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Biomedical subjects

J J Grantham

Publications and source records attributed to J J Grantham.

At least 109 records · Page 6Linked to original sources
PubMed1985

Tubular basement membrane changes in 2-amino-4,5-diphenylthiazole-induced polycystic disease.

Polycystic renal disease was induced in rats by feeding 2-amino-4,5-diphenylthiazole. Tubular (TBM) and glomerular basement membranes (GBM) were purified and analyzed for possible structural changes that may be a factor in the development of the tubular dilations and cysts. Changes in the relative quantities of TBM polypeptides were detected by sodium dodecylsulfate polyacrylamide gel electrophoresis. An overall increase in the concentration of high molecular weight components and a decrease in concentration of those of low molecular weight components were observed. Changes which were particularly notable included a twofold increase in a component of Mr = 380,000 and a decrease in one of Mr = 55,000 as analyzed without reduction of disulfide bonds. With reduction of disulfide bonds, the Mr = 380,000 component dissociates, whereas the Mr = 55,000 polypeptide does not, and polypeptides of Mr = 245,000 and 145,000 are observed to does not, and polypeptides of Mr = 245,000 and 145,000 are observed to increase about twofold in concentration (approximate molecular weights were determined using globular protein standards). These changes take place most rapidly from 4 to 8 weeks of drug administration and remain relatively constant between 8 and 16 weeks. If feeding of the drug is discontinued, the distribution of TBM polypeptides returns to normal. These results indicate that tubular basement membrane from animals with 2-amino-4,5-diphenylthiazole-induced polycystic renal disease is abnormal, and this should be considered as a possible contributing factor in the formation of cysts.

Amino Acids↗
PubMed1985

High-density renal cysts in autosomal dominant polycystic kidney disease demonstrated by CT.

Unenhanced abdominal CT scans of 35 patients with autosomal dominant polycystic kidney disease (ADPKD) showed multiple high-density (58-84 HU) renal cysts in 42.9% of patients, occasional high-density cysts in 25.7%, and no high-density cysts in 31.4%. These high-density cysts were usually subcapsular and were more frequent in patients with markedly enlarged kidneys and flank pain at the time of CT. Several were found to contain altered blood on pathological analysis. Follow-up CT often showed a reduction in cyst densities, although some cysts developed mural calcification and calcification of their contents. High-density cysts are probably produced by cyst hemorrhage. This may occur randomly as part of the natural history of the disease or may result from minor trauma to the enlarged kidneys. Renal carcinomas occur rarely in ADPKD and may occasionally be hyperdense. However, high-density cysts may usually be distinguished from carcinomas on CT by their smooth contours, sharp interfaces with renal parenchyma, homogeneity, and lack of contrast enhancement.

Adult↗
PubMed1985

Liver cysts in autosomal-dominant polycystic kidney disease: clinical and computed tomographic study.

Hepatic CT findings were analyzed in 44 patients with autosomal-dominant polycystic kidney disease and were correlated with liver and renal function tests and liver, splenic, and renal CT volume measurements. CT showed many large liver cysts in 31.8% of patients, small liver cysts in 25%, and no liver cysts in 43.2%. Patients with many large cysts often showed increased liver volumes. Splenic volumes did not differ significantly in patients with and without liver cysts, suggesting that portal hypertension is rarely associated with cystic liver disease. There was no correlation between severity of liver involvement and extent of renal cystic disease as determined from urea nitrogen and creatinine levels and renal volumes. Liver function tests were normal except in two patients, one with a cholangiocarcinoma, which may have arisen from a cyst, and the other with an infected liver cyst and chronic active hepatitis. Accordingly, if liver function tests are abnormal, an attempt should be made to identify complications of polycystic liver disease such as tumor, cyst infection, and biliary obstruction. Such complications are rare but may be seen in patients whose lives are prolonged by dialysis and renal transplantation. CT is a useful method for detecting liver cysts and identifying patients at risk for these complications.

Adult↗
PubMed1984

CT of acquired cystic kidney disease and renal tumors in long-term dialysis patients.

The kidneys of long-term dialysis patients frequently demonstrate multiple small acquired cysts and renal cell tumors on pathologic examination. The original kidneys of 30 long-term dialysis patients and six renal transplant patients were evaluated by computed tomography to determine the incidence of these abnormalities. Among dialysis patients, 43.3% had diffuse bilateral cysts, while 16.7% had occasional cysts (fewer than five per kidney), and 40% showed no renal cysts. Seven solid renal tumors were detected in four dialysis patients with renal cysts. Acquired cystic kidney disease tends to result in renal enlargement, is more common in patients who have been maintained on dialysis for prolonged periods, and may lead to spontaneous renal hemorrhage. The six transplant patients showed no evidence of renal cysts, and all had markedly shrunken kidneys. Acquired cystic disease and renal cell tumors in the original kidneys of dialysis patients may be due to biologically active substances that are not cleared effectively by dialysis but that are removed by normally functioning transplant kidneys.

Adult↗
PubMed1983

Polycystic kidney disease: a predominance of giant nephrons.

Polycystic kidney disease is a bilateral disorder that affects approximately 200,000-400,000 persons in the United States. The most common form of the disease is inherited as an autosomal dominant trait (ADPKD). It typically causes renal insufficiency by the fifth or sixth decade of life. The disease is characterized by the progressive enlargement of a portion of renal tubule segments (proximal, distal, loop of Henle, collecting duct). The tubules enlarge from a normal diameter of 40 microns to several centimeters in diameter, causing marked gross and microscopic anatomic distortion. The cause of the cystic change in the tubules is unknown, but current possibilities include obstruction of tubule fluid flow by hyperplastic tubule cells, increased compliance of the tubule basement membranes, and/or increased radial growth of cells in specific portions of the renal tubule. Several studies show that the epithelia of the cysts continue to transport Na+, K+, Cl-, H+, and organic cations and anions in a qualitative fashion similar to that of the tubule segment from which they were derived. ADPKD, then, is a disease in which some gigantic renal tubules, over a period of several decades, impair the function of nonaffected nephrons and thereby lead to renal failure.

Aging↗
PubMed1983

Evidence for an inhibitor of renal urate and PAH secretion in rabbit blood.

Results of previous studies of urate secretion in isolated perfused S2 segments of the rabbit proximal tubule suggested that a bath of rabbit serum may inhibit urate transport in comparison to a synthetic medium. In the current study we tested for a urate transport inhibitor by determining the steady-state tissue-to-medium ratio (T/M) of [14C]urate in nonperfused S2 segments during incubation in synthetic medium (BSA-Burg) and commercial rabbit serum (RS-PF). With 80-120 microM urate in the bath the T/M ratio was 7.66 +/- 0.53 (n = 29) in BSA-Burg and 5.29 +/- 0.40 (n = 29) in RS-PF. RS-PF decreased the influx of urate into the cells but had no effect on urate efflux. Freshly drawn rabbit serum and plasma also inhibited urate accumulation, and the inhibition was reversible. p-Aminohippurate accumulation was inhibited by RS-PF, but tetraethylammonium bromide uptake was not. RS-PF inhibited transepithelial secretion of urate and PAH, but net fluid absorption was not decreased. The inhibitory material in rabbit serum could not be removed by extensive dialysis (14,000-dalton exclusion), by ultrafiltration (50,000-dalton exclusion), or by charcoal or ethanol extraction. Inhibitory activity was detected in both albumin and globulin fractions of rabbit serum. The relation between bath and intracellular urate concentrations of nonperfused tubules in rabbit serum was sigmoidal, whereas the relation in the BSA-Burg medium was more nearly hyperbolic. We conclude that organic anion transport in rabbit S2 segments is inhibited or suppressed by normal serum and suggest that urate secretion and excretion may be subject to allosteric modification by serum proteins.

Aminohippuric Acids↗
PubMed1983

Inhibition of vasopressin action by vanadate in the cortical collecting tubule.

The effect of vanadate, a potent inhibitor of Na-K-ATPase, on the hydroosmotic response to vasopressin (AVP) and transepithelial voltage (Vt) in cortical collecting tubules was examined. At 37 degrees C, exposure of collecting tubules to bath vanadate (10(-4) M) for 30 min inhibited the increase in hydraulic water permeability (Lp) in response to AVP or 8-bromo-cyclic adenosine monophosphate by 68 and 76%, respectively. When vanadate was present only in the lumen no inhibition of the AVP response was observed. Incubation of tubules with ouabain (10(-5) M) for 30 min inhibited the AVP-induced increase in Lp to the same extent as vanadate. At 25 degrees C, vanadate inhibited the increase in Lp by AVP if added before but not after the hormone. Addition of vanadate to the bath caused a rapid decrease in the lumen-negative Vt that is consistent with Na-K-ATPase inhibition. Luminal vanadate also inhibited Vt but the rate of decrease of Vt was much slower than in the presence of bath vanadate. We conclude that vanadate inhibits the development but not the maintenance of the AVP-induced increase in water permeability in the collecting tubule. Since the effect of ouabain was similar to that of vanadate, the results suggest that inhibition of Na-K-ATPase directly or indirectly interferes with the initiation of the AVP-induced increase in luminal membrane water permeability at a site distal to cAMP formation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1982

Marshall Barber and the origins of micropipette methods.

Current methods for the study of renal physiology depend heavily on the use of micropipettes fashioned from glass capillary tubes. The technique for making glass micropipettes and manipulating them in the field of a compound microscope appears to have been invented about 1904 by Marshall A. Barber, a bacteriologist at the University of Kansas. Barber's methods were passed on and successively modified by G. L. Kite and R. Chambers, and were finally adapted for renal studies by A. N. Richards. The apparatus for perfusing isolated segments of renal tubules in vitro is remarkably similar to the original device used by Barber over three-quarters of a century ago.

Bacteriological Techniques↗
PubMed1982

The transport and accumulation of oxyvanadium compounds in human erythrocytes in vitro.

Metavanadate, at physiologic pH the oxyanion form of pentavalent vanadium, is a potent reversible inhibitor of the sodium pump. Vanadium must enter cells to inhibit the sodium pump, and metavanadate may be converted to an inactive form inside of cells. Because of these factors and the complex inorganic chemistry of vanadium, we examined the kinetics of vanadium uptake and accumulation in normal erythrocytes in vitro at 37 degrees C. The kinetics of vanadium influx, efflux, and accumulation in erythrocytes in Tris-buffered, isotonic salt medium were fit closely by a model with vanadium in two possible oxidation states and with the vanadium permeating between two compartments. The equation for this model is: (formula: see text) in which subscripts i and o signify "inside" and "outside" the cells, respectively, and k1, k-1, and k2 are rate constants. 48V or EPR of vanadium(IV) gave similar estimates of the concentrations of the components. The k1 was 0.37 +/- 0.06 (S.E.M.) min-1 and k2 was 0.04 +/- 0.01 min-1. In control Tris-medium, k1 exceeded k-1 by a factor of 1.8. After 120 min of incubation in media with initial concentrations of 1, 10, or 100 microM vanadium(V), the total intracellular vanadium concentration exceeded that in the bath 4.5 to 18-fold. Vanadium influx was not appreciably changed by variations of external sodium or glucose levels. The k1 and k-1 were inversely related to external pH over the range 6.5 to 8.2. High O2 tension (95% to 100% O2) caused a decrease in k2, and the lipophilic oxidant, cumene hydroperoxide, accelerated the loss of accumulated vanadium from the cells, indicating that the k2 step represents reduction of vanadium(V) to vanadium(V) within the cells. On the basis of these studies we suggest that the intracellular concentration of vanadium(V), the inhibitor of the sodium pump, is determined by the combined effects of the rate of vanadium influx (dependent on the extracellular concentration of free metavanadate), the rate of vanadium efflux, and the rate of conversion of vanadium(V) to vanadium(IV).

Biological Transport↗
PubMed1981

Characterization of the collagenous domain of tubular basement membrane.

The collagenous domain of rabbit renal tubular basement membrane was solubilized by controlled pepsin digestion. Complete solubilization occurred within 24 h at 4 degrees C, and the sodium chloride precipitable polypeptides remained resistant to further degradation for at least 72 h. These products, which represent 35 to 40% of the basement membrane, possess a composition similar to that od the collagenous domain of bovine glomerular basement membrane. Agarose gel electrophoresis in the presence of sodium dodecyl sulfate resolved 11 components, several of which comprise the majority of the protein in the system. Components I (Mr approximately 1,500,000) and II (Mr approximately 1,200,000), together with a minor component, III, comprise 45% of the Coomassie blue-staining material. An additional 25% is represented by component IV (Mr approximately 375,000) plus a minor component, V. The remaining components (VI through XI) span a molecular weight range from 34,000 to 200,000. Two-dimensional gel electrophoresis was used to establish which of these components contain disulfide cross-linked polypeptides and the number and molecular weight of such polypeptides. Components I, II, and IV each contained intensely staining polypeptides of Mr = 160,000, 140,000, and 80,000 plus lightly staining polypeptides of Mr = 43,000 and 34,000. Lightly staining polypeptides of Mr = 390,000, 180,000, and 125,000 were also detected among the reduction products of components I and II. In addition, evidence for the presence of aldehyde-derived cross-linked polypeptides within the structures of components I and II was observed in the form of reduction products whose molecular weight occurs in multiples of the smaller monomeric polypeptides.

Amino Acids↗
PubMed1981

Basis for heterogeneity of para-aminohippurate secretion in rabbit proximal tubules.

Para-aminohippurate (PAH) is secreted at different rates in S1, S2, and S3 segments of isolated perfused proximal tubules of rabbit kidney. To characterize PAH transport we determined the maximal rate of secretion (Vmax) and the apparent Michaelis constant (Km) for each segment by examining the relationship between bath concentration of PAH and net PAH secretion (Jb leads to lPAH) transposed for Lineweaver-Burk analysis. The passive component of secretion for all segments was estimated by slope analysis at relatively high concentrations of PAH, by the component of PAH secretion insensitive to inhibition by probenecid, and, additionally, in S2 segments, from PAH efflux from lumen to bath. Subtraction of the passive component from Jb leads to lPAH (probenecid method) gave Vmax values for S1, S2, and S3 segments of 1,097 +/- 336 (n = 6), 7,430 +/- 1,338 (n = 6), 1,647 +/- 138 (n = 8) X 10(-15) mol.min-1.mm-1 (+/- SE) and apparent Km values of 139 +/- 37 (n = 6), 195 +/- 37 (n = 6), and 113 +/- 16 (n = 6) X 10(-6) M, respectively. Thus, Vmax for S2 greater than S3 congruent to S1, whereas apparent Km was not consistently different among the segments. On the basis of these results we suggest that axial heterogeneity of PAH secretion may reflect an increased basolateral membrane density of PAH transporters of common affinity in the S2 segment of the proximal tubule.

Aminohippuric Acids↗