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Biomedical subjects

H Yoshimura

Publications and source records attributed to H Yoshimura.

At least 487 records · Page 27Linked to original sources
PubMed1985

Cross-tolerance to the hypothermic effect of delta 8-tetrahydrocannabinol 11-hydroxy-delta 8-tetrahydrocannabinol and chlorpromazine in the mouse.

When a 5 mg/kg i.v. dose of delta 8-tetrahydrocannabinol (delta 8-THC) and 11-hydroxy-delta 8-tetrahydrocannabinol (11-OH-delta 8-THC) was administered daily to mice, tolerance to their hypothermic effects developed quickly. Cross-tolerance to the hypothermic effect also developed between delta 8-THC and 11-OH-delta 8-THC. Tolerance development was dose-dependent and dose-effect experiments indicated that the magnitude of the tolerance developed to 11-OH-delta 8-THC was greater than that to delta 8-THC. Both cannabinoids were cross-tolerant to chlorpromazine in the hypothermic effect, but not to morphine, pentobarbital and reserpine under the conditions used. The present results suggest that 11-OH-delta 8-THC has some role in the development of tolerance to the hypothermic effect of delta 8-THC in mice.

Animals↗
PubMed1985

Synthetic and natural Escherichia coli free lipid A express identical endotoxic activities.

The recently chemically synthesized Escherichia coli lipid A and the natural free lipid A of E. coli were compared with respect to their endotoxic activities in the following test systems: lethal toxicity, pyrogenicity, local Shwartzman reactivity, Limulus amoebocyte lysate gelation capacity, tumour necrotizing activity, B cell mitogenicity, induction of prostaglandin synthesis in macrophages, and antigenic specificity. It was found that synthetic and natural free lipid A exhibit identical activities and are indistinguishable in all tests.

Animals↗
PubMed1985

Lack of mutagenicity of fasciolicides.

Six fasciolicides, bithionol, bromofenofos, DS-6, nitroxynil, oxyclozanide and tribromsalan, were tested for mutagenicity in the Salmonella reverse mutation test using S. typhimurium tester strains TA100, TA98, TA1535, TA1537 and TA1538 and the micronucleus test in mice. None of the fasciolicides increased the number of revertant colonies in any tester strain in the presence and absence of S9 mix, nor did they induce a significant increase of the micronuclei in erythrocytes. Taking the high correlation between mutagenicity and carcinogenicity into consideration, these results suggest that the fasciolicides tested in this investigation are devoid of carcinogenic action.

Animals↗
PubMed1985

Reconstructive surgery of head and neck cancer using various pedicle flaps.

Various pedicle flaps were used for the reconstruction of large defects following extirpation of head and neck malignant tumors of 55 patients. Although there are several complications, myocutaneous (MC) island flap surpassed the deltopectoral (DP) flap in the reconstruction of the pharyngo-esophagus, tongue, oral cavity, mandible, and of a massive defect. However, DP flap is still valuable material because of its steadiness in pharyngo-esophageal reconstruction in patients who have background disorders, such as serious heart disease and diabetes. Forehead or DP flap is valuable in the reconstructive surgery of full-thickness defect of the cheek. Reconstruction of extremely large defect of the head and neck could be accomplished by use of latissimus dorsi flap and/or combination with DP flap. Selection of the flap should be made in accordance with the region of the reconstruction, size of region, sex, and individual considerations.

Esophageal Neoplasms↗
PubMed1985

Purification and characterization of seven distinct forms of liver microsomal cytochrome P-450 from untreated and inducer-treated male Wistar rats.

A total of nine forms of cytochrome P-450 were purified to homogeneity from liver microsomes of male Wistar rats. They were P-451 I and P-451 II from untreated rats, P-450 II and P-450 III from phenobarbital-treated rats, MC-P-448 L and MC-P-448 H from 3-methylcholanthrene-treated rats, and P-452, P-448 L, and P-448 H from 3,4,5,3',4'-pentachlorobiphenyl-treated rats. Among them, MC-P-448 L and MC-P-448 H were indistinguishable from P-448 L and P-448 H, respectively, with regard to electrophoretic, spectral, catalytic and immunochemical properties, and thus seven forms were distinct hemoproteins. The minimal molecular weight of each form was as follows: P-451 I (49,000), P-451 II (52,000), P-450 II (52,000), P-450 III (53,500), P-452 (48,000), P-448 L (56,000), P-448 H (54,000). Judging from the oxidized absolute spectra, P-448 H was a high-spin form and the others were of low-spin type. In a reconstituted system, N-demethylations of benzphetamine and aminopyrine were catalyzed by most of the forms at comparable rates. On the other hand, the activities for the oxidations of benzo[a]pyrene, 7-ethoxycoumarin, biphenyl, and estradiol-17 beta varied greatly among the forms of cytochrome P-450. The most efficient catalysts were as follows: P-448 L and P-451 II for benzo[a]pyrene 3-hydroxylation; P-448 L for 7-ethoxycoumarin O-deethylation; P-448 L, P-451 II, and P-448 H for biphenyl 4-hydroxylation; P-448 L and P-448 H for biphenyl 2-hydroxylation; and P-451 II and P-448 H for estradiol 2-hydroxylation. P-451 I, P-450 II, and P-450 III were somewhat poorer catalysts in metabolizing all the substrates except for benzphetamine and aminopyrine, but their substrate specificities were still distinguishable from one another. Of all the purified cytochrome P-450's, P-452 showed the least ability to metabolize all the substrates. Judging from the properties, it appears that six forms in male Wistar rats correspond to the distinct forms of cytochrome P-450 in Long-Evans and/or Sprague-Dawley rats reported by other workers, but P-451 I is a new constitutive isozyme in Wistar rats.

Animals↗
PubMed1985

An improved assay method for thyroid peroxidase applicable for a few milligrams of abnormal human thyroid tissues.

A peroxidase assay method (Mini assay method) which is applicable for a minute amount (as small as a few mg) of thyroid tissue was developed, employing guaiacol or iodide as the second substrate. This method is a modification of the previous one (Ordinary assay method): the volume of the reaction mixture was reduced to about one-tenth with prior solubilization of the enzyme. The correlation between the Mini assay and Ordinary assay methods, and between the guaiacol and iodide assays by both methods were satisfactorily good, but the iodine content of thyroglobulin was found to be not directly correlated to the peroxidase activities. Protein-based specific activities of peroxidase from normal human thyroid tissue were about 0.030 guaiacol units/mg protein and 0.0066 iodide units/mg protein, which were slightly higher than those of porcine thyroid tissue. The Mini assay method developed in the present study was used for the determination of peroxidase activity in a small amount (1-8 mg) of thyroid tissue obtained by means of a needle biopsy from patients with thyroid disorders. One specimen (goitrous cretinism) showed no peroxidase activity in both the guaiacol and iodide assays, and three specimens (two chronic thyroiditis, one familial nontoxic goiter) possessed no ability to catalyze the oxidation of iodide in spite of the high reactivity towards guaiacol, suggesting the presence of an abnormal peroxidase in these tissues.

Animals↗
PubMed1985

Hepatocellular carcinoma detected by iodized oil. Use of anticancer agents.

Transcatheter arterial embolization (TAE) was performed in 97 patients with hepatocellular carcinoma. Ethiodol (iodized oil) containing an anticancer drug was infused via the hepatic artery followed by Gelfoam particles. The Ethiodol emulsion was selectively retained in the tumor vessels and also remained in the small daughter nodules that could not be detected by angiography or computed tomography (CT) prior to TAE. Ethiodol remained in the tumor for more than 1 year. Following TAE, main tumors and small daughter nodules appeared as areas of markedly high density on CT. In most patients there was a reduction in the tumor size following TAE, and serum alpha-fetoprotein levels were reduced in all patients whose initial levels had exceeded 400 ng/ml. This method is considered to be effective not only for treatment of hepatic tumor but also useful for evaluation of post-TAE changes in the tumor and diagnosis of small daughter nodules, due to the long-term accumulation of Ethiodol in tumor vessels.

Adult↗
PubMed1985

Noninvasive pulsed Doppler echocardiographic detection of the direction of shunt flow in patients with atrial septal defect: usefulness of the right parasternal approach.

Noninvasive pulsed Doppler echocardiography combined with two-dimensional echocardiography by the right parasternal approach was performed to detect the shunt flow through the defect in 31 patients with suspected secundum atrial septal defect (ASD). A defect of the interatrial septum was seen on the two-dimensional echocardiograms of 30 of 31 patients. In all the 30 patients, Doppler signals of shunt flow could be recorded by placing the sample volume in the center of the defect on the two-dimensional echocardiogram. Neither a defect nor Doppler signal indicating shunt flow were demonstrated in any of 15 normal control subjects. Cardiac catheterization indicated significant shunt flow in all the 31 patients with suspected ASD. Doppler signals obtained from the center of the defect showed left-to-right and/or right-to-left shunt flow patterns. The direction of the shunt flow was mainly left to right, with its peak in late systole and atrial systole in 28 of 30 patients; mainly right-to-left flow was present in the remaining two patients, who had Eisenmenger's syndrome. The direction of flow as predicted by the Doppler signal was confirmed by the coincidence of direction of flow as seen on the contrast two-dimensional echocardiogram. In 22 patients for whom the measurement of the pulmonary-to-systemic flow ratio by oximetry was believed to be reasonably accurate, the ratio was fairly well correlated with Doppler-determined left-to-right shunt flow velocity (r = .71, SEE = 6.7 cm/sec).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Production of systolic anterior motion of the mitral valve in dogs.

Production of an experimental preparation of systolic anterior motion (SAM) of the mitral valve was attempted for the purpose of clarifying its causal factors. Fourteen thoracotomized dogs under pentobarbital anesthesia were administered dobutamine, and the echocardiogram, left ventricular pressure, and aortic pressure of each were simultaneously recorded. In two of the dogs in which SAM was produced, two-dimensional echocardiograms were also obtained. Although SAM was absent in all 14 dogs before the administration of dobutamine, it appeared in nine of them after the drug was given. In seven of these dogs, the magnitude of SAM and outflow pressure gradient varied in a dose-dependent manner. No signs of asymmetric septal hypertrophy were observed in any of these dogs. SAM tended to occur even when there was no reduction in preejection period when narrowing of the left ventricular outflow tract was observed. On the two-dimensional echocardiograms, the position of coaptation of the mitral valve was shifted closer to the base of the anterior leaflet in the presence of dobutamine-induced SAM than before the drug was administered. Although the left ventricular cavity became narrow, it was not completely obliterated. This study demonstrates that experimental preparations of SAM can be produced by the administration of dobutamine with a relatively high success rate in normal dogs, and that experimental SAM is accompanied by an outflow tract pressure gradient.

Animals↗
PubMed1985

Effect of liver S9 from 3,4,5,3',4'-pentachlorobiphenyl-pretreated rats on the mutagenic activity of the various carcinogens toward Salmonella typhimurium TA 98.

Effects of liver 9000 X g supernatant fraction from 3,4,5,3',4'-pentachlorobiphenyl- and 2,4,5,2',4',5'-hexachlorobiphenyl-pretreated rats (PenCB-S9 and HexCB-S9, respectively) on the mutagenic activities of well-known carcinogens, benzo-[a]pyrene (BP), Glu-P-1 (2-amino-6-methyldipyrido [1,2-a:3',2'-d]imidazole), Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole), and aflatoxin B1 (AFB), toward Salmonella typhimurium TA 98 have been described. Although the mutagenic activities of all of these carcinogens were enhanced by these S9, PenCB-S9 especially highly activated BP, Glu-P-1, and Trp-P-1. The ability of PenCB-S9 to activate the carcinogens was much higher than that of liver 9000 X g supernatant fraction from 3-methylcholanthrene-pretreated rats (MC-S9). PenCB-S9 enhanced the mutagenic activity of BP 8 times higher than MC-S9, while Glu-P-1 and Trp-P-1 were activated by PenCB-S9 twice as much as by MC-S9. Effect of HexCB-S9 on the mutagenic activities of the above-mentioned three carcinogens was much less than those of PenCB- and MC-S9 and a little higher than that of 9000 X g supernatant fraction from rats pretreated with phenobarbital. As for AFB, phenobarbital was the most potent inducer, and HexCB and PenCB were next to this. Data suggest that PenCB is a strong inducer of P-448 species which activate environmental toxicants.

Aflatoxin B1↗
PubMed1985

Promotion of the selective lymphatic delivery of cyclosporin A by lipid-surfactant mixed micelles.

The absorption of an immunosuppressive drug, cyclosporin A (CsA), with the aid of lipid-surfactant mixed micelles from the rat gastrointestinal (GI) tract and lymphatic delivery were studied. The administration of CsA in oily solution, sesame oil or linolic acid, into the rat duodenum indicated a small amount of CsA both in the plasma and lymph for about 6 h. The administration of CsA in the mixed micellar solution composing of linolic acid and HCO-60, polyoxyethylated (60 mol) hydrogenated castor oil, accelerated the absorption of CsA from the GI tract, and CsA was delivered into the lymphatics with an extremely high selectivity.

Animals↗
PubMed1985

Accumulation, excretion and effects on hepatic enzymes of polychlorinated quaterphenyl congeners in rats.

Six skeletal congeners of polychlorinated quaterphenyls (PCQs), namely polychlorinated o-quaterphenyl (2,2'-PCQ), 2,3'-diphenylbiphenyl (2,3'-PCQ), 2,4'-diphenylbiphenyl (2,4'-PCQ), m-quaterphenyl (3,3'-PCQ), 3,4'-diphenylbiphenyl (3,4'-PCQ) and p-quaterphenyl (4,4'-PCQ), were orally administered to Wistar rats at a dose of 10 mg/rat. On the 5th day after administration of PCQs, the rats were examined for accumulation of PCQ congeners, hepatic enzyme activities and organ weight changes. Accumulation of 3,3'-PCQ, 3,4'-PCQ and 4,4'-PCQ were 1.5-3.2% of dose in the liver, while those of 2,2'-PCQ, 2,3'-PCQ and 2,4'-PCQ were only 0.1 to 0.2%. The amount of 4,4'-PCQ accumulated in the mesenteric adipose tissue, 20 micrograms/rat, was much higher than those of other PCQ congeners. Large amounts of the PCQ congeners administered were excreted in the feces on the first day, accounting for 96 to 98% of dose for 2,2'-PCQ and 4,4'-PCQ, and 55 to 75% for the other PCQ congeners, and the daily excretions of PCQs after the second day were very small, less than 10% of the dose. Benzo [a] pyrene 3-hydroxylase activity was significantly depressed by the treatment with 3,3'-PCQ, 3,4'-PCQ and 4,4'-PCQ, contrasting to the toxic congeners of polychlorinated biphenyls and dibenzofurans which enhanced markedly this enzyme activity. DT-Diaphorase activity was also depressed by the treatment with 2,3'-PCQ, 2,4'-PCQ and 3,4'-PCQ. Significant atrophy of the thymus was observed by the treatment with 4,4'-PCQ.

Adipose Tissue↗
PubMed1985

Unique induction of cytochrome P-450 isozymes in rat liver microsomes by treatment with 3,4,5,3',4'-pentachlorobiphenyl and its effect on testosterone metabolism.

Pretreatment of male Wistar rats with 3,4,5,3',4'-pentachlorobiphenyl (PenCB), a potent 3-methylcholanthrene-type inducer, increased selectively 7 alpha-but strongly repressed 2 alpha-, 6 beta- and 16 alpha-hydroxylations of testosterone in the liver microsomes. To understand this unique phenomenon, the testosterone metabolism by three isozymes (P-452, P-448 L and P-448 H) of cytochrome P-450 purified from Wistar rats treated with PenCB was studied in a reconstituted system. For comparison 4 other isozymes (P-451 I, P-451 II, P-450 II and P-450 III) of cytochrome P-450 from untreated and phenobarbital-treated rats were also studied. In addition, the contribution of cytochrome P-450's to testosterone hydroxylation was examined by an immune complex inhibition of the activity and by a determination of the individual cytochrome P-450 in microsomes using antibodies. In the reconstituted system, 7 alpha-hydroxylation of testosterone was catalyzed almost exclusively by P-452, with the exception of P-451 I. On the other hand, the 6 beta-hydroxylation was catalyzed by most of the cytochrome P-450's tested at considerably lower rates. Among the seven forms, P-451 II was the most effective catalyst for 2 alpha- and 16 alpha-hydroxylations, with equally high turnover numbers, while other forms showed only low or no activity for either or both hydroxylations. The microsomal activity of 7 alpha-hydroxylation in PenCB-treated rats was inhibited almost completely by anti-P-452. A partial inhibition of the 16 alpha-hydroxylation was achieved by anti-P-451 II and anti-P-452 while the 6 beta-hydroxylation was insensitive to anti-P-451 II but slightly sensitive to anti-P-452. The activity of 2 alpha-hydroxylation was not detected in the liver microsomes from PenCB-treated rats. Immunochemical quantitation showed that in the microsomes from PenCB-treated rats, P-451 II, P-452, P-448 L and P-448 H accounted for 4.1, 3.6, 31.6 and 62.8%, respectively, of the total cytochrome P-450 (2.69 nmol/mg protein). On the other hand, the microsomal cytochrome P-450 in untreated rat livers (0.83 nmol/mg protein) consisted of 62.7% as P-451 II, less than 1% as P-452 and the remainder as P-451 I and other unknown forms.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Metabolism and nephrotoxicity of phenacetin and sulfanilamide.

The mechanisms of renal damage produced by sulfanilamide and phenacetin were studied. N-Hydroxyphenacetin, 4-hydroxylaminobenzenesulfonamide (4-HABSA) and p-aminophenol were established to be nephrotoxic metabolites. As well as N-hydroxylase activity of sulfanilamide, that of phenacetin in kidney microsomes of rats was increased about 4 times by pretreatment with 3, 4, 5, 3', 4'-pentachlorobiphenyl (PenCB) which is a potent inducer of cytochrome P-448. Parallel to this enzyme induction, pretreatment with PenCB enhanced the nephrotoxicity of phenacetin and sulfanilamide in rats. On the other hand, the formation of p-aminophenol from phenacetin was also confirmed in rat kidney in vitro. These results suggested that 4-HABSA, N-hydroxyphenacetin and p-aminophenol formed in kidney play an important role in the renal damage produced by sulfanilamide and phenacetin.

Animals↗
PubMed1985

Inductive effect on hepatic enzymes and toxicity of congeners of PCBs and PCDFs.

The present paper describes a marked induction of liver microsomal cytochrome P-450 and cytosolic DT-diaphorase to cause possible disorder of steroid homeostasis and promotion of carcinogenicity of 4-nitroquinoline N-oxide (4-NQO) in rats by pretreatment with 3,4,5,3',4'-pentachlorobiphenyl (PenCB) or 2,3,4,7,8-pentachlorodibenzofuran (PenCDF). The animals were sacrificed 5 days after the pretreatment. These induction experiments showed that 7 alpha-hydroxylation of both progesterone and testosterone in liver microsomes was selectively increased to a great extent, but hydroxylations at the 2 alpha-, 6 beta- and 16 alpha-positions were depressed, together with 5 alpha-reduction. From the same microsomes, three of the strongly induced P-450 isozymes, i.e., high- and low-spin P-448s and P-452, were purified. The last isozyme was most responsible for 7 alpha-hydroxylation of testosterone. The pretreatment, also increased activity of DT-diaphorase and reduction of 4-NQO about 10-fold in liver 9000g supernatants. This reduction of 4-NQO was solely catalyzed by DT-diaphorase and the only product was 4-hydroxylaminoquinoline N-oxide, a proximate carcinogen, indicating that the pretreatment strongly increased production of a proximate carcinogen from 4-NQO. Such an enhancement of the metabolic activation of 4-NQO by the pretreatment was also observed to some extent in the lung and the skin. Persistency of PenCB and PenCDF in the liver of rats was also discussed.

4-Nitroquinoline-1-oxide↗
PubMed1985

Stereospecific hydrolysis of 8 alpha,9 alpha- and 8 beta,9 beta-epoxyhexahydrocannabinols in the mouse in vivo and in vitro.

After i.v. injections to the mouse, both 8 alpha,9 alpha- and 8 beta,9 beta-epoxyhexahydrocannabinols (EHHCs) were easily hydrolysed to 8 beta,9 alpha-dihydroxyhexahydrocannabinol (dihydroxy-HHC) rather than 8 alpha,9 beta-dihydroxy-HHC in the liver. 8,9-Dihydroxy-HHCs hydroxylated at the 2' or 3' position of a pentyl side-chain were identified in vivo as liver metabolites of the epoxides. The same stereospecific hydrolysis of 8,9-EHHCs were observed in vitro using liver-microsomal fractions of mice, though both epoxides were resistant to enzymic hydrolysis. Several monohydroxylated 8,9-EHHCs, together with small amounts of 8,9-dihydroxy-HHCs were identified as in vitro liver metabolites of the epoxides. These metabolites could be formed not only by epoxide hydrolase but also by a mono-oxygenase system involving cytochrome P-450. The magnitude of the binding affinities of cannabinoids to cytochrome P-450 was ranked in the following order: delta 8-tetrahydrocannabinol (spectral dissociation constant Ks = 9.4 microM) greater than 8 beta,9 beta-EHHC (13.3 microM) greater than 8 alpha,9 alpha-EHHC (34.5 microM).

Animals↗