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Biomedical subjects

K Okajima

Publications and source records attributed to K Okajima.

At least 271 records · Page 15Linked to original sources

Plasma clearance of sulfobromophthalein and its interaction with hepatic binding proteins in normal and analbuminemic rats: is plasma albumin essential for vectorial transport of organic anions in the liver?

To investigate a possible function of plasma albumin in the vectorial transport of organic anions by the liver, the plasma disappearance of sulfobromophthalein (BSP) and its interaction with plasma and liver cytosolic proteins were studied in normal rats and mutant Nagase analbuminemic rats (NAR). After intravenous administration of BSP, plasma BSP decreased rapidly in both NAR and control animals: plasma clearance values of BSP in NAR and controls were 12.45 and 7.40 ml/min per kg, respectively. Gel exclusion Sephadex G-100 chromatography of BSP with control rat serum revealed a protein peak in the void volume and another in the albumin fraction. BSP chromatographed exclusively with the albumin fraction; binding of BSP to plasma albumin occurred stoichiometrically. Similar studies with NAR serum revealed a single protein peak, in the void volume; a small amount of BSP chromatographed with this protein peak. The amount of BSP that chromatographed with NAR serum protein(s) was 8% of that with control rat serum albumin. Sephadex G-100 chromatography of BSP with control rat liver cytosol revealed four peaks of protein-bound BSP in fractions corresponding to the void volume (fraction X), albumin, glutathione S-transferases (fraction Y, Mr 45,000), and fraction Z (Mr 12,000); fraction Y was the major component of BSP binding. Gel chromatography of NAR liver cytosol with BSP revealed three BSP peaks, fractions X, Y, and Z; fraction X was the major component of BSP binding. Total BSP binding by 30 mg of hepatic cytosolic proteins was 4.5 nmol for controls and 10.4 nmol for NAR. Isoelectric focusing of liver cytosol revealed no quantitative or qualitative differences in glutathione S-transferase isozymes between control and mutant animals. Intravenously administered BSP (5 mumol/kg) rapidly appeared in bile as the free form and the glutathione conjugate in normal rats and NAR; 41% and 57% of injected BSP was excreted within 60 min in NAR and control rat bile, respectively. These results indicate that binding of BSP to plasma albumin is not indispensable to transhepatocyte transport of BSP in vivo.

Animals↗

Topology and some properties of the renal brush border membrane-bound peptidase(s) participating in the metabolism of S-carbamidomethyl glutathione.

Topological features and some properties of the membrane-bound peptidase(s) participating in the metabolism of a glutathione S-conjugate in the kidney were studied. S-Carbamidomethyl glutathione, a model compound for glutathione S-conjugate, was demonstrated to be sequentially hydrolyzed by gamma-glutamyltransferase (5-glutamyl)-peptide:amino-acid 5-glutamyltransferase; EC 2.3.2.2) and peptidase(s) bound to rat renal brush border membrane vesicles. Hydrolysis of S-carbamidomethyl cysteinylglycine was found to be inhibited by 1,10-o-phenanthroline, suggesting a participation of a metal-requiring peptidase in this process. The hydrolytic activity of the membranous peptidase was markedly depressed by cysteinylglycine S-acetyldextran polymer (molecular weight, 500 000), a nonpermeating derivative for cysteinylglycine. Papain treatment of brush border membrane vesicles resulted in the solubilization of most hydrolytic activity toward S-carbamidomethyl cysteinylglycine. Amino-peptidase M was also solubilized from the membrane and the increase in the specific activity of this enzyme in the papain-soluble fraction was in parallel within that of the peptidase activity for hydrolysis of S-carbamidomethyl cysteinylglycine. The hydrolytic activity of purified brush border membrane vesicles toward S-carbamidomethyl glutathione was fully reconstituted by the combined use of purified gamma-glutamyltransferase and aminopeptidase M. These findings indicated that, as in the case of the cleavage of gamma-glutamyl linkage of glutathione and related compounds, hydrolysis of the S-substituted cysteinylglycine occurred exclusively on the lumenal surface of renal brush border membrane as catalyzed mainly by aminopeptidase M.

Aminopeptidases↗

Renal transtubular transport of mercapturic acid in vivo.

When S-benzyl-N-acetyl-L-[U-14C]cysteine, a mercapturic acid, was administered to rats intravenously, the plasma level of radioactivity decreased very rapidly with a concomitant increase in the renal level of radioactivity. The renal radioactivity reached its maximum within 2 min and then decreased rapidly with concomitant appearance of the radioactive mercapturic acid in the urine. Bilateral ligation of the ureters resulted in only a slight decrease in the rate of disappearance of mercapturic acid from the plasma, while bilateral nephrectomy caused a marked retardation of its clearance from the plasma. Intravenous administration of probenecid, a well known inhibitor of a renal transtubular transport system for organic acids, caused a significant retardation of mercapturate clearance from the plasma in both of the control and ureter-ligated animals. The renal accumulation of this mercapturic acid as well as its excretion into urine was inhibited by probenecid. All these data suggested that a mercapturic acid in the plasma was preferentially taken up by renal tubule cells from the basolateral side of plasma membranes via the probenecid-sensitive transtubular transport system and then excreted rapidly into the lumenal space. This transtubular transport of a mercapturic acid seems to constitute an important process in the hepato-renal cooperation in the mercapturic acid biosynthesis in vivo.

Acetylcysteine↗

Diagnostic evaluation of CT and ERCP based on a retrospective analysis of hepato-biliary and pancreatic diseases.

A retrospective analysis was performed in order to evaluate diagnostic accuracies by computed tomography (CT) and by endoscopic retrograde cholangiopancreatography (ERCP). Materials studied were 67 lesions out of 56 cases with hepato-biliary and pancreatic diseases confirmed mainly at surgery. Diagnostic accuracy of the CT & ERCP for the hepato-biliary lesions was 59.5% & 86.5% and that of CT & ERCP for the pancreatic lesions was 60% & 80% respectively. CT scan is useful for diagnosing abscess, cyst or tumors. On the contrary, lesions which invade the hepato-biliary tract or pancreatic duct can be readily diagnosed by ERCP examination. ERCP is less useful for the diagnosis of parenchymatous lesions or infiltration of lesions into the surrounding organs. Therefore, the combined use of both CT and ERCP is important for the diagnosis of hepato-biliary or pancreatic disease.

Biliary Tract Diseases↗

Study on cases of nonvisualized cholecystogram by the use of ERCP.

We used Endoscopic Retrograde Cholangiopancreatography (ERCP) in 77 patient in whom oral cholecystography failed to visualize the gallbladder. ERCP did not visualize the gallbladder in 42%, and poorly visualized it in 58%, however, there was no significant difference in the disease distribution between non- and poorly visualized cases. 63 of the 77 patients underwent surgery. In cases postoperatively diagnosed as gallbladder carcinoma, the prognosis was better in poorly than in non-visualized gallbladder cases. Non- or poor visualization by ERCP in operated cases was due to gallstones in 71%, to common duct stones with intrahepatic calculi in 22%, and to malignant tumors in 17.5%. Our findings suggest that non-visualization of the gallbladder by ERCP should alert the diagnostician to the possibility of malignancy, especially in patients over 50 years of age.

Adolescent↗

Cell injury by antineoplastic agents and influence of coenzyme Q10 on cellular potassium activity and potential difference across the membrane in rat liver cells.

Potential difference across the cell membrane and intracellular activity of the potassium ion in rat liver cells were measured simultaneously using double-barreled potassium ion-selective microelectrodes. Both potential difference across the membrane and K+ activity in liver cells were depressed after treatment with the antineoplastic agents mitomycin C and 5-Flourouracil Dry Syrup, suggesting that these drugs would induce disturbances of cellular energy metabolism in liver cells. When the antineoplastic agents were used in combination with coenzyme Q10, the depression of potential difference across the membrane and K+ activity and the hypofunction of liver cells in energy metabolism were significantly prevented.

Animals↗

Perfusion techniques of the canine pancreas for physiological and secretin response studies.

In vivo and in situ perfusion techniques of the canine pancreas for physiologic and secretin response to studies are described. We developed these modified techniques to clarify the mechanism of the pancreatic exocrine secretion. An analysis was made of some physiological parameters of the pancreas and our findings were compared with those obtained in secretin stimulation of the pancreas. The composition of secretin induced venous effluent and pancreatic juice was investigated. A decrease of pH, pO2 and (HCO-3) in the venous blood and a temporary efflux of K+ from the cell to the perfusate were observed after secretin stimulation. A temporary decrease of perfusion pressure was observed after secretin stimulation and the change is thought to be due to vascular dilatation. Ultrastructural findings from the pancreas perfused for about 1 hour showed no prominent changes.

Animals↗