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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

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

Lower intestinal modification of ureteral urine in hydrated house sparrows.

The ureters of birds empty into the posterior portion of the lower intestine, thereby providing the possibility for modification of ureteral urine by this latter organ. We have used in vivo perfusion to measure the transport of Na+, K+, and water across the lower intestine (colon and coprodaeum) of anesthetized house sparrows (Passer domesticus). Na+ was reabsorbed from (Vmax = approximately 22 mu eq . cm-2 . h-1, Km = approximately 69 meq/l) and K+ was secreted (at variable rates) into all saline perfusion fluids. The osmotic permeability of the intestinal epithelium was 0.39 microliter . cm-2 . h-1 . mosM-1 in the mucosal-to-serosal direction and 0.43 microliter . cm-2 . h-1 . mosM-1 in the serosal-to-mucosal direction. At isosmotic perfusion, Na+-linked water transport occurred at a rate of 1.7 microliter/mu eq Na+. In hydrated house sparrows the composition of ureteral urine (osmolarity = 351 mosM, Na+ = 86.5 meq/l, K+ = 60.5 meq/l) was significantly modified by transport in the lower intestine (voided fluid osmolarity = 344 mosM, Na+ = 60 meq/l, K+ = 90 meq/l). Interspecific comparisons of lower intestinal resorptive surface area and transport parameters at the level of the tissue, organ, and whole animal reveal no consistent pattern of adaptation related to habitat.

Animals

Osmotic and volemic regulation of plasma arginine vasotocin in conscious domestic fowl.

Recently developed radioimmunoassay methods were utilized to quantitatively characterize secretion of the avian antidiuretic hormone [arginine vasotocin (AVT)] by the hypothalamo-neurohypophyseal system (HNS) of the conscious domestic fowl. The functional characteristics of the osmoreceptor-HNS were evaluated during independent experimental manipulations of extracellular osmolality or volume. Simultaneous measurements of plasma AVT (PAVT) and either plasma osmolality (Posm) or blood volume (BV) in these experiments permitted determination of osmoreceptor sensitivity to independent osmotic or volemic stimuli and set point of the AVT secretory system under conditions of normal hydration. In normally hydrated birds, PAVT and Posm averaged 2.7 +/- 0.2 microU/ml (12.9 +/- 1.0 pg/ml) and 308.1 +/- 0.6 mosmol/kg H2O, respectively (means +/- SE). Characterization of AVT secretion revealed that Posm is a primary determinant of AVT secretion by the HNS of the domestic fowl. Highly correlated and significant relationships between Posm and PAVT exist both above and below the observed basal Posm of normally hydrated birds, with an apparent osmotic threshold for AVT secretion at a Posm of 288.8 mosmol/kg H2O. Analysis of the data also suggested that the HNS is insensitive to changes in BV less than or equal to 10%, because neither isotonic expansion nor reduction of BV altered PAVT. Comparison of past and present avian data with that of the mammalian HNS indicates that 1) the osmotic regulation of antidiuretic hormone secretion is qualitatively and quantitatively similar in birds and mammals, and 2) the volemic regulation of antidiuretic hormone secretion is substantially more important in mammals than in birds.

Animals

Regulation of plasma arginine vasotocin in conscious water-deprived domestic fowl.

Radioimmunoassay methods were employed to quantitatively characterize secretion of the avian antidiuretic hormone [arginine vasotocin (AVT)] by the hypothalamo-neurohypophyseal system (HNS) of the conscious domestic fowl in response to chronic dehydration. Water deprivation permitted characterization of AVT secretion in response to the combined stimuli of extracellular hyperosmolality and hypovolemia; the subsequent repletion of extracellular volume permitted separation of potential osmotic and volemic factors involved in the regulation of AVT secretion. In normally hydrated birds, plasma AVT (PAVT) and plasma osmolality (Posm) averaged 2.2 +/- 0.3 microU/ml (10.5 +/- 1.4 pg/ml) and 309.3 +/- 0.7 mosmol/kg H2O, respectively (means +/- SE). With water deprivation, PAVT and Posm of the birds increased in parallel in a curvilinear manner to maxima of 13.1 +/- 0.6 microU/ml (62.4 +/- 2.9 pg/ml) and 346.6 +/- 2.0 mosmol/kg H2O, respectively, at 96 h of dehydration. The isosmotic repletion of extracellular volume at 96 h by acute intravenous infusion failed to alter 96-h PAVT values. The results indicate that AVT secretion is closely linked to the state of hydration during negative fluid balance in the domestic fowl. Analysis of the data indicated that increases in PAVT that occur with dehydration are mediated primarily by extracellular hyperosmolality and that the HNS of the domestic fowl is relatively insensitive to the simultaneous hypovolemia incurred with fluid deprivation.

Animals

Cecal degradation of uric acid in Gambel quail.

In birds, urine enters the lower gastrointestinal tract from paired ureters and can be moved in a retrograde fashion into the colon and digestive ceca. As a major constituent of urine, uric acid is carried into these regions of the gastrointestinal tract. In these locations the chemical composition of the urine, including uric acid, could be altered. To examine this possibility the postrenal degradation of uric acid in the hindgut (ceca, colon, and ileum) of the Gambel quail (Callipepla gambelii) was investigated in vitro to determine the location of activity and the possible source of uricolytic enzymes. Significant breakdown of uric acid was observed in all cecal preparations; only minor amounts were degraded in the ileum and colon. The cecal degradation amounted to 15-49% of the uric acid estimated to be produced by the quail. Attempts to demonstrate uric acid decomposition by bacteria cultured from ceca gave inconclusive results.

Animals

Contributions of glomerular and tubular mechanisms to antidiuresis in conscious domestic fowl.

Recently developed radioimmunoassay (RIA techniques were employed in a quantitative investigation of the renal actions of the avian antidiuretic hormone arginine vasotocin (AVT) in the conscious domestic fowl. Constant intravenous infusion of AVT at doses of 0.125-1.00 ng . kg-1 . min-1 was used to produce plasma AVT (PAVT) concentrations (verified by RIA) over the entire range of physiological PAVT levels in the domestic fowl. Comparison of the dose-response relationships between PAVT and glomerular and tubular mechanisms of antidiuresis revealed that tubular mechanisms are of primary importance and glomerular mechanisms of secondary importance in the conservation of water by the avian kidney. The greatest proportion of the total AVT-induced reduction in renal water excretion occurred at low physiological PAVT levels (less than 5 microU/ml), prior to any significant reduction in glomerular filtration rate (GFR), and appeared to be the exclusive result of tubular mechanisms of antidiuresis. At high PAVT levels (5-16 microU/ml), glomerular and tubular mechanisms overlapped, and their effects on water conservation could not be separated. Although GFR was reduced by nearly 30% at the highest dose of AVT, only minor additional amounts of water were conserved by the combined actions of glomerular and tubular mechanisms. The glomerular mechanisms appear to have only a minor secondary effect on water-conserving ability of the avian kidney.

Animals