Yoichi Matsuoka

Sibling cases of chronic recurrent hepatocerebral disease with hypercitrullinemia

SummaryTwo sibling cases with chronic recurrent hepato-cerebral syndrome which correspond to the nutritional form of hepato-cerebral disease entitled by Shikata et al. and the data of plasma free aminoacids analyses of these cases were reported. The one case is 27 years old male and the other case is 36 years old female. Their parents were cousins. Both cases have had unbalanced diet, especially liked legumes unusually. Their main symptom was recurrent disturbance of conciousness and convulsive seizures. Slight abnormality of liver function test and hyperammonemia were demonstrated. Electroencephalogram showed the pattern of triphasic wave. Coeliac angiography did not revealed a portal-systemic shunt. Hepatic biopsy specimen revealed liver fibrosis with fatty change in the one case and mild fatty change in the other case. Analyses of plasma free aminoacids showed particurally high level of citrulline in both cases. From the results of plasma free aminoacids analyses, it is considered that pathogenesis of these patients is congenital hereditary urea cycle disorders.

Clinical significance of serum bile acid measurement in liver diseases.

SummaryTo determine the clinical significance of serum bile acid measurements, changes in the serum bile acid composition in liver diseases and endogenous bile acid clearance due to test meal loads were investigated. In the case of changes in the serum bile acid composition, a characteristic pattern of a remarkable increase of chenodeoxycholic acid (CDCA) was found in fulminant hepatitis. In patients with acute hepatitis, increases in CDCA were somewhat greater than those of cholic acid (CA) and there was tendency for these changes to precede changes in other liver function tests. In cases of extrahepatic obstructive jaundice, the CA/CDCA ratio was a large value exceeding 1.0. In investigations of endogenous bile acid clearance, serum bile acid concentration two hours after the test meal load clearly reflected the hepatic disorder and it was useful in differentiating between active and inactive form in chronic hepatitis and compensation and decompensation in liver cirrhosis.

Liver protocollagen proline hydroxylase in human liver diseases and experimental liver fibrosis.

SummaryLiver protocallagen proline hydroxylase activity (PPH activity) was determined in patients with various liver diseases, CCl4-induced liver fibrosis rats and cholin deficiency (CD) fatty liver rats. The following results were obtained: Liver PPH activity in patients with chronic hepatitis was higher than that in patients with acute hepatitis, while the activity in patients with liver cirrhosis was much higher than that in patients with chronic hepatitis. The activity was higher in patients with chronic active hepatitis than in those with chronic inactive hepatitis. Patients with active and progressive liver cirrhosis were found to have an especially high PPH activity, in whom the activity reflected well the degree of liver fibrosis. Even though fibrosis in persistent hepatitis was almost negligible or slight, the degree of liver PPH activity in persistent hepatitis was similar to that in liver cirrhosis. Liver PPH activities in CCl4-induced liver fibrosis rats and CD fatty liver rats elevated proportionally to the lapse of time. Whilst liver PPH activity in rats of CD fatty liver without fibrosis in 23 to 31 weeks after the start of the experiment was slightly lower than that in rats of CD fatty liver with fibrosis. But liver PPH activity of the former was considerably higher than that of control rats.

General Physical Examination for Vertigo

Vertigo is closely related not only with central nerve disorders but with peripheral, circulatory and autonomous nerve disorders and such general disorders. We, therefore, conducted hematological examinations and hemadynamometric measurement at the time of change of bodily position on patients of vertigo in order to see if the hematological and hemadynamometric factors can be predispositions for vertigo. The subjects were the patients with established diagnosis of Menieres disease, or suspected of Menieres disease, or had vertigo accompanying cerebro-circulatory disturbances, or of vertigo unknown origin who visited Nara Prefectural Medical Colleges Otolaryngological Department in the period covering April 1978 through October 1979. For control, normal individuals and patients of sensorineural deafness were selected. The results of the above tests were compared between the group of vertigo and the group of having no vertigo, and the possible predispositions were compared between the time having vertigo and the time not having vertigo in order to determine if those could be factors for causing the disease. The results were as follows.1. Of all the items of hematological examination, total cholesterol, neutral fats, free fatty acids could be considered as predispositions for vertigo particularly in the cases of cerebro-circulatory disturbances. It was also considered that total cholesterol, free fatty acids, HDL and blood platelet aggregation were possibly the factors to cause vertigo.2. In hemadynamometry, the fluctuations of the mean arterial pressure and of the pulse pressure at change of bodily position were great in the cases of Menieres disease while those in the cases of cerebro-circulatory disorders were small. Also in the patients having vertigo, decline of pulse pressure and differences of mean arterial blood pressure and pulse pressure between the right and left were observed. However, the hemadynamometric examination of this time did not differentiate critical factors of vertigo from predispositions.

The mechanism underlying the appearance of sex difference in hepatic injury of rats treated with chenodeoxycholic acid

CDCA投与ラットの肝障害出現には性差があり,雌の変化は雄よりも明らかに強い.著者らは,このような性差出現の機序をうかがう目的で,雌雄ラットに1日200mgのCDCAを8週間経口投与し,門脈血,胆汁中の胆汁酸構成ならびに血漿,肝の脂質変動を検討した.胆汁酸構成では,門脈血,胆汁ともLCAには性差はないが,CDCAは雌が雄よりも著明に高値な示し,門脈血で1.8倍,胆汁中で数倍に達した.かかる性差は,胆汁酸の肝における6β-hydroxyl-ase systemの差に起因するものであり,雌は雄に比して胆汁酸肝毒性に対する防禦機構が劣っていることを示している.脂質代謝面については,雄ではCDCAを投与しても目立った変動はないが,雌では肝コレステロールは増加し,中性脂肪の肝での増加,血漿での減少がみられた.このことは,雌ではCDCAのコレステロール合成段階に対する抑制効果が少なく,また肝中性脂肪の血中への転送が障害されたことを示している.

Studies on the inhibition of experimental liver fibrosis

SummaryIn the previous experiments, it was demonstrated that high purity elastase extracted from porcine pancreas remarkably inhibits liver fibrosis of rats having chronic liver injury caused by carbon tetrachloride. This time, with the purpose to clarify the mechanism of inhibition of liver fibrosis by elastase, comparative study was made on the activity of lysosomal enzymes by measuring β-glucuronidase, cathepsin and collagenolytic activity, with the rats administered with elastase and with those untreated, during the period of development of liver fibrosis and the recovery from it.In addition to it, in vitro experiments were made by having elastase act on the substrate comprising mixed collagen of acid soluble and neutral soluble collagens extracted from the skin of guinea pig and by observing collagen components by disc electrophoresis.With any lysosomal enzymes, no marked difference was noticed between elastase group and non-administered group and thus the possibility of inhibition of liver fibrosis through activation of lysosomal enzyme by elastase was denied. The results of disc electrophoretic observation of the performance of elastase on collagen revealed that β-component of collagen is disappeared but α-component remained. From the above, inhibition of liver fibrosis by elastase may be due to direct affection of elastase to telopetide portion of collagen.

Studies on liver cirrhosis—effect of elastase on development and recovery of experimental liver fibrosis

Previous experiment showed that serum monoamine oxidase (MAO) level was moderately elevated in hepatic fibrosis and in serious hepato-cellular necrosis. Present study describes the partial purification of MAO in serum, liver mitochondria and various connective tissues such as granuloma, bone and lung by starch block electrophoresis and by ammonium sulfate fractionation. MAO from liver mitochondria has a different properties in heat sensitiveness and in lathyrogen inhibition from that of serum and various connective tissues. Three types of seurm MAO are determined electrophoretically. One of them are markedly elevated in the serum of liver cirrhosis. MAO fi-om liver mitochondria moves towards anode with two peaks. On the other hand MAO from various connective tissues moves towards cathod with two peaks. MAO in the saturation from twenty to thirty-five percent of ammonium sulfate markedly elevated in the serum of liver cirrhosis. Serum MAO in hepatoceUular necrosis can not be completely inhibited by 0 . I / t mole of aminoacetonitrile in vitro and has a similar electrophoretic pattern like that of liver mitochondria On the contrary, serum MAO in hepatic fibrosis has a different electrophoretic pattern from that of liver mitochondria and completely inhibited by lathyrogens. These results suggest that (i) elevation of serum MAO in hepatic fibrosis and in serious hepatocellular necrosis may be depend on the elevation of different component of isozyme. (ii) Serum MAO in hepatic fibrosis may be responsible with that of connective tissue. (iii) Serum MAO in hepatocellular necrosis may be originated from that of liver mitochondria.

Studies on carbohydrate metabolism in experimemtal fatty liver (III) With special reference to metabolism of glucose or xylitol

ConclusionIn choline-deficient fatty liver, oxidation of xylitol or glucose and its participation in glycogenesis dropped in parallel with development of fatty liver, while the mechanism of emitting liver TG was rather in promoted state at the initial stage, and decreased thereafter, which suggests that the administration of xylitol or glucose may favour glycogenesis and maintenance of energy metabolism and, moreover, it may play some role in the maintenance of mechanism of emitting liver TG.

Studies on carbohydrate metabolism in experimental fatty liver with special reference to variation of liver enzymes on xylitol or glucose administration

Serial hepato-cholecysto-scintiphotography af ter in t ravenous adminis t ra t ion of l~lI-rose bengal in doses of one hundred micro curies was taken in pat ients with different types of jaundice. Employing gamma camera, hepatic uptake of the dye from the circulat ion and the mode of excret ion to the bi l iary t rac t and intest ine as well as the shape and the space occupying lesion of the liver, if any, was easily observed even in deeply jaundiced patients . Differentiation of jaundice caused by ext rahepat ic obstruct ion f rom tha t of intraor prehepatic causes can be made by analysis of hepatic uptake curves of the dye. The superior i ty of gamma camera compared with the external count ing technique reported previously by Tapl in et al, in the accuracy and reproducibil i ty of the s tudy was stressed.