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J L Troy

Publications and source records attributed to J L Troy.

At least 55 records · Page 3Linked to original sources

Renal and systemic hemodynamic effects of synthetic atrial natriuretic peptide in the anesthetized rat.

To characterize the hemodynamic events responsible for alterations in renal function during administration of atrial natriuretic peptide, we studied the systemic, renal, and glomerular circulatory effects of intravenous rANP[126-149], administered as a 4 micrograms/kg prime and 0.5 microgram/kg per minute continuous infusion in anesthetized, euvolemic rats. With this protocol, a small decline in mean systemic arterial blood pressure occurred in the context of markedly enhanced urinary sodium excretion, hemoconcentration, and reduced left ventricular end-diastolic pressure and +dP/dt. However, despite a significant decrement in renal vascular resistance, total peripheral resistance remained constant, thereby denoting a preferential renal vasodilatory effect of this peptide in vivo. Whole kidney and single nephron GFR increased by approximately 20%, while effective renal and glomerular plasma flow rates remained stable, resulting in a substantial rise in filtration fraction. Of all the parameters potentially capable of augmenting single nephron GFR, only glomerular capillary hydraulic pressure increased significantly and therefore accounted entirely for the hyperfiltration observed during ANP infusion. This rise in glomerular capillary pressure, in turn, resulted from afferent arteriolar vasodilatation and concurrent efferent arteriolar vasoconstriction, findings that proved independent of both endogenous angiotensin II activity and ANP-induced reductions in renal perfusion pressure. These renal hemodynamic effects are unique when compared with actions of previously studied renal vasodilatory agents.

Anesthesia, General↗

Modulation of the natriuretic response to atrial natriuretic peptide by alterations in peritubular Starling forces in the rat.

The mechanisms underlying the natriuretic response to infusions of atrial natriuretic peptide (ANP) remain incompletely defined. By acting as renal vasodilators, atrial peptides may serve to alter peritubular capillary physical forces and favor a decrease in tubule solute reabsorption. Therefore, we studied the effects of known modifiers of intrarenal Starling forces on the natriuresis induced by infusion of intravenous hANP [4-28] (0.5 microgram/kg/min) in anesthetized, euvolemic Munich-Wistar rats. In the first series of studies, infusion of ANP resulted in a significant natriuresis, diuresis, and increase in inulin clearance and in a slight fall in systemic arterial pressure, as compared to vehicle infusion. Subsequent elevation of renal perfusion pressure by superimposition of angiotensin II infusion (0.1-0.2 microgram/kg/min i.v.) on continued ANP infusion resulted in marked further enhancement of natriuresis, independent of changes in glomerular filtration rate (GFR). In the second set of experiments, in which oncotic pressure in the postglomerular capillaries was elevated by hyperoncotic exchange transfusion, administration of ANP did not result in natriuresis, even though GFR increased by the same magnitude as that seen in isooncotic animals given ANP. These observations are consistent with the view that peritubular capillary hydraulic and oncotic pressures modulate the natriuretic and diuretic effects of ANP.

Angiotensin II↗

Sebaceoma. A distinctive benign neoplasm of adnexal epithelium differentiating toward sebaceous cells.

Sebaceoma is a new term proposed to designate a distinctive benign neoplasm of adnexal epithelium with differentiation toward sebaceous cells. Clinicopathologic correlation of the condition is presented in a study of 14 cases. This neoplasm has many histologic features in common with trichoepithelioma and cylindroma, both of which are benign neoplasms of adnexal epithelium, one with follicle-like and the other with eccrine-like differentiation. Sebaceoma is a recently recognized entity, and the term is recommended to supersede, not merely to redefine, what has been previously called sebaceous epithelioma.

Adult↗

Role for intrarenal mechanisms in the impaired salt excretion of experimental nephrotic syndrome.

A unilateral model of puromycin aminonucleoside (PAN)-induced albuminuria was produced in Munich-Wistar rats to examine the mechanisms responsible for renal salt retention. 2 wk after selective perfusion of left kidneys with PAN (n = 8 rats) or isotonic saline (control, n = 7 rats), increases in albumin excretion and decreases in sodium excretion were demonstrated in PAN-perfused but not in nonperfused kidneys of PAN-treated rats although systemic plasma protein concentration remained at control level. Total kidney glomerular filtration rate (GFR) and superficial single nephron (SN) GFR were also reduced selectively in PAN-perfused kidneys, on average by approximately 30%, due primarily to a marked decline in the glomerular capillary ultrafiltration coefficient (Kf), which was also confined to PAN-perfused kidneys. Values for absolute proximal reabsorption (APR) were also selectively depressed in PAN-perfused kidneys, in keeping with a similarly selective decline in peritubular capillary oncotic pressure measured in these kidneys, the latter also a consequence of the fall in Kf. In a separate group of seven PAN-treated rats, however, no differences were detected between PAN-perfused and nonperfused kidneys in the absolute amount of sodium reaching the early (0.77 +/- 0.09 neq/min vs. 0.74 +/- 0.08, P greater than 0.40) and late portions of superficial distal tubules (0.31 +/- 0.02) neq/min vs. 0.32 +/- 0.05, P greater than 0.50), despite the lesser filtered load of sodium in PAN-perfused kidneys. Suppressed sodium reabsorption in both proximal convoluted tubules and short loops of Henle of PAN-perfused kidneys contributed to this equalization of sodium delivery rates to the late distal tubule, as did comparable reabsorption along distal convolutions. In two additional groups of PAN-treated rats, infusion of saralasin (0.3 mg/kg per h, i.v.) led to substantial increases in total kidney GFR and SNGFR in PAN-perfused but not in nonperfused kidneys. Despite these increases in total and SNGFR, urinary sodium excretion by PAN-perfused kidneys remained at a level far below that for nonperfused kidneys, again indicating that the antinatriuresis characterizing the PAN-perfused kidney is due to alterations in sodium handling by the tubules rather than changes in GFR. These results therefore indicate (a) that reductions in Kf and depressed sodium reabsorption by proximal tubules and Henle's loop segments in this model are brought about by intrarenal rather than circulating or systemic factors, and (b) assuming that superficial nephrons are representative of the entire nephron population, renal salt retention in this model is due primarily to intrarenal factor(s) acting beyond the distal convolution.

Animals↗

Effects of catecholamines on electrolyte transport in cortical collecting tubule.

We examined the direct effects of isoproterenol (ISO) and L-norepinephrine (NE) on electrolyte transport in isolated rabbit cortical collecting tubules (CCT) perfused in vitro. The addition of either ISO (10(-6) M) or NE (10(-6) M) to the bath decreased transepithelial potential difference (PD), on average by 51 and 25%, respectively. These effects of ISO and NE were abolished by prior addition of the beta-adrenergic blocker, L-propranolol. ISO (10(-5) M) had no effect from lumen. Also, osmotic water permeability was not influenced by ISO. Ouabain and ISO had additive effects on PD. Elimination of chloride from both perfusate and bath, or addition of acetazolamide, abolished the effect of ISO on PD. Although isotopic sodium flux for lumen to bath was not influenced by ISO, chemical net chloride absorption increased from 1.1 +/- 0.4 to 2.7 +/- 0.6 peq . cm-1 . sec-1 (n = 8, p less than 0.005). In conclusion, both ISO and NE and capable of decreasing PD in rabbit CCT perfused in vitro. This effect is mediated by beta-adrenergic receptors and is accompanied by the increase in net chloride absorption. Although the mechanism responsible for this decrease in PD with ISO in unclear, active chloride absorption, active hydrogen secretion, or membrane chloride permeability changes may account for the effects of ISO.

Acetazolamide↗

Penicillamine-associated pemphigus: is it really pemphigus?

Penicillamine-associated bullous eruptions share with spontaneously occurring pemphigus intraepidermal acantholysis, epidermal intercellular deposition of immunoglobulin, and circulating serum antibody against the intercellular regions of the epidermis. We report the case of a penicillamine-associated bullous eruption in which there were some of the histologic features of pemphigus, but none of the immunofluorescent features. Instead, the immunofluorescent findings of bullous pemphigoid were demonstrated. Review of the literature reveals that clinical and histologic features of penicillamine-associated bullous eruptions differ in important respects from those of spontaneously occurring pemphigus. Our report adds immunologic data to evidence that the penicillamine-associated bullous eruptions may not be the same disease as spontaneously occurring pemphigus.

Arthritis, Rheumatoid↗

Pathophysiology of altered glomerular function in aminoglycoside-treated rats.

To evaluate the relative influences of gentamicin and tobramycin on glomerular function, we studied three groups of normal hydropenic rats. Group 1 had 8 rats that served as control. Group 2 had 9 rats that were given gentamicin (40 mg/kg of body wt per day for 10 days). Group 3 had 10 rats that received tobramycin instead of gentamicin. In addition, we attempted to suppress angiotensin II (AII) generation in two additional groups of rats and then study the glomerular response to gentamicin: in 6 rats, isotonic sodium chloride was substituted for tap water for drinking throughout the period of study (group 4), and in 7 other gentamicin-treated rats, captopril was given orally (group 5). A sixth group received captopril alone (group 6). Following gentamicin treatment in group 2, values for single nephron GFR (SNGFR) were markedly lower (21.7 +/- 2.1 nl/min) than they were in groups 1(35.7 +/- 1.4) or 3(34.1 +/- 2.9). Declines in whole kidney GFR in group 2 paralleled the fall in SNGFR. Reduction in SNGFR with gentamicin was due both to a marked decline in the glomerular capillary ultrafiltration coefficient, Kf, and in the initial glomerular plasma flow rate, QA. With saline administration (group 4), the decline in SNGFR was partially blunted, whereas with captopril (group 5) the effects of gentamicin on SNGFR, QA, and Kf were largely abolished. Morphologic studies revealed no discernible glomerular defects in any groups, whereas proximal tubule damage was evident with both aminoglycosides, irrespective of the state of the renin-angiotensin system. Thus, in the dosage used, gentamicin elicits greater impairment in glomerular function than does tobramycin, and by mechanism(s) that are at least partially responsive to suppression of AII generation.

Animals↗

Glomerular hemodynamics in experimental diabetes mellitus.

Micropuncture studies were performed in three groups of euvolemic male Munich-Wistar rats: 8 control rats, 7 severely hyperglycemic rats made diabetic with streptozotocin (60 mg/kg, i.v.), and 6 moderately hyperglycemic rats made diabetic by the same method but given 2 U of NPH insulin daily. Glucose concentrations at the time of micropuncture study averaged 115 +/- (sem) 10, 565 +/- 12, and 375 +/- 23 mg/dl, respectively. Single nephron GFR (SNGFR) values were significantly lower (28.8 +/- 1.9nl/min) in severely hyperglycemic rats than they were in controls (48.9 +/- 3.8). This reduction in SNGFR was due mainly to a fall in glomerular plasma flow rate ((Q(A)). In contrast, moderately hyperglycemic rats exhibited glomerular hyperfiltration, with SNGFR values averaging 69.0 +/- 8.0 nl/min. This hyperfiltration, with resulted from elevations in values for Q(A) and glomerular transcapillary hydraulic pressure difference (delta P) to levels significantly above control. These alterations in SNGFR in severely hyperglycemic and moderately hyperglycemic rats, relative to controls, were paralleled by changes in whole kidney GFR and mimic the changes in GFR observed in diabetic patients with analogous degrees of hyperglycemia. Measurements of blood volumes in separate groups of control, severely, and moderately hyperglycemic rats revealed equivalent absolute blood volumes in all three conditions and increased blood volumes, relative to body weight, in both groups of hyperglycemic rats. Thus, SNGFR is increased in diabetic rats with moderate hyperglycemia but decreased in those with severe hyperglycemia, and these changes are not simply related to variations in circulating blood volume.

Animals↗

Basal-cell carcinomas on the scalp of a black patient many years after epilation by x rays.

The development of skin cancers in areas treated with X rays for benign dermatoses has not been common. Moreover, basal-cell carcinomas in blacks are exceedingly rare. We report successive development of two basal-cell carcinomas in the hair-covered scalp of a black man three decades after he had undergone epilation of the scalp by X rays of tinea capitis while a youth.

Black People↗

Squamous-cell carcinoma arising in a leprous neurotrophic ulcer: report of a case.

Exophytic neoplasms arise rarely in neurotrophic ulcers of leprosy. When such a lesion does develop, it has clinical resemblance to an indolent and locally invasive epithelioma cuniculatum, may invade deeply, and may metastasize. The case described showed deep invasion and extensive involvement of bone. Exophytic neoplasms in neurotrophic ulcers of leprosy should be considered to be squamous-cell carcinomas, not epitheliomata cuniculata, because of their potential for rapid, deep invasion and metastases.

Aged↗

Mechanism of reduced glomerular filtration rate in chronic malnutrition.

To determine the physiological basis for the low glomerular filtration rate in chronic malnutrition, micropuncture studies were performed in Munich-Wistar rats chronically pair-fed isocaloric diets of either low (group 1, nine rats) or high protein content (group 2, nine rats). Despite the absence of hypoalbuminemia, average values for single nephron and total kidney glomerular filtration rate were nearly 35% lower in group 1 than in group 2. Mean values for glomerular capillary and Bowman's space hydraulic pressures were essentially identical in the two groups, thereby excluding glomerular transcapillary hydraulic pressure difference as the cause for the low filtration rates in group 1 animals. On the other hand, average glomerular capillary plasma flow rate and glomerular capillary ultrafiltration coefficient were significantly lower (by approximately 25 and approximately 50%, respectively) in group 1 than in group 2. The fall in glomerular capillary plasma flow rate was the consequence of increased afferent and efferent arteriolar resistances. Plasma and erythrocyte volumes were found to be equal in five additional pairs of group 1 and group 2 rats. Thus, the substantial alterations in the ultrafiltration coefficient, glomerular capillary plasma flow rate, and renal arteriolar resistances responsible for the low filtration rate in group 1 animals were not merely a consequence of decreased circulating blood or plasma volumes. Mean values for glomerular cross sectional area were significantly lower in group 1 than in group 2 despite similar values for kidney weight in the two groups. This reduction in glomerular cross sectional area in group 1 rats is presumed to reflect a decrease in effective filtration surface area and therefore likely accounts, at least in part, for the decline in ultrafiltration coefficient observed in this group.Finally, since the daily caloric intake of group 2 animals was restricted because of pair feeding requirements tied to the group 1 rats, we studied a third group of seven rats (group 3) allowed an ad lib. intake of the same high protein diet as given to group 2 rats. Average values for single nephron glomerular filtration rate and its determinants were found to be indistinguishable between groups 2 and 3. These results suggest that low protein intake, rather than calorie deficiency per se, is primarily responsible for the reduction in filtration rate seen in this experimental model of chronic malnutrition.

Animals↗

Influence of molecular configuration on the passage of macromolecules across the glomerular capillary wall.

The influence of molecular configuration on the filtration of macromolecules across glomerular capillary walls was examined by comparing fractional clearances of two uncharged polysaccharides of distinctly different molecular configuration in the Munich-Wistar rat. The macromolecules employed were dextran, a slightly branched polymer of glucopyranose, and ficoll, a highly cross-linked copolymer of sucrose and epichlorohydrin. Differences in effective shape between these two polymers were determined from measurements of several physical properties of aqueous solutions containing either dextran or ficoll. It was found that dextran is best represented as a prolate ellipsoid with axial ratios of 4, 9, and 16 for molecules with Stokes-Einstein radii of 22, 32, and 40 A, respectively. On the other hand, ficoll is more closely approximated as spherical since the axial ratio was found to be between 1 and 2 for all molecular sizes. Fractional clearances of dextran and ficoll ranging in effective radius from 18 to 44 A were determined in each of seven Munich-Wistar rats. Fractional clearances of dextran were found to be greater than those of ficoll, the difference being significant for molecular radii ranging from 24 to 44 A. In addition, as shown previously for dextran, ficoll was found to be neither secreted nor reabsorbed by the renal tubules. These results, therefore, suggest that in addition to molecular size and charge, molecular configuration is also a determinant of the filtration of macromolecules across the glomerular capillary wall.

Animals↗

Evidence for a parathyroid hormone-dependent influence of calcium on the glomerular ultrafiltration coefficient.

Experiments were performed on 36 plasma-expanded Munich-Wistar rats to examine the effects of acute hypercalcemia on the determinants of glomerular ultrafiltration. Elevation of total plasma calcium concentration to an average value of 13.2 +/- 0.5 mg/dl, by acute infusion of calcium chloride into nonthyroparathyroidectomized (non-TPTX) rats, resulted in significant declines in single nephron and whole kidney glomerular filtration rate. These declines were due primarily to a fall in the glomerular capillary ultrafiltration coefficient (Kf), to a mean value approximately 60% below that determined in the pre-infusion period. These changes were not seen in a separate group of sham-treated non-TPTX rats. It is of interest that these effects of acute hypercalcemia were largely abolished in rats that underwent acute TPTX before hypercalcemia. Infusion of a submaximally phosphaturic dose of parathyroid hormone, together with calcium chloride, into a second group of acute TPTX rats, however, had the effect of reproducing the striking declines in filtration rate and Kf noted in non-TPTX rats given calcium chloride alone. These findings suggest that the decline in filtration rate associated with hypercalcemia is due largely to the reduction in Kf, the latter dependent upon the presence of parathyroid hormone.

Animals↗

Mechanisms of the puromycin-induced defects in the transglomerular passage of water and macromolecules.

To investigate the mechanism(s) of increased filtration of serum proteins after glomerular injury, polydisperse samples of uncharged [(3)H]dextran (D) or anionic [(3)H]dextran sulfate (DS) were infused into 14 control and 16 puromycin aminonucleoside- (PAN) treated Munich-Wistar rats. Fractional clearances of D or DS ranging in radius from 18 to 42A were determined in these rats, together with direct measurements of the forces governing the glomerular filtration rate of water. Whole kidney and single nephron glomerular filtration rates were approximately 40% lower in PAN-treated rats, relative to controls, due mainly to a marked reduction in the glomerular capillary ultrafiltration coefficient and, to a lesser extent, to a small reduction in glomerular plasma flow rate as well. In PAN-treated rats, as in normal controls, inulin was found to permeate the glomerular capillary wall without measurable restriction, and both D and DS were shown to be neither secreted nor reabsorbed. Fractional clearances of uncharged D were reduced after PAN administration, falling significantly for effective D radii from 22 to 38A. Utilizing a theory based on macromolecular transport through pores, these results indicate that in PAN-treated rats, effective pore radius is the same as in controls, approximately 44A. In PAN nephrosis, however, the ratio of total pore surface area/pore length, a measure of pore density, is reduced to approximately one-third that of control, due very likely to a reduction in filtration surface area. In contrast to the results with uncharged D, fractional clearances of DS were found to increase after PAN administration for all DS radii studied. These results with D and DS suggest that proteinuria in PAN nephrosis is due, not to an increase in effective pore radius or number of pores, but rather to a diminution of the electrostatic barrier function of the glomerular capillary wall, thereby allowing increased passage of polyanions such as DS and albumin.

Animals↗