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Biomedical subjects

N W Levin

Publications and source records attributed to N W Levin.

At least 145 records · Page 8Linked to original sources

Uridine triphosphate and RNA synthesis during diabetes-induced renal growth.

UTP, CTP, and RNA synthesis were studied in the renal cortex of diabetic and control rats in vivo. The incorporation of UTP into RNA (nmol/h DNA) was used as estimate of RNA synthesis rate. Two to three days after streptozotocin injection, UTP and CTP ppol size and orotate incorporation into UTP and RNA were greater in diabetic animals than in controls. In addition, RNA content and RNA synthesis rate were increased. These changes were corrected by insulin infusion. In diabetic animals, additional increases in UTP pool, RNA content, and RNA synthesis rate followed contralateral nephrectomy. This increase in RNA content was greater than in uninephrectomized controls. The changes in the diabetic renal cortex were not accompanied by increased plasma concentrations of growth hormone. The increase in RNA content in the diabetic renal cortex is probably due to increased RNA synthesis. Increased synthesis of pyrimidines and expansion of the UTP pool may make this substrate more readily available for the synthesis of UDP sugars and may facilitate the synthesis of basement membrane in diabetes.

Animals↗

Glomerular pyrimidine metabolism in experimental diabetic nephropathy.

Glomerular uracil nucleotide metabolism was studied in vivo in control and diabetic rats 48 h after the injection of streptozotocin. The animals were infused for 2 h with 3H-orotate and the fraction of infused dpm incorporated into glomerular uracil nucleotides and RNA/mg of glomerular DNA was calculated. Diabetic glomeruli showed an increase in RNA/DNA compared to controls (p less than 0.05) and a greater incorporation of 3H-orotate into uracil nucleotides and RNA. These changes were reversed by insulin therapy. In separate experiments the renal cortical uracil nucleotide pool was expanded by feeding chow supplemented with 0.5% orotate to rats for 6 months. Normal animals fed orotate developed significant glomerular basement membrane thickening (p less than 0.01) when compared to age-matched controls, which was morphologically indistinguishable from that of diabetics. Orotate feeding also produced further basement membrane thickening in diabetic rats. These results suggest that early diabetes is characterized by an increase in glomerular uracil nucleotides, and that chronic expansion of the uracil nucleotide pool is associated with glomerular basement membrane thickening.

Animals↗

Renal scleroderma: comparison of different modalities of treatment.

A patient with scleroderma and severe renal failure was initially treated with hemodialysis and minoxidil (Loniten) without any improvement in her skin involvement. At a later date bilateral nephrectomy and a successful cadaveric renal transplant were performed. Her cutaneous manifestations have improved remarkably during the four years since transplantation. Because these patients do not tolerate hemodialysis very well, renal transplantation appears to be the most effective form of treatment, with the possible added benefit of cutaneous improvement.

Adult↗

Sonographic features of ATN and of acute rejection in renal allografts.

The sonographic changes occurring during post transplant acute tubular necrosis and rejection are discussed. Seven patients with proven ATN are shown to maintain normal sonographic features and exhibit normal hypertrophy. In contrast during acute rejection the findings in 21 patients included in order of frequency the following 1) sudden increase in renal volume, 2) prominent medullary pyramids, 3) abnormal echogenicity, 4) decreased amplitude of the central sinus echoes, 5) increased cortical thickness, 6) crescent shaped fluid collections and 7) indistinct corticomedullary boundary.

Acute Kidney Injury↗

Incorporation of exogenous precursors into uridine nucleotides and ribonucleic acid. Nucleotide compartmentation in the renal cortex in vivo.

The possibility of compartmentation of UTP in vivo was investigated in the renal cortex of unanaesthetized rats. In addition, liver and spleen were studied in order to compare tissues with different utilization of precursors for pyrimidine nucleotide synthesis. After continuous 2h infusions of [(3)H]uridine or [(3)H]orotate, their incorporation into UTP, UDP-sugars and RNA was quantified. Rates of RNA synthesis were calculated by dividing the incorporation of precursor into RNA by the average specific radioactivity of the UTP pool. Although similar RNA-synthesis rates might have been expected with the two precursors, higher rates were found with uridine than with orotate. The relative incorporation into UDP-sugars of these precursors was also different. Similar results were obtained in the liver. In the spleen, equal amounts of both precursors were incorporated into UTP, but [(3)H]orotate incorporation did not lead to labelling of RNA. To evaluate the heterogeneity of cells with respect to the metabolism of pyrimidines, precursor incorporation was studied in isolated glomeruli and by radioautography. Incorporation into glomeruli was qualitatively similar to but quantitatively different from results in the renal cortex. Although there is obvious tissue heterogeneity, compartmentation of UTP pools is the most credible explanation for the results obtained with the renal cortex and liver. Consequently RNA and UDP-sugars may originate from two different UTP pools. Tissue heterogeneity is the likely explanation for the results obtained in the spleen. Studies of synthesis of pyrimidine and RNA, particularly in relation to growth and regeneration, must take into consideration the precursor used, the apparent existence of UTP compartmentation and the degree of cellular heterogeneity.

Animals↗

Leukopenia and hypoxemia. Unrelated effects of hemodialysis.

Hemodialysis-induced hypoxemia has been attributed to membrane-related complement activation leading to pulmonary leukostasis and to hypoventilation secondary to carbon dioxide losses via the dialyzer. We have separately assessed the role of membrane- and dialysis-related factors by using different dialyzers and sequential ultrafiltration and hemodialysis with first-use cellulose dialyzers produced both leukopenia and hypoxemia. With reused cellulose and polyacrylonitrile dialyzers, hypoxemia still occurred, but without leukopenia. Ultrafiltration produced leukopenia and no changes in Pao2; during the subsequent hemodialysis, hypoxemia developed as the leukocyte count increased by 50%. Our data indicate that leukopenia and hypoxemia are unrelated effects of hemodialysis, and favor hypoventilation as the major determinant of hypoxemia during hemodialysis.

Adult↗

Effect of diuretics on ADP incorporation in kidney mitochondria.

The effect of diuretics on incorporation of ADP in mitochondria isolated from rabbit renal cortex and medulla was examined. Inhibition of incorporation of [14 C]ADP into both types of mitochondria was observed following pretreatment with furosemide, ethacrynic acid and meralluride at high drug concentrations (7.5 x 10-4 M furosemide and ethacrynic acid, 6.4 x 10-3 M meralluride). At lower concentrations (7.5 x 10-5 M furosemide and ethacrynic acid, 6.4 x 10-4 M meralluride), only entry of ADP in medullary mitochondria was inhibited. Chlorothiazide, 1.7 x 10-3 M, did not inhibit incorporation of ADP into either mitochondrial preparation. Atractyloside, a classic inhibitor of ADP-ATP exchange, showed inhibition in both preparations. Furosemide, injected in vivo inhibited incorporation of ADP into medullary but not cortical mitochondria. These results are consistent with the possibility that loop diuretics may reduce tubular sodium reabsorption by inhibiting ADP-ATP exchange across the mitochondrial membrane, thereby depriving active transport processes of ATP. The differential action on cortical and medullary mitochondria by loop diuretics is consistent with their predominant site of action in the tubule and with the different morphologic characteristics of both types of mitochondria.

Adenosine Diphosphate↗