PubMed Health⌕ Search

Biomedical subjects

V Batuman

Publications and source records attributed to V Batuman.

15 recordsLinked to original sources
PubMed1991

Possible pathogenetic role of low-molecular-weight proteins in Balkan nephropathy.

Balkan endemic nephropathy (BEN) is a tubulointerstitial disease characterized by increased-low-molecular-weight protein (LMWP), most notably, beta 2-microglobulin (beta 2m) excretion in urine. We previously demonstrated that two species of LMWPs, immunoglobulin light chains (LC) and recombinant alpha interferon (rIF), are toxic at proximal tubule cell membrane level. Myeloma LCs and rIF inhibit Na-dependent uptake of 14C-L-alanine and 14C-D-glucose by rat renal brush border membrane (BBM) vesicles at half-maximal inhibitory concentrations, IC50, ranging from 68 to 140 microM for LCs, and 5.4 to 18 nM for rIF. We further demonstrated that LCs bind to high-capacity, low-affinity sites on BBM with dissociation constants (Kd) ranging from 16 to 118 microM, a range similar to IC50s observed with the same LCs. Binding site occupancy is inversely related to alanine (r = -0.95, P less than 0.01), and glucose uptake (r = -0.96, P less than 0.01), implying that LC nephrotoxicity is determined by its binding to BBM. beta 2m shares behavioral and structural similarities with both LC and rIF. Preliminary studies in our laboratory showed that unlabeled LCs compete for the same binding sites on BBM with beta 2m. These observations confirm that all LMWP, including beta 2m, are potentially nephrotoxic. Thus, the characteristic beta 2-microglobulinuria of BEN may be more than a consequence of tubular dysfunction, and may play a pathogenetic role.

Animals↗
PubMed1990

Effect of alpha interferon on glucose and alanine transport by rat renal brush border membrane vesicles.

To investigate the pathogenetic mechanisms of interferon nephrotoxicity, we studied the effect of recombinant interferon alfa-2b on the uptake of 14C-D-glucose and 14C-L-alanine by rat renal brush-border-membrane vesicles. Interferon significantly inhibited 20 sec. sodium-dependent and 5 and 10 min. equilibrium uptake of both glucose and alanine. The inhibitory effect was dose dependent with maximum effect achieved at interferon concentration of 5 X 10(-8)M in the uptake media. The half-maximal inhibitory concentrations, IC50, of interferon on glucose uptake was 1.8 X 10(-8)M, and 5.4 X 10(-9)M on alanine uptake. Dixon plot analysis of uptake data was consistent with pure non-competitive inhibition. The inhibition constants, Ki, 1.5 X 10(-8)M for glucose uptake, and 7.3 X 10(-9)M for alanine uptake, derived from Dixon plots were in close agreement with the IC50s calculated from the semilog dose response curves. These observations reveal that direct interactions at the proximal tubule cell membrane are involved in the pathogenesis of interferon nephrotoxicity, and that its mechanism of nephrotoxicity is similar to that of other low molecular weight proteins.

Alanine↗
PubMed1990

Light-chain binding sites on renal brush-border membranes.

Immunoglobulin light chains are low-molecular-weight proteins filtered at the renal glomerulus and catabolized within the proximal tubular epithelium. Excessive production and urinary excretion of light chains are associated with renal dysfunction. They also interfere with proximal renal tubule epithelial functions in vitro. We studied the binding of 125I-labeled kappa- and lambda-light chains, obtained from the urine of multiple myeloma patients, to rat and human renal proximal tubular brush-border membranes. Light-chain binding to brush borders was also demonstrated immunologically by flow cytometry. Computer analysis of binding data was consistent with presence of a single class of low-affinity, high-capacity, non-cooperative binding sites with relative selectivity for light chains on both rat and human kidney brush-border membranes. The dissociation constants of light chains ranged from 1.6 X 10(-5) to 1.2 X 10(-4) M, and maximum binding capacity ranged from 4.7 +/- 1.3 X 10(-8) to 8.0 +/- 0.9 X 10(-8) (SD) mol/mg protein at 25 degrees C. Kappa- and lambda-light chains competed with each other for binding with comparable affinity constants. Competition by albumin and beta-lactoglobulin, however, was much weaker, suggesting relative site selectivity for light chains. These binding sites probably function as endocytotic receptors for light chains and possibly other low-molecular-weight proteins.

Animals↗
PubMed1990

Hyponatremia and hypouricemia: differentiation from SIADH.

Hypouricemia in coexistence with hyponatremia often differentiates the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) from most other causes of hyponatremia. We report clearance studies in 5 cases of hyponatremia and hypouricemia that were not due to SIADH. One had metastatic pancreatic carcinoma with ascites, edema, hypoalbuminemia and hypophosphatemia. Two had adenocarcinoma of the lung with metastasis to the brain in 1, 1 had disseminated cryptococcus and 1 had Hodgkin's disease. None received radiation or known nephrotoxins at least 4 months prior to study. None had serum creatinine greater than 106.1 mumol/l (1.2 mg/dl). Two had postural hypotension and hyponatremia that responded to saline therapy. Fluid restriction corrected the hyponatremia in all patients, but the hypouricemia, high fractional excretion (FE) of urate, and high urine sodium concentration persisted. In 2 patients studied, ADH was appropriately suppressed after volume repletion but there was a defect in free water clearance due to high renal solute excretion. In contrast to patients with SIADH who correct their defect in renal urate transport with correction of hyponatremia by water restriction, our patients appear to have a persistent renal urate transport defect and abnormality in sodium conservation. Elevated FE urate of greater than 10% after correction of hyponatremia can thus differentiate these patients from SIADH. The diametrically opposing goals of fluid therapy emphasize the importance of differentiating one group from the other.

Adult↗
PubMed1989

Reducing bone lead content by chelation treatment in chronic lead poisoning: an in vivo X-ray fluorescence and bone biopsy study.

A stained-glass artist with longstanding exposure to lead presented with neuropsychiatric symptoms. He was evaluated before and after chelation treatment by the CaNa2 EDTA lead mobilization test, iliac crest bone lead measurement, and in vivo tibial X-ray fluorescence (XRF). The three methods showed a progressive fall in body lead stores during chelation therapy in association with improvement in symptoms and a fall in blood lead and zinc protoporphyrin levels. In vivo tibial XRF is a safe, rapid, and noninvasive technique for detecting excessive body lead burdens. XRF measurement of bone lead content is a practical method for monitoring the efficacy of therapy as well as for establishing the diagnosis.

Biopsy↗
PubMed1989

Lead increases red cell sodium-lithium countertransport.

The effect of 1, 3, 5, and 20 mumol/L lead on normal red cell sodium-lithium countertransport was studied in vitro. Red cell suspensions incubated with lead had increased sodium-lithium countertransport at all concentration levels compared with paired, unleaded controls when all groups were evaluated by analysis of covariance (F = 19.2, P less than 0.001). The effect of lead was concentration dependent (r = 0.998, P less than 0.001). These observations suggest that abnormalities in sodium transport are involved in the pathogenesis of lead-induced hypertension. Because increased red cell sodium-lithium countertransport is characteristic of essential hypertension, these observations further suggest that lead-induced and essential hypertension may share common pathophysiological mechanisms.

Antiporters↗
PubMed1989

Effects of chronic peritoneal dialysis on thyroid function tests.

Peritoneal dialysis is associated with large losses of protein. In order to quantify thyroid hormone excretion in the dialysate and to examine the possibility that peritoneal dialysis may result in clinical hypothyroidism, nine endstage renal disease (ESRD) patients undergoing either continuous ambulatory peritoneal dialysis (CAPD) or chronic intermittent peritoneal dialysis (IPD) were studied. Total protein excretion in the peritoneal fluid was 21.5 +/- 2.1 g/24 h and did not vary with the mode of peritoneal dialysis. Thyroid binding globulin (TBG) excretion was 6.4 +/- 1.3 mg/24 h, higher than the values reported in the literature for urinary TBG excretion in patients with the nephrotic syndrome. Despite the higher TBG losses, serum TBG remained in the normal range. Mean peritoneal total T4 and T3 were 8.1 +/- 1.6 micrograms/24 h and 89.5 +/- 14.6 ng/24 h, and there was a significant correlation between peritoneal T4 and TBG (r = 0.69; P less than 0.01) and between peritoneal total proteins and T4 (r = 0.80; P less than 0.001). Despite the finding that large amounts of protein are lost in peritoneal fluid, T4 and T3 losses were relatively modest and remained below their daily production rates, and none of the patients were overtly hypothyroid. Serum thyroid stimulating hormone (TSH) was mildly elevated in three of nine patients and was consistent with early thyroid failure. The patients' serum iodine levels were higher than normal but did not predict the patients' thyroid status. We conclude that major protein losses could predispose patients undergoing CAPD to thyroid failure and that long-term follow-up of thyroid function is warranted in these patients.

Aged↗
PubMed1986

Light chain effects on alanine and glucose uptake by renal brush border membranes.

Effect of varying concentrations (0 to 800 microM) of three different light chains on sodium-dependent L-(14C)alanine and D-(14C)glucose uptake by rat renal brush border membrane vesicles were studied. One kappa and two lambda type light chains (lambda-1 and lambda-2) were isolated from urines of patients with multiple myeloma. At maximal inhibitory concentrations the kappa chain reduced alanine uptake from 206 +/- 18 to 77 +/- 18 pmole/mg protein (P less than 0.005) and glucose uptake from 357 +/- 22 to 146 +/- 8 pmole/mg protein (P less than 0.001). lambda-1 reduced alanine uptake from 136 +/- 17 to 60 +/- 8 pmole/mg protein (P less than 0.005) and glucose uptake from 354 +/- 17 to 77 +/- 14 pmole/mg protein (P less than 0.001). lambda-2 reduced alanine uptake from 105 +/- 9 to 28 +/- 5 pmole/mg protein (P less than 0.001) and glucose uptake from 194 +/- 7 to 66 +/- 7 pmole/mg protein (P less than 0.001). The half maximal inhibitory concentrations (I50) of kappa, lambda-1 and lambda-2 light chains were 68, 76 and 140 microM for alanine uptake and 120, 70 and 105 microM for glucose uptake. Control experiments using bovine serum albumin and beta-lactoglobulin showed no inhibitory effect on alanine and glucose uptake by either protein. These data reveal brush border membrane effects by myeloma light chains and confirm that direct Bence Jones protein nephrotoxicity may play an important role in the pathogenesis of kidney dysfunction associated with multiple myeloma.

Alanine↗
PubMed1979

Detection and treatment of occupational lead nephropathy.

Reduced glomerular filtration rates (GFR less than 90 ml/min/1.73 sq m) were found in 21 of 57 lead workers in whom excessive body lead burdens had been shown by the urinary excretion of more than 1,000 microgram of lead per day during an edetate disodium calcium lead-mobilization test. In 12 patients, renal biopsies confirmed the diagnosis of occupational lead nephropathy and further excluded other possible causes of kidney disease. Glomerular and tubular immunoglobulin deposition in seven of eight biopsy specimens examined by immunofluorescent microscopy raises the possibility that an autoimmune response may contribute to the interstitial nephritis of occupational lead nephropathy. The GFR increased 20% or more in four of eight patients treated with 1 g of edetate disodium calcium three times weekly for from six to 50 months, further confirming the diagnosis of lead nephropathy and indicating a favorable response to prolonged chelation therapy.

Adult↗
PubMed1978

Geophagic lead nephropathy: case report.

An adult presenting with anemia and seizures was found to have lead poisoning. Chelation therapy undertaken before the source of exposure was known was accompanied by clinical improvement. Recurrence of an excessive body lead burden despite chelation led to the discovery of pica for lead-contaminated garden soil. Lead nephropathy progressed when the geophagia was resumed.

Black or African American↗
PubMed1978

Relation of tubular interstitial disease to renal function.

In vitro concentrative transport of PAH-3H was evaluated in human renal biopsies by section freeze-dry autoradiography. Renal cortical tissue obtained by biopsy was incubated in vitro in medium containing PAH-3H, and section freeze-dry autoradiographs prepared. The autoradiographs demonstrated that the number of proximal tubules which accumulate PAH-3H in vitro varies inversely with the amount of tubular interstitial disease and directly with glomerular filtration rate. In order to further examine the mechanisms of tubular-interstitial disease, we have developed a technique for simultaneous fluorescent microscopy and autoradiography in single freeze-dried sections. This technique permits evaluation of the relationship between concentrative transport and immunoglobulin deposition in individual tubules and should increase our knowledge of the biologic significance of immunoglobulin deposits in proximal tubules.

Autoradiography↗