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Biomedical subjects

J Rapoport

Publications and source records attributed to J Rapoport.

At least 55 records · Page 3Linked to original sources

Active urea transport in toad skin is coupled to H+ gradients.

Active transport of urea exists inwardly through the skin of the toad Bufo viridis and is enhanced by adapting the toads to hypertonic saline solutions. In this paper, we report our studies on the energy coupling of this active transport system. We have shown previously that this system is independent of sodium transport. We thus studied the possibility of coupling to proton transport by studying the following: 1) the effect of acidifying the epithelium by means of CO2 and protonophores, 2) the effect of alkalinizing the epithelium with the anion-exchange inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and by removal of chloride from the serosal medium, 3) the effect of inhibiting the proton-translocating ATPase of the skin, 4) dependence on mucosal pH. We found that 1) acidification of the epithelium by means of 5% CO2 and the protonophores carbonyl cyanide m-chlorophenylhydrazone (CCCP) and nigericin inhibited urea influx; 2) alkalinization of the epithelium by means of the disulfonic stilbene DIDS and by removal of serosal chloride increased urea influx; 3) inhibition of the proton-translocating ATPase of the skin by means of 1,3-dicyclohexylcarbodiimide (DCCD), N-ethylmaleimide (NEM), and sodium orthovanadate inhibited urea transport; 4) urea influx was unaffected by alkalinizing the external medium to 8.5 or by acidifying to 6.5; it was significantly suppressed by a mucosal pH of 5.5.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Nephrotic syndrome associated with transitional cell carcinoma of the bladder.

We describe the occurrence of a nephrotic syndrome in association with transitional cell carcinoma of the bladder. The proteinuria disappeared several weeks after removal of the tumor. Light and electron microscopy were compatible with a minimal-change lesion, but immunofluorescence showed linear immunoglobulin deposition. Immunoglobulins eluted from the tumor reacted specifically with the kidney and vice versa. We conclude that antibody formation against a specific component of basement membrane common to both kidney and tumor gave rise to the nephropathy in this case.

Biopsy↗

Peritonitis in continuous ambulatory peritoneal dialysis patients in southern Israel.

We report our experience of peritonitis in a group of continuous ambulatory peritoneal dialysis (CAPD) patients in the south of Israel during a 3-year period. During this period, 51 patients were treated with CAPD, comprising a total of 999 patient months of treatment. One hundred and forty-three episodes of peritonitis occurred in 42 patients. When the patients were divided into high risk and low risk groups, the overall incidence was one episode every 5.7 months in the high risk group and one episode every 13.2 months in the low risk group. Gram-positive organisms accounted for 62.2% of the infections, and coagulase negative Staphylococcus for 35% of infections. The recurrence rate was 12%. Catheter removal was required in seven patients, and three patients were transferred to hemodialysis because of recurrent infections. We conclude that CAPD is a safe and viable modality of treatment for end-stage renal disease in our patient population.

Adult↗

Renal cortical mitochondrial transport of calcium in chronic uremia.

Calcium overload of tubular cells may occur in uremia, and may be the underlying functional abnormality in the continued deterioration of renal function in chronic renal failure. In order to study this question further, the effect of chronic uremia on the calcium transport properties and respiratory rates was examined in mitochondria (Mi) isolated from the cortex of the remnant kidneys of subtotally nephrectomized rats (SNX) and sham operated controls (C). Plasma calcium concentration was similar in both groups of rats, but a significant hyperphosphatemia was seen in SNX, 8.6 +/- 0.6 mg%, as compared to 7.2 +/- 0.2 mg% in C (P less than 0.001). Mi calcium and phosphate concentrations (nmol/mg protein) were significantly elevated in SNX, 49.9 +/- 7.9 and 35.1 +/- 4.2, respectively, in SNX compared to C, 21.2 +/- 4.2 and 21.4 +/- 2.7, respectively (P less than 0.01). Mi respiratory control ratio and ADP/O were similar in both experimental groups. Kinetic parameters for calcium uptake (Ca2+ concentrations in the medium of 1.25 to 16 microM) revealed initial velocities 1.5-fold higher in SNX Mi than in C. Mi retention of calcium in the presence of medium Ca2+ concentrations up to 500 microM was studied. Calcium retention was reduced in SNX: the Mi were unable to retain calcium at concentrations of 250 microM. The addition of ruthenium red to the medium substantially improved calcium retention by the uremic Mi. Chronic parathyroidectomy did not correct either the increased calcium uptake or the poor retention of uremic Mi.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Active urea transport by the skin of Bufo viridis: amiloride- and phloretin-sensitive transport sites.

Urea is actively transported inwardly (Ji) across the skin of the green toad Bufo viridis. Ji is markedly enhanced in toads adapted to hypertonic saline. We studied urea transport across the skin of Bufo viridis under a variety of experimental conditions, including treatment with amiloride and phloretin, agents that inhibit urea permeability in the bladder of Bufo marinus. Amiloride (10(-4) M) significantly inhibited Ji in both adapted and unadapted animals and was unaffected by removal of sodium from the external medium. Phloretin (10(-4) M) significantly inhibited Ji in adapted animals by 23-46%; there was also a reduction in Ji in unadapted toads at 10(-4) and 5 x 10(-4) M phloretin. A dose-response study revealed that the concentration of phloretin causing half-maximal inhibition (K1/2) was 5 x 10(-4) M for adapted animals. Ji was unaffected by the substitution of sucrose for Ringer solution or by ouabain. We conclude 1) the process of adaptation appears to involve an increase in the number of amiloride- and phloretin-inhibitable urea transport sites in the skin, with a possible increase in the affinity of the sites for phloretin; 2) the adapted skin resembles the Bufo marinus urinary bladder with respect to amiloride and phloretin-inhibitable sites; 3) we confirm earlier observations that Ji is independent of sodium transport.

Amiloride↗

Neuroanatomical abnormalities in obsessive-compulsive disorder detected with quantitative X-ray computed tomography.

New brain imaging techniques may provide evidence for a biological basis for severe psychiatric disorders. The authors used quantitative X-ray computed tomography (CT) to analyze the brain volume of 10 male patients with severe primary obsessive-compulsive disorder and 10 healthy male control subjects. Caudate nucleus volume in the patients with obsessive-compulsive disorder was significantly less than that of control subjects, but lenticular nuclei, third ventricle, and lateral ventricle volumes did not differ between these two groups, and no abnormal asymmetry of bilateral structures was detected. These findings support other evidence of involvement of the caudate nucleus in obsessive-compulsive disorder.

Adolescent↗

Extreme hypermagnesemia due to ingestion of Dead Sea water.

We describe 3 patients who developed extreme hypermagnesemia due to ingestion of water of the Dead Sea, which would have been fatal were it not for the protective effects of the accompanying hypercalcemia. We emphasize the clinical features of this condition and the importance and effectiveness of early hemodialysis as the main modality of treatment.

Aged↗

Aluminum-related osteomalacia: clinical and histological improvement following treatment with desferrioxamine (DFO).

Aluminum-related osteomalacia has been a topic of major interest for some time. Patients on dialysis who are affected exhibit reduced parathyroid function and osteomalacia associated with high levels of aluminum in the extracellular fluid and tissues. In bone, aluminum is found in the interface between mineralized and nonmineralized osteoid. In the present study we attempted treatment of the aluminum-related bone disease with DFO, a potent chelating agent. A thyroparathyroidectomized patient on hemodialysis with proven osteomalacia and aluminum deposits in bone received DFO 3 times/week for 1 year. Consequently, there was a marked improvement in his skeletal status, both clinically and histologically. This was associated with aluminum deposits within the mineralized component of bone as well as elevated parathyroid function measured in blood and bone. These findings suggest that calcification may occur despite the presence of aluminum in the mineralizing front. The main beneficial effect of DFO could be relief of the inhibitory action of aluminum on parathyroid cells and osteoblasts.

Adult↗

Enhancement of 24,25-dihydroxyvitamin D levels in patients treated with continuous ambulatory peritoneal dialysis.

We measured 24,25-dihydroxyvitamin D [24,25(OH)2D] levels in patients treated with chronic ambulatory peritoneal dialysis (CAPD), before and after receiving vitamin D2 or 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3). Vitamin D2 administration led to an increase in 25-hydroxyvitamin D (25-OH-D) and a concomitant rise in 24,25(OH)2D. No change was observed in 1,25-dihydroxyvitamin D [1,25(OH)2D]. Administration of 1 alpha-OH-D3 resulted in an increase in 1,25(OH)2D3, and a concomitant rise in 24,25(OH)2D, but no change in 25-OH-D3. Thus, 24,25(OH)2D levels may be increased in CAPD patients by raising 25-OH-D levels, or by raising 1,25(OH)2D3 levels. Since the latter enhances specifically the renal 24-hydroxylase enzyme, we conclude that this enzyme is present in CAPD patients with kidneys in situ, and may be stimulated by adequate 1,25(OH)2D3 levels. Thus, administration of 1 alpha-OH-D3 to CAPD patients with kidneys in situ seems to be sufficient to obtain normal levels of 1,25(OH)2D3 and 24,25(OH)2D3. However, anephric patients require vitamin D2 in addition as a source of 25-OH-D, the substrate for extrarenal production of 24,25(OH)2D.

Calcifediol↗

Verapamil improves defective duodenal calcium absorption in experimental chronic renal failure.

Experiments were carried out to establish whether abnormalities in cellular calcium metabolism in chronic renal failure contributed to the impaired production of 1,25-dihydroxy vitamin D3 [1,25(OH)2D3]. For this purpose the calcium influx blocker verapamil was administered chronically to 5/6 nephrectomized rats (SNX) and sham-operated rats (sham). SNX and sham-nontreated animals served as controls. Fractional duodenal calcium absorption was severely depressed in SNX rats, compared to sham group. Administration of verapamil to SNX rats caused an improvement in calcium absorption despite similar degrees of renal insufficiency as in the nontreated SNX animals. The effect of verapamil requires residual renal parenchyma, since it was not reproduced in bilaterally nephrectomized rats. 45Ca uptake by renal cortical slices obtained from SNX rats was significantly elevated, as compared to sham group, and was corrected in uremic rats treated with verapamil. Plasma concentrations of 25-hydroxy vitamin D3 (25-OH-D3) were similar in all experimental groups. The 1,25(OH)2D3 plasma level in SNX rats was similar to values obtained in the control group, with an almost 2-fold increase in verapamil-treated animals. Quin-2 measurements of cytoplasmic calcium concentration in cultured proximal tubular cells revealed that verapamil prevents calcium bursts provoked by anoxic insult, by parathyroid hormone and by alpha 1-adrenergic stimuli. We conclude that verapamil treatment of SNX rats improves the duodenal absorption of calcium via augmentation of 1,25(OH)2D3 production.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoquinolines↗

Autoradiographic studies of solute transport across the toad bladder.

The autoradiography of diffusible, hydrophilic solutes presents special problems in localization of the labeled solute under study. We present studies of the movement of 14C-labeled urea, and 14C- and 3H-labeled sucrose across the isolated urinary bladder of the toad, a vasopressin-sensitive epithelium, using a technique that avoids exposure to water throughout all processing steps and minimizes error caused by isotope scatter. We have shown a significant increase in 14C urea entry into epithelial cells following vasopressin, and a significant decrease following phloretin, an agent that selectively blocks vasopressin-stimulated urea transport. The autoradiographic technique confirms the luminal site of action of phloretin. Studies of 14C and 3H sucrose labeling show that this molecule is virtually excluded from the cell. The current method of grain counting is capable of yielding reliable information in studies of epithelial transport.

Animals↗

Calcium metabolism in uremic nephrocalcinosis: preventive effect of verapamil.

The aim of the present study was to examine calcium metabolism of the renal cortex in experimental chronic renal failure, together with morphologic criteria of nephrocalcinosis and to determine the effect of chronic verapamil administration on these parameters. In subtotally nephrectomized (SNX) rats 3 weeks after surgery, renal cortical calcium content increased more than two-fold. 45Ca incorporation into renal cortical slices in SNX revealed a 35% increase, associated with a 50% increase in a lanthanum-resistant fraction of 45Ca uptake. Radiocalcium wash-out curves in this group demonstrated abnormal retention of the isotope for up to 30 min of incubation. In contrast, radiocalcium incorporation and wash-out in SNX rats chronically treated with verapamil were similar to that obtained in the sham group. Verapamil administration significantly reduced, but did not normalize, renal cortical calcium content. Von Kossa staining demonstrated the deposition of calcium in the renal parenchyma of SNX rats. Ultrastructurally, it was accompanied by mitochondrial disorganization and calcification, as well as by the tubular basement membrane destruction and mineralization. These morphologic patterns of nephrocalcinosis were significantly ameliorated in SNX rats treated with verapamil. We conclude that chronic verapamil administration results in amelioration of uremic nephrocalcinosis.

Animals↗

X-ray microanalysis of uremic nephrocalcinosis: cellular distribution of calcium, aluminium and silicon in uremic nephrocalcinosis.

Nephrocalcinosis with a deposition of aluminum and silicon has been previously reported in uremic rats. To clarify the origin of these elements thin sections of renal cortex were examined by means of electron microscopy and energy dispersive x-ray microanalysis. Studies were performed on subtotally nephrectomized rats (SNX) and sham-operated control animals. Electron microscopy of proximal tubular epithelial cells in SNX rats unlike control rats revealed severe mitochondrial disorganization; irregularity of the tubular basement membrane which exhibited various inclusions; and lamellar bodies within the brush border membrane. On x-ray microanalysis disorganized mitochondria contained calcium and silicon, while secondary lysosomes displayed aluminum and silicon. The tubular basement membrane of SNX rats, as well as lamellar body-like inclusions within the brush border contained calcium, aluminum and silicon together. It is suggested that lysosomal and mitochondrial interaction in proximal tubular cells of uremic rats may contribute to the deposition of calcium together with aluminum and silicon in the renal parenchyma, resulting in nephrocalcinosis.

Aluminum↗