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Biomedical subjects

H Ichimiya

Publications and source records attributed to H Ichimiya.

At least 37 records · Page 2Linked to original sources

Cholesterol crystal appearance time of gallbladder bile in middle-aged women.

The aim of our study was to examine the hypothesis that the cholesterol nucleation time of gallbladder bile might be rapid in women in their fourth and fifth decades, which increases their risk of cholesterol gallstones. Fifty-four gallbladder bile samples were collected from gallstone-free patients and patients with cholesterol gallstones in a functioning gallbladder. We examined the relations of nucleation time to age and sex in each group. The nucleation time of gallbladder bile tended to be prolonged with age, but there was no correlation between nucleation time and age in each group. Cholesterol nucleation time was not significantly different between age-matched females and males in each group, nor was it faster in middle-aged females than in older females. Thus, nucleation time was not rapid in middle-aged females even in the gallstone-free group. These results indicate that cholesterol nucleation time is not significantly influenced by either sex or age, and cannot therefore account for the higher frequency of cholesterol gallstone disease in females in the fourth and fifth decades.

Age Factors↗

Composite glandular-endocrine cell carcinoma of the extrahepatic bile duct: immunohistochemical study.

A composite glandular-endocrine cell carcinoma of the extrahepatic bile duct in a 64 yr old Japanese man is reported. A nodular polyp measuring 1.9 x 1.1 cm was located in the confluence of the extrahepatic bile duct. Histologically, the tumor was composed of well differentiated tubular adenocarcinoma and small cell neuroendocrine carcinoma with a transition between the 2 components. The 2 areas of the tumor immunohistochemically revealed a clear-cut difference in functional differentiation. Tumor cells in the glandular component were immunoreactive to both carcinoembryonic antigen (CEA) and CAM 5.2, while those in the small cell area were immunoreactive to neuroendocrine markers such as neuron specific enolase (NSE), chromogranin A and serotonin. These results suggest that the tumor arose from a multipotential stem cell capable of differentiation in 2 directions.

Adenocarcinoma↗

Late development of cholangiocarcinoma after the treatment of hepatolithiasis.

Although the association of cholangiocarcinoma with intrahepatic calculi (hepatolithiasis) is well recognized, the late development of cholangiocarcinoma after the treatment of hepatolithiasis has not been reported in detail. Of 109 consecutive patients with hepatolithiasis treated during 19 years, eight patients had cholangiocarcinoma, seven of whom had cholangiocarcinoma two to 14 years, with a mean of eight years, after the treatment of hepatolithiasis. Absence of cholangiocarcinoma was confirmed when stones were removed at the time of the initial treatment. The mean age was 56 years, with a female to male ratio of 2:5. At the time of detecting cholangiocarcinoma, three patients had no gallstones and four had gallstones at the corresponding site to the carcinoma. Cystic dilatation of the intrahepatic bile duct was often observed on the direct cholangiogram. The biles were all infected mainly with Escherichia coli and Klebsiella species. Thus, bile stasis and bacteria infection seems to be the important causative factor, causing cholangiocarcinoma rather than the calculi itself. Because the symptoms only mimic those of cholangitis, the possible presence of cholangiocarcinoma should be considered even after the treatment of hepatolithiasis for early detection and curative resection.

Adenoma, Bile Duct↗

Metabolism of intravenously administered 7 alpha-hydroxycholesterol-3 beta-stearate in the hamster.

In order to investigate the metabolic fate of serum esterified 7 alpha-hydroxycholesterol, [4-14C]7 alpha-hydroxycholesterol-3 beta-stearate was synthesized from labeled cholesterol and administered to bile fistula hamsters intravenously. Bile samples were collected at every 20 min for 7 h. Radioactivity was detected in bile 40 min after the beginning of the infusion of the labeled compound and 56.5 +/- 5.7% (48.7-66.0%) of the administered radioactivity was recovered in bile during 7 h. The liver contained appreciable radioactivity (19.5 +/- 7.6% of the administered dose) at the time of sacrifice. Only a trace amount of radioactivity was detected in urine and blood. Cumulative recovery of the radioactivity was 76.3 +/- 8.6% (63.3-90.4%). Major radioactive metabolites in the bile samples were identified to be taurine- and glycine-conjugated cholic acid and chenodeoxycholic acid by radioactive thin-layer chromatographic analysis of the bile samples before and after enzymatic hydrolysis and 3 alpha-hydroxysteroid dehydrogenase treatment. The conversion was nearly complete and we could not detect neutral metabolites, such as the mother compound, free 7 alpha-hydroxycholesterol and bile alcohols, as well as glucuronidated or sulfated bile acids. It is concluded that serum esterified 7 alpha-hydroxycholesterol could be effectively taken up by the liver, hydrolyzed by cholesterol esterase and metabolized via the normal biosynthetic pathway to taurine- or glycine-conjugated primary bile acids to be excreted into bile.

Animals↗

Intraoperative endoscopic electrohydraulic lithotripsy of pancreatic stones.

Two male patients with complications associated with chronic pancreatitis are described. In each patient, preoperative examinations revealed a large stone obstructing the main duct in the head of the pancreas. Lateral pancreaticojejunostomy was performed to relieve pain and prevent further attacks of pancreatitis. During each operation, the stone was fragmented under direct visual control with the use of a flexible choledochoscope and a contact electrohydraulic lithotriptor. The stone was removed and ductal flow through the head of the pancreas was reestablished. Our experience shows that endoscopic electrohydraulic lithotripsy facilitates operative removal of pancreatic stones deeply located in the head of the pancreas.

Adult↗

Profiling of eicosanoids in inflamed gall bladder wall by gas chromatography with selected-ion monitoring.

The profiling of eicosanoids, including prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), thromboxane B2 (TXB2) and leukotriene B4 (LTB4), in dog and human gall bladders was carried out by a combination of an effective and convenient clean-up procedure and gas chromatography with selected-ion monitoring. The clean-up procedure was based on the stepwise elution of their methyl ester derivatives from a silica gel column with n-hexane-ethyl acetate and ethyl acetate-methanol in various ratios. The LTB4 methyl ester was eluted with an n-hexane-ethyl acetate (2:1, v/v) fraction because LTB4 is more lipophilic than the other eicosanoids. The present method permitted the quantitation of trace amounts of eicosanoids, including LTB4, present in tissues in the order of pg/mg of protein, without interference from other endogenous substances. In experimental acalculous cholecystitis produced in dog, the levels of eicosanoids (except LTB4) were significantly changed. Of these eicosanoids, the level of 6-keto-PGF1 alpha was significantly higher in the seromuscular layer and correlated with the observed severe morphological changes. In human chronic cholecystitis with gallstones, the level of 6-keto-PGF1 alpha in the mucosal layer was significantly higher than that in the seromuscular layer. These data suggest that prostaglandin I2 may play an important pathophysiological role in the course of cholecystitis.

6-Ketoprostaglandin F1 alpha↗

Bile acids and bile alcohols in a child with hepatic 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency: effects of chenodeoxycholic acid treatment.

Duodenal bile, urine, plasma, and feces from a child with hepatic 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency were analyzed by fast atom bombardment mass spectrometry and gas chromatography-mass spectrometry to investigate the formation and excretion of abnormal bile acids and bile alcohols. The biliary bile salts consisted of glycocholic acid (25%) and of sulfated and glycine conjugated di- and trihydroxycholenoic acids (55%), two C27 bile acids, and eleven sulfated bile alcohols (mainly tetrols, 20%), all having 3 beta,7 alpha-dihydroxy-delta 5 or 3 beta,7 alpha,12 alpha-trihydroxy-delta 5 ring structures. In plasma, sulfated cholenoic acids constituted 65% and unconjugated 3 beta,7 alpha-dihydroxy-5-cholestenoic acid 25% of the total level, 71 micrograms/ml. The urinary excretion of the former was 30.4 mg/day and that of unsaturated bile alcohol sulfates, mainly pentols, 7 mg/day. The predominant bile acid in feces was an unconjugated epimer of 3 beta,7 alpha,12 alpha-trihydroxy-5-cholenoic acid, and small amounts of cholic acid were present. The minimum total excretion was 11.3 mg/day. Treatment with chenodeoxycholic acid resulted in marked clinical improvement and normalized liver function tests. Further studies are needed to define the mechanism of action. Plasma bile acids decreased to 1.6 micrograms/ml and urinary excretion to 3.4 mg/day. Chenodeoxycholic and ursodeoxycholic acids became predominant in all samples. The fecal excretion of unsaturated cholenoic acid sulfates increased to 40 mg/day compared to 89 mg/day of saturated bile acids. The results provide further support for a defective hepatic 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency, and indicate that the 3 beta-hydroxy-delta 5 bile acids are formed via 7 alpha-hydroxycholesterol. The formation of glycocholic acid may be due to an incomplete enzyme defect or to transformation of the 3 beta-hydroxy-delta 5 structure by bacterial and hepatic enzymes during an enterohepatic circulation.

3-Hydroxysteroid Dehydrogenases↗

Asymptomatic primary sclerosing cholangitis treated with ursodeoxycholic acid.

Ursodeoxycholic acid treatment (600 mg/day) was evaluated in a patient with asymptomatic primary sclerosing cholangitis. Serum levels of biliary enzymes decreased to normal ranges within 1 month's treatment and remained normal for 26 months. Serum chenodeoxycholic acid had been replaced by ursodeoxycholic acid, and hepatic copper metabolism, assessed by x-ray probe analysis, improved during the treatment. However, neither biliary tract sclerosis nor portal tract pathology changed with the treatment. These observations suggest that ursodeoxycholic acid protects the liver in primary sclerosing cholangitis by improving the metabolism of bile acid and copper.

Adult↗

Treatment of chronic liver disease caused by 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency with chenodeoxycholic acid.

Deficiency of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase, the second enzyme in the sequence that catalyses the synthesis of bile acids from cholesterol, leads to chronic liver disease in childhood as well as to malabsorption of fat and fat soluble vitamins. A 4 year old boy with this condition has been successfully treated by oral administration of a bile acid--chenodeoxycholic acid. He had been jaundiced since birth, grew poorly because of rickets, and had severe pruritus. Plasma transaminase activities were persistently raised. Chenodeoxycholic acid 125 mg twice daily for two months, and then 125 mg daily, cured his jaundice and pruritus, returned his transaminase activities to normal, and eliminated the need for calcitriol for prevention of rickets. On this treatment he has so far remained well for two years. A diagnosis of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency should be considered in any child with unexplained chronic hepatitis or cirrhosis, especially if the liver disease is accompanied by a clinically obvious malabsorption of fat soluble vitamins. A simple colorimetric test of the urine confirms the diagnosis and effective treatment can be started.

3-Hydroxysteroid Dehydrogenases↗

Pilot study of recombinant human alpha-interferon for chronic non-A, non-B hepatitis.

Recombinant human alpha-interferon was administered to 15 patients with chronic non-A, non-B hepatitis as a part of a pilot study. Patients received injections of 2 million units per day of interferon three times weekly for 16 wk. The treatment schedule was completed in all but one, whose serum aminotransferase levels were continuously elevated during treatment. In seven of the 15 patients, elevated serum aminotransferase levels decreased rapidly during therapy and eventually fell into the normal or nearly normal range. However, once the therapy was stopped, a prompt return of aminotransferase levels to pretreatment values usually was observed. After 3 months of follow-up, aminotransferase activities remained normal in only two patients in whom liver histology showed marked improvement in intralobular degeneration and focal necrosis of hepatocytes. Anti-interferon antibody was detected in four patients at the end of therapy, and decreased 2',5'-oligoadenylate synthetase activity occurred in two patients and in another with relapsed aminotransferase level. Whether alpha-interferon therapy could control the disease activity in patients with chronic non-A, non-B hepatitis deserves further evaluation in a prospective controlled trial.

2',5'-Oligoadenylate Synthetase↗

Copper-induced hypercholesterolemia of golden hamsters: enhanced synthesis of cholesterol in the liver.

Effects of a subtoxic dose of copper on cholesterol metabolism were studied in male golden hamsters. Intraperitoneal injections of cupric acetate increased serum levels of cholesterol and phospholipids without liver damage. This lipidemia was associated with increased cholesterol of the liver. The participation of hemolysis was denied by peripheral red blood cell tests. Hepatic microsomal 3-hydroxy-3-methyl-glutaryl-CoA reductase was also elevated by copper administration. Biliary secretion of cholesterol increased but that of bile acids remained unchanged, suggesting no impaired degradation of cholesterol. We conclude that hepatic synthesis of cholesterol is enhanced by a subtoxic dose of copper, resulting in hypercholesterolemia.

Animals↗

Type of gallstones and deaths from stroke and coronary heart disease among cholecystectomized patients.

A total of 841 Japanese patients who had undergone cholecystectomy for choleithiasis (550 for cholesterol stones and 291 for pigment stones) from 1951 to 1970 were investigated on death from stroke, coronary heart disease (CHD) and heart disease other than CHD in relation to the type of gallstones. Compared to patients with pigment stones, those having cholesterol stones had a 50% lower risk of dying from stroke which was statistically significant. The findings support the idea that westernization of Japanese diets may be responsible both for the decline in stroke mortality and for the changing pattern of gallstones in this country. The risk of CHD among cholesterol-stone patients was higher, but not significantly so, than that of pigment-stone patients whereas mortality from heart disease other than CHD did not differ much between the two groups. There were, however, few deaths from these diseases and the findings were therefore not conclusive.

Adult↗

An outbreak of foodborne hepatitis A in a factory: a possible shift in age of patients in Japan.

We investigated extensively an outbreak of hepatitis A at a factory in suburban Nagoya. Epidemiological study indicated a foodborne outbreak by a supplier of lunches. Serologically, all the employees younger than 30 years of age had been susceptible to hepatitis A virus, but the highest morbidity was observed in the 40-44 age group. The age difference in morbidity from foodborne hepatitis and susceptible populations suggests a shift in mean patient age linked to a shift in antibody prevalence to hepatitis A virus. In communities where the prevalence started shifting after development of sanitary systems, effective prophylaxis for foodborne hepatitis A will be necessary to prevent the disease in an increasing number of older patients in a few decades.

Adult↗

Altered metabolism of bile alcohol and bile acid in complete extrahepatic cholestasis: qualitative and quantitative aspects.

Urinary excretion of bile alcohols and bile acids in patients with complete extrahepatic cholestasis before and after the release by external biliary drainage was studied. Following extraction, isolation, and hydrolysis, bile alcohols were determined by capillary gas-liquid chromatography-mass spectrometry as dimethylethylsilyl derivatives. During cholestasis, 8.89 mumol/day of bile alcohol and 140.4 mumol/day of bile acid were excreted in urine. The amount of bile alcohol excreted was 6.1% of that of bile acid. Positive correlation between excretion of bile alcohols and bile acids was observed. The major bile alcohols excreted were also present in urine from healthy individuals but in much smaller amounts. After the release of extrahepatic cholestasis, urinary excretion of bile acid decreased rapidly, but that of bile alcohol decreased only gradually. The latter often increased again and remained high. The results indicate that the increased excretion of bile alcohols in complete extrahepatic cholestasis may reflect the expansion of a normally existing pathway of bile alcohol synthesis and excretion leading to the modification of bile alcohols for their efficient urinary elimination. It is also suggested that the rate of synthesis of bile alcohols is determined partly by the size of the substrate pool available.

Adult↗

Hepatolithiasis in East Asia. Retrospective study.

Hepatolithiasis is a major disease in Asia but differences in operative incidence between countries have not been examined. A retrospective study was conducted in Taiwan, Hong Kong, and Singapore, and the results were compared with those in Japan with the aim of defining factors involved in the etiology of the condition. In order to ensure uniformity of the data collected, the same form was used throughout the study and was completed by the same personnel after reviewing the patient's record and radiographs in each case. The years 1976-1980 were chosen for the study, since the newer methods of diagnosis such as ultrasound, endoscopic retrograde cholangiography, and percutaneous transhepatic cholangiography became available during that period. The most significant finding was the difference in the relative prevalence of hepatolithiasis as a proportion of all gallstone cases in Taiwan, Hong Kong, and Singapore, where the majority of the population consisted of patients of Chinese descent. The highest prevalence, 53.5%, was found in Taiwan, while in Hong Kong it was 3.1% and in Singapore 1.7%. Environmental rather than ethnic factors are implicated in the cause of hepatolithiasis.

Adult↗