Search PubMed⌕ Search

Biomedical subjects

S Barnes

Publications and source records attributed to S Barnes.

At least 217 records · Page 12Linked to original sources
PubMed1982

Methotrexate levels in the interstitial space and seminiferous tubule of rat testis.

The ability of methotrexate (MTX) to pass from the blood into the interstitial space and seminiferous tubule of the rat was investigated using testicular micropuncture. MTX was administered to anesthetized adult Wister rats via a femoral vein cannula. Constant plasma levels of MTX were achieved by giving a priming dose followed by a constant infusion of 1, 10, or 100 mg/kg/hr with 6 to 27 rats studied at each dose. Blood (via a jugular vein cannula), testicular interstitial fluid, and seminiferous tubule fluid (via direct micropuncture) were periodically sampled during the 4 hr of drug infusion. Under steady-state conditions, when compared to corresponding plasma values, MTX levels were 2- to 4-fold lower in the testicular interstitial fluid and 18- to 50-fold lower in the seminiferous tubule. These results indicate that, in the rat, a significant blood-testis barrier to MTX exists at the tubular but probably not at the capillary-interstitial level. If these results can be extrapolated to humans, they do not provide a pharmacological explantation for the frequent occurrence of leukemic relapse in the interstitium of the testes in boys with acute lymphocytic leukemia.

Animals↗
PubMed1981

Syndromatic hepatic ductular hypoplasia (arteriohepatic dysplasia): a clinical and hepatic histologic study of three patients.

Clinical and pathologic features of three patients with chronic intrahepatic cholestasis from birth are described. Each patient exhibited a paucity and hypoplasia of interlobular bile ducts, unusual facies, short stature, a pulmonary ejection systolic murmur, and structural anomalies of vertebrae. This constellation of defects constitutes a distinct syndrome to which the terms arteriohepatic dysplasia and syndromatic hepatic ductular hypoplasia are applied. Clinically, cholestasis was not progressive and, although the SGPT was chronically elevated (122--520 units/liter), features of liver cell failure did not develop. Changes in plasma lipids and lipoproteins and serum bile acids were consistent with chronic cholestasis. Liver biopsies from the three cases revealed pseudoxanthomatous change, increased stainable copper and mild hepatocellular degenerative changes. Electron microscopy of one of the liver biopsies revealed extension of thick bundles of collagen from portal areas into hepatic lobules with obliteration of the space of Mall. With increasing age, portal tracts contained fewer bile ducts. This apparent progression of the lesion was not associated with an inflammatory cell infiltrate, progressive fibrosis, or the development of cirrhosis.

Abnormalities, Multiple↗
PubMed1981

Postnatal physiologic hypercholemia in both premature and full-term infants.

Previous studies have shown that bile salt concentrations in human blood taken from the placenta at birth of term infants are in the range found in adults. A 125I-radioimmunoassay procedure and capillary gas liquid chromatography-mass spectrometry have been used in this investigation to measure serum bile salt concentrations in premature and normal term infants. It was found that the serum bile salt concentration in samples taken at birth in premature infants were also similar to that of adults. In the week after birth the serum bile salt concentration rose four- to sevenfold in each of the infant groups. The increase was independent of gestational age and the "health" of the child. A similar increase was observed in term infants. Thus, hypercholemia is physiologic in newborn infants. In conjunction with other abnormalities of the enterohepatic circulation of bile salts there are profound implications in the newborn for the metabolism and excretion of those endogenous and exogenous substances that are dependent on the secretion of bile salt by the liver. In addition, speculations concerning the role of parenteral nutrition in the induction of cholestasis in premature infants should be made with caution.

Age Factors↗
PubMed1980

Stoichiometry of the NADH-oxidoreductase reaction for dehydrogenase determinations.

The NADH oxidoreductase reaction with resazurin was most rapid at pH 6.5. FMN (10 mumol/l) markedly stimulated the reaction, and the optimal concentration of resazurin was 50 mumol/l. The oxidation of NADH by NADH oxidoreductase with resaruzin as electron acceptor gave a variable yield of fluorescent product, resorufin. The yield was pH dependent and was greatest at pH 6.5. Measurements of oxygen consumption in the reaction mixture demonstrated that dissolved O2 was an alternative electron acceptor. The increased yield of resorufin at pH 6.5 was due to more rapid reduction of resazurin rather than oxygen. In contrast, at pH 9.0 oxygen was the preferred electron acceptor. The sensitivity of assays utilizing this indicator reaction can be improved by these optimized conditions.

Dihydrolipoamide Dehydrogenase↗
PubMed1980

Determination of the pool size and synthesis rate of bile acids by measurements in blood of patients with liver disease.

1. A simplified technique for the measurement of bile-acid pool size and synthesis rate has been developed in patients with liver disease. Isotope dilution studies in blood and bile were performed after intravenous injection of [24-14C]cholic acid with radioimmunoassay for the measurement of the bile-acid concentration. The interpolated pool sizes and synthesis rates, determined from results from both blood and bile, were not significantly different. The concentration of bile acids in the blood of healthy controls was not sufficiently elevated to permit application of this technique. 2. Three out of six patients with cirrhosis had a markedly reduced pool size compared with that of controls, whereas those with cholestasis had an unchanged pool size. The daily synthesis rate was reduced in both groups. Liver disease caused a redistribution (0.5-16%) of the bile-acid pool to the blood, which was associated with enhanced urinary excretion of cholic acid and its metabolites.

Adult↗
PubMed1979

Modification of D-galactosamine-induced liver injury in the rat by spironolactone.

Spironolactone, a competitive inhibitor of mineralocorticoid effects on the distal tubule of the kidney, has recently been found to have other metabolic effects. In these studies, spironolactone (200mg/kg intraperitoneally) for 3 days was found to have a marked protective effect against the hepatotoxic effect of D-galactosamine (275 mg/kg) in rats. Further progress in defining the mechanism of protection from D-galactosamine hepatic necrosis by spironolactone will require assessment of effects of spironolactone on uridine nucleotide metabolism.

Animals↗
PubMed1979

Enzymatic sulfation of glycochenodeoxycholic acid by tissue fractions from adult hamsters.

Using a radiometric assay with glycochenodeoxycholic acid as substrate, bile acid:3'-phosphoadenosine-5'-phosphosulfate sulfotransferase activity was found in 105,000 g supernatant fractions of liver, proximal intestine, and adrenal gland homogenates from adult hamsters. Optimum conditions for measurement of the hepatic enzyme were determined. In both male and female animals sulfation only occurred at the 7 alpha-position. Saturation analysis with glycohenodeoxycholic acid revealed that the higher activity observed in fractions from female compared to male hamsters was due to a 4-fold lower apparent Km (79 muM vs. 317 muM) for this bile acid in the females. The sulfation of glycohenodeoxycholic acid was competitively inhibited by glycolithocholic acid, chenodeoxycholic acid, and ursodeoxycholic acid. The data are consistent with the concept that sulfation of many, if not all, bile acids can occur in vivo.

Adrenal Glands↗
PubMed1977

The role of tubular reabsorption in the renal excretion of bile acids.

1. The renal excretion of bile acids was studied in an isolated rat kidney preparation perfused with a protein-free medium. 2. Tubular reabsorption exceeded 95% for both non-sulphated and sulphated bile acids at filtered loads of less than 30 nmol/min. 3. At low filtered loads the reabsorption of taurocholate and taurochenodeoxycholate was almost complete. Efficient reabsorption of taurochenodeoxycholate was maintained over a wider range of filtered loads than for taurocholate. These observations suggest that active transport may occur. 4. At high filtered loads saturation of reabsorption of taurocholate and taurochenodeoxycholate did not occur, which indicates that passive diffusion is involved in reabsorption. 5. Active proximal-tubular secretion of bile acids was not demonstrated in competition experiments with p-aminohippurate. 6. The fractional reabsorption of taurocholate, chenodeoxycholate 3,7-disulphate and chenodeoxycholate 7-monosulphate was decreased by the addition of taurochenodeoxycholate to the perfusate, so that their renal excretion was enhanced. This interaction between the bile acids for reabsorption may explain the different composition of bile acids in urine compared with that in plasma in cholestasis in man. 7. Conjugated bilirubin decreased the fractional reabsorption of both taurocholate and taurochenodeoxycholate at low filtered loads (less than 30 nmol/min) but not at high filtered loads (400 nmol/min).

Absorption↗
PubMed1977

Rickets in adult cystic fibrosis with myopathy, pancreatic insufficiency and proximal renal tubular dysfunction.

Rickets is reported in a 19 year old white man with cystic fibrosis in whom pancreatic and hepatic involvement was advanced. There was evidence of secondary hyperparathyroidism with proximal renal tubular acidosis, aminoaciduria, phosphaturia and hypophosphatemia. Treatment with oral pancreatic and parenteral vitamin D supplements led to full recovery of the rachitic syndrome and the proximal renal tubular dysfunction.

Adult↗