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Biomedical subjects

E J Braun

Publications and source records attributed to E J Braun.

At least 19 recordsLinked to original sources

Kidney structure and function of obligate and facultative hibernators: the white-tailed prairie dog (Cynomys leucurus) and the black-tailed prairie dog (Cynomys ludovicianus).

The white-tailed prairie dog is an obligate hibernator that enters a heterothermic phase when maintained in the cold with low intensity light and ad libitum food and water. The black-tailed prairie dog (a facultative hibernator) will not hibernate under similar conditions. It has been suggested that the black tailed prairie dog remains active during the winter because it can conserve water more effectively due to a more efficient kidney. The present study revealed no significant differences between the species in renal morphology: relative medullary thickness, nephron heterogeneity, renal vasculature, or fornix dimensions, all of which are structures associated with the urinary concentrating mechanism. In addition, there was no difference in number of nephrons between the two species. The black-tailed prairie dog does produce a more concentrated urine when food and water deprived. However, this difference was not observed when the animals were salt loaded. The water-deprivation and salt-loading experiments suggest that the higher urine osmolality produced by the back-tailed prairie dog during fasting is a result of a higher urea load due to a greater protein catabolism and not because of a differential capacity to concentrate urine.

Adaptation, Physiological

Renal response of roosters with diabetes insipidus to infusions of arginine vasotocin.

In a strain of white Leghorn chicken with symptoms of hereditary diabetes insipidus (DI) and with elevated circulating levels of the antidiuretic hormone arginine vasotocin (AVT), we investigated whether the defect is based on nonfunctional endogenous AVT or on a diminished renal response to AVT. DI chickens responded to hyposmotic infusions with a higher urine flow and lower glomerular filtration rate (GFR) than healthy control birds. Urine osmolality, fractional excretion, and clearance of sodium were lower in DI birds while potassium values were similar in both groups. Hence, the high urine flow rates of the DI birds were predominantly based on a water diuresis. When infused with AVT, the GFR and the urine flow of the control birds decreased and urine osmolality increased, showing both glomerular and tubular effects of AVT. During AVT infusion, the GFR of DI birds increased, urine flow decreased only moderately, and urine osmolality was half that of the control birds. In control birds, the clearance of sodium was unchanged, whereas that of potassium decreased. In DI birds, which experienced a strong natriuresis, the clearance of both sodium and potassium increased. These data suggest that the sensitivity of the DI birds to AVT is reduced at the tubular level. The AVT-induced increase in GFR may be related to vascular effects of high AVT doses, added to the already high basal AVT level of the DI birds, in combination with an imbalance in the function of V1 and V2 receptor subtypes in these chickens.

Animals

Characterization of organic cation transport by avian renal brush-border membrane vesicles.

Organic cations are actively secreted by the renal proximal tubule. Studies on perfused tubules and isolated membranes from mammals and reptiles have demonstrated that organic cations (OC) are transported across the luminal (brush-border) membrane by OC/H+ exchange. Our objective was to determine whether a similar mechanism was present in the avian kidney. Uptake of [14C]tetraethylammonium (TEA) was assayed under various ionic conditions by rapid filtration in brush-border membrane vesicles (BBMV) isolated from chicken kidney (Gallus domesticus). An outwardly directed proton gradient (pHin = 6.0: pHout = 7.5) stimulated concentrative TEA uptake. TEA/H+ exchange was saturable, having a maximal rate of uptake of approximately 25 nmol.mg protein-1.min-1 and a Michaelis constant for TEA of approximately 500 microM. TEA transport could be indirectly coupled to sodium transport. Unlabeled TEA, N'-methylnicotinamide (NMN), choline, cimetidine, mepiperphenidol, quinidine, quinine, and ranitidine markedly cis-inhibited uptake of [14C]TEA. However, the organic anions probenecid and p-aminohippurate poorly inhibited uptake. Unlabeled TEA and NMN also trans-stimulated [14C]TEA uptake. Thus, in avian renal BBMV, organic cations are transported by an OC/H+ exchange mechanism qualitatively similar to that present in mammals.

Animals

Growth of an androgen-sensitive human prostate cancer cell line, LNCaP, in nude mice.

This study was undertaken to establish an androgen-sensitive model of human prostatic carcinoma in nude mice. The androgen-sensitive prostatic carcinoma cell line, LNCaP, was suspended in reconstituted basement membrane (Matrigel) and injected subcutaneously into nude mice. The LNCaP cell line was chosen for the study, because the cell line is androgen-sensitive and secretes prostate specific antigen (PSA) into culture media. Following injection of 1 x 10(6) LNCaP cells with 0.25 ml of Matrigel, 88% of mice exhibited palpable tumor burdens after 12 weeks of observation. In addition, significant levels of PSA were observed in the serum of LNCaP-bearing mice. Bilateral orchiectomy of mice resulted in tumor regression and stabilization of serum PSA levels, compared to testis-intact controls. A significant correlation of PSA to tumor volume and weight was observed. The castrate level of testosterone was confirmed by radioimmunoassay and was similar to testosterone levels in female nude mice. Matrigel allows for a conducive environment to propagate LNCaP cells in nude mice. Furthermore, the growth can be manipulated by castration, leading to involution of tumor and stabilization of serum PSA level. This in vivo model of hormone-sensitive human prostate cancer cell line will serve as a model for the study of prostate tumor biology and treatment.

Animals

Effect of retinoic acid on the proliferation and secretory activity of androgen-responsive prostatic carcinoma cells.

We studied the effect of retinoic acid on the growth and secretory activity of the androgen-responsive prostatic carcinoma cell line LNCaP. Our data showed that retinoic acid at 0.01 microM. stimulated the proliferation of LNCaP cells but inhibited their growth at 0.1 microM. under androgen-free conditions. In the presence of 0.1 nM. dihydrotestosterone (DHT), LNCaP cell proliferation was inhibited by 10 microM. retinoic acid but not by lower concentrations of retinoic acid. Retinoic acid reduced LNCaP cell growth at concentrations of 0.1 microM. in the presence of 10 nM. DHT. Retinoic acid (10 microM.) also reduced the growth response of LNCaP cells to epidermal growth factor and transforming growth factor alpha and potentiated the inhibitory effect of transforming growth factor beta. In additional studies, retinoic acid induced a dose-dependent increase in prostate specific antigen (PSA) secretion at concentrations of 0.1 to 1 microM. Dihydrotestosterone (10 nM.) also enhanced the secretion of PSA by LNCaP cells, and this effect was potentiated in a dose-dependent fashion by the addition of retinoic acid at 0.1-10 microM. Competitive binding studies showed that retinoic acid did not bind to androgen receptors. Overall, retinoic acid had a biphasic effect on LNCaP proliferation and promoted the secretion of PSA. The biphasic effect of retinoic acid on LNCaP growth should be considered in designing in vivo studies to determine the impact of retinoic acid on solid prostatic tumor growth. In addition, the ability of retinoic acid to increase PSA secretion may complicate the interpretation of serum PSA levels used for diagnostic and prognostic purposes.

Androgens

Regulation of prostatic carcinoma cell proliferation and secretory activity by extracellular matrix and stromal secretions.

Previous studies from our laboratory have shown that reconstituted basement membrane and stromal secretory products are important regulators of benign prostatic epithelial cell growth and differentiation. In the present study we evaluated the impact of extracellular matrix (ECM) and soluble stromal secretory products on the proliferation and secretory activity of the androgen-responsive prostatic carcinoma cell line LNCaP. In these studies, dihydrotestosterone (DHT) was a potent mitogen for LNCaP cells cultured on plastic or on type I collagen. The growth response to DHT was greatly attenuated when LNCaP cells were grown on prostatic stromal ECM. Cells grown on stromal ECM also exhibited clustered morphology compared to the monolayer growth observed on plastic and secreted elevated levels of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). These findings indicate that cultivation of LNCaP on stromal ECM will promote the expression of differentiated functions. In additional studies, stromal cell conditioned medium (SCM) significantly increased PSA/PAP secretion by LNCaP cells in the presence of 10 nM DHT. The enhancement of DHT-induced PSA/PAP secretion by SCM was most pronounced when LNCaP cells were grown on stromal ECM. SCM did not significantly alter LNCaP proliferation. These studies indicate that prostatic stromal ECM and soluble secretory products will promote differentiated function in cultured LNCaP cells. In addition, we show that DHT can act as either a growth or differentiation-promoting stimulus depending on the presence of stromal factors.

Acid Phosphatase

Injury of rat renal vessels following extracorporeal shock wave treatment.

The locations of extracorporeal shock wave treatment induced renal vascular injury and the sources of significant renal hemorrhage were determined in a rat model by means of two different vascular casting procedures. Silicone-rubber injected vascular preparations for light microscopy or corrosion casts for scanning electron microscopy were made following gross examination of the treated organs and their contralateral controls. After 1000 shock waves at 18 kV, five out of 20 treated kidneys appeared to be normal or minimally affected, while 15 showed gross evidence of marked vascular injury. Gross interstitial hemorrhage (15/20), subcapsular hematomas (7/20), and hemorrhages into the renal pelvis (5/20) were confirmed by extravasations of casting materials. These could be traced back to their vascular sources in several instances. Disruptions of interlobar and arcuate veins gave rise to most significant interstitial, subcapsular, and renal pelvic extravasations. On a microscopic scale cortical venules were among the most frequently injured vessels. The arterial vasculature was not spared. Arterial injury ranged from complete arcuate occlusion to small afferent arteriolar and glomerular capillary extravasations. The significance of shock wave induced vascular injury is discussed with respect to potential clinical side effects of ESWL.

Animals

Morphometry of the galliform cecum: a comparison between Gambel's quail and the domestic fowl.

Tissues from the proximal, middle, and distal regions of the ceca of Gambel's quail and domestic fowl were examined by scanning and transmission electron microscopy. Cellular and subcellular structures, including epithelial cell height, mitochondrial volume fraction, microvillous surface area, proportion of goblet cells, and junctional complex characteristics, were quantified by a variety of stereologic procedures and other measurement techniques. The mucosal surface of quail cecum shows a much more highly developed pattern of villous ridges and flat areas than that of fowl cecum. The fowl has significantly greater cell heights than the quail in all cecal regions. The mitochondrial volume fraction does not differ significantly with species or region, but mitochondria are concentrated on the apical side of the nucleus. In both species, the proximal cecal region has the greatest microvillous surface area. All 3 components of junctional complexes, including zonula occludens, zonula adhaerens, and macula adhaerens, are quantified. When all factors are considered, the quail cecum appears to have morphological characteristics consistent with a greater potential capacity for absorption than the fowl cecum.

Animals

Avian cecal microanatomy: a morphometric comparison of two species.

Tissues from the proximal, middle, and distal regions of the ceca of Gambel's quail and domestic fowl were examined by scanning and transmission electron microscopy for ultrastructural detail. Cellular aad subcellular structures, including epithelial cell height, mitochondrial volume fraction, microvillar surface area, and junctional complex characteristics, were quantified by stereologic procedures. The mucosal surface of the quail ceca shows a more highly developed pattern of ridges and flat areas than that of the fowl. The fowl has significantly greater cell heights than the quail in all cecal regions. The mitochondrial volume fraction does not differ significantly with species or region, but the mitochondria in all samples tend to be concentrated on the apical side of the nucleus. In both species, the proximal cecal region has the greatest microvillar surface area. In the fowl cecum, the zona occludens and macula adherans heights are significantly less in the proximal than in the middle or distal regions. In the quail cecum, the zona adherans height is least is the distal region. The zona occludens height in the fowl middle and distal regions is significantly greater than those for the quail. The middle region of the quail cecum has the lowest proportions of cell boundaries with zona adherans and macula adherans in the junctional complexes. When all factors are considered, the quail ceca appear to have morphological characteristics consistent with a greater potential capacity for absorption by passive diffusion than the fowl ceca.

Analysis of Variance

Uric acid decomposition in the lower gastrointestinal tract.

Uric acid is the end product of nitrogen metabolism in birds. Despite the very low aqueous solubility of this purine compound, few crystals of uric acid are found in the urine. Instead, uric acid is packaged into small spheres that can pass easily through the duct system of the kidney. After entering the cloaca, these spheres are moved with the urine by antiperistalsis into the rectum and digestive ceca. In the ceca, the uric acid is exposed to a large population of bacteria that can use the uric acid as a metabolic substrate. These bacteria degrade the uric acid to volatile fatty acids (VFA) and ammonia. The VFA are absorbed by the cecal tissue, and the ammonia is incorporated into the production of glutamine. The refluxing of uric acid into the ceca and its subsequent degradation by bacteria provides an effective mechanism for the reclamation of carbon and nitrogen from the urine.

Animals

Structure and concentrating ability in the avian kidney.

We quantified various aspects of the morphology of the kidney in seven bird species and related these measures to urinary concentrating ability (the concentration of ureteral urine in dehydrated animals) for six of the species. Kidney mass, number of glomeruli, and number of medullary cones all tended to increase with body mass. Smaller birds, with smaller kidneys, had smaller nephrons with smaller glomeruli. Lengths of medullary cones tended to increase with body mass and were exceptionally long in the macaroni penguin. The proportion of nephrons that were mammalian-type (MT, with loops of Henle) ranged from 7% (ring-necked pheasant) to 30% (zebra finch, glaucous-winged gull) and was unrelated to kidney mass. The percent of kidney mass comprised of medullary cones varied from 5 to 13%, unrelated to kidney mass. The number of reptilian-type (without loops of Henle) nephrons associated with each medullary cone tended to increase with kidney mass. Of the variables examined, length of the medullary cones, and hence of the longest loops of Henle, was most strongly correlated with urinary concentrating ability; however, this correlation was negative. Concentrating ability was also strongly negatively correlated with body mass (small birds concentrate better). No significant relation existed between concentrating ability and proportion of MT nephrons. Our data suggest that, in a broad interspecific comparison, the quantitative extent of the renal medulla is not the primary determinant of urinary concentrating ability in birds.

Animals

The occurrence of nephrogenic diabetes insipidus in domestic fowl.

Nephrogenic diabetes insipidus (NDI) results from an inability of the kidney to concentrate the urine. The underlying cause of NDI is the failure of the collecting ducts to respond to antidiuretic hormone, however, the specific tubular defect is not well understood. In the present investigation an apparent case of NDI was studied in a strain of White Leghorn domestic fowl. In this strain, water intake of the males equaled 24.0% (controls 5.4%) of their body mass (BM) per day while that of the females equaled 51.4% (controls 11.7%) of their BM per day. Plasma osmolality (mosmol/kgH2O) of the NDI birds was significantly higher than that of controls (males 319 +/- 1.7 vs. 311 +/- 1.2; females 323 +/- 1.5 vs. 310 +/- 2.2). Urine osmolality of NDI birds was substantially lower than that of controls (males 90 +/- 6.2 vs. 524 +/- 4.0; females 70 +/- 4.7 vs. no value). In response to water deprivation, plasma osmolality of the NDI birds increased more markedly than that of the control animals (males 357 +/- 2.5 vs. 331 +/- 1.2; females 375 +/- 6.0 vs. 348 +/- 1.4 at 48 h of water deprivation). Basal plasma antidiuretic hormone (plasma arginine vasotocin, PAVT) levels in male NDI birds (9.9 +/- 0.7 microU/ml) and in female NDI birds (7.0 +/- 0.5 microU/ml) were nearly sixfold or nearly threefold higher, respectively, than in control birds. In response to water deprivation, PAVT of both NDI and control birds increased to similar levels, although the absolute increases in PAVT levels were substantially less in NDI birds.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Sodium chloride and water transport in the thin descending limb of Henle of the quail.

Birds and mammals can produce hyperosmotic urine, but their renal morphology and urine-concentrating mechanisms differ. To elucidate the countercurrent urine concentration mechanism in birds, we examined the structure and transport properties of the descending limb (DL) of Henle of mammalian-type nephrons in Japanese quail, Coturnix coturnix. In the avian renal medulla, a prominent ring of collecting ducts and scattered thick limbs surrounds a core of capillaries and DLs. Epithelial cells in the upper DL (DLu) have abundant microvilli and shallow, tight junctions; cells in the lower DL are flat and have little interdigitation. Transepithelial voltage was zero when the DLu was perfused and bathed in isosmotic avian Ringer solution. The efflux coefficients (10(-7) cm2/s) for Na (31.7 +/- 2.3) and Cl (24.9 +/- 3.6) were not significantly different and were unaltered by ouabain (10(-4) M) (32.5 +/- 2.2). Diffusional water permeability measured by [3H]H2O was low (73.0 +/- 7.8, 10(-7) cm2/s). Volume flux was nearly zero and increased only slightly when an osmotic gradient was imposed. These results suggest the DLu is highly permeable to Na and Cl and virtually impermeable to water; thus NaCl extruded actively from the thick ascending limb may enter the DL unaccompanied by water. This countercurrent multiplication system by use of single-solute recycling and a transport cascade of graded hairpin turns may help establish an osmotic gradient along the medullary cone. Thus avian and mammalian renal countercurrent multiplication systems may differ.

Animals

Contributions of the kidneys and intestines to water conservation, and plasma levels of antidiuretic hormone, during dehydration in house sparrows (Passer domesticus).

The contributions of the kidneys, the small intestine and the lower intestine (rectum plus cloaca) to water conservation during dehydration in unanaesthetized, unrestrained house sparrows (Passer domesticus) were assessed. Thirty hours of acute dehydration resulted in a 12% loss in body mass and a significant increase in plasma osmolality. Glomerular filtration rate declined by 55%, from 7.7 to 3.5 ml/h, and urine flow rate delined by more than 80%, from 0.2 to 0.03 ml/h. These changes are likely attributable to a large increase in plasma levels of arginine vasotocin during dehydration, from less than 26 pg/ml in hydrated birds to greater than 200 pg/ml after 30 h dehydration. Flow of water from the ileum to the lower intestine was reduced during dehydration, primarily because of a reduced flow of dry matter (with no significant reduction in water content). The rate of water loss in the excreta declined from 0.2 ml/h in hydrated birds to 0.04 ml/h in dehydrated birds. The rate of water reabsorption in the lower intestine (equal to the rate of water loss in the excreta minus the combined rates of inflow into the lower intestine from the urine and the ileal contents) slightly exceeded the rate of water flow from the ileum in both hydrated and dehydrated birds. We suggest that much of the water reabsorbed in the lower intestine of hydrated birds derives from the urine, but that primarily water from ileal contents is reabsorbed in dehydrated birds. That is, urine undergoes significant post-renal modification in hydrated but not dehydrated house sparrows.

Animals

Regulation of plasma antidiuretic hormone in the dehydrated kangaroo rat (Dipodomys spectabilis M.).

A sensitive and specific radioimmunoassay was used to measure plasma antidiuretic hormone (plasma arginine vasopressin, PAVP) concentrations in a conscious desert-adapted mammal, the banner-tailed kangaroo rat (Dipodomys spectabilis; 131 +/- 2.3 g body mass), during normal hydration and in response to progressive dehydration. Simultaneous measurements of PAVP and plasma osmolality (POSM) in these experiments permitted determination of the hypothalamo-neurohypophyseal system-osmoreceptor set point and sensitivity to extracellular hyperosmolality during dehydration. In normally hydrated kangaroo rats, acclimated to room temperature (20-24 degrees) and fed a dry grain diet, POSM and PAVP averaged 308.6 +/- 0.7 mosmol/kg H2O and 6.0 +/- 0.7 pg/ml (2.2 +/- 0.2 microU/ml), respectively (means +/- SE). In separate groups of animals subjected to 48, 96, 144, or 192 hr of dehydration, POSM and PAVP increased in a parallel linear manner with time to maxima of 329.7 +/- 2.4 mosmol/kg H2O and 68.8 +/- 4.4 pg/ml (24.9 +/- 1.6 microU/ml), respectively, at 192 hr of dehydration. Thus, a highly correlated and significant relationship between POSM and PAVP (r2 = 0.941, P less than 0.001) exists in dehydrated kangaroo rats, quantitatively defined by the linear regression equation PAVP (pg/ml) = 2.99 (POSM - 306.4), with an apparent osmotic threshold for AVP release at a POSM of 306.4 mosmol/kg H2O.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Allometry of the kidney: implications for the ontogeny of osmoregulation.

In reptiles, there are two pairs of kidneys at birth: the mesonephros and the metanephros. The metanephric kidney in reptiles, as in all amniote vertebrates, is retained as the functional kidney in adults. However, the reptilian mesonephros does not degenerate until after birth, and its function during this time is unknown. In neonates of the iguanid lizard Sceloporus jarrovi, the metanephric kidney is only 63% as large as predicted from the allometric relationship between kidney mass and body mass in adults. However, the kidney mass of neonatal lizards conforms to this prediction if the mesonephric and metanephric masses are combined. Some other amniote vertebrates appear to follow this pattern as well: in marsupials, which retain the mesonephros for a short period after birth, the sum of mesonephric and metanephric mass in neonates conforms to the allometry of kidney mass on body mass for adults. In contrast, the mesonephros of eutherian mammals is degenerate at birth and the metanephric kidney alone is of the predicted size. That the scaling of kidney mass in neonatal lizards and marsupials is the same as that of adults only if the mass of both the mesonephros and metanephros are combined suggests that the mesonephric kidney in these vertebrates plays a significant role in the regulation of water and ion balance during development and for at least a short time after birth.

Animals

Structure of avian loop of Henle as related to countercurrent multiplier system.

The ultrastructural detail of the avian loop of Henle was examined, and comparisons were made to the loop of Henle of mammalian kidneys. Birds are the only group of vertebrates other than mammals that have the capability of elaborating a urine more concentrated than the plasma. Therefore, a comparison of the principal tubular element responsible for this phenomenon was made. Gambel's quail (Callipepla gambelii) were used as experimental animals. The animals were anesthetized with Inactin, and the kidneys were perfused-fixed in situ. The results show that the transition from the pars recta of the proximal tubule to the thin descending limb of Henle's loop (DLLH) is very abrupt. The upper part of the DLLH appears to be composed of type 2 and the lower part of type 3 epithelia, a condition somewhat similar to mammals. The junctions of the upper portion of DLLH are of the zonula adherens type and those of the lower portion of DLLH are of the macula adherens type. The epithelium of the loop always thickens before the formation of the hairpin turn with the thick descending limb being approximately 15% of the total DLLH. The structure of the avian renal medulla, in particular that of the loop of Henle, appears to parallel quite closely that postulated by the original formulation of the countercurrent multiplier system for the mammalian kidney.

Animals