Tomofumi Morita

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.

Plasma levels of atrial natriuretic peptide in patients with liver cirrhosis and its relation to ascites and renal function

SummaryPlasma immunoreactive a-human atrial natriuretic polypeptide (Ir-α-hANP) was measured by radioimmunoassay in 21 cirrhotics and 10 normal subjects. Average of Ir-α-hANP level in cirrhotics was significantly higher than in normal subjects (125.8 ± 79.6 versus 28.7 ± 12.2 pg/ml, P< 0.001). In cirrhotics without ascites, Ir-α-hANP levels were positively correlated with creatinine clearance (Ccr) and urinary sodium excretion, suggesting that α-hANP was closely related to renal circulation and sodium homeostasis. One the contrary, in cirrhotics with ascites Ir-α-hANP levels were negatively correlated with Ccr. Urinary sodium excretion in cirrhotics with ascites and Ccr more than 50 ml/min was positively correlated with Ir-α-hANP levels. However, cirrhotics with ascites and Ccr less than 50 ml/min excreted little sodium in spite of high Ir-α-hANP levels. On the basis of the Ir-α-hANP before and after treatment of ascites, cirrhotics with ascites were subdivided into 2 groups. In group I Ir-α-hANP decreased from high values and in group II it was further elevated from slightly high values by treatment. The difference in renal function and plasma volume may account for the difference in Ir-α-hANP changes in the 2 groups.

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.

Glucagon-induced alteration of serum bile acid level in patients with liver cirrhosis

Percent changes in serum total bile acid level after IV administration of 1 mg glucagon were measured in 61 cirrhotics. Thirty-three of 38 cases with Childs grade A disease showed a reduction of total bile acid level at 15 minutes; this level was maintained in the majority of them until 120 minutes. A similar mode of serial changes in total bile acid level was also shown in the cases with Childs grade B disease. On the other hand, only 2 of 10 cases with Childs grade C showed a reduction of total bile acid level at 15 minutes. Reduction of total bile acid level at 15 minutes after glucagon administration was mimicked by infusion of dibutyryl cyclic adenosine monophosphate. However, in 3 of 6 cases with elevated total bile acid level at 15 minutes after glucagon administration, dibutyryl cyclic adenosine monophosphate induced a reduction of total bile acid level. Also, it was confirmed that glucagon enhances the uptake of taurocholate into freshly isolated rat hepatocytes by activating Na(+)-dependent, carrier-mediated membrane transport system and observed that its effect is associated with elevation of Vmax (0.6114 nmol.min-1 x 10(6) cells-1 without glucagon; 0.975 nmol.min-1 x 10(6) cells-1 in glucagon added) but not with affecting Km (13.58 mumol/L without glucagon; 13.71 mumol/L with glucagon) or protein synthesis which is inhibited by cycloheximide. These observations suggest that glucagon enhances Na(+)-coupled membrane transport of bile acids in the liver and causes the reduction of serum total bile acid level and that a lack of this response may be indicative of membrane dysfunction in the liver.

AN AUTOPSY CASE OF PRIMARY CARDIAC HEMANGIOSARCOMA WITH SPECIAL REFERENCE TO THE LITERATURES CONCERNED

症例は62才の男性で,呼吸困難と血痰を主訴とし,胸部X線像で心陰影の左右への著明な拡大と肺野に数個の異常陰影を指摘され,悪性腫瘍の肺転移と腫瘍性心外膜炎の疑いの下に入院し,精査をすすめたが,原発巣不明のまま制癌薬に対しても反応せず,入院後2カ月半で死亡した.病理解剖により,右房原発の血管肉腫と判明した.転移巣は両側肺,肝,両側副腎,大網,横隔膜,肺門,腸間膜,腹部大動脈の各リンパ節にみられ,腫瘍性心外膜炎,腫瘍性胸膜炎の所見がみられた.心臓に原発する腫瘍はきわめてまれであるが,なかでも悪性腫瘍の占める頻度はさらに低い.また悪性腫瘍のほとんどは肉腫といわれ,血管肉腫が多いようである.本邦における心血管肉腫は自験例を含めて12例を数えるにすぎない.今回著者らは自験倒を含めて心血管肉腫62例(外国50例,本邦12例)を対象に統計的観察を試みた.本症の原発部位は右心房にもつとも多く(64.5%),転移臓器は広いがとくに肺転移が多い(61.3%).発生年令は各層にわたるが,ピークは中年層にみられる.性別では2: 1で男性に多い.症状は上大静脈症候群症状を示すものが多く,その他心臓部痛,発熱,咳嗽,血痰なども高頻度にみられる.本症の診断にあたつては症状が多彩で特異性に乏しく,また,きわめて希な疾患だけに,鑑別診断の過程において常に心臓腫瘍の存在を念頭において積極的に検索する事が必要と考える.

Study on hepatocarcinogenesis in hypercitrullinemia Promoting effect of citrulline in experimental hepatocarcinogenesis

Abstract Hypercitrullinemia (adult type) is known to be complicated by hepatocellular carcinoma at a high incidence. We have previously reported that citrulline (Cit) acts as a hepatocarcinogenesis promoter in the in vitro tumor promotion analyzing system (Hepatology 1990;11:819–823). In this report, the tumor-promoting effect of Cit was further studied in the in vivo experimental hepatocarcinogenic model using diethylnitrosamine and 2-acetylaminofluorene as initiators. The incidence rate of hyperplastic nodules in the liver was significantly higher in the phenobarbital-fed group (83.3%) and Cit-fed group (100%) than in the control group (16.7%). Enzyme-altered islands, strongly positive for γ-GTP staining, were observed in the hyperplastic nodules. The promoting effect of Cit on hepatic carcinogenesis was confirmed also in the in vivo system.

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.