater increase in renal plasma flow and GFR than when inhibition was accomplished after release of the obstruction.

Role of atrial peptide in the natriuresis and diuresis that follows relief of obstruction in rat.

The present studies demonstrate that endogenous levels of atrial peptide are significantly elevated in the plasma of rats with bilateral ureteral obstruction (BUO) compared with control rats or rats with unilateral ureteral obstruction. The contribution of endogenous atrial peptide to the natriuresis and diuresis that follows release of BUO was examined by the intravenous infusion of heparin with or without the exogenous administration of atrial peptide. Infusion of heparin, which binds atrial peptide and interferes with its biological effect, decreased the natriuresis and diuresis observed after release of BUO.

Eicosanoids: role in experimental renal disease.

Because of their vasodilator and vasoconstrictor properties, vasoactive prostaglandins and thromboxane A2 have been proposed as modulators of the hemodynamic changes that occur in experimental models of renal disease. Increased synthesis of vasodilatory prostaglandins (PGE2) and perhaps prostaglandin I2 (PGI2) play a role in the maintenance of renal blood flow and GFR during states of impaired perfusion. In contrast, thromboxane A2 has been implicated as the vasoconstrictor responsible for the reduction of renal blood flow and GFR in certain animal models of experimental renal disease.

Effect of heparin on the glomerular structure and function of remnant nephrons.

The development of glomerular structural abnormalities in remnant nephrons, after ablation of renal mass (subtotal nephrectomy), in rats is largely prevented by the daily injection of heparin. To investigate if this protective effect of heparin is due to attenuation of glomerular hyperperfusion, hypertension and hyperfiltration, which develop in remnant nephrons soon after subtotal nephrectomy, we measured various parameters of glomerular hemodynamics at two weeks (Group 1) and four weeks (Group 2) after removal of 1-3/4 of total kidney mass in heparin-treated (Groups 1A and 2A) and untreated (Groups 1B and 2B) Munich-Wistar rats. When compared to normal non-nephrectomized rats (Group 1C), the values for glomerular capillary hydraulic pressure (PGC), glomerular plasma flow rate (QA) and single nephron filtration rate (SNGFR) in remnant nephrons were found to be markedly and similarly elevated in both Groups 1A and 1B, averaging 71 +/- 4 and 73 +/- 4 mm Hg, 229 +/- 41 and 176 +/- 13 nl/min, 58.

Immunological aspects of acute ureteral obstruction: immune cell infiltrate in the kidney.

Kidneys from rats subjected to bilateral ureteral obstruction (BUO), unilateral ureteral obstruction (UUO) and UUO with subsequent release were analyzed for leukocyte infiltration. A time-dependent influx of leukocytes, predominantly macrophages and suppressor T lymphocytes, occurred in both the cortex and medulla following obstruction, and disappeared with release of the obstruction. Glomerular macrophages declined following obstruction but increased to levels above control following release.

Effect of diet, age and sex on the renal response to immune injury in the rat.

We investigated the effect of three factors, namely dietary protein intake, age and sex, on the susceptibility of the renal glomerulus to the binding of antiglomerular basement membrane antibody (anti-GBM) in the early (heterologous) phase of anti-GBM nephritis, and the consequent reduction in glomerular filtration rate (GFR) as measured by inulin clearance (CIn). The effect of diet was examined in approximately equal to 8 week-old female Munich-Wistar rats fed a 40% high (HP) or a 6% low (LP) protein diet, and that of sex and age in male and female rats, 6 week or 10 month old. Following an intravenous dose (3 to 20 micrograms/g body wt) of radiolabeled nephritogenic anti-GBM, assessment of glomerular function was followed by quantitation of anti-GBM binding (values corrected for GBM surface area) in isolated glomeruli.

N-desulfated/acetylated heparin ameliorates the progression of renal disease in rats with subtotal renal ablation.

The effect of administration of N-desulfated/acetylated heparin, almost completely devoid of anticoagulant activity, on the progression of renal disease was examined in rats with 13/4 nephrectomy. Three groups of rats with 13/4 nephrectomy were studied. Group I (control, n = 11) received 0.

Effects of obstruction on renal functions.

Following ureteral obstruction there is a progressive fall in glomerular filtration rate (GFR) due to a reduction in single nephron glomerular filtration rate (SNGFR) and a reduced number of filtering nephrons. Renal plasma flow also declines after a transient, prostaglandin-dependent increase, due to afferent and efferent arteriolar vasoconstriction. The vasoactive hormones thromboxane A2 and angiotensin II are implicated in the pathogenesis of the vasoconstriction following ureteral obstruction and they also reduce the glomerular ultrafiltration coefficient by causing mesangial contraction.

Effect of dietary lipids on renal function in rats with subtotal nephrectomy.

Female rats with 1-3/4 nephrectomy were divided in two groups and pair fed for five weeks diets differing in their linoleic acid content. Five weeks after subtotal nephrectomy, values for glomerular filtration rate and renal plasma flow were significantly higher and the values of blood pressure significantly lower in rats fed a diet rich in linoleic acid. Systolic blood pressure averaged 156 +/- 5.

Role of hypertension and coagulation in the progressive glomerulopathy of rats with subtotal renal ablation.

Administration of heparin to rats with 1 3/4 nephrectomy prevents the development of glomerulosclerosis, hypertension and retards the decrease in renal function seen in these rats. To further define the role of hypertension and/or coagulation in the pathogenesis of the glomerulopathy seen in this model we studied several groups of rats with 1 3/4 nephrectomy: (1) a control group; (2) a group receiving a 'high dose' of acetylsalicylic acid (50 mg/kg) plus dipyridamole (10 mg/kg); (3) a group receiving a 'low' dose (5 mg/kg body weight) of acetylsalicylic acid alone; (4) a group receiving OKY 1581, an inhibitor of thromboxane synthesis; (5) a group treated with antihypertensive medications; (6) a group receiving heparin subcutaneously twice daily, and (7) a group given oral Coumadin. Drugs in all groups were administered daily for 4 weeks.

Thromboxane synthesis and blood pressure in spontaneously hypertensive rats.

The present study examines effects of administration of OKY 046, an inhibitor of thromboxane synthesis, for 100 days on systemic blood pressure and renal function in spontaneously hypertensive rats and in normotensive control rats. Untreated spontaneously hypertensive rats had higher values for thromboxane excretion in the urine and higher values for blood pressure than did normotensive control rats. Administration of OKY 046 decreased systolic and mean arterial blood pressure and urinary excretion of thromboxane and protein in spontaneously hypertensive rats.