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Biomedical subjects

J J Grantham

Publications and source records attributed to J J Grantham.

At least 127 records · Page 7Linked to original sources
PubMed1981

Transmembrane electrical potential differences in cells of isolated renal tubules.

Isolated fragments of renal tubules were prepared by treating rabbit kidneys removed from animals on a normal diet with proteolytic enzymes. The intracellular potential of tubule cells was measured either by impaling cells across the luminal membrane at the everted end of the tubule or by impaling cells across the basolateral membrane along the shaft of the tubule. The mean intracellular potential recorded from 163 cells at the everted ends of proximal tubules was -49 +/- 12 mV (SD) compared with a mean value of -29 +/- 9 mV (SD) recorded from 199 cells along the shaft of the tubules. In papillary collecting ducts there was no significant difference between the intracellular potential of cells at the everted end of the tubules compared with those of cells along the shaft of the tubule. However, two distinctly different types of intracellular potentials were recorded from collecting duct cells regardless of the location of the cells: 93 cell impalements gave a mean intracellular potential of -15 +/- 8 mV (SD), whereas 135 cell impalements gave a mean potential of +24 +/- 12 mV (SD). The data presented in this paper demonstrate that intracellular potentials can be recorded from isolated renal tubule fragments of papillary collecting ducts and proximal convoluted tubules.

Animals↗
PubMed1980

Ultrastructure and function of cysts from human adult polycystic kidneys.

Twenty cysts from five patients with adult polycystic kidney disease were evaluated morphologically by electron microscopy and functionally by cyst fluid chemical analysis in order to correlate the structure with the function of the cyst wall. Thirteen proximal cysts, as defined by cyst fluid/serum sodium ratios of 0.8 to 1.2, were lined by epithelial cells with open or short closed apical junctions that appeared permeable to lanthanum. In contrast, seven distal cysts, as defined by cyst fluid/serum sodium ratios of less than 0.4, were lined by epithelial cells with long closed apical junctions that appeared impermeable to lanthanum. Cell organelles showed no distinction between proximal and distal cysts. Cyst basement membranes appeared abnormal, but there was no consistent pattern. The fluid of proximal cysts contained lower creatinine, potassium, and hydrogen ion, and higher chloride concentrations than did the distal cysts. These studies provide morphologic and chemical evidence consistent with te view that cysts originate from nephrons. Moreover, the maintenance of the epithelial lining and transmembrane solute gradients over many years extending up to and beyond the development of renal insufficiency suggests that the cysts function as nephronsthrughout the life of the patient.

Adult↗
PubMed1980

The effects of vanadate on the fluxes of sodium and potassium ions through the sodium pump.

1. The effects of sodium orthovanadate on the fluxes of sodium and potassium (or rubidium) ions through the sodium pump have been investigated in intact human red cells and in resealed ghosts prepared from them. Sodium-potassium exchange, potassium-potassium exchange, pump reversal, sodium-sodium exchange and uncoupled sodium efflux have each been studied.2. When intact human red cells were incubated in high-sodium media containing vanadate in low concentrations, inhibition of potassium or rubidium influx was marked only if the potassium or rubidium concentration in the medium was sufficiently high to cause nearly maximal influx in the absence of vanadate. The absence of inhibition at lower potassium or rubidium concentrations cannot be explained by supposing that the onset of inhibition by vanadate is slower in these conditions.3. Lowering the extracellular sodium concentration, or raising the vanadate concentration, decreased the minimum concentration of extracellular potassium or rubidium at which inhibition by vanadate was detected.4. Experiments on potassium influx into intact red cells treated with the ionophore A23187 showed that magnesium ions act at intracellular sites to promote inhibition by vanadate.5. Measurements of potassium efflux from intact red cells incubated in high-sodium media, with or without potassium, showed that potassium-potassium exchange was inhibited by vanadate at low concentrations whereas reversal of the pump was not.6. Measurements of sodium efflux from intact red cells or resealed ghosts incubated in high-sodium media, with or without potassium, showed that vanadate had little or no effect on sodium-sodium exchange at concentrations at which sodium-potassium exchange was markedly reduced. Much higher concentrations of vanadate did cause partial inhibition of sodium-sodium exchange.7. Experiments to determine whether vanadate in low concentrations inhibited uncoupled sodium efflux were inconclusive, but suggested that the flux was inhibited. Measurements of the ATP hydrolysis that is thought to be associated with the uncoupled sodium efflux showed that this hydrolysis was strongly inhibited.8. The different effects of vanadate on the different fluxes are discussed, and related to the way in which vanadate is thought to act on the sodium pump.

Biological Transport, Active↗
PubMed1980

Effect of collagenase and ouabain on renal cell volume in hypotonic media.

Proximal straight tubules (S2 segments) swell rapidly in hypotonic media, but within a few minutes their volume returns toward control levels due to extrusion of K, Na, Cl, and water from the cytoplasm. In the present studies we determined the extent to which hydrostatic pressure (derived from the elastic tubule basement membrane (TBM) as the tubule enlarged in hypotonic medium) contributed to the regulation of cell volume. Removal of the TBM by collagenase had no effect on cell volume regulation in otherwise normal tubules. By contrast, tubules treated with ouabain, though they appeared to regulate their volumes in hypotonic media, were unable to do so in the presence of glycoside if the TBM had been removed with collagenase. This latter result is interpreted to show that hydrostatic pressure generated by extension of the TBM can cause "apparent" volume regulation when the sodium pump is blocked by ouabain. We conclude that normal proximal renal tubules regulate cell volume in hypotonic solutions by mechanisms that are dependent on the normal operation of the classical sodium pump.

Animals↗
PubMed1980

Temperature effect on ADH response of isolated perfused rabbit collecting tubules.

The time course of the water permeability response to synthetic arginine vasopressin (AVP) was examined in isolated perfused rabbit collecting tubules. When experiments were conducted at 37 degrees C, addition of AVP in a concentration of 100 microU/ml increased hydraulic water permeability (Lp) from 18 +/- 4 X 10(-7) to 153 +/- 15 X 10(-7) cm x s-1 x atm-1. However, in contrast to results obtained at 25 degrees C, the Lp immediately decreased in spite of the continued presence of AVP, reaching half the peak value in 67 +/- 6 (SE) min. A similar decline was observed at 37 degrees C when a cyclic 3',5'-adenosine monophosphate analogue was added to the bathing medium. Corticosteroids greatly enhanced the peak water absorption but did not stabilize the subsequent response to AVP at 37 degrees C. A decline in diffusional water permeability measured in the absence of a transtubule osmotic gradient excluded the possible roles of cellular hypotonicity, increased cell volume, or osmotic water absorption in the unstable response to hormone. The peritubular membrane remained highly permeable to water, independent of AVP and temperature. Duration of exposure to 37 degrees C was more important than AVP in determining the unstable response. On the basis of these studies we conclude that isolated rabbit cortical collecting tubules progressively become insensitive to AVP at 37 degrees C, possibly due to alterations in the responsiveness of the urinary plasma membrane to cAMP.

Aldosterone↗
PubMed1980

Comparison of the chemical and polypeptide composition of tubular and glomerular basement membranes.

Renal tubular and glomerular basement membranes were isolated from rabbit, rat and mouse kidneys. Methods were developed to obtain the basement membrane from limited numbers of animals. Rabbit and mouse tubular basement membrane as well as rabbit and rat glomerular basement membrane were obtained from single animals in quantities sufficient for electrophoresis and chemical analysis. The chemical composition of all the basement membranes were compared and sodium dodecylsulfate-polyacrylamide gel electrophoresis was performed on rabbit tubular and glomerular basement membranes in order to compare their polypeptide composition. The chemical composition of the tubular basement membranes were similar, each species having nearly equal concentrations of glycine, hydroxyproline and hydroxylysine, respectively. Glomerular basement membranes were also similar to each other and close to tubular basement membranes in chemical composition. Within each species, the glycine, hydroxyproline and hydroxylysine values for tubular basement membrane were about 10% higher than for glomerular basement membrane. The polypeptide composition of a reduced, sodium dodecylsulfate-soluble fraction of the rabbit basement membranes appeared to be alike with two exceptions. A prominent band of Mr = 160,000 seen in gels of tubular basement membrane was present as a lightly staining band in glomerular basement membrane samples and a prominent band of Mr = 140,000 in gels of glomerular basement membrane was seen as a light band in samples of tubular basement membrane.

Animals↗
PubMed1979

Rabbit tubular basement membrane. Isolation and analysis of polypeptides.

Renal tubules from rabbit kidneys were isolated from thin shavings of the kidney surface. Basement membrane was then prepared following sonication of the isolated tubules. To insure preservation of the integrity of the basement membrane polypeptides, the protease inhibitors, diisopropyl fluorophosphate, ethylenediaminetetraacetic acid, N-ethylmaleimide, and epsilon-amino-caproic acid were used at all stages of the preparations. The optimal conditions of sonication and centrifugation were established and the chemical composition of basement membrane prepared under these conditions was examined in detail. Glycine, hydroxyproline, and hydroxylysine were found in concentrations of 206, 65, and 18 residues per thousand, respectively, in basement membrane from young kidneys. About 38% of the basement membrane was found to be soluble in sodium dodecyl sulfate upon incubation at 90 degrees C, and to possess relatively low amounts of the amino acids characteristic of collagen. Electrophoretic analysis of this fraction revealed that the major subunits ranged in approximate molecular weight from 18,500 to greater than 10(6). When analyzed with disulfide bonds reduced, a molecular weight range from 31,000 to 275,000 was observed for this fraction. The sodium dodecyl sulfate-insoluble fraction could be dissolved upon reduction and alkylation and its composition was enriched in the amino acids characteristic of collagen. Polypeptides from this fraction were analyzed by electrophoresis in agarose and in agarose-acrylamide gels. The approximate molecular weight of the smallest component was 164,000. Additional polypeptides were observed whose molecular weights occurred in multimers of this component, up to 1.1 x 10(6), possibly indicating covalent cross-linked multimers of a basic collagen-like polypeptide(s).

Amino Acids↗
PubMed1977

Effect of hypotonic medium on K and Na content of proximal renal tubules.

The intracellular content of K and Na was measured in isolated nonperfused proximal straight renal tubules (PST) in order to determine the mode of cell volume regulation in hypotonic bathing media. Immersion in hypotonic medium caused PST to lose K and Na (with anions) in a magnitude sufficient to account for the regulation of cell volume. Hypothermia (10 degrees C) blocked cell volume regulation in hypotonic medium by promoting net accumulation of Na, although K loss was equivalent to that observed at 37 degrees C. Ouabain (10(-5) M) caused rapid loss of cell K and gain of Na in an isotonic bath, but the glycoside did not inhibit the subsequent adjustment of cell volume in hypotonic medium. In hypotonic medium ouabain-treated tubules lost Na, but not K, to account for hypotonic volume adjustment of PST in ouabain. We conclude that proximal straight tubules extrude electrolytes (K, Na, and anions) in the adjustment of cell volume in hypotonic media; in normal tubules K and Na are lost whereas Na moves primarily in ouabain-treated tubules. The adjustment of size through the extrusion of intracellular solutes in dilutional states appears to be a general property of mammalian cells.

Animals↗
PubMed1977

Effect of basement membrane and colloid osmotic pressure on renal tubule cell volume.

Renal tubule cell volume is thought to be kept constant by a cation pump. When active transport is blocked, intracellular impermeant solutes cause cells to swell. Cell size is then determined by transmembrane hydrostatic and colloid osmotic forces. We studied the importance of passive transmembrane forces in determining cell size in isolated rabbit proximal straight tubules (PST). We blocked active solute transport with ouabain and evaluated subsequent changes in cell size by measuring outer diameter of nonperfused tubules. Tubules in a ouabain and 6 g/100 ml protein bath swelled only 40% above control. However, removal of the tubule basement membrane with collagenase dissipated a transmembrane hydrostatic pressure and caused more swelling. Final cell volume was determined largely by bath protein concentration. Tubules in ouabain and collagenase swelled enormously in hyponcotic protein, moderately in isoncotic protein, and could be shrunk below control in hyperoncotic protein. Intracellular colloid osmotic pressure was estimated to exceed 38 cmH20. We conclude that hydrostatic and colloid osmotic forces are major determinants of cell size in isolated PST treated with ouabain.

Animals↗
PubMed1976

Fluid secretion in the nephron: Relation to renal failure.

It had been generally accepted that glomerular filtration and tubular reabsorption were the basic modes of fluid transport in mammalian nephrons. Recently, evidence was obtained to indicate that net fluid secretion may occur in mammalian nephrons as well. In the pars recta portion of proximal tubules of rabbit kidney net fluid secretion was observed in vitro in response to PAH and other aryl acids in the peritubular bathing medium. Net fluid secretion appeared to be coupled to the transcellular transport of aryl acid from bath to lumen. Serum from uremic subjects stimulated net fluid secretion in the pars recta in a manner similar to PAH. The accumulation of high levels of endogenous aryl acids may contribute to the general organ dysfunction that is a part of the uremic syndrome of advanced renal insufficiency. Futhermore, there is evidence to suggest that the fluid-secretion phenomenon in association with aryl acids may significantly affect renal excretion and morphology in slow-flow states, in patients with cystic kidney disease, and in obstructive nephropathy.

Aminohippuric Acids↗
PubMed1976

Prognosis for recovery of function in acute renal failure. Value of the renal image obtained using iodohippurate sodium I 131.

Twenty-four survivors of acute, nonobstructive, nonnephritic renal failure had a renal scan using iodohippurate sodium I 131 performed early in the acute illness. Scans were judged according to whether the renal images were prominent, faint, or absent during the first 30 minutes after intravenous injection of 100 to 250 microcuries of iodohippurate sodium I 131. All ten patients with prominent renal images attained life-sustaining renal function with an average postrecovery creatinine clearance of 80 ml/min. Of the seven patients with faint renal images, six recovered life-sustaining renal function (average creatinine clearance of 39 ml/min), and one required chronic hemodialysis. Seven patients had no renal image initially; four recovered life-sustaining renal function with an average creatinine clearance of 25 ml/min; three required chronic hemodialysis. We conclude that, for patients with acute renal failure, the appearance of the renal image obtained using this substance is an important indicator of renal viability and of the likelihood for functional recovery.

Acute Kidney Injury↗