A neuropathological study was performed in autopsy specimens of the esophagus of 8 cirrhotic patients with large esophageal varices, in which cases marked dilatation as well as motility disorders of the esophagus were demonstrated by esophagography, esophagoscopy and esophageal manometry. Histological findings of the esophagus of cirrhotics were also compared to those of 7 control patients without esophageal or liver disease. Total and normal ganglion cell counts/cm² at the Auerbach's plexus were found to have been significantly decreased, while the rate of the ganglion cells with the deformity of nucleus or with degenerated Nissl granules significantly increased at the upper, middle and, in particular, lower esophagus.
Thus, the reduction of the number of and the degeneration of ganglion cells at the Auerbach's plexus in the esophagus of cirrhotic patients with large varices are clearly demonstrated, and it is further suggested that such neuropathological changes as described above may have contributed to, at least in part, the development of impaired motility of the esophagus with large varices.

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We have developed a simple but reliable method for assessing gastric emptying, a sulfamethizole capsule food method. The capsule food contains egg albumin and sulfamethizole. In saline or hydrochloride solution only a small amount of sulfamethizole, in sodium bicarbonate solution, however, a large amount of the drug was released from the capsule food. In this method, sulfamethizole concentrations in blood were measured in subjects after ingestion of 15 pieces of capsule food containing 1.0g of sulfamethizole, and area under the curve of the blood concentrations was calculated as an index of gastric emptying. Gastric emptying of capusle food had a lag phase of 15 minuites, which was already reported in gastric emptying of radioisotope labeled solid food. Bread combined with the capsule food caused a delay in gastric emptying and a larger volume of the bread was associated with a longer gastric emptying time. In conclusion, our sulfamethizole capsule food method is useful in clinical practice to assess gastric emptying of solid food.

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Sialylated Lewis^x and sialylated Lewis^a antigens, which are structural isomer each other, were serologically tested to determine the clinicopathological differences and correlation between two antigens, and were also compared with thoses of serum CEA in 141 patients with gastric cancer. Percent positives in sialylated Lewis^a, CEA and sialylated Lewis^x showed 26.9%, 21.8% and 17.0% respectively. Percent positive of sialylated Lewis^x correlated with degree of liver metastasis and peritoneal dissemination. Therefore, it is emphasized that the role of sialylated Lewis^x is characteristics of detecting a presence of liver matastasis and/or peritoneal dissemination. On the other hand, sialylated Lewis^a showed high percent positive in cases which had lymph nodes metastasis and mucinous or papillary adenocarcinomas. These two carbohydrate antigens indicated no correlation (r=0.062) in the spectrum of sera. It is suggested that combination assay of sialylated Lewis^x and sialylated Lewis^a is useful in detecting many gastric cancer patients including CEA-egative one.

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The effect of feeding a small-peptide elemental diet on brush border membrane aminopeptidase activities and amino acid absorption in guinea-pigs was investigated. The latter effect and its mechanism were studied by measuring the transmural potential difference. Aminopeptidase activities on brush border membrane were significantly higher in the group fed a small-peptide elemental diet (SP group) than in the group fed an amino acids elemental diet (AA group).
In the SP group, the absorption of both glycyl-L-leucine and L-leucine was greater than that in the AA group. The increase of ΔPDmax of L-leucine in the SP group indicated that the acceleration of mucosal uptake of an amino acid in the SP group was due to an increased number of carriers.

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The aim of this study is to evaluate the risk of infection of non-A, non-B acute hepatitis (NANB-AH) in hospital employees.
Among 593 patients with acute viral hepatitis (AVH), hospital employees were 3/147 (2%) in type A, 19/174 (11%) in type B and 21/272 (8%) in non-A, non-B (NANB). All 43 patients were medical staffs such as doctors, nurses and laboratory technicians. Out of 21 patients with NBNB hepatitis of hospital employees, 7 were doctors, 14 nurses and 6 laboratory technicians. Eight of them had preceding accidental needlestick exposures. Out of 17, 290 employees of our hospital during 18 years, 27 medical persons developed AVH. They were 2 hepatitis A, 10 hepatitis B and 15 hepatitis NANB. No non-medical staff developed AVH. Out of 15 NANB hepatitis patients, 7 had needlestick accidents 4 to 6 weeks before development of the illness, and all donor patients showed liver diseases. During 3 years (1985 to 1987), there were 116 needlestick accidents in our hospital which happened in medical staffs alone, and 50 of them were NANB hepatitis-related accidents. Three ml of human immune serum globulin (ISG) was administered intramuscurally just after accidents to 23 persons but not to 27 persons. NANB hepatitis were developed in 2 doctors who were not treated with ISG. In conclusion, NANB hepatitis occurred in hospital employees especially in medical staffs.

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Zinc is an essential trace metal in the body. It's deficiency is known to induce skin lesions and hypogusia. It also has an important role as a core element of various enzymes. In the liver, ornithine carbamyl transferase (OCT), a metal enzyme in the urea cycle, where ammonium is metabolized, contains zinc. The previous report showed that patients with liver cirrhosis (LC) were in a state of zinc deficiency. The present study investigated the possible involvement of hypozincemia in the functional failure of the urea cycle in hepatic insufficiency in rats with experimental LC. Compared with control rats, rats with LC showed a decrease in the serum zinc concentration (LC 118.6±33.7μg/dl: control 161.6±13.9μg/dl p<0.05), a decrease in the zinc content of the liver (LC 81.4±16.3μg/g DW: control 108.1±6.9μg/g DW p<0.01), a decrease in the OCT activity in the liver (LC 24.7±4.0U/mg prot: control 42.4±3.8U/mg prot p<0.01), and an increase in srum ammonium (LC 87.2±38.5μg/dl: control 38.5±10.6μg/dl p<0.05). There was a significant correlation between the zinc content and OCT activity in the cirrhotic liver (r=0.6075, p<0.01). In additon, to evaluate the effect of dietary zinc on rats with LC, we divided these rats into two groups and fed them a diet with or without zinc for 4 weeks. The group on the diet restricting zinc showed decreases in the serum zinc concentration (p<0.01), the zinc content of the liver (p<0.01) and the OCT activity in the liver (p<0.01) and an increase in serum ammonium (p<0.01). These results strongly suggest that zinc deficiency occurs in association with LC, enhancing hyperammonemia through a decrease in the OCT activity of the liver.

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It has been reported that cAMP in hepatocytes plays an important role in bile discharge. Therefore, in order to examine the action mechanism of the cholestatic factor, we studied the effect of the cholestatic factor and prostaglandin E₁ derivative which inhibits the activity of the cholestatic factor on the cAMP level in hepatocytes. As a result, the cAMP level in hepatocytes was decreased by treatment with the cholestatic factor, but was increased by the prostaglandin E₁ derivative. Furtheremore, the cAMP level which was decreased by the cholestatic factor returned to the original level by treatment with the prostaglandin E₁ derivative.
Because the increase in the cAMP level in hepatocytes promotes the bile acid independent bile discharge, it is suggested that the cholestatic factor reduces the bile flow by the decrease in the cAMP level in hepatocytes, and that the prostaglandin E₁ derivative competes with the action of the cholestatic factor through the increase in the cAMP level in hepatocytes.

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The biliary excretion of ceftizoxime (CZX) in the presence and after relief of biliary obstruciton was experimentally investigated in twelve dogs.
In the presence of biliary obstruciton, the biliary excretion of CZX was impaired and, immediately after relief of biliary obstruciton, the existance of reverse shunt from the vascular system to the biliary tract was suggested.
After relief of biliary obstruction, the biliary excretion of CZX and the ratio of [lithocholic acid+ deoxycholic acid]/[cholic acid + chenodeoxycholic acid] in the bile were impaired one group with external drainage as compared to the other group with internal drainage.
It was experimentally proved that the biliary excretion of antibiotics seemingly related very closely to the bile acid metabolism and that it was increased by administration of the bile acid after external drainage or by normalization of the enterohepatic circulation of the bile acid after internal drainage.

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Serum and ascitic phospholipase A₂ (PLA₂) activity was assayed in rat model of acute pancreatitis. Serum PLA₂ activity was increased at the onset of acute pancreatitis, but had no correlation with severity of disease. The increase of PLA₂ in ascites was, on the other hand, correlated well with severity of disease. Pancreatic PLA₂ activity was also increased in the course of acute pancreatitis, which reflects increase in particulate fraction and showed obviously different pattern from amylase activity. Increase of PLA₂ activity on particulate fraction was due to activation of membrane bound PLA₂. These data suggest that activated membrane bound PLA₂ exacerbates pancreatitis. The possibility of participation of endotoxin was also to be considered.

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New cholecystokinin (CCK) receptor antagoinst, CR 1409 (lorglumde), was evaluated for anti-CCK activity on pancreatic exocrine secretion in anesthetized rats in vivo, compared with proglumide. Both CR 1409 in a dose range of 0.04-25mg/kg-hr and proglumide in a dose range of 30-600mg/kg-hr given intravenously, showed significant inhibitory effect on pancreatic secretion in terms of juice volume and amylse output stimulated by intravenous CCK-8 (0.06μg/kg-hr), in a dose-related manner. CR 1409 is about 1000 times more potent than proglumide, based on ED 50. Furthermore, intravenous administration of either CR 1409 (5mg/kg-hr) or proglumide (600mg/kg-hr) resulted in significant suppression on pancreatic secretion stimulated by intraduodenal casein in a dose of 400mg/hr. Thus, very potent CCK receptor antagonist, CR 1409, inhibited pancreatic exocrine secretion stimulated by not only exogenous CCK, but also intraduodenal casein in rats.

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The effect of new proglumide derivative, loxiglumide (DL-4-(3, 4-dichloro-benzoyl-amino)-5-(N-3-methoxy-propyl-pentylamino)-5-oxo-pentanic acid; CR 1505), on binding of ¹²⁵I-CCK-8 and amylase release stimulated by CCK-8 was investigated in isolated rat pancreatic acini. Loxiglumide inhibited CCK-8-stimulated amylase release and binding of ¹²⁵I-CCK-8 to rat pancreatic acini in a dose-dependent manner. Loxiglumide caused a concentration-dependent rightward shift of the dose-response curve for CCK-8-stimulated amylase release without altering the maximal response. Schild plots showed a slope of 0.82 and pA₂ value of 7.05. The inhibitory effect of loxiglumide on amylase release was reversible. Loxiglumide significantly inhibited amylase release in response to CCK-8, caerulein and gastrin-I. However, loxiglumide had no effect on amylase release stimulated by other receptor secretagogues (bombesin, carbamylocholine, secretin and vasoactive intestinal polypeptide) or by agents bypassing receptors (A23187 and TPA). These results indicate that loxiglumide acts as a potent, competitive and specific CCK antagonist on the pancreatic acini.

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