PubMed Health⌕ Search

Biomedical subjects

Y Shiozaki

Publications and source records attributed to Y Shiozaki.

At least 19 recordsLinked to original sources
PubMed2000

Effects of rifampin on the glutathione depletion and cytochrome c reduction by acetaminophen reactive metabolites in an in vitro P450 enzyme system.

The present study examined whether rifampin attenuated glutathione (GSH) depletion by acetaminophen reactive metabolites generated in the in vitro P450 enzyme system prepared from mouse liver and the possible mechanism involved in this effect. The results showed that GSH concentration was decreased concentration-dependently by acetaminophen in the in vitro P450 enzyme system. Rifampin significantly attenuated acetaminophen-mediated GSH depletion in a concentration-dependent manner. The concentration-response curve for GSH depletion of acetaminophen was shifted to the right in a parallel fashion in the presence of rifampin at the concentration of 3.2 x 10(-5) M, which appeared to result from the competitive binding of rifampin to acetaminophen metabolites. Cytochrome c was markedly reduced by acetaminophen metabolites in this enzyme system, and GSH concentration-dependently increased the cytochrome c reduction by acetaminophen metabolites. These findings suggested that cytochrome c was reduced by the GSH conjugate of acetaminophen metabolites rather than by acetaminophen-derived superoxide anion (O2*-) and other unbound free radicals. Rifampin was shown to possess an effect similar to that of GSH. It is concluded that the decrease in GSH depletion by rifampin is most likely attributable to the binding of rifampin to the acetaminophen toxic species, and the increase in cytochrome c reduction by rifampin is attributable to the conjugate formed between rifampin and acetaminophen metabolites.

Acetaminophen↗
PubMed1997

MRI of normal anterior cruciate ligament (ACL) and reconstructed ACL: comparison of when the knee is extended with when the knee is flexed.

The purpose of this study was to evaluate, using MRI, the morphology of normal anterior cruciate ligament (ACL) and ACL grafts when the knee was extended compared with when the knee was flexed. Eighteen normal controls and 22 ACL graft patients were studied. Spin-echo (SE) T1-weighted images (TR 330 ms/TE 15 ms, NEX 1) were obtained with a slice thickness of 3 mm. Oblique sagittal images parallel to the ACL were obtained at various flexed angles of the knee joint. In 12 of the 18 normal controls the ACL appeared convex toward the posterior side when the knee was extended and gradually became straight when the knee was flexed. In 15 of the 22 ACL graft patients the grafts appeared straight when the knee was extended and became convex toward the anterior side when the knee was flexed. It is concluded that the morphological changes seen on MR images of ACL grafts from when the knee is extended to when the knee is flexed are different from those in the normal ACL.

Adolescent↗
PubMed1995

Lewis Y antigen expression in hepatocellular carcinoma. An immunohistochemical study.

BACKGROUND: The altered expression of the Lewis blood group-related antigens during malignant transformation can be used clinically as a tumor marker or as a prognostic indicator. The Lewis Y (LeY) antigen, which is one of the Type 2 human blood group-related antigens, also is thought to behave as an oncodevelopmental cancer-associated antigen. In this study, the authors examined the association between human LeY antigen expression and the clinicopathologic features of HCC, including its proliferative activity. METHODS: Forty-six histologically confirmed cases of HCC were studied retrospectively. Liver biopsy specimens from the main tumor of each case were obtained under ultrasonic guidance before treatment was initiated. The formalin fixed, paraffin embedded serial sections were immunostained using a modification of the avidin-biotin-peroxidase complex method, with a primary monoclonal antibody (MoAb) directed against the LeY antigen (BM-1/JIMRO). The relationship between LeY antigen expression and the HCC's proliferative activity was analyzed similarly by immunohistochemical methods using a primary MoAb directed against the Ki-67 antigen (MIB 1). In addition, to clarify the relationship between LeY antigen expression and the histologic heterogeneity within HCC, seven cases of surgically resected HCC also were immunostained. RESULTS: The LeY antigen was detected on the membrane and in the cytoplasm of the cancer cells. Of the 46 HCC cases, 20 (43.5%) expressed the LeY antigen in the tumor cells. There was no correlation between LeY antigen expression and the maximum tumor dimension or the Stage. However, the incidence of LeY antigen-positive cases in poorly differentiated HCCs was found to be significantly higher than that in well or moderately differentiated HCCs (P < 0.01). In resected HCC cases, LeY antigen expression within HCC nodules was frequently greater in the less differentiated tumor than in adjacent differentiated tumor. Moreover, the incidence of LeY antigen expression in alpha-fetoprotein (AFP)-positive (AFP > or = 200 ng/ml) HCC cases was significantly higher than that in AFP-negative (AFP < 200 ng/ml) HCC cases (P < 0.05). Furthermore, the mean value of the Ki-67 labeling index in LeY antigen-positive HCC cases (25.2 +/- 11.3%) was significantly higher than that in LeY antigen-negative HCC cases (9.4 +/- 4.1%) (P < 0.001). CONCLUSIONS: These results suggest that LeY antigen expression correlated closely to the dedifferentiation and proliferative activity of HCC.

Antibodies, Monoclonal↗
PubMed1995

Protective effect of rifampicin against acute liver injury induced by carbon tetrachloride in mice.

Rifampicin conferred significant protection against carbon tetrachloride (CCl4)-induced liver injury. Serum alanine transaminase (ALT) and aspartate transaminase (AST) activities were not markedly altered and only hepatocellular fatty degeneration was found in mice pretreated with rifampicin (200 mg/kg), whereas severe centrilobular necrosis was observed and serum ALT and AST activities were as high as 281 and 271 I.U./l, respectively, in the control group following administration of CCl4 (400 microliters/kg). The contents and activities of microsomal drug-metabolizing enzymes in rifampicin-pretreated animals were also much higher than those of the controls. CCl4-mediated malondialdehyde (MDA) formation was increased in rifampicin-treated liver microsomes, demonstrating that rifampicin was capable of increasing the NADPH-dependent metabolism of CCl4 catalyzed by P-450 2E1 to produce free radicals. However, MDA formation was obviously depressed by rifampicin at varying concentrations from 2 to 32 x 10(-6) M in an in vitro cytochrome P-450 (P-450) enzyme system. On the other hand, NADPH oxidation in the metabolism of CCl4 and aniline hydroxylation were not suppressed in the presence of rifampicin in this systems, suggesting that rifampicin did not influence the biotransformation of CCl4 by P-450 2E1 in vitro. Therefore, the protective effect of rifampicin against CCl4 hepatotoxicity appeared to result from the direct inhibition of lipid peroxidation generated by CCl4-derived free radicals.

Animals↗
PubMed1994

A low prevalence of anti-hepatitis C virus antibody in patients with hepatocellular carcinoma in Guangxi Province, southern China.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) in southern China, including Guangxi Province, is among the highest in the world. Investigations of the etiology of HCC in this area have focused on hepatitis B virus (HBV) and aflatoxin. However, hepatitis C virus (HCV) has been shown to be a possible pathogenic agent for HCC in a number of countries. METHODS: Antibodies to HCV (anti-HCV), determined by second-generation enzyme immunoassay, and hepatitis B surface antigen (HBsAg) were assayed in the sera of 186 patients with HCC and 48 healthy control subjects from Guangxi Province in southern China. RESULTS: HBsAg was detected in 131 (70.4%) of 186 patients with HCC, whereas only 10 (5.4%) patients were found to be positive for anti-HCV. The prevalence of anti-HCV in patients with HBsAg-positive HCC was 6.9% (9 of 131) and that in patients with HBsAg-negative HCC was 1.8% (1 of 55); there was no significant difference between these two groups. Anti-HCV was not detected in any of the healthy control subjects, in whom the prevalence of HBsAg was 10.4% (5 of 48). CONCLUSIONS: These findings indicate that HCV does not seem to play an important role in the development of HCC in Guangxi Province; however, HBV infection appears to be a major pathogenic factor for HCC in this area.

Adult↗
PubMed1994

[Interferon-associated retinopathy].

During interferon (IFN) treatment for chronic hepatitis C, retinopathy develops in about one half of the patients. This "IFN-associated retinopathy" is characterized by cotton-wool spots (ischemic lesions) and superficial hemorrhage around the optic disc. It usually occurs 1 to 3 months after initiation of IFN therapy. Most of the patients with retinopathy have no symptoms, while some complain of impairment of visual acuity or flying specks. IFN-associated retinopathy tends to improve without any ophthalmic treatment and IFN therapy can be continued under careful observation. A complication of diabetes mellitus or a decrease in platelet count during IFN treatment may aggravate IFN-associated retinopathy. We emphasize that careful ophthalmologic follow-up is needed for all patients under IFN therapy.

Adult↗
PubMed1994

[Evaluation of the biological malignancy in hepatocellular carcinoma by argyrophilic nucleolar organizer region (AgNOR) staining--morphological study of AgNOR using image analyzer].

Using the Colloid silver staining technique to reveal AgNOR and immunostaining for anti-PCNA monoclonal antibody, 23 resected specimens with hepatocellular carcinoma (HCC, < or = 3.5cm in diameter) were examined. These cases were divided into two groups; Group A [9 cases without vascular invasion and a satellite nodule] and Group B [14 cases with satellite nodules]. Comparison of AgNOR score, the morphological features of AgNOR (the area and roundness factor of AgNOR) and PCNA labeling index between Group A and Group B was made by a image analyzer (SP-500). The AgNOR scores and PCNA labeling indices of HCCs in Group B were significantly higher than those of HCCs in Group A. And a close correlation was shown between AgNOR score and PCNA labeling index. Further more, the area, form, and distribution of AgNORs within the nucleus were also different in the two study groups. In Group A, many AgNORs were regular and medium-sized brown dots (AgNOR-roundness factor; > or = 80%, AgNOR-area; 1.5-4.5 microns 2). But in Group B, AgNORs showed marked variation in size and form. These results suggest that HCCs with multiple, smaller, irregular, and widely dispersed AgNOR in combination with high AgNOR scores have a more aggressive potential. The morphological features of AgNOR may be useful indicators for evaluating the proliferative activity of HCC.

Antigens, Neoplasm↗
PubMed1993

Protothecosis in a patient with systemic lupus erythematosus.

A rare case of protothecosis in a 40-year-old Japanese woman with systemic lupus erythematosus, under long-term prednisolone treatment is presented. The patient developed extensive ulcerative skin lesions after injury. The characteristic histopathological findings and biochemical sugar assimilation tests indicated infection by Prototheca wicherhamii. The lesions improved following treatment with amphotericin B. The immunodeficient state of this patient seemed to contribute to the infection with Prototheca.

Abscess↗
PubMed1993

Depression of drug-metabolizing activity in the human liver by interferon-beta.

The depressant effect of interferon beta on drug-metabolizing activity in the human liver was investigated. Seven patients with chronic hepatitis C were treated with interferon beta at doses of 3 x 10(6) to 9 x 10(6) IU/day for 8 wk. The activities of 7-methoxycoumarin O-demethylase and 7-ethoxycoumarin O-deethylase in specimens obtained by liver biopsy were examined before and after interferon treatment. Theophylline pharmacokinetics were also examined before and after interferon treatment. Interferon beta treatment reduced the activities of both O-dealkylases from 6.0 (100%) to 3.2 (53%) nmol/gm liver per minute and from 1.9 (100%) to 1.1 (58%) nmol/gm liver per minute, respectively (p < 0.05). The total body clearance of theophylline was also decreased (from 0.76 to 0.56 ml/kg/min; p < 0.05), and its elimination half-life was increased (from 8.4 to 11.7 hr; p < 0.05); however, the volume of distribution was not significantly affected. The magnitude of the decreases in enzyme activities and in theophylline clearance varied widely in individual patients and did not correlate with the dose of interferon administered. This study provides the first direct evidence that interferon beta can depress the activity of drug-metabolizing enzymes in the human liver.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1992

The role of mu- and kappa-opioid receptors in cocaine-induced conditioned place preference.

Effects of buprenorphine, U-50,488H, naltrexone and lithium chloride on cocaine conditioned place preference were examined. Buprenorphine, a mixed opioid agonist-antagonist, blocked the cocaine-induced place preference. Furthermore, the kappa-receptor agonist U-50,488H and the mu-receptor antagonist naltrexone both antagonized the cocaine preference. U-50,488H or naltrexone alone induced a place aversion in a dose-dependent manner. However, the cocaine-induced conditioned place preference was not blocked by lithium chloride, although the latter induced a conditioned place aversion, indicating that the antagonism of cocaine-induced place preference by U-50,488H or naltrexone does not result from a functional antagonism. These results suggest that mu- and kappa-opioid receptors may be involved in cocaine-induced conditioned place preference.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1992

5-HT3 receptor antagonists block cocaine- and methamphetamine-induced place preference.

The effects of 5-HT3 receptor antagonists, MDL72222 and ICS205-930, on cocaine- and methamphetamine-induced place preference were examined. Cocaine (0.5-4.0 mg/kg, ip) and methamphetamine (0.25-2.0 mg/kg, ip) induced a dose-dependent place preference. The cocaine (4 mg/kg)-induced place preference was blocked by both MDL72222 and ICS205-930 (0.1 mg/kg, ip). On the other hand, the dose (0.1 mg/kg) of 5-HT3 antagonists did not block the methamphetamine (2 mg/kg)-induced place preference, although a higher dose (1.0 mg/kg) of 5-HT3 receptor antagonists did block it. The difference in sensitivity may reflect a difference in attack point in dopaminergic system of these two psychostimulants. Our findings suggest that the rewarding effects of cocaine and methamphetamine may be indirectly regulated by 5-HT3 receptor; cocaine being more sensitive to 5-HT3 receptor antagonists than methamphetamine.

Animals↗