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Biomedical subjects

H Yoshimura

Publications and source records attributed to H Yoshimura.

At least 325 records · Page 18Linked to original sources
PubMed1990

[Serial changes of the myocardium in patients with Duchenne's muscular dystrophy followed by cardiac nuclear imaging. 5 years' observation].

In order to evaluate the natural course of Duchenne's cardiomyopathy (DMD), 201T1-SPECT and RI cardioangiography with 99mTc-albumin were performed in 14 patients. They were examined once a year for five years except for 6 patients. Hypo-perfusion were observed in both posterior-inferior and anterior wall at 12 years of age and extended to the lateral wall and septum with aging. The degree of cardiac involvement was different in each case. Systolic parameters (LVEF, 1/3 EF, 1/3 ER-mean) tended to decrease with aging from 15 years of age. Diastolic parameters (%EFV, 1/3 FF, 1/3 FR mean) decreased gradually after 16 years of age. Hypokinetic changes of regional wall motion were observed at 15 years of age and they became severely with aging. Although phase delay appeared visually at 16 years of age, standard deviation of phase angle increased from 15 years of age. Follow up studies by 201T1 myocardial SPECT and gated pool scintigraphy revealed well the progression of cardiac involvement in patients with DMD.

Adolescent↗
PubMed1990

Purification of a cytochrome P450 isozyme belonging to a subfamily of P450 IIB from liver microsomes of guinea pigs.

An isozyme of cytochrome P450 was purified from liver microsomes of guinea pigs by HPLC with anion-exchange and hydroxylapatite columns. The isozyme showed a single band of 52 kdalton on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Oxidation activities of the final preparation towards p-nitroanisole, aniline and d-benzphetamine were 1.3 to 15.4-fold comparing with those of microsomal fraction. This isozyme was also concerned with oxidation of delta 9-tetrahydrocannabinol (THC) to 8 alpha-hydroxy- (8 alpha-OH-), 2'-OH- and 3'-OH-delta 9-THCs. The N-terminal region of the isozyme was considerably hydrophobic, and 13 of the first 20 amino acid residues was leucine. Since this first 20 amino acid sequence is 80% homologous with that of cytochrome P450 LM2 purified from rabbit liver microsomes, this isozyme can be categorized to a subfamily of P450 IIB.

Amino Acid Sequence↗
PubMed1990

[Fundamental studies on efficacy of intraoperative radiotherapy on pancreatic carcinomas transplanted into the pancreas of hamsters].

Efficacy of intraoperative electron beam radiotherapy (IOER) on N-nitrosobis (2-hydroxypropyl) amine (BHP) induced pancreatic carcinomas transplanted into the pancreas of the Syrian golden hamsters were studied and the following results were obtained. 1. Selective electron beam application to the carcinoma transplanted into the pancreas of hamsters was accomplished using an electron beam collimator. 2. Intra-pancreatic transplantability of BHP-induced serially transplantable subcutaneous pancreatic carcinomas was 100%. 3. Intra-pancreatic transplanted pancreatic carcinomas disappeared in 2 out of 19 hamsters (11%) by 10 Gy irradiation and 7 out of 15 (47%) by 20 Gy irradiation given 2 weeks after intra-pancreatic transplantation. 4. In contrast to the linear growth of tumor size in the non-irradiated group, the tumor size showed an electron dose-dependent reduction in the irradiated group. 5. Histologically, marked necrosis was noted in the irradiated group, and the intensity of necrosis differed between the 10 Gy and 20 Gy groups. 6. Direct invasion of tumor to the stomach, small intestine, large intestine, liver and abdominal wall was noted. Its incidence tended to decrease as the electron dose increased (5/19 or 26% for the control group, 4/19 or 21% for the 10 Gy group, and 1/17 or 6% for the 20 Gy group), although the difference was not statistically significant. 7. The incidences of liver and lymph node metastasis were not different between the non-irradiated and the irradiated groups. These results suggest that selective IOER on BHP-induced pancreatic carcinomas has an effectiveness to kill cancer cells in hamsters.

Animals↗
PubMed1990

Multiplicity of liver microsomal flavin-containing monooxygenase in the guinea pig: its purification and characterization.

Two distinct forms (FMO-I and FMO-II) of flavin-containing monooxygenase were purified from the liver microsomes of guinea pig. The minimum molecular weights estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were 54,000 for FMO-I and 56,000 for FMO-II, respectively. Tryptic digestion of these enzymes gave different electrophoretic patterns, suggesting that FMO-I and -II have distinct amino acid sequences. The amino terminal sequence of FMO-II could not be estimated probably due to its blocking while that of FMO-I was determined to be highly homologous to the rabbit liver flavin-containing monooxygenase (J. Ozols, 1989, Biochem. Biophys. Res. Commun. 163, 49-55). Absorption maxima of FMO-I and -II were recorded at 368 and 440 nm and 381 and 456 nm, respectively. Molar ratios of FAD to both of these apoenzymes were shown to be one to one. Substrate specificity of FMO-I and -II was determined using 15 compounds as the substrate. The results showed two enzymes that exhibited overlapped but different specificity toward these substrates although FMO-I had lower activity than did FMO-II with all compounds except thiobenzamide. Of particular interest, only FMO-II showed considerably high activities for primary amines, n-octylamine, and n-decylamine. Immunoglobulin G raised against FMO-II could recognize FMO-I as well as FMO-II, but the reactivity of FMO-I toward the antibody was obviously lower than that of FMO-II. Electrophoresis followed by immunostaining revealed that microsomes of lung, kidney, urinary bladder, testis, and spleen contain the same protein as FMO-II and/or FMO-I. Only lung was shown to have an additional isozyme of FAD-monooxygenase with a molecular weight apparently higher than those of FMO-I and -II. These results strongly suggest that at least two forms of flavin-containing monooxygenases distinct from the lung-type isozyme are expressed in liver of guinea pigs.

Amino Acid Sequence↗
PubMed1990

Hepatic microsomal oxygenation of aldehydes to carboxylic acids.

Hepatic microsomal oxygenation of aldehydes to carboxylic acids was investigated. Aldehydes (veratrum aldehyde, cinnamic aldehyde, myrtenal, cuminaldehyde, 3-phenylpropionaldehyde, perillaldehyde and 9-anthraldehyde) were incubated with hepatic microsomes of mice in the presence of an NADPH-generating system under 18O2 (97 atom%). The incorporation of oxygen-18 into carboxylic acids formed was determined by gas chromatography-mass spectrometry. Oxygen-18 was incorporated into the carboxylic acids formed from all aldehyde substrates examined. Hepatic microsomal formation of 3,4-dimethoxybenzoic acid and cumic acid from veratrum aldehyde and cuminaldehyde, respectively, was inhibited by CO and SKF 525-A. These results indicate that the oxygenation of aldehydes which may be catalyzed by cytochrome P450 is a common reaction in the biotransformation of xenobiotic aldehydes.

Aldehydes↗
PubMed1990

Teratological assessment of the antiprotozoal, diminazene diaceturate, in rats.

Diminazene diaceturate was dissolved in deionized water and administered to pregnant rats by oral gavage once daily on days 8-15 of pregnancy at dose levels of 0, 100, 250, 500 and 1000 mg/kg. On day 21 of pregnancy, the dams were killed and the number of implants, resorptions and live fetuses counted. All fetuses were examined by routine teratological method. A significant increase in fetal resorptions and decrease in fetal body weights were found at the 1000 mg/kg dose. No significant increase in the incidence of anomalous fetuses was observed in external, skeletal and internal examinations even at the maternally toxic dose of 1000 mg/kg. Thus, these data indicate that diminazene diaceturate is not teratogenic in rats.

Administration, Oral↗
PubMed1990

Purification and characterization of two forms of 2,3,4,7,8-pentachlorodibenzofuran-inducible cytochrome P-450 in hamster liver.

Two forms of cytochrome P-450 (P-450) from liver microsomes of hamsters treated with 2,3,4,7,8-pentachlorodibenzofuran (PenCDF), which possesses the potent acute toxicity and 3-methylcholanthrene (MC)-type inducing ability of liver microsomal monooxygenases in animals, were purified and characterized. These P-450 forms, designated as hamster P-450H and hamster P-450L, had the molecular masses of 52 and 50 kDa, respectively, and showed the absorption maximum of CO-reduced difference spectra at 446 nm. The absolute spectra of their oxidized forms indicated that hamster P-450H was in high-spin state and hamster P-450L was in low-spin state. A part of PenCDF injected into hamster was tightly bound to purified hamster P-450H at a ratio of 0.107 nmol PenCDF/nmol P-450. In a reconstituted system, both hamster P-450H and hamster P-450L showed relatively low catalytic activities for 3-hydroxylation of benzo[a]pyrene and O-deethylations of both 7-ethoxyresorufin and 7-ethoxycoumarin, while they both catalyzed 7 alpha- and 2 alpha-hydroxylations of testosterone effectively to a similar extent. Addition of cytochrome b5-to a reconstituted system accelerated the formation of 7 alpha-hydroxytestosterone 5.3-fold with hamster P-450L and 2.2-fold with hamster P-450H. In addition, hamster P-450H catalyzed estradiol 2-hydroxylation at a high rate but hamster P-450L did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1990

Equilibrium radionuclide ventriculography in Duchenne's cardiomyopathy.

Myocardial dysfunction in 14 patients with Duchenne's muscular dystrophy (DMD) was evaluated by Tc-99m HSA multigated radionuclide ventriculography (MGRV). Follow-up studies were performed on eight patients for 5 years. Left ventricular ejection fraction and standard deviation of the phase angle were abnormal in all patients older than 15 years. Hypokinetic changes and phase delay were recognizable in most patients older than 17 years. Peak filling rate decreased in patients older than 17 years. MGRV was considered an effective method for evaluating serial changes in cardiomyopathy of patients with DMD.

Adolescent↗
PubMed1990

A human case of zoonotic onchocerciasis in Japan.

A 2-year-old girl living in southwestern Japan had a nodule of 2 months' duration on the left foot. A biopsy from the lesion showed transverse sections of a worm surrounded by granulomatous tissue. The worm was identified as an Onchocerca sp. from the morphological characteristics such as relatively thick cuticles, annular ridges on the cortical layer, and high somatic muscles. Positive serological tests using ELISA for Onchocerca gutturosa and Onchocerca volvulus supported the diagnosis. This was the first case of zoonotic Onchocerca infection detected in Japan. The clinicopathological aspects of zoonotic onchocerciasis of this case were discussed.

Child, Preschool↗
PubMed1990

Pharmacokinetic data of bromofenofos in calves.

Bromofenofos (BF) was administered orally to six calves at a dose of 12 mg/kg and the concentrations of BF and its metabolite dephosphate bromofenofos (DBF) in plasma were determined using a high-performance liquid chromatographic method. DBF reached maximum concentration of 45.9 +/- 16.3 micrograms/ml, which occurred at 1.3 +/- 0.4 days. The elimination half life was calculated to be 1.8 +/- 0.3 days and the area under the plasma concentration versus time curve was 185.1 +/- 49.4 micrograms.day/ml. The ultrafiltrate of plasma samples revealed no free metabolite, indicating a binding of greater than 99% to plasma protein. DBF disappeared from plasma in all calves 21 days after administration. No BF was detected in plasma at any time.

Administration, Oral↗
PubMed1990

Expandable metallic biliary endoprostheses: preliminary clinical evaluation.

A biliary endoprosthesis constructed of self-expanding metallic "Z" stents was placed in 23 patients with obstructive jaundice. The biliary obstruction was due to a malignant neoplasm in 21 patients and a postoperative biliary stricture in two patients. The lesions affected the intrahepatic biliary ducts in 13 patients. Twelve patients had undergone radiation therapy before stent placement. The endoprostheses consisted of 196 expandable metallic biliary stents placed singly (n = 10) or in tandem (n = 186). As many as 18 stents were used to relieve an obstruction in one patient. A transhepatic approach was employed in all patients except one in whom stents were placed through a T-tube tract. Within 1 week after placement, all stents expanded to at least 90% of their original diameter. Three misplaced, two deformed, and two dislodged stents caused no obvious clinical problems. At follow-up, which ranged from 2 to 59 weeks, five patients experienced recurrent jaundice. Two patients with recurrent jaundice due to obstruction of the bile duct containing the stent were treated with external catheter drainage. The expandable biliary endoprosthesis is suggested as an effective treatment for benign and malignant biliary obstruction.

Adult↗
PubMed1990

Species difference in metabolism of strychnine with liver microsomes of mice, rats, guinea pigs, rabbits and dogs.

The metabolism of strychnine was studied with hepatic microsomes of rats, mice, guinea pigs, rabbits and dogs, using high-performance liquid chromatography. Eight metabolites were found by the incubation with rabbit liver microsomes. Five of them were identified as strychnine N-oxide (St N-oxide), 2-hydroxystrychnine (2-OH St), strychnine 21,22-epoxide, 16-hydroxystrychnine (16-OH St) and 18-oxostrychnine by comparing the chromatographic and spectral data to those of authentic samples. Significant differences in metabolic profiles of strychnine were observed among the above species. The main metabolite in rats and mice was 16-OH St, while in guinea pigs and rabbits, and in dogs, it was 2-OH St, and St N-oxide, respectively. The metabolic activity in guinea pig liver microsomes was much higher than those of other species. There seems to be a fairly good inverse correlation between the metabolic activity and strychnine toxicity in guinea pigs and other animal species.

Animals↗
PubMed1990

Metabolism in vivo of 3,4,5,3',4'-pentachlorobiphenyl and toxicological assessment of the metabolite in rats.

Metabolism in vivo of 3,4,5,3',4'-pentachlorobiphenyl (PenCB) and toxicological assessment of the metabolite were investigated using male Wistar rats. Only one metabolite was isolated from the feces of rats administered 3,4,5,3',4'-PenCB. By gas chromatography-mass spectrometry, the methylated metabolite was identified with the synthesized authentic sample, 4'-methoxy-3,4,5,3',5'-PenCB. This indicated that the metabolite was 4'-hydroxy-3,4,5,3',5'-PenCB, which was produced via a 4',5'-epoxide formation and subsequent NIH-shift of the 4'-chlorine to the 5'-position. Administration of the metabolite at either single i.p. dose of 3 or 10 mg/kg to rats did not cause any toxic and biological effects such as body weight loss, atrophy of thymus and spleen, liver hypertrophy, increase of liver lipids, or 3-methylcholanthrene-type induction of liver enzymes. These changes were observed in rats administered with 3,4,5,3',4'-PenCB at a single dose of 3 mg/kg. In addition, a trace amount of 4'-hydroxy-3,4,5,3',5'-PenCB could be detected in rat liver 5 d after treatment with 3,4,5,3',4'-PenCB or 4'-hydroxy-3,4,5,3',5'-PenCB. The amount of this metabolite excreted in feces during 5 d after treatment with 3,4,5,3',4'-PenCB accounted for only 1.3% of dose. In 4'-hydroxy-3,4,5,3',5'-PenCB-treated rats, about 60% of dose was excreted as unchanged in feces for 5 d. These results suggest that this metabolite is a detoxified product and has no longer the high affinity for the liver, being excreted rapidly into the feces.

Animals↗
PubMed1990

Species difference in codeine uridine diphosphate-glucuronyltransferase activity of liver microsomes.

Species difference in codeine uridine diphosphate-glucuronyltransferase (UDPGT) activity was studied in liver microsomes of mice, rats, guinea pigs and rabbits. Codeine UDPGT activity was the highest in guinea pigs, followed by that in rabbits, and the lowest in mice and rats among these four animal species. The specific activities of codeine UDPGT in liver microsomes were not correlated well with those toward morphine, 4-nitrophenol, and 4-hydroxybiphenyl in liver microsomes of each of the species. Inducibility of liver microsomal codeine UDPGT activity in rats was examined by pretreatment with phenobarbital and 3-methylcholanthrene and compared with those of other UDPGT activities. The activity was inducible by phenobarbital pretreatment as the activity toward morphine and 4-hydroxybiphenyl. The inducibility of codeine UDPGT activity by phenobarbital pretreatment was not as high as that of morphine UDPGT activity.

Animals↗
PubMed1990

Rat liver DT-diaphorase as a nitroso-reductase.

Reduction of several nitroso-compounds by purified DT-diaphorase from rat liver cytosol was investigated. Among nitroso-compounds tested, 1-nitroso-2-naphthol and p-nitrosophenol were reduced in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH) at rates much faster than that of nitrosobenzene. On the contrary, none of the N-nitroso-compounds tested was reduced by this enzyme. Experiments on the identification of reduction products and on the inhibition with dicoumarol and the antiserum indicated that DT-diaphorase catalyzes 4-electron reduction of C-nitroso-compounds and plays a major role in the reduction of these compounds by rat liver cytosol.

Animals↗
PubMed1990

Inhibition of hepatic microsomal cytochrome P450 by cannabidiol in adult male rats.

The mechanism of inhibitory effect of cannabidiol (CBD) on the hepatic drug-metabolizing enzyme system was studied in adult male rats in vivo. Time course studies revealed that microsomal d-benzphetamine N-demethylation and testosterone 2 alpha-, 16 alpha- and 17-oxidation were markedly suppressed 6 to 48 h after the single administration of CBD (10 mg/kg, intraperitoneally). Decreases in activities of aniline hydroxylation and p-nitroanisole O-demethylation and in content of total cytochrome P450 were intermittent and moderate. On the other hand, no change was observed in reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase activity or cytochrome b5 content in the hepatic microsomes of the CBD-treated rats. Western blotting analysis showed a marked decrease in the male-specific cytochrome P450 UT-2 in the hepatic microsomes, especially 24 to 48 h after pretreatment with CBD. It is possible that CBD given 6 to 12 h before the sacrifice might interact with cytochrome P450 as a substrate, resulting in inhibition of the drug-metabolizing enzyme activities in the earlier stages. In the later stages from 24 to 48 h after CBD treatment, the reduction in content of the male-specific cytochrome P450 UT-2 may play a major role in the inhibitory effect of CBD on the hepatic drug-metabolizing enzyme system in the adult male rat in vivo.

Animals↗