M Kurosu

Nippon Medical School, Tokyo, Tokyo-to, Japan

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Publications (5)3.2 Total impact

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    ABSTRACT: Two major ADH isozymes of mouse liver, basic ADH (Class I) and acidic ADH (Class III) were purified and the effects of various hydrophobic substances (t-butanol, butyramide, trifluoroethanol, trichloroacetic acid, stearic acid, oleamide, phenylalanine and norleucine) on their activities were investigated. All these hydrophobic substances activated acidic ADH with a range of from 15 to 560%, and reversely inactivated basic ADH activity with a range of from 10 to 100%, when 150 mmol/l ethanol was used as a substrate. Among these substances, t-butanol, which was the most potent activator of acidic ADH, enhanced the activity by 560% and completely inactivated basic ADH at a concentration of 1.0 mol/l. Kinetics studies demonstrated that the activation of acidic ADH by the hydrophobic substances was due to marked decreases of Km for ethanol in spite of decreases of Vmax, suggesting these substances were positive allosteric effectors for the isozyme. The inactivation of basic ADH by the hydrophobic substances was due to a decrease of Vmax without changing Km for ethanol. These results indicate that the activities of two ADH isozymes are regulated reversely by the hydrophobicity of the reaction environment which changes their kinetics constants. The ELISA method using the isozyme-specific antibody demonstrated that the content of acidic ADH in mouse liver was about 7 times larger than that of basic ADH (5.3 +/- 0.86 vs 0.72 +/- 0.06 mg/g-liver). In the light of the hydrophobic regulation of ADH isozyme activities and their liver contents, the role of acidic ADH on alcohol metabolism may be more predominant than basic ADH in the liver under hydrophobic condition.
    Nippon Ika Daigaku Zasshi 05/1992; 59(2):136-44.
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    ABSTRACT: Effects of chronic ethanol treatment with liquid diet (ethanol constituted 28% of the calories) on hepatic aldehyde dehydrogenase (ALDH) isozymes were studied in mice. One week of ethanol feeding caused 66% loss of mitochondrial low Km ALDH activity and 80% loss of mitochondrial high Km ALDH activity, compared with the control-fed group. However, these decreases recovered after 4 weeks of ethanol feeding. The cytosolic ALDH activity increased up to 140% after 10 weeks of ethanol feeding, compared with the control-fed group. Effects of acute ethanol injection on ALDH activity after prolonged ethanol feeding were studied. The severe acute ethanol injection (4.5 g/kg body wt) after 4 weeks of ethanol feeding caused a drastic decrease of the mitochondrial low Km ALDH activity; however, that did not affect the ethanol-fed group. After 10 weeks of ethanol feeding, acute ethanol injection (4.5 g/kg body wt) caused about twofold increase in mitochondrial low Km ALDH activity. From the agarose IEF study, it was found that ethanol intoxication does not affect the number and pI value of ALDH isozymes.
    Alcohol and Alcoholism 04/1992; 27(2):171-80. · 1.96 Impact Factor
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    ABSTRACT: In light of recent developments and public interest on the issue of organ transplant and the definition of death by neurological function ("brain death"). A more expansive role of medicolegal investigation of deaths may be needed. This article was presented for the purpose of understanding the medicolegal investigative system in the United States. The traditional coroner system in the United States was taken from the English system and was established as an elected coroner system during a colonial period. The coroner system became more politically involved and the coroner was elected by popular votes. The political aspect was the main driving force and the medicolegal aspect was ignored, thus, the Commonwealth of Massachusetts was the first state to adopt the medical examiner system. In 1991, 41 out of 50 states have adopted the medical examiner system, either state-wide or on a local option. One of the principal differences between coroner and medical examiner systems is the qualification of the head of the agency. The coroner is an elected individual who acts as an administrator and conducts quasi-judicial function of the department. The medical function is delegated to a physician who performs his duty often on a part-time basis. The medical examiner's office is headed by a Board certified Forensic Pathologist who acts as an administrator and directs all functions including medical and scientific investigation. He is a public employee and is protected under the civil service rules, thus, his decision would be less likely influenced by political pressure. The jurisdiction of the coroner and medical examiner is generally the same by law, however a medical examiner's approach and decision-making is more medically oriented and tends to be more expansive and ready to adopt to the needs in medicolegal issues arising from scientific progress.(ABSTRACT TRUNCATED AT 250 WORDS)
    Nihon hōigaku zasshi = The Japanese journal of legal medicine 09/1991; 45(4):351-9.
  • D Shibata, M Kurosu, T T Noguchi
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    ABSTRACT: Polymorphic genetic loci of the deoxyribonucleic acid (DNA) present in formalin-fixed, paraffin-embedded tissues were successfully analyzed by utilizing the polymerase chain reaction. Using this analysis, with three different polymorphic loci [human leucocyte antigen (HLA) DQ alpha, low-density lipoprotein receptor, and parathyroid hormone], fixed tissues representing 14 different individuals were genotyped and could be distinguished from each other. The techniques were further applied to the fixed autopsy tissues of a man in which a question of paternity arose postmortem. Since many individuals have surgical procedures or autopsy, these readily available fixed tissues represent an additional resource for the identification of individuals.
    Journal of Forensic Sciences 08/1991; 36(4):1204-12. · 1.24 Impact Factor
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    ABSTRACT: To elucidate the effects of acute ethanol intoxication on hepatic aldehyde dehydrogenase (ALDH), the activities of these isozymes were measured after acute ethanol injection at the doses of 1, 3 or 5 g/Kg body weight in mice. At the same time, blood ethanol and acetaldehyde levels were measured to consider their correlation to the changes in ALDH activities. In the cytosolic fraction, acute ethanol injection caused no effects on high Km ALDH. However, low Km ALDH activity decreased significantly after 0.5 and 12 hr at the dose of 5 g/Kg body weight. In the granule fraction, acute ethanol injection caused more than 50% loss of low Km ALDH activity after 2 to 8 hr at the dose of 1 g/Kg and after 0.5 to 8 hr at the dose of 3 or 5 g/Kg body weight, in comparison with the untreated group. However, high Km ALDH activity decreased only after 4 hr at the dose of 3 or 5 g/Kg body weight. The elimination rate of blood ethanol was 158.0 mumol/min/1 and 125.6 mumol/min/1 after 0.5 to 4 hr of ethanol injection at the dose of 3 or 5 g/Kg body weight, respectively. However, these elimination rates decreased drastically after 4 to 8 hr following ethanol injection. The elimination rate of blood acetaldehyde was 116.6 nmol/min/1 after 1 to 2 hr, and the rate decreased to 6.9 nmol/min/1 after 2 to 8 hr following ethanol injection at the dose of 5 g/Kg body weight. These drastic decreases in acetaldehyde elimination rate appear to be caused by reduction of the granule low Km ALDH activity.
    Arukōru kenkyū to yakubutsu izon = Japanese journal of alcohol studies & drug dependence 05/1990; 25(2):116-28.