Toshikazu Takagi

Lack of alcohol dehydrogenase isoenzyme activities in the stomach of Japanese subjects

Alcohol dehydrogenase (ADH) isoenzymes different from those of the liver were shown to be present in the human gastric mucosa. Two ADH activity bands present in the gastric mucosa of surgical specimens from all 7 black and 11 white Americans studied were absent in 14 and barely detectable in 3 of 21 Japanese subjects evaluated. Similar ethnic differences pertained to both genders and were independent of the gastric pathology. The mobility of these bands on starch gel electrophoresis corresponded to those recently reported and named mu-ADH or sigma-ADH. The absence of these bands was associated with a 70% decreased capacity to reduce m-nitrobenzaldehyde, a preferred substrate for sigma-ADH, suggesting that the bands missing from the Japanese stomachs comprise this isoenzyme.

Potentiation of halothane hepatotoxicity by chronic ethanol administration in rat: An animal model of halothane hepatitis

To determine if chronic ethanol administration modifies the effect of halothane on the liver, fourteen male Wistar rats were pair-fed nutritionally adequate liquid diets containing either ethanol (36% of calories) or isocaloric carbohydrate (controls) for 6 weeks. After halothane anesthesia of these animals under different oxygen concentration, the livers were examined light microscopically as well as biochemically. The livers from rats fed ethanol which received halothane at low oxygen concentration showed multifocal or patchy necrosis primarily in the centrilobular regions with parenchymal lipid accumulation, whereas no such lesions were not observed in pair-fed controls. Hepatic necrosis was also seen after halothane anesthesia even at ambient oxygen concentrations, although the degree of necrosis was much milder. Hepatic microsomal cytochrome P450 content was increased by 30% after ethanol but was decreased following halothane anesthesia. These data suggest that halothane is hepatotoxic to liver of rats chronically pretreated with ethanol, especially under hypoxic condition.

Significance of serum gamma glutamyl transpeptidase as a marker of alcoholism

To study the effect of chronic ethanol administration on the activity of gamma glutamyl transpeptidase (GGTP) in various tissues, female rats were pair-fed liquid diets with 36% of total calories either as ethanol or as isocaloric carbohydrate (controls). Six weeks of ethanol feeding resulted in a significant increase of cytochrome P450 content. Hepatic microsomal GGTP activity was almost doubled after ethanol feeding whether expressed per g of liver or per mg of microsomal protein. Furthermore, intestinal GGTP activity was significantly enhanced after ethanol, whereas there was no change in the enzyme activity in either kidney or pancreas. There was a concomitant elevation of plasma GGTP activity. Phenobarbital administration to rats resulted in an enhancement of GGTP activity in the liver whether given orally or intraperitoneally. In addition, intestinal GGTP activity after oral phenobarbital was also significantly increased, although its activity after intraperitoneal administration was not enhanced. These results suggest that enhanced hepatic and intestinal GGTP activities may contribute, at least in part, to an increased level of serum GGTP frequently seen in chronic alcoholics.

Increase in mitochondrial GOT (m-GOT) activity after chronic alcohol consumption: clinical and experimental observations

In order to clarify the origin and the mechanism of increased serum activity of glutamic oxalacetic transaminase (GOT) in chronic alcoholics, clinical and experimental investigations were carried out. Mitochondrial (m-GOT) and cytosolic GOT (c-GOT) isoenzymes were separated chromatographically by using a mini-column packed with Sephadex A50. Sixty percent of 63 alcoholics had elevated serum GOT. The m-GOT activity in alcoholics with total serum GOT activity of over 50 Karmen Units was 17.2 +/- 1.6 K.U. and the m-GOT/GOT ratio was the highest when compared to those in non-alcoholic liver diseases. In in vitro study, six hours of incubation of isolated hepatocytes from rats fed ethanol chronically resulted in an increased leakage of m-GOT into the incubation medium and also showed a tendency of a higher m-GOT/GOT ratio than that from control rats. The m-GOT activity thus released into the medium showed a highly significant inverse correlation with the viability of hepatocytes. These data suggest that m-GOT substantially contributes to an increased serum GOT often observed in chronic alcoholics.

Microangiographic findings of massive intestinal bleeding in a patient with Crohn's disease: a case report.

A 16 year old man with complaints of abdominal pain, diarrhea, high fever and loss of body weight was made a diagnosis of Crohns disease. During the administration, he had intestinal obstruction and several episodes of massive intestinal bleeding. Selective angiography of the superior mesenteric artery demonstrated the bleeding site in the ileum. Microangiography of the surgical specimens revealed abrupt interruptions of arteriae rectae in the submucosa indicating the bleeding site from the diseased intestine.