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Biomedical subjects

M Nakano

Publications and source records attributed to M Nakano.

At least 973 records · Page 54Linked to original sources

On the mechanism of the peroxidase-catalyzed oxygen-transfer reaction.

We reported evidence that horseradish peroxidase (HRP) and chloroperoxidase (CPO) catalyze oxygen transfer from H2O2 to thioanisoles [Kobayashi, S., Nakano, M., Goto, T., Kimura, T., & Schaap, A. P. (1986) Biochem. Biophys. Res. Commun. 135, 166-171]. In the present paper, the reaction mechanism of this oxygen transfer is discussed. The oxidation of para-substituted thioanisoles by HRP compound II showed a large negative rho value of -1.46 vs. the sigma + parameter in a Hammett plot. These results are in accord with the formation of a cation radical intermediate in the rate-determining step. Hammett treatments for HRP- and CPO-dependent S-oxygenations did not provide unequivocal proofs to judge the reaction mechanism, because of the poor correlations for sigma + and sigma p parameters. Different behavior was found in kinetics and stereoselectivity between the two enzymes. Results in the present study and recent studies strongly suggested the formation of a cation radical intermediate. The oxygen atom would transfer by reaction of compound II and the cation radical intermediate. Although involvement of the cation radical was not confirmed in the CPO system, a similar mechanism was proposed for CPO.

Chloride Peroxidase↗

Comparison of Streptomyces griseus and bovine trypsin by active site analysis using fluorescent acyl groups.

The preparation of fluorescence labeled acyl enzymes (Streptomyces griseus trypsin) was successfully carried out using specific trypsin substrates, 'inverse substrates'. The topographical analysis of the structures of the area around the active site was carried out by measuring the fluorescence spectra of the acyl enzyme preparations and these results were compared with those of bovine trypsin. It was found that the polarity of the active site vicinity at pH 5 was similar to that of bovine trypsin, whereas considerable differences were noticed at lower pH as a result of pH-induced transformation. Conformational changes of the active site induced by the interaction with the specific ligand were analyzed from the fluorescence spectra. In these responses the two enzymes were quite distinguishable. The two enzymes active sites were also different in the energy transfer experiments. The spatial arrangements of the catalytic residues relative to the intrinsic tryptophan residues were suggested to be substantially different for the two enzymes.

Affinity Labels↗

Selective anticancer effects of 3',5'-dioctanoyl-5-fluoro-2'-deoxyuridine, a lipophilic prodrug of 5-fluoro-2'-deoxyuridine, dissolved in an oily lymphographic agent on hepatic cancer of rabbits bearing VX-2 tumor.

3',5'-Dioctanoyl-5-fluoro-2'-deoxyuridine (FdUrd-C8), one of the lipophilic prodrugs of 5-fluoro-2'-deoxyuridine (FdUrd) was dissolved in an oily lymphographic agent (Lipiodol Ultra-Fluid), which had been studied as a carrier of the anticancer drug for hepatic cancer. The prodrug was administered into the left proper hepatic artery of rabbits bearing VX-2 tumor in the liver in order to examine the anticancer effects and possible adverse effects on nontumorous hepatic cells. Lipiodol or FdUrd-C8*Lipiodol selectively remained in the hepatic cancer area but disappeared from nontumorous parts of the liver 7 days after injection. Tumor growth rates in 1 week of the untreated group, a group given injections of 0.2 ml of Lipiodol alone, and groups given injections of 0.2 ml of Lipiodol containing 30, 50, 70, and 100 mg of FdUrd-C8 were 636, 436, 34.8, 14.9, -2.4, and -10.4% of the size at the time of treatment, respectively. Pathological observation also showed that FdUrd-C8 had a strong anticancer effect on VX-2 tumor growing in the liver of the rabbits. In contrast to the effect on the cancerous cells, that on nontumorous hepatic cells was very slight. In pathological observation, necrosis or degeneration of nontumorous hepatic cells was hardly observed. Plasma glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase levels temporarily rose 1 day after injection but returned to the initial levels within 7 days in all groups.

Animals↗

Novel and potent biological antioxidants on membrane phospholipid peroxidation: 2-hydroxy estrone and 2-hydroxy estradiol.

Catechol estrogens, 2-hydroxy estrone, 2-hydroxy estradiol and 2-hydroxy estriol, were tested as possible antioxidants of phospholipid peroxidation induced by Fe3+-ADP-adriamycin, using phospholipid liposomes as lipid source and alpha-tocopherol or other steroids as reference compounds. The parameters of antioxidant activities were: elongation of induction period, inhibition of O2 consumption required for lipid peroxidation and inhibition of peroxidative cleavage of unsaturated phospholipid. Of the tested compounds, 2-hydroxy estradiol or 2-hydroxy estrone had more potent activity than that of tocopherol.

Adenosine Diphosphate↗

Estrogens as natural antioxidants of membrane phospholipid peroxidation.

Estrogens, such as estrone, estradiol and estriol, were tested as possible antioxidants of lipid peroxidation induced by Fe3+-ADP-adriamycin or Fe3+-ADP-ascorbate. The estrogens with phenolic structure possessed substantial activities with respect to the inhibition of lipid peroxidation. Concentrations of estradiol and estriol required to achieve 50% inhibition of membrane phospholipid peroxidation were about 4- and 6-times that of alpha-tocopherol, respectively.

Animals↗

Elevation of urinary trehalase activity in patients of itai-itai disease.

The elevation of urinary trehalase activity in patients of itai-itai disease was examined. Urinary trehalase was correlated with tubular reabsorption of phosphorus (%TRP): the lower the trehalase activity, the worse was %TRP. Furthermore, this activity was inversely correlated with urinary glucose and urinary total protein. In itai-itai disease, the excretion of beta 2-microglobulin seems to be maximal, and urinary trehalase activity was low in the latter stages of the disease. It is inferred that itai-itai disease produces extremely severe tubular damage as well as glomerular dysfunction.

Aged↗

Portal hemodynamics in idiopathic portal hypertension (Banti's syndrome). Comparison with chronic persistent hepatitis and normal subjects.

A comparative study of portal hemodynamics was made in 17 patients with idiopathic portal hypertension, 5 patients with chronic persistent hepatitis having no portal hypertension, and 21 healthy adults who served as the control for certain measurements. Venous pressures were measured by portal and hepatic vein catheterizations, blood flow by the pulsed Doppler flowmeter, organ volume by computed tomography, and intrahepatic shunt index by 99mTc-macroaggregated albumin instilled in the portal vein. The patients with idiopathic portal hypertension were divided into two groups: group A (n = 8) and group B (n = 9), consisting of those who respectively had portal venous flow per liver volume above and below the mean + 2 SD of healthy adults. In group A, portal vein pressure was moderately elevated, portal venous flow was significantly increased compared with the control, and portal vascular resistance was not much altered. In group B, portal vein pressure was markedly elevated above that of control, portal venous flow was comparable, and portal vascular resistance was significantly elevated. Splenic venous flow measured in the splenic vein between the left and short gastric veins was markedly increased in groups A and B, the increase being greater in the former. It was concluded that in some patients with idiopathic portal hypertension, increased portal venous flow, partly a result of increased splenic venous flow secondary to splenomegaly of an undetermined process, is the main contributor initially to the elevation of portal vein pressure; in others, possibly later, increased portal vascular resistance plays an important role.

Adult↗

Response of pancreatic tumor to intraoperative radiotherapy: medical imaging and pathologic system approach.

For analyzing the local reaction of pancreatic carcinoma to electron intraoperative radiotherapy, successive computed tomography scanning for tumor volumetry was employed, together with surgical clip localization for tumor area using orthogonal x-rays. Soon after radiotherapy the tumor volume and clipped tumor region began to decrease. After a certain interval, computed tomography volumetry revealed that the irradiated tumor had started to increase in size again, whereas the clipped area had not. Autopsies demonstrated that the increase related chiefly to cancer regrowth outside the primary radiation field.

Aged↗

Muscle D-glyceraldehyde-3-phosphate dehydrogenase from Anas sp.--1. Purification and properties of the enzyme.

Muscle D-GPDH from Anas sp. ws isolated and purified. Basic kinetic constants and physico-chemical studies are reported. The enzyme is a tetramer with a mol. wt of 140,000. Sodium dodecyl sulfate polyacrylamide gel electrophoresis gave s single band with a mol. wt of approx. 36,000. The other catalytic properties of the enzyme are discussed relative to those of enzyme obtained from other sources.

Animals↗

Severity of tubular brush border damage in cadmium-polluted area (Jinzu river basin): clinical role of urinary trehalase.

Urinary trehalase activity and leucine aminopeptidase activity were parabolically correlated with urinary beta 2-microglobulin, and these enzymes were observed to be biphasic in relation to urinary beta 2-microglobulin when the study populations included patients of Itai-itai disease and inhabitants of a cadmium-polluted area. Furthermore, urinary trehalase activity was parabolically correlated with urinary total protein and urinary glucose. From these results, it is inferred that by measuring both urinary trehalase and urinary beta 2-microglobulin, one can elucidate the degree of tubular damage.

Aged↗

Two cases of NADH-coenzyme Q reductase deficiency: relationship to MELAS syndrome.

Muscle biopsy specimens from two patients with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) were studied biochemically. 14CO2 production rates from (1-14C)pyruvate, (U-14C)malate, and (1-14C)2-ketoglutarate were all decreased in intact mitochondria in both patients. Rotenone-sensitive NADH cytochrome c reductase activities were decreased to 8% (patient 1) and 6% (patient 2) of control values; succinate cytochrome c reductase and cytochrome c oxidase values were within normal limits. These results indicate that both patients have a defect of NADH-CoQ reductase of the respiratory chain and that MELAS can be brought about by a defect of NADH-CoQ reductase.

Acidosis, Lactic↗

Operative fiberoptic nephroureteroscopy: removal of upper ureteral and renal calculi.

We tested 2 prototypes of an operating fiberoptic nephroureteroscope, measuring 3.5 and 4.5 mm. in diameter, that have an adequate working channel for auxiliary instruments and irrigation. Difficulty in passing the fiberscope through the ureteral orifice was overcome by dilation with balloon and polytetrafluoroethylene (Teflon) dilators. Our initial trial for stone retrieval under fiberscopic control was performed on 21 patients with upper ureteral and renal calculi. A stone was removed successfully in 15 of the 21 patients (71 per cent). After electrohydraulic lithotripsy calculi were extracted successfully in 9 of 11 patients (82 per cent). Three patients suffered ureteral perforation. The fiberscope was especially helpful when an upper ureteral stone moved back to the kidney during stone manipulation.

Adult↗

Fetal ascites. A report of 3 autopsy cases.

Three rare autopsy cases of fetal ascites were presented and the etiology of each case was described. Case 1 was a male neonate, delivered by cesarean section at 32 weeks' gestation, and died of respiratory failure. The abdomen was remarkably distended with 1020 ml of ascites. The etiology of Case 1 remained unknown even after macroscopic and microscopic examinations. We considered this as "idiopathic" fetal ascites. Case 2 was a female neonate, delivered at 31 weeks' gestation, with marked abdominal distension and cyanosis. Autopsy revealed 435 ml of ascites, and she was considered to have had "polysplenia syndrome" with cardiovascular malformations. Intrauterine heart failure due to cardiac anomalies was thought to be the cause of this ascites. In case 3 embryotomy was carried out under the diagnosis of fetal ascites by ultrasound examination at 22 weeks' gestation. An urachal cyst connected to the dilated urinary bladder and deficiency of musculature of the abdominal wall composed of loose connective tissue with calcification were observed. The abdominal wall was ruptured and 1,960 ml of ascites was measured. Polycystic kidney with renal dysplasia was also found. Case 3 showed "Prune-Berry syndrome" and fetal ascites may have arisen from these anomalies.

Abortion, Induced↗

The intestinal dialysis of intravenously administered phenytoin by oral activated charcoal in rats.

The effect of oral administration of activated charcoal on total body clearance of phenytoin following intravenous administration was studied in rats. In situ single-pass perfusion study showed that phenytoin was exsorbed into the small intestinal lumen. The exsorption of the drug from blood into the intestinal lumen was increased in a dose-dependent manner. The exsorption rate of the drug at the dose of 10 mg/kg was 1.1% in 120 min, while that at 50 mg/kg was 2.5% in 120 min. The excretion of the conjugate of 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) into the bile was greater than phenytoin and unconjugated p-HPPH and the total percentage of excretion of p-HPPH was significantly decreased by increasing the dose. Oral activated charcoal had little effect on the serum phenytoin levels after the 10 mg/kg dose. On the other hand, charcoal reduced the serum phenytoin levels after the 50 mg/kg dose as compared with the corresponding controls. Oral administration of activated charcoal decreased the serum half-life to 77% and the area under the serum concentration-time curve to 75% after the 50 mg/kg dose of phenytoin. The apparent volume of distribution was not significantly different between rats with activated charcoal treatment and rats without charcoal treatment. Based on these results, a mechanism of the enhanced clearance of phenytoin at a high dose (50 mg/kg) may be due to the adsorption of the drug and its metabolites transported into the gastrointestinal tract by the charcoal.

Animals↗

Evaluation of orally administered activated charcoal on intestinal dialysis of intravenously administered M79175, an aldose reductase inhibitor, in rats.

The effect of oral administration of activated charcoal on serum elimination of 14C-M79175 injected intravenously in rats was studied. In situ single-pass perfusion studies showed that M79175 and/or its metabolites was transported into the small intestinal lumen. Total radioactivity expressed as equivalents of M79175 exsorbed in the perfusate and excreted in the bile juice was 3.2% and 2.0%, respectively, of dose. Oral administration of multiple doses of activated charcoal significantly decreased the serum concentration and serum half-life of 14C-M79175. The fecal excretion of 14C-M79175 after treatment with activated charcoal was increased when compared to that in the control. On the other hand, urinary excretion of 14C-M79175 after treatment with activated charcoal was decreased. However, there was no significant difference in the cumulative amounts of total excretion (fecal plus urinary excretion) between rats with activated charcoal treatment and rats without charcoal treatment. These results suggest that intestinal dialysis by oral activated charcoal is a reasonable method to enhance the elimination of M79175 from the serum in case of overdose of the drug.

Administration, Oral↗

Effect of activated carbon beads on serum lipid levels and fecal bile acid excretion in rats.

The effects of oral activated carbon beads on the total serum cholesterol and triglyceride levels and on the fecal bile acid excretion in rats fed a basal or high cholesterol diet containing 5% activated carbon beads for 6 weeks were investigated. The beads appeared to exert little effect on the growth rate of rats and no tendency towards constipation was also observed. Although treatment with activated carbon beads gave little influence on the total serum cholesterol and serum triglyceride levels in rats fed either a basal or high cholesterol diet, the beads did produce a significant rise in the total fecal bile acid excretion. The extra fecal bile acids resulted chiefly from an increase in lithocholic acid. Furthermore, the beads showed a tendency to inhibit absorption of dietary cholesterol from the gastrointestinal tract in rats fed a high cholesterol diet. These results suggested the possibility of activated carbon beads as a hypocholesterolemic agent through binding with bile acids in the intestine.

Animals↗