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Detailed fecal bile acid profiles of healthy Japanese subjects were studied using a lipophilic anion exchanger, capillary gas chromatography and mass spectrometry. Total dairy excretion of bile acid into feces corrected for by fecal markers were between 127.99 to 366.33 mumole per day. Unconjugated bile acids constituted a major part, between 80 and 96%, of fecal bile acids. Glycine conjugated, taurine conjugated and sulfated bile acids were between 1 to 6, 0 to 3 and 1 to 10%, respectively. Esterified bile acids at C-24 position existed between 1 to 5%. Primary bile acids ranged from 0 to 55%. There were a number of epimers of hydroxy- and keto-bile acids, and lithocholic and deoxycholic acid were major secondary bile acids among them. A cholenoic acid was detected in the unconjugated fraction of one subject. It seems necessary to analyze the details not only on the type of bile acids but also on the mode of conjugation in biological samples. Thus, the methodology described in this study has made it easier to investigate on the role of bile acid in the physiology or pathophysiology of the gastrointestinal tract.

The clinical usefulness as a tumor-associated antigen of the new monoclonal antibody CSLEX1, which reacts with the sialylated LewisX antigen, has been evaluated serologically in 141 patients with a gastric cancer. The serum sialylated LewisX was measured by fluorescent EIA. The percent positive figure of these gastric cancer patients was 17.0% (24/141), which indicates a significant increase when compared with that of the controls. The percent-positive values, according to the clinical stage, were 9.2%, 9.1%, 15.6%, and 36.4% for stages I, II, III, and IV, respectively. The degree of liver metastasis and peritoneal dissemination of the cancer correlated with the percent-positive values of the antigen. This suggests that sialylated LewisX is useful as a tumor-associated antigen.

Significant decrease in serum very low density lipoproteins and low density lipoproteins was observed after Bay g 5421 trial (300 mg/day for 6 weeks) in 14 hyperlipidemic patients. Although no significant changes were demonstrated in serum fractions of bile acids, the alteration in the patterns of fecal bacterial flora including the increase in obligate anaerobes was observed after the trial and this was accompanied by the increase in fecal fat excretion. Thus, the possible change in the intestinal bile acid metabolism with the altered flora may lead to an increased catabolism of cholesterol and to the reduction of serum low density lipoproteins. The meteorism developed in several patients but its etiology was shown to be independent of the patterns of the pre-trial bacterial flora and diet composition.

Studies were made on the dose and sex dependence of thyroid tumor development in rats pretreated with N-bis(2-hydroxypropyl)nitrosamine (DHPN) followed by exposure to various doses of phenobarbital (PB). A direct dose-response relationship in induction of thyroid tumors was found in both male and female rats. Upon feeding the DHPN-treated rats with basal diet containing 20, 100, 500, and 2500 ppm of PB, the incidences of follicular adenoma were, respectively, 8, 45, 70, and 66% in male rats and 12, 17, 50, and 58% in female rats. Development of papillary adenomas in male rats was observed only at the higher doses of PB, at incidences of 12 and 20% for doses of 500 and 2500 ppm. Follicular carcinoma was also seen at higher doses of PB, at 16 and 12%, respectively, for the 500- and 2500-ppm groups. Neither follicular nor papillary carcinomas were induced in female rats; only a low incidence of papillary adenoma (4%) was observed with a PB concentration as high as 2500 ppm. A single injection of DHPN resulted in production of approximately 1 tumor/female rat and 2.5 tumors/male rat. DHPN combined with posttreatment with PB at doses up to 500 ppm did not increase tumor yield in female rats, whereas a 3-fold increase was observed in male rats for the 500-ppm-treated groups. When PB was increased to 2500 ppm a marked increase (8-fold) in tumor yield in male rats was observed, in contrast to a less than 3-fold increase in similarly treated female rats.

Fecal bile acid profiles of 14 patients with ulcerative colitis in the active phase were analyzed to study the potential significance of bile acids in the pathophysiology of this disease, and the results were compared with those in 12 healthy controls. The excretion levels of total bile acids (mean +/- SD) in patients were higher than in controls, 445.1 +/- 392.1 vs 215.5 +/- 148.0 mumol/day, 3.1 +/- 1.7 vs 1.6 +/- 1.0 mumol/g wet feces (P less than 0.05), and 17.2 +/- 9.2 vs 12.4 +/- 13.3 mumol/g dry feces. Fecal profiles of individual bile acids showed higher levels of primary bile acids (52 +/- 27%) in patients compared to those (26 +/- 21%) in controls. Proportions of glycine and taurine conjugates in patients (26 +/- 24%) were higher than in controls (5 +/- 2%) (P less than 0.05), whereas proportions of unconjugates and sulfates were lower in patients than in controls. Accordingly the extent of deconjugation and dehydroxylation of bile acids was lower in patients than in controls. These trends were prominent in patients with more severe disease activity. A high concentration of bile acids in the intestine may have a significant role in the pathophysiology of ulcerative colitis at active phase.

The development of renal tumors was examined in rats given 1000 p.p.m. N-ethyl-N-hydroxyethylnitrosamine (NEELA) and then 30 000, 10 000 or 3000 p.p.m. of trisodium nitrilotriacetate monohydrate (Na3 X NTA X H2O) in their food. The incidences of renal tumors in rats treated with NEELA for 2 weeks and then 30 000, 10 000 and 3000 p.p.m. Na3 X NTA X H2O for 30 weeks were 100, 86 and 22%, respectively, while they were 16 and 0% in rats treated with NEELA or 30 000 p.p.m. Na3 X NTA X H2O alone. Na3 X NTA X H2O at 30 000 or 10 000, but not 3000 p.p.m., also increased the size and number of renal tumors in rats treated with NEELA, and Na3 X NTA X H2O at 30 000 p.p.m., but not 10 000 or 3000 p.p.m., also induced hydronephrosis in rats irrespective of whether they were treated with NEELA. Thus, Na3 X NTA X H2O has a dose-related effect on the kidney.

SM-4300, a newly developed human immunoglobulin preparation, has been studied for the safety and effectiveness/efficacy in the 16 patients with severe bacterial and/or fungal infections which are resistant to antibiotic therapy. Clinical effect of 16 cases were excellent 1 case, good 4, fair 4, poor 4 and unknown 3. The efficacy rate was 38.5% and the efficacy rate including fair was 69.2%. No remarkable adverse reaction due to administration of SM-4300 were observed.

An autopsy case of primary systemic amyloidosis with severe cardiac amyloidosis in a 75-year-old Japanese man is reported. The initial signs were dyspnea and cough, followed by general fatigue and loss of appetite. Heart failure, pleural effusion, and liver cysts were found on physiological examination. Autopsy findings were primary systemic amyloidosis with severe diffuse cardiac amyloidosis and cardiac hypertrophy (585 g). Focal necrosis by infarction was found in the liver and spleen. The cause of amyloidosis was unknown.

Faecal bile acid excretion was examined in 13 patients with adenomatous polyps of the large bowel and compared with a series of matched healthy subjects. Bile acids were analysed in detail with respect to the composition of individual bile acids and their mode of conjugation. The total excretion of bile acids by the patient group and the healthy subjects ranged from 55.0-837.6 mumol/day (median 233.8, mean 346.9) and 93.8-712.3 mumol/day (median 489.2, mean 386.7) respectively. Expressed as mumol/g faecal weight these values were 0.6-4.8 (median 2.2, mean 2.4) and 0.4-5.8 (median 2.2, mean 2.8) and in terms of mumol/g faecal dry weight, 1.9-50.7 (median 10.1, mean 16.5) and 3.9-32.4 (median 16.3, mean 16.7) respectively for the two groups. The composition of the individual bile acids and their distribution within the various conjugate fractions was essentially the same for both groups. Cholenoic acid (5 beta-chol-3-enoic acid), an unusual bile acid, was detected in one patient and three healthy subjects. These results revealed no significant quantitative differences in bile acid excretion between the group of patients with adenomatous polyps and those of healthy subjects.

A 39-year-old woman was admitted to our hospital complaining of hemosputum and right neck swelling. Pharyngography, neck CT scan and laryngoscopy revealed moderately differentiated squamous cell carcinoma of the right pyriform sinus. After series of examinations, it was found that she had pancytopenia, hypoplastic bone marrow, hyperpigmentation of the skin, cardiac anomaly, small stature, hypogonadism, chromosomal aberrations and consanguinity in her parents. These findings suggested that she was the congenital aplastic anemia, that is Fanconi's anemia, variant form. Although pepleomycin and corticosteroids were administrated for the treatment of squamous cell carcinoma and aplastic anemia, she died of cardiovascular shock due to massive hemorrhage. Flow cytometric analysis of squamous cell carcinoma showed an unusual aneuploidy DNA histogram. This is the first report on Fanconi's anemia with squamous cell carcinoma in Japan. It is said that chromosomal aberrations and impairment of DNA cross-links repair may play an important role developing of malignancy in Fanconi's anemia.

Taste recognition thresholds for four basic tastes, sweet, salty, and bitter, have been examined in 36 advanced lung cancer patients to identify the presence or absence of taste abnormalities in such patients. Twenty-six untreated lung cancer patients, or 65.3%, demonstrated an abnormal taste threshold for at least one of the 4 taste, a result varying significantly from suitable controls (p less than 0.05). Among the total 36 lung cancer patients, the number of those showing a threshold abnormality was no different between the smoker and non-smoker groups, though abnormalities were higher in the low serum zinc level group than in the normal serum zinc level group (p less than 0.05). We also observed transient threshold elevations after chemotherapy including Cisplatin. Thus, it is thought that taste abnormalities are more prevalent in advanced lung cancer patients.

The dose-dependent effect of trisodium nitrilotriacetate monohydrate (Na3.NTA.H2O) as a promoter in 2-stage carcinogenesis in the urinary bladder of male Wistar rats was investigated. Carcinogenesis was initiated by administration of 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in the drinking water for 4 weeks, then Na3.NTA.H2O was given at 1%, 0.5% and 0.3% in the diet for 28 weeks, and rats were killed in week 32. The incidences and numbers of preneoplastic lesions [papillary or nodular hyperplasia (PN hyperplasia)] in rats treated with 0.3% to 1% Na3.NTA.H2O increased progressively with increasing concentration of Na3.NTA.H2O. The incidences of papillomas in rats treated with 1% and 0.5% Na3.NTA.H20 in the diet and the incidence of transitional cell carcinoma (TCC) of the urinary bladder in the rats treated with 1% Na3.NTA.H2O (P less than 0.05) were significantly higher than those in rats treated with BBN only. Administration of various doses of Na3.NTA.H2O without BBN did not cause any histological changes (PN hyperplasia, papilloma or TCC) in the urinary bladder. These findings showed that Na3.NTA.H2O is a potent promoter of urinary bladder carcinogenesis initiated by BBN in rats, and that its effect is dose-dependent.

Protein and RNA content in accumulated G1 cells was measured with B16 melanoma cells by flow cytometer to study the mechanism of antineoplastic action of delta 12PGJ2. DNA histogram showed that, after a 6 hr exposure to delta 12PGJ2, the percentage of tumor cells in G2M phase increased, and G1 accumulation with depletion of cell population in S phase was seen after 12-24 hr exposure to 2.0 micrograms/ml of delta 12 PGJ2. Protein content in accumulated G1 cells increased at 6 hr after exposure, and subsequently decreased. However, the protein content treated with delta 12PGJ2 was higher than that of the control. A reduction of RNA content in G1 cells was seen after delta 12PGJ2 exposure. As the result, it was found that delta 12PGJ2 made cell progression ceased in G1 phase of cell cycle, and where protein and RNA content was higher than that of control. It is suggested that some hyper-metabolite state was caused by delta 12 PGJ2 in cultured B16 melanoma cells.

A monoclonal antibody, NR-2 MAb, against one of the rat renal cell tumor-associated antigens was developed. NR-2 MAb belonged to IgM class and recognized a polypeptide of 81,000 daltons designated as NR-2 antigen, which is of non-glycoprotein nature with a pI of 4.6. NR-2 MAb was employed to probe the histogenesis of renal cell tumors in rats treated with N-ethyl-N-hydroxyethylnitrosamine followed by trisodium nitrilotriacetate monohydrate. Immunohistochemical analysis indicated that NR-2 antigen was expressed in simple hyperplasia, adenomatous hyperplasia and renal cell tumors. Both clear cells and basophilic cells of the simple hyperplasia showed equally strong positive reactions with NR-2 MAb, whereas the vacuolated epithelium was negative. Furthermore, the proximal tubules in nontumorous areas also expressed NR-2 antigen, suggesting that the hyperplastic lesions which eventually lead to renal cell tumors may derive from epithelia of proximal tubules and not directly from vacuolated epithelium. Such NR-2 antigen-positive epithelia of proximal tubules seem to be initiated cells. NR-2 MAb also cross-reacted with preneoplastic liver lesions.

4,4'-Diaminodiphenylmethane (4,4'-methylenedianiline) (DDPM) promoted the development of thyroid tumors in rats treated with a subeffective dose of N-bis(2-hydroxypropyl)nitrosamine (2,2'-dihydroxy-N-nitrosodipropylamine) (DHPN) for thyroid tumorigenesis. Male inbred W rats were given a single ip injection of 280 mg DHPN/100 g body weight and fed diets with or without 1,000 ppm DDPM. Thyroid tumor incidences at the end of week 20 of the experiment were 90% (19/21) in rats given DHPN and then DDPM and 28% (6/21) in rats given DHPN alone. The incidence of thyroid cancers was 9.5% (2/21) in rats first given DHPN and then DDPM. Untreated rats and rats given DDPM alone had no thyroid tumors after 20 weeks. Incidences of kidney tumors were 38% (8/21) in rats given DHPN and then DDPM and 28% (6/21) in rats given DHPN alone. No tumors were found in the kidneys and lungs of rats given DDPM alone and in those of control rats. Treatment with DDPM alone slightly but not significantly decreased the serum concentrations of thyroxine and triiodothyronine; treatment with DHPN plus DDPM had no such effect.

A 27-year-old woman was admitted to our hospital complaining of purpuras and legs' edema in the 38th week of pregnancy. On admission, the hemoglobin was 7.8 g/dl, platelets 20,000/microliter and WBC 6,600/microliters with 52% blast cells. Bone marrow aspirate demonstrated 77.2% myeloblasts with prominent Auer rods, consistent with acute myelogenous leukemia. Receiving packed-red-cell and platelet transfusions, she delivered a normal male infant in the 39th week of pregnancy by normal labor. After delivery, she was placed on a combination chemotherapy of BHAC-MMP, subsequently DNR added. Four weeks later, a complete remission was obtained, lasting for almost one year, and her child has grown well without hematological disorder. Microscopic findings of the placenta obtained at delivery revealed no invasion of leukemic cells, but 9% blast cells were present in the placental cord blood. We reviewed 18 cases reported in Japan of acute leukemia in gestational period, that could obtain complete remission and keep the children growing well. Placental transmission of leukemic cells from mother to infant was discussed.

Essential fatty acid deficiency was found on four occasions in three adult patients with malabsorption after intestinal resection. Diagnosis was primarily based on the gas chromatographic finding of the abnormal fatty acid 5, 8, 11- (omega9) eicosatrienoic acid in plasma lecithin. None of the patients had received parenteral nutrition with a fat-free source of calories but all had been on a reduced intake of dietary fat at some stage. Treatment with intravenous Intralipid rapidly reversed the abnormal plasma fatty acid pattern and also cleared the rash in the patient wih he most severe deficiency.

The effect of 5 beta-chol-3-en-24-oic acid (delta 3) on N-methyl-N-nitrosourea (MNU)-induced colonic tumorigenesis was studied by intrarectal injection of these compounds in rats. Female Fischer rats received 0.5 ml of distilled water (DW) alone or DW containing 2.5 mg of MNU twice in one week followed by 0.5 ml of peanut oil (PO) alone or PO containing 1 mg of delta 3, or 1 mg of lithocholic acid (LC) thrice weekly for 48 weeks. Thus, 6 groups were employed as follows: group I, DW + PO (n = 12); group II, DW + delta 3 (n = 30); group III, DW + LC (n = 30); group IV, MNU + PO (n = 30); group V, MNU + delta 3 (n = 30) and group VI, MNU + LC (n = 37). Fecal bile acid profiles were analyzed before and during the treatment. Numbers of rats bearing colonic tumor were none in the groups without MNU, but 5 (17%) in group IV, 15 (50%) in group V and 12 (32%) in group VI (corrected X2 = 6.07, P less than 0.025 for group IV vs V, and 1.42, P less than 0.3 for group IV vs VI). Total numbers of tumors were 7, 17 and 15 in group IV, V and VI, respectively, and they were mostly adenomas and adenocarcinomas. A breast fibroadenoma in one rat of group VI was the sole extracolonic neoplasm in these rats. Total fecal bile acids ranged from 7.7 to 10.5 mumol/g dry feces during the study without any significant quantitative or qualitative difference with respect to with or without bile acids and MNU treatment. These results indicated that delta 3 promoted MNU-induced colonic tumorigenesis in rats without alteration in bile acid metabolism.

The concentration of Tegafur, 5-FU and Uracil in tumor and normal tissue were measured in 47 colorectal cancer patients who had been administered UFT (400/mg) for seven days before operation. The concentration of Tegafur, 5-FU and Uracil in tumor was higher than in normal tissue (p less than 0.01), and the concentration of 5-FU was correlative to the concentration of Tegafur and Uracil in both tissues. The Dukes group and histological type were not related to the concentration of Tegafur, 5-FU and Uracil in either tissue. The uptake of each drug was good and high in tumor tissue.

Sodium oleate was added to the drinking-water of groups of 50 male and 50 female F344 rats at levels of 2.5 and 5.0% for 108 wk. The mean liver weight in males given 5% oleate was lower than that of the males given 2.5% oleate or distilled water alone. The mean thymus weight of females given 5% oleate was higher than that of females given 2.5% oleate or distilled water. There were no statistically significant differences between treated and control rats in the results of the urine and serum analyses or haematological determinations or in the incidence of tumours, apart from pancreatic tumours. The latter, in the males, showed some increase over the concurrent controls but did not differ significantly from the reported spontaneous incidence in this strain. It was concluded that sodium oleate does not induce tumours when given orally to F344 rats.

In order to evaluate the factors affecting patient survival, 32 patients with a solitary hepatocellular carcinoma (HCC) smaller than 5 cm have been studied. Most patients were diagnosed as having a HCC during the periodic follow-up examinations for their underlying liver disease. For HCCs smaller than 2 cm, ultrasonography demonstrated the highest detection rate compared with CT and angiography. In patients with tumors larger than 2 cm, a portal vein thrombus and/or satellite tumors were frequently recognized, resulting in a lower patient survival rate when compared to those with a smaller HCC. Results have indicated that early detection of such tumors without a portal vein thrombus and/or a satellite tumor, and an adequate hepatic resection, such as segmentectomy or subsegmentectomy, are most important factors HCC patient survival.

The relationship between cholecystectomy and large-bowel cancer development was investigated in animal models. Female ICR mice underwent cholecystectomy, and received 15 weekly intragastric administrations (Experiment 1) or 10 weekly subcutaneous injections (Experiment 2) of 15 mg/kg body weight of large-bowel carcinogen 1,2-dimethylhydrazine (DMH). Autopsy at 28 weeks after surgery showed that cholecystectomized mice had a nonsignificantly increased incidence of large-bowel carcinomas, compared to sham-operated and/or unoperated control mice (85 vs. 64 percent in Experiment 1; 31 vs. 16 and 20 percent in Experiment 2). Cholecystectomy alone without DMH treatment did not produce any cancer. Cholecystectomized mice excreted a significantly increased level of primary bile acids but an unchanged level of secondary bile acids in the feces, compared with unoperated control mice. It is obvious that cholecystectomy enhanced the development of DMH-induced, large-bowel carcinomas along with the change of fecal bile acid composition, suggesting that changes of bile acid metabolism after cholecystectomy may enhance or promote large-bowel carcinogenesis in man as well. This association of cholecystectomy and large-bowel cancer is not a strong one, however, as presented in epidemiologic as well as experimental studies.

Carcinoembryonic antigen (CEA) titer (Dinabot-Kit) were determined in proven 177 patients with colorectal carcinoma preoperatively, and at routine intervals following operation. The assay was positive in 39.1% with stage I, II, 65.9% with III, 65.9% with IV and 85.7% with V. Elevated CEA levels were noted in those who had infiltration of cancer cells extending through the proper muscle layer. In 79.2% of curative resections CEA levels returned to normal within one month, but the titers remained elevated in 73.3% of palliative resections. Among 26 patients with recurrent disease, 16 had a hepatic metastasis showing a previous or simultaneous CEA rise, whereas 10 had a local recurrence with a slow rise or normal. In addition, a quantitative study of CEA in extracts of 87 tumors was made in order to examine the factors affecting the level of circulating CEA. There was no significant difference between the CEA contents of the tumor and its level of circulating CEA. The level of circulating CEA might be influenced by the spread cancer cells, rather than the tumor contained CEA.

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 those 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 metastasis 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-negative one.

Transplantable renal adenocarcinoma can be readily induced in Wistar strain male rats by initiation with N-ethyl-N-hydroxy-ethylnitrosamine followed by promotion with beta-cyclodextrin. The transplantability rates of the tumors by s.c. inoculation in newborn rats were 33 and 50%, respectively, for tumors of the first and second passages, and 100% for both third and fourth passages. The transplantability rates were affected by route of inoculation; rates of 50 and 100% were observed for s.c. and i.p. inoculations, respectively. The growth rate of tumors induced by i.p. inoculation was 3-fold higher than that induced by s.c. injection. Macroscopically, most of the tumors grew in the s.c. tissue of inoculation sites. However, invasive growth of tumors in spleen, liver, stomach, peritoneum, and intestine were seen in 50% of the animals inoculated i.p.; metastatic cancers to lung were seen in 16%. Histologically, the tumors were well-differentiated adenocarcinomas composed of uniform cells resembling kidney tubular cells and appeared to be derived from normal kidney tissues. A 5-fold decrease in gamma-glutamyl transferase activity in tumor tissues was found as compared with that of nontumorous kidney tissues. Electrophoretic analysis of cellular proteins in polyacrylamide gels revealed that tumor tissues exhibited five new polypeptides with molecular weights of 81,000, 64,000, 59,000, 50,000, and 36,000 which were either lacking or undetectable in the nontumourous area and control kidney. In addition, protein banding patterns of transplantable renal tumor appeared to be more heterogeneous than those of primary kidney tumor.

We report the successful treatment of gastrointestinal amyloidosis with dimethyl sulfoxide. A 37 year-old man with adult-onset Still's disease suffered from diarrhea. Upper and lower gastrointestinal endoscopy revealed edematous mucosa, white patches, erosions and bleeding and amyloid deposits were demonstrated in biopsy specimens. After a period of 3 months dimethyl sulfoxide and prednisolone therapy, improvement in the endoscopic appearance of the gastrointestinal tract was observed. Amyloid deposits in biopsy specimens were reduced in the stomach and negative in the large intestine.

The effects of erythrosine (Red 3), rose bengal B (Red 105) and thyroidectomy on the development of thyroid tumor were examined in male Wistar rats treated with N-bis(2-hydroxypropyl)nitrosamine (DHPN). Red 3 and Red 105 were used at 4% in the basal diet and were administered for 19 weeks from week 2 to 20. Thyroidectomy was performed by resection of the left lobe at week 4. Single injection of DHPN was performed intraperitoneally at 280 mg per 100 g body weight at the beginning of the experiment. Red 3 and Red 105 significantly promoted the development of thyroid tumors in thyroidectomized rats given DHPN, but had no significant effect in non-thyroidectomized rats. The incidence of thyroid tumors was 91% in rats with partial thyroidectomy, Red 3 and DHPN, 100% in rats with partial thyroidectomy, Red 105 and DHPN, and 64% in rats with partial thyroidectomy and DHPN. Serum TSH was 5.5 +/- 3.1 ng/ml in rats with partial thyroidectomy, Red 3 and DHPN, 2.1 +/- 2.2 ng/ml in rats with partial thyroidectomy, Red 105 and DHPN, and 1.5 +/- 0.5 ng/ml in rats with partial thyroidectomy and DHPN.

The effects of bile salts on the output of prostaglandin E2(PGE2) were studied in rats by colonic perfusion. Bile salts and their concentrations in infusates were as follows; chenodeoxycholic acid sodium salt (CDCNa), sulfolithocholic acid disodium salt (SLCNa) and sulfotaurolithocholic acid disodium salt (STLCNa) were at 1 mmol/l, lithocholic acid sodium salt (LCNa) was at 0.6 mmol/l, 5 beta-chol-3-en-24-oic acid sodium salt (delta 3Na) was at 0.006 mmol/l, and sulfoglycolithocholic acid disodium salt (SGLCNa) was at 0.8 mmol/l. Median values of PGE2 outputs were 40.9, 52.4, 65.5, trace, 7.6, 9.8 and 9.8 pg/10 min/cm in the CDCNa, LCNa, delta 3Na, SLCNa, STLCNa, SGLCNa and control groups, respectively (control vs CDCNa, LCNa, delta 3Na, SLCNa group, p less than 0.01 by median test). There was such a dissociation in PGE2 output and electrolyte concentration in the perfusates that high concentration of Na+ and Cl- ions was observed only in the SGLCNa group (p less than 0.01 by t-test compared with the control group), whereas in the remainder of the groups substantial net movement of electrolytes and water was not observed. Light microscopy showed no evidence of morphological damage in any group. These results indicated that CDCNa, LCNa and delta 3Na increased PGE2 outputs in the colon at low concentration without functional or morphological changes.

The effects of sodium chloride and alcohol on esophageal carcinogenesis induced by N-nitrosopiperidine (NNP) were studied in male F-344 rats. Sodium chloride given concomitantly with NNP during the first 8 weeks of the experiment and followed by sodium chloride increased the incidence of esophageal tumors in week 20. Sodium chloride given after NNP during the second 12 weeks of the experiment increased the incidence of esophageal hyperplasia. In the present experiment, no clear effect of alcohol on esophageal carcinogenesis was demonstrated, but alcohol slightly increased the incidence of preneoplastic esophageal tumors in groups given alcohol with and after NNP. These results suggest that sodium chloride may be able to be a potent promoter of the development of esophageal tumors in rats if the conditions of initiation are appropriate. Examination of the incidences of tumors in 9 segments of the esophagus gave no evidence of any portion that was especially susceptible to induction of esophageal tumors.

We report on a case of fulminant hepatic failure induced by a hepatitis-B virus. Computed tomography (CT) was valuable in the recognition of severe liver atrophy with ascites. CT was also an efficient means for evaluating the progress of fulminant hepatic failure.

Contradictory results in the studies on experimental gallstone formation using conventional and germfree mice have been reported. To study the role of bacteria in gallstone formation in the animal model JCL:ICR male germfree mice were monocontaminated with Clostridium butyricum MIYAIRI No. 588. Gallstone formation, biliary lipid composition and bile acid profiles in the bile, small intestinal contents and feces were analyzed after feeding the diet containing cholesterol and cholic acid. The rate of gallstone formation in the monocontaminated mice (38%) was less than that in the germfree mice (100%). The relative concentrations of biliary lipids of the two groups were located out of the micellar zone on the triangular co-ordinates by Admirand and Small. The bile acid concentrations in the small intestine and fecal excretions in the monocontaminated mice were higher than in the germfree mice. The composition as well as the mode of conjugation of the bile acids did not differ significantly between the two groups. The infestation of bacteria in the intestine enhanced the excretion of bile acids and inhibited the gallstone formation in mice, in which direct metabolic activity by bacterial enzymes on bile acid did not seem necessary to exert such effect.

Rats were given intrarectal instillations of N-methylnitrosourea. The experimental groups with right hemicolectomy and oral indomethacin had a significantly reduced rate of large bowel tumors. The inhibition rate of tumor development was 88% in incidence and 94% in number. This inhibition was associated with a decrease of fecal bile acid level and a shortened intestinal transit time. It was hypothesized that the change of fecal bile acid composition after surgery and the prostaglandin synthesis inhibition by indomethacin affected the promotion phase of large bowel carcinogenesis.

A 67-year-old man with angiomyolipoma on the sigmoid colon is reported. The colonic polyp was pedunculated and diagnosed histologically after endoscopic polypectomy. Angiomyolipoma is one of the benign hamartomas arising principally in the kidneys of patients with or without tuberous sclerosis. Extrarenal angiomyolipoma is rare and this may be the first report of colonic angiomyolipoma.

The plasma levels of epirubicin and its metabolite, epirubicinol, were measured by HPLC following intravenous administration of epirubicin to cancer patients at doses of 40, 60, 80, and 100 mg/m2. The blood concentration/time curve declined as a tri-phasic function. The mean t1/2 alpha, beta, and gamma were 4.67 min, 1.15 h, and 36.5 h, respectively, which were characterized by a short distribution phase (alpha) and a prolonged elimination phase (gamma). The distribution volume of the central compartment (V1 = 0.351 l/kg) was small, while that of the tissue compartment (V2 = 0.254, V3 = 45.8 l/kg) was large, which could be explained by the binding of the drug to cellular components. The concentration of epirubicinol, although having a wide variation among individuals, was less than that of the unchanged drug and showed a gradual decline. The area under the curve (AUC) of epirubicin increased in proportion to the increase of dosage. These types of pharmacokinetic behavior of epirubicin appeared to be similar to those of doxorubicin.