Faculty Profiles - TOYOKUNI Shinya

Papers - TOYOKUNI Shinya

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A case of undifferentiated sarcoma of the liver

OKUYAMA Takazo, TOYOKUNI Shinya, OKADA Shigeru, NAKASHIMA Yasuaki, YAMABE Hirohiko, KAN Shugen, MORI Keiichiro, OZAWA Kazue

The Journal of the Japanese Society of Clinical Cytology Vol. 31 page： 89 - 90 1992

A case of undifferentiated sarcoma of the liver.

OKUYAMA Takazo, TOYOKUNI Shinya, OKADA Shigeru, NAKASHIMA Yasuaki, YAMABE Hirohiko, KAN Shugen, MORI Keiichiro, OZAWA Kazue

The Journal of the Japanese Society of Clinical Cytology Vol. 31 ( 1 ) page： 89 - 90 1992

A case of undifferentiated sarcoma of the liver

OKUYAMA Takazo, TOYOKUNI Shinya, OKADA Shigeru, NAKASHIMA Yasuaki, YAMABE Hirohiko, KAN Shugen, MORI Keiichiro, OZAWA Kazue

The Journal of the Japanese Society of Clinical Cytology Vol. 31 page： 89 - 90 1992

Iron-mediated DNA damage: Sensitive detection of DNA strand breakage catalyzed by iron

Toyokuni S., Sagripanti J.

Journal of Inorganic Biochemistry Vol. 47 ( 1 ) page： 241 - 248 1992

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Journal of Inorganic Biochemistry

Oxidative DNA damage is involved in mutagenesis, carcinogenesis, aging, radiation effects, and the action of several anticancer drugs. Accumulated evidence indicates that iron may play an important role in those processes. We studied the in vitro effect of low concentrations of Fe(II) alone or Fe(III) in the presence of reducing agents on supercoiled plasmid DNA. The assay, based on the relaxation and linearization of supercoiled DNA, is simple yet sensitive and quantitative. Iron mediated the production of single and double strand breaks in supercoiled DNA. Iron chelators, free radical scavengers, and enzymes of the oxygen reduction pathways modulated the DNA damage. Fe(III)-nitrilotriacetate (NTA) plus either H2O2, L-ascorbate, or L-cysteine produced single and double strand breaks as a function of reductant concentration. A combination of 0.1 μM Fe(III)-NTA and 100 μM L-ascorbate induced detectable DNA strand breaks after 30 min at 24°C. Whereas superoxide dismutase was inhibitory only in systems containing H2O2 as reductant, catalase inhibited DNA breakage in all the iron-mediated systems studied. The effect of scavengers and enzymes indicates that H2O2 and .OH are involved in the DNA damaging process. These reactions may account for the toxicity and carcinogenicity associated with iron overload. © 1992.

DOI： 10.1016/0162-0134(92)84069-Y

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Erratum: Combined histochemical and biochemical analysis of sex hormone dependence of ferric nitrilotriacetate-induced renal lipid peroxidation in ddY mice (Cancer Research (September 1, 1990) (5574-5580)) Reviewed International journal

Toyokuni

Cancer Research Vol. 52 ( 21 ) 1992

Histochemical detection of burn-induced lipid peroxidation in sebaceous glands of rat skin. International journal

Kitajima T, Hamanaka H, Miyachi Y, Ono Y, Moriguchi T, Toyokuni S, Imamura S

The Journal of dermatology Vol. 18 ( 7 ) page： 393 - 6 1991.7

Language：English Publishing type：Research paper (scientific journal) Publisher：Journal of Dermatology

Increased lipid peroxide levels both in skin and serum have been reported after cutaneous thermal injury. However, it still remains unclear where lipid peroxides are produced at the site of burned skin. In the present study, a histochemical method using cold Schiff's reagent was applied in order to detect the localization of lipid peroxide. Schiff positivity was detected in sebaceous glands, and the extent of positivity seemed to correlate with the serum lipid peroxide levels. These results may suggest that lipid peroxides produced in sebaceous glands after thermal injury enter the blood stream and are partially responsible for the elevated serum lipid peroxide levels.

DOI： 10.1111/j.1346-8138.1991.tb03104.x

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SEX-DIFFERENCES IN THE LOCALIZATION AND SEVERITY OF FERRIC NITRILOTRIACETATE-INDUCED LIPID-PEROXIDATION IN THE MOUSE KIDNEY

OKADA, S; FUKUNAGA, Y; HAMAZAKI, S; YAMADA, Y; TOYOKUNI, S

ACTA PATHOLOGICA JAPONICA Vol. 41 ( 3 ) page： 221 - 226 1991.3

Sex differences in the localization and severity of ferric nitrilotriacetate-induced lipid peroxidation in the mouse kidney

OKADA S.

Acta Pathol. Jpn. Vol. 41 ( 3 ) page： 221 - 226 1991.3

Sex Differences in the Localization and Severity of Ferric Nitrilotriacetate‐induced Lipid Peroxidation in the Mouse Kidney International journal

Okada S., Fukunaga Y., Hamazaki S., Yamada Y., Toyokuni S.

Pathology International Vol. 41 ( 3 ) page： 221 - 226 1991.3

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Pathology International

Male mice are much more susceptible than female mice to acute renal proximal tubular necrosis as well as the carcinogenic effect induced by an iron chelate, ferric nitrilotriacetate (Fe‐NTA). In the present study, iron‐promoted lipid peroxidation was analyzed histochemically in frozen kidney sections using cold Schiffs reagent and biochemically by measuring thiobarbituric acid‐reactive substance in the kidney. When untreated mouse frozen kidney sections were exposed to ascorbic acid‐Fe‐NTA (0.8 mM, 0.2 mM and 0.4 mM) in vitro for 40 min and washed, diffuse Schiff positivity was obtained along the proximal tubules, and no sex differences were evident. When non‐reduced Fe‐NTA (0.2 mM and 0.4 mM) was layered on untreated kidney sections from males, about half of the cortical proximal tubules showed a positive reaction with Schiffs reagent, whereas in females the proximal tubules of the outer stripe of the outer medulla were positive. In an ex vivo study, 30 to 40 min after i.p. injection of Fe‐NTA (5 mg Fe/kg), Schiff‐positive areas corresponded to those observed in the in vitro non‐reduced Fe‐NTA study in each sex. However, in males, the positive tubular cells gradually became necrotic, whereas in females the positivity disappeared with time and there was no tubular necrosis. Results of the thiobarbituric acid test were correlated with the above findings. In conclusion, the localization and severity of FeNTA induced lipid peroxidation in the tubules differed between the sexes. We suspect that these results reflect functional heterogeneity in the ability of the tubules to reduce iron. Copyright © 1991, Wiley Blackwell. All rights reserved

DOI： 10.1111/j.1440-1827.1991.tb01651.x

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CONGENITAL MYOTONIC-DYSTROPHY WITH PROGRESSIVE EDEMA AND HYPOPROTEINEMIA

FUJII T, YORIFUJI T, OKUNO T, TOYOKUNI S, OKADA S, MIKAWA H

BRAIN & DEVELOPMENT Vol. 13 ( 1 ) page： 58 - 60 1991

Congenital myotonic dystrophy with progressive edema and hypoproteinemia

FUJI T

Brain Develop Vol. 13 ( 1 ) page： 58 - 60 1991

Congenital myotonic dystrophy with progressive edema and hypoproteinemia

Fujii T., Yorifuji T., Okuno T., Toyokuni S., Okada S., Mikawa H.

Brain and Development Vol. 13 ( 1 ) page： 58 - 60 1991

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Brain and Development

We report a patient with congenital myotonic dystrophy who had progressive edema and hypoproteinemia. An atrioseptal defect and patent ductus arteriosus were noted and were considered to be the cause of the right heart failure and edema. Although urinary protein levels were minimal, infusion of albumin did not improve the hypoproteinemia. Administration of dexamethasone increased the serum protein level, but the edema was not ameliorated. Autopsy revealed a slight lymphatic dilatation in the small intestine, suggesting protein-losing enteropathy. © 1991, All rights reserved.

DOI： 10.1016/S0387-7604(12)80300-7

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A CASE OF BIOPSY-PROVEN MYOCARDITIS PROGRESSING TO AUTOPSY-PROVEN DILATED CARDIOMYOPATHY

MATOBA Y, MATSUMORI A, OHTANI H, TOMINAGA M, FUJIWARA H, TOYOKUNI S, TAKAHASHI K, MIDORIKAWA O, KAWAI C

CLINICAL CARDIOLOGY Vol. 13 ( 10 ) page： 732 - 737 1990.10

A case of biopsy‐proven myocarditis progressing to autopsy‐proven dilated cardiomyopathy

Matoba Y., Matsumori A., Ohtani H., Tominaga M., Fujiwara H., Kawai C., Toyokuni S., Midorikawa O., Takahashi K.

Clinical Cardiology Vol. 13 ( 10 ) page： 732 - 737 1990.10

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：Clinical Cardiology

A 22‐year‐old man presented with congestive heart failure following flulike symptoms. The diagnosis of acute myocarditis was confirmed by endomyocardial biopsy, which revealed mild infiltration of inflammatory cells. A favorable response to beta‐adrenergic receptor blockade was seen, and the patient was discharged without symptoms. Five months later, however, congestive heart failure recurred, and intracardiac thrombi were demonstrated. The patient died after two months. Postmortem examination revealed left ventricular dilatation with slight interstitial fibrosis; the diagnosis was dilated cardiomyopathy. Thus, progression of biopsy‐proven myocarditis to dilated cardiomyopathy 10 months after the onset of disease was documented. Copyright © 1990 Wiley Periodicals, Inc.

DOI： 10.1002/clc.4960131013

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A case of biopsy-proven myocarditis progressing to autopsy-proven dilated cardiomyopathy

MATOBA Y.

Clinical Cardiol Vol. 13 ( 10 ) page： 732 - 737 1990.10

COMBINED HISTOCHEMICAL AND BIOCHEMICAL-ANALYSIS OF SEX-HORMONE DEPENDENCE OF FERRIC NITRILOTRIACETATE-INDUCED RENAL LIPID-PEROXIDATION IN DDY-MICE

TOYOKUNI S, OKADA S, HAMAZAKI S, MINAMIYAMA Y, YAMADA Y, LIANG P, FUKUNAGA Y, MIDORIKAWA O

CANCER RESEARCH Vol. 50 ( 17 ) page： 5574 - 5580 1990.9

Combined histochemical and biochemical analysis of sex hormone dependence of ferric nitrilotriacetate-induced renal lipid peroxidation in ddY mice

TOYOKUNI S.

Cancer Res Vol. 50 ( 17 ) page： 5574 - 5580 1990.9

Combined Histochemical and Biochemical Analysis of Sex Hormone Dependence of Ferric Nitrilotriacetate-induced Renal Lipid Peroxidation in ddY Mice Reviewed International journal

Toyokuni S., Okada S., Hamazaki S., Minamiyama Y., Yamada Y., Liang P., Fukunaga Y., Midorikawa O.

Cancer Research Vol. 50 ( 17 ) page： 5574 - 5580 1990.9

Language：English Publishing type：Research paper (scientific journal) Publisher：Cancer Research

Ferric nitrilotriacetate (Fe-NTA) induces renal proximal tubular necrosis, a consequence of lipid peroxidation, that finally leads to a high incidence of renal adenocarcinoma in rats and mice. Male animals are much more susceptible than female animals to both effects. Moreover, the distribution of the susceptible proximal tubules is different between male and female animals. The present study investigated the effects of castration and sex hormones on Fe-NTA-induced renal lipid peroxidation. Male and female ddY mice were either left untreated, castrated, and/or treated with testosterone or estriol. Histochemical (reactivity to cold SchifTs reagent) and biochemical (thiobarbSturic acid-reactive substance) evaluations were performed 1 h after the i.p. injection of Fe-NTA (5 mg iron/kg). Testosterone treatment and/or oophorectomy increased the Schiff pos-itivity of the renal cortical proximal tubules and the amount of thiobar-bituric acid-reactive substance (testosterone-treated female > intact female, P < 0.005; castrated female > intact female, P < 0.1; castrated and testosterone-treated female >intact female, P < 0.005). In contrast, estriol treatment and/or orchiectomy decreased the Schiff positivity of the renal cortical proximal tubules and the amount of thiobarbituric acid-reactive substance (estriol-treated male < intact male, P < 0.01; castrated male < intact male, P < 0.01; castrated and estriol-treated male < intact male, P < 0.005). Estradiol treatment produced similar results to estriol treatment (estradiol-treated male <intact male, P < 0.005). Castration and/or administration of the opposite sex hormone reversed the sex difference in the distribution of proximal tubules susceptible to lipid peroxidation. However, the i.v. injection to male mice, 5 min prior to the Fe-NTA treatment, of conjugated estrogen that is promptly excreted via the urine produced no significant effect. Thus, altered metabolic pathways rather than the direct scavenging activity of estrogens seem to be involved in the sex hormone-dependent difference of lipid peroxidation. Genetically determined sex hormone status appears to have influenced the incidence of Fe-NTA-induced renal adenocarcinoma in intact animals. © 1990, American Association for Cancer Research. All rights reserved.

Scopus

Combined histochemical and biochemical analysis of sex hormone dependence of ferric nitrilotriacetate-induced renal lipid peroxidation in ddY mice.

Toyokuni S, Okada S, Hamazaki S, Minamiyama Y, Yamada Y, Liang P, Fukunaga Y, Midorikawa O

Cancer research Vol. 50 ( 17 ) page： 5574 - 80 1990.9

THIOBARBITURIC ACID-REACTIVE SUBSTANCE FORMATION OF RAT-KIDNEY BRUSH-BORDER MEMBRANE-VESICLES INDUCED BY FERRIC NITRILOTRIACETATE

HAMAZAKI S, OKADA S, TOYOKUNI S, MIDORIKAWA O

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS Vol. 274 ( 2 ) page： 348 - 354 1989.11

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