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Biomedical subjects

J J Grantham

Publications and source records attributed to J J Grantham.

At least 145 records · Page 8Linked to original sources
PubMed1975

Secretory activity and aryl acid content of serum, urine, and cerebrospinal fluid in normal and uremic man.

Serum from uremic human subjects causes net fluid secretion in proximal straight tubules isolated from rabbit kidneys in a manner similar to paraaminohippuric acid. In the present study, we determined the relation between the concentration of aryl acids (hippuric acid, benzoic acid, etc.) In serum, urine, and cerebrospinal fluid (CSF) and the capacity of the biologic fluids to cause fluid secretion in renal tubules. The concentration of aryl acids in serum and urine as estimated by fluorometric assay (Fl-Hipp) was related to the secretory activity (SA) estimated by bioassay in a direct linear fashion over a 10,000-fold range of concentrations. Fl-Hipp and SA were strikingly elevated in the serum of uremic patients. Hippuric acid determined by gas-liquid chromatography accounted for approximately one-fourth of the secretory activity of serum and urine; benzoic acid was present only in trace amounts; the remainder of the secretory activity of uremic serum is probably due to derivatives of aryl acids which are detected as Fl-Hipp. The relation between creatinine clearance and the SA or Fl-Hipp concentration of serum was hyperbolic; both the SA and Fl-Hipp content of serum increased sharply when creatinine clearance fell below 10 ml. per minute. The SA and Fl-Hipp content of CSF was increased in uremic patients; however, the serum content exceeded that of the CSF by more than fourfold suggesting an exclusion mechanism for aryl acids in the central nervous system. We conclude that the secretory activity of uremic serum is due to the accumulation of aryl acids, probably of the hippurate class, and, further, that relatively high levels of these biologically active substances may contribute to general organ dysfunction in uremia owing to their potential to act as competitive inhibitors of organic anion transport.

Animals↗
PubMed1975

Hypothyroidism.

We found biochemical evidence of hypothyroidism (low T3 and T4 and elevated TSH) in azotemic patients. Hemodialysis did not correct the hypothyroidism but renal transplantation did. The hypothyroidism is probably a consequence of impaired thyroidal elaboration of thyroid hormone, as well as decreased peripheral conversion of T4 to T3. The impaired thyroidal gland function may be secondary to the increased concentration of aryl acids found in chronic renal disease.

Blood Urea Nitrogen↗
PubMed1973

Fluid secretion in isolated proximal straight renal tubules. Effect of human uremic serum.

We have examined the effect of normal and uremic human sera on the transtubular flow of fluid in isolated perfused segments of rabbit proximal convoluted and straight renal tubules. Proximal convoluted and straight tubules absorbed fluid from the lumen when the external bath was normal rabbit serum. Normal human sera in the bath depressed net fluid absorption in both tubular segments, but more importantly, uremic human serum caused proximal straight tubules to secrete fluid into the lumen. Fluid secretion was also demonstrated indirectly by observing in nonperfused proximal straight, but not proximal convoluted tubules, that the normally collapsed lumens opened widely in uremic serum. Nonperfused proximal straight tubules developed expanded lumens even after a 25-fold dilution of human uremic serum with normal rabbit serum, whereas lumen expansion occurred only in undiluted normal human serum, on the average. Serum from acutely uremic rabbits possessed secretory activity but normal rabbit serum did not. The secretory effect of uremic sera in proximal straight tubules was inhibited by cooling and ouabain and probenecid. The secretory activity of uremic sera was removed by dialysis, but not by freezing or boiling. Para-aminohippurate and benzoate caused fluid secretion in proximal straight tubules but urea, creatinine, guanidinosuccinate, and urate did not. On the basis of these results, we suggest that the secretory factor in serum may be a substance or group of substances possibly related to the hippurate class of organic molecules that are accumulated to relatively high concentrations in renal failure. The secretory material in the serum of uremic patients may significantly influence the transport of salt and water in relatively intact residual nephrons.

Acetates↗
PubMed1972

Physical properties of isolated perfused renal tubules and tubular basement membranes.

To study the physical properties of renal tubular basement membranes directly, the epithelial layer of single isolated perfused rabbit proximal convoluted, proximal straight, and cortical collecting tubules was removed with sodium desoxycholate. Tubular segments were perfused using micropipets. The distal end of each segment was occluded in order to simplify the measurement of transmembrane water flow. The relation between outer tubular diameter and applied transmural pressure was identical in intact tubules and their respective isolated tubular basement membranes indicating that the basement membrane determines tubular distensibility. Young's modulus for basement membranes from all tubular segments corresponded to that of tendon collagen. Membrane hydraulic conductivity was measured in two ways: (a) from the rate of transmural flow in response to an applied difference in hydrostatic pressure and, (b) from the rate of transmural flow in response to a difference in colloid osmotic pressure. The hydraulic conductivity of tubular basement membranes was 300-800 times greater than that of the intact epithelial layer. Basement membrane hydraulic conductance was similar to that of peritubular and glomerular capillaries in vivo. The hydrostatic conductance of tubular basement membranes exceeded the osmotic conductance by 3-10-fold owing largely to the fact that the membranes were moderately permeable to the osmotic solute (albumin). In view of these findings we suggest that oncotic and hydrostatic pressure may play an important role in the movement of tubular absorbate from the epithelial compartment into the renal interstitium.

Albumins↗
PubMed1970

Vasopressin: effect on deformability of urinary surface of collecting duct cells.

In isolated renal collecting ducts vasopressin decreased the negative pressure required to suck a hemispherical bulge of the epitheliat cells' urinary surface into the tip of a micropipette. Increased surface deformability may be related to the increased permeability to water which also occurs in the apex of the cells in response to the hormone.

Animals↗
PubMed1970

The nature of transtubular Na and K transport in isolated rabbit renal collecting tubules.

In order to investigate the mechanism of Na and K transport, rabbit cortical collecting tubules were perfused in vitro and the concentrations of Na and K in lumen and bathing fluid and the transtubular electrical potential difference (PD) were measured. When the perfusate and external bath contained 150 Na-5 K (mEq liter(-1)), the sodium concentration decreased and the potassium concentration increased by an approximately equal amount in collected tubular fluid. The transtubular electrical potential was equal at both ends of the tubule in the steady state and ranged between 21 and 67 mv, lumen negative. In all tubules perfused at rates less than 0.5 nl min(-1), the K concentration of the collected fluid was higher and the Na concentration lower than that predicted for electrochemical equilibrium between lumen fluid and external bath, evidence for active transtubular transport of both cations. These results differ from those observed in rat distal tubule in which potassium secretion is passive. Active Na and K transport and the transtubular PD were decreased by (a) ouabain, (b) removal of sodium from the perfusate, or (c) removal of potassium from the external bath, evidence of interdependence of Na and K transport. The dependence of active K secretion on intraluminal Na concentration accounts for the phenomenon of "distal" Na-K exchange noted previously in clearance and stop-flow studies. The mechanism of Na transport may in part be electrogenic since the rate of decline of the transtubular PD in low K media was faster than could be accounted for on the basis of a reduction in cell potassium concentration.

Animals↗
PubMed1969

Paths of transtubular water flow in isolated renal collecting tubules.

The cells of perfused rabbit collecting tubules swell and the intercellular spaces widen during osmotic flow of water from lumen to bath induced by antidiuretic hormone (ADH). Ouabain had no influence on these changes. In the absence of net water flow intercellular width was unaffected when tubules were swollen in hypotonic external media. Therefore, during ADH-induced flow widening of intercellular spaces is not a consequence of osmotic swelling of a closed intercellular compartment containing trapped solutes, but rather is due to flow of solution through the channel. Direct evidence of intercellular flow was obtained. Nonperfused tubules swollen in hypotonic media were reimmersed in isotonic solution with resultant entry of water into intercellular spaces. The widened spaces gradually collapsed completely. Spaces enlarged in this manner could be emptied more rapidly by increasing the transtubular hydrostatic pressure difference. In electron micrographs a path of exit of sufficient width to accommodate the observed rate of fluid flow was seen at the base of the intercellular channel. It is concluded that the intercellular spaces communicate with the external extracellular fluid and that water, having entered the cells across the luminal plasma membrane in response in ADH, leaves the cells by osmosis across both the lateral and basilar surface membranes.

Animals↗
PubMed1968

Ultrastructural studies of vasopressin effect on isolated perfused renal collecting tubules of the rabbit.

Isolated cortical collecting tubules from rabbit kidney were studied during perfusion with solutions made either isotonic or hypotonic to the external bathing medium. Examination of living tubules revealed a reversible increase in thickness of the cellular layer, prominence of lateral cell membranes, and formation of intracellular vacuoles during periods of vasopressin-induced osmotic water transport. Examination in the electron microscope revealed that vasopressin induced no changes in cell structure in collecting tubules in the absence of an osmotic difference and significant bulk water flow across the tubule wall. In contrast, tubules fixed during vasopressin-induced periods of high osmotic water transport showed prominent dilatation of lateral intercellular spaces, bulging of apical cell membranes into the tubular lumen, and formation of intracellular vacuoles. It is concluded that the ultrastructural changes are secondary to transepithelial bulk water flow and not to a direct effect of vasopressin on the cells, and that vasopressin induces osmotic flow by increasing water permeability of the luminal cell membrane. The lateral intercellular spaces may be part of the pathway for osmotically induced transepithelial bulk water flow.

Animals↗