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Biomedical subjects

T Osuga

Publications and source records attributed to T Osuga.

At least 73 records · Page 4Linked to original sources
PubMed1993

[Pathogenesis and animal model of gallstone disease].

Both cholesterol and pigment gallstones are multifactorial diseases. The broad outlines of the mechanism and limit of cholesterol solubilization in bile are well-understood, whereas the physical-chemical solubilities of unconjugated bilirubin and other calcium salts remain unclear. The importance of crystallization kinetics in gallstone formation is also well-recognized and several protein determinants of such process have been reported in bile. The chances of crystal growth and stone formation are further enhanced by mucus hypersecretion and gallbladder hypomotility. The use of animal models will continue to be useful not only in promoting our understanding of the pathogenesis but also in developing new chemicals for dissolution and prevention of gallstone diseases.

Animals↗
PubMed1992

Transfer of specific IgG and IgG subclasses to herpes simplex virus across the blood-brain barrier and placenta in preterm and term newborns.

The kinetics of virus-specific IgG subclasses (IgG 1-4) among newborns and their mothers has not yet been determined. In this report, we examined anti-herpes simplex virus IgG activities (HSV-IgG) and its subclasses in CSF and serum of premature or term newborns without HSV infection and in the serum of their mothers using ELISA. We found that CSF/serum ratios of HSV-IgG and IgG subclasses (IgG 1-4) in newborns with a gestational age less than 38 weeks were higher than those of term newborns. These findings indicate that the blood-brain barrier against HSV-IgG and IgG subclasses is insufficient in newborns. Furthermore, we found that HSV-IgG subclasses, which were transferred across the placenta and later transferred across the blood-brain barrier had a tendency to be proportional to each of the maternal HSV-IgG subclasses.

Antibodies, Viral↗
PubMed1991

Simultaneous assay of the activities of two key enzymes in cholesterol metabolism by gas chromatography-mass spectrometry.

A very sensitive and specific method for the simultaneous assay of the activities of two key regulatory enzymes in cholesterol metabolism, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.34), and cholesterol 7 alpha-hydroxylase (EC 1.14.13.7), is described. The assay is based on the measurement of [2H3]mevalonolactone and 7 alpha-hydroxycholesterol produced by the incubation of [2H3]HMG-CoA and endogenous cholesterol with hamster liver microsomes using isotope dilution mass spectrometry. The incubation mixture was purified by means of solid extraction cartridges, and the extract was treated with benzylamine followed by dimethylethylsilyl imidazole. The resulting ether derivatives of the mevalonylbenzylamide and 7 alpha-hydroxycholesterol were quantified by gas chromatography-mass spectrometry with selected-ion monitoring in a high resolution mode. The method made it possible to assay simultaneously the activities of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase in hamster liver microsomes with high sensitivity and accuracy.

Animals↗
PubMed1991

Microanalysis of bile acid composition in intrahepatic calculi and its etiological significance.

Brown pigment stones in the intrahepatic bile ducts were compared with those found in the extrahepatic bile ducts with special reference to the bile acids modified by bacterial intervention, that is, unconjugated, glucuronidated, secondary, and ketonic bile acid fractions. The former showed significantly lower amounts of total bile acids (P less than 0.01) and lower proportions of unconjugated bile acid fraction (P less than 0.01), secondary bile acid fraction (P less than 0.05), and ketonic bile acid fraction (P less than 0.05) to total bile acids than the latter. The discriminant analysis using these bile acid parameters led to complete separation between intrahepatic and extrahepatic stones in the case of brown pigment stones. In contrast, cholesterol stones in the intrahepatic bile ducts showed the bile acid composition close to those found in the extrahepatic ducts and gallbladder. The above data show that the bacterial infection plays a less important role in the formation and ensuing growth of most intrahepatic brown pigment stones than in extrahepatic stones, and that factors other than or in addition to bacterial infection are involved.

Bacterial Infections↗
PubMed1990

Identification of 3,6,7,12-tetrahydroxy-5 beta-cholan-24-oic acids in human biologic fluids.

Unusual bile acids, 3 alpha, 6 alpha, 7 alpha, 12 alpha-, and 3 alpha, 6 beta, 7 beta, 12 alpha-tetrahyroxy-5 beta-cholan-24-oic acids, were identified in all amniotic fluid (four samples) and urine (six samples) from adult patients with cholestatic liver disease by gas-liquid chromatography/mass spectrometry. For the certain identification of these bile acids in the biologic samples, the chemical syntheses of 3 alpha, 6 beta, 7 alpha, 12 alpha- and 3 alpha, 6 beta, 7 beta, 12 alpha-tetrahydroxy-5 beta-cholan-24-oic acids were conducted.

Amniotic Fluid↗
PubMed1990

Improvement of biliary enzyme levels and itching as a result of long-term administration of ursodeoxycholic acid in primary biliary cirrhosis.

Ursodeoxycholic acid (UDCA) was administered to 10 patients diagnosed as having primary biliary cirrhosis (PBC) after liver biopsy. Eight patients were anicteric, and two were icteric cases. One patient was in stage I, seven were in stage II, one in stage I-III, and one in stage III-IV of Scheuer's classification. Six hundred milligrams of UDCA were administered orally after meals three times daily to all of the patients for more than 1 yr. The period of UDCA administration ranged from 6 to 41 months. The major findings are as follows: 1) in six out of seven patients with pruritus, itching disappeared 1 month after administration of UDCA; 2) both serum alkaline phosphatase and gamma-glutamyltranspeptidase levels began decreasing significantly the first month after the onset of UDCA treatment, and continued decreasing throughout the treatment; 3) GOT and GPT levels also decreased significantly during the administration of UDCA, compared with before-treatment levels; 4) in one icteric patient with portal hypertension, although serum biliary enzyme levels improved after treatment, serum bilirubin level got worse, and the patient died of esophageal variceal hemorrhage. In another icteric case, biliary and bilirubin levels improved slightly after treatment; 5) antimitochondrial antibody titer decreased in four cases, but IgM levels and other immunological parameters were not changed; 6) serum UDCA increased significantly during UDCA treatment; in particular, glyco-UDCA occupied up to 40% of the total bile acid and CDC decreased to 25%; 7) portal inflammation activity decreased in all five patients who had undergone follow-up liver biopsy, more than 1 yr after UDCA administration--bridging fibrosis decreased in three cases; and 8) no side effects were observed in any of the cases. Although large-scale, randomized, controlled, double-blind tests are necessary, it is speculated that the long-term administration of UDCA is a safe and effective treatment for the improvement of biliary enzyme levels and pruritus in anicteric PBC.

Adult↗
PubMed1990

[Dental management of the medically compromised patient. A study of 162 cases].

Dental management of 162 cases of medically compromised patients was reviewed. Over the past 3 years and 2 months, 130 patients with certain medical problems underwent 162 cases of dental treatment under local anesthesia. In the present study, research was done chiefly on intraoperative management of these patients. The following results were obtained: 1) In the population of 130 patients, those in their 7th decade were the most numerous. Among the subjects, essential hypertension was the most common underlying disease, and the majority of the patients had accompanying cardio-vascular diseases. 2) When the pre- and post-65-year-old patient groups were compared, the latter group had a higher frequency of multiple medical problems. 3) It is suggested that, to manage patients having hypertension or ischemic heart diseases as a complication, continuous blood pressure measurement and ECG monitoring are essential. 4) Among several local anesthetics, 3% prilocaine with 0.03 U/ml felypressin was used most frequently, especially for those with cardiovascular diseases. 5) In the management of hypertensive and ischemic heart patients, nitrous oxide inhalation sedation was effective. 6) For those who required vasodilation, administration of nifedipine or nitroglycerin was effective. 7) Although one case of syncope and another in which dental treatment procedure had to be suspended were found, no severe complications were encountered.

Aged↗
PubMed1990

Advanced carcinoma of the stomach treated with definitive proton therapy.

We report the case of a 72-yr-old man who suffered from severe chronic emphysema with poor pulmonary function, and who had advanced cancer of the stomach. Proton beam radiotherapy was applied to the lesion, since surgery was contraindicated. The total dose to the stomach lesion was 61 Gy in 7 wk. The tumor on the stomach regressed, with flattening of the round wall of the lesion. The reactive changes of the proton beam radiotherapy, based on the histopathological examination, revealed extensive tumor necrosis and sparing of vital architecture of normal tissue around the irradiated tumor tissue. Only small clusters of vital or devitalized tumor cells with less than approximately 5% of the whole tumor tissue remained after treatment. We suggest that a high dose of radiation delivered by well-defined proton field could result in an improved therapeutic outcome without undue risk of injury to normal tissue.

Adenocarcinoma↗
PubMed1990

[Combined treatment of esophageal small cell carcinoma with radiation and chemotherapy].

A 61-year-old male complaining of dysphagia and precordial chest pain was admitted to hospital. A series of upper G.I. examinations revealed an ulcerative tumor, approximately 8 cm in diameter, in the esophagus. A biopsy of a specimen led to the histological diagnosis of a small cell carcinoma (oat cell type). The cells were uniformly argentaffin-negative (Masson-Fontna) and many contained numerous tiny argyrophylic granules (Grimelius). Therefore, a combined therapy of radiation (70 Gy) and CDDP (total dose: 210 mg) was used to treat the lesion, and the disappearance of the mass shadow, as well as no narrowing of the esophagus, was noted without residual ulceration, indicating a complete response. Four months after the therapy, however, an extensive multiple liver metastasis occurred, and the patient died of hepatic and renal failure. His overall survival time was 7 months from start of the combined therapy. It thus is felt that a multi-drug regimen and systemic chemotherapy are important in treating small cell carcinomas of the esophagus.

Carcinoma, Small Cell↗
PubMed1990

Altered bile acid metabolism in liver disease: concurrent occurrence of C-1 and C-6 hydroxylated bile acid metabolites and their preferential excretion into urine.

C-1 and C-6 hydroxylated bile acid metabolites in various biological specimens from subjects with liver disease (cholestasis, liver cirrhosis, chronic hepatitis, acute hepatitis) were determined by gas-liquid chromatography-mass spectrometry. Five C-1 hydroxylated bile acids and nine C-6 hydroxylated bile acids were identified in the urine studied; 1 beta,3 alpha,12 alpha-trihydroxy-, 1 beta,3 alpha,7 alpha-trihydroxy-, 1 beta,3 alpha,7 alpha,12 alpha-tetrahydroxy-, 3 alpha,6 alpha,7 alpha-trihydroxy-, and 3 alpha,6 alpha,7 alpha,12 alpha-tetrahydroxy-5 beta-cholanoic acids were found as the major components. Most of the 1 beta- and 6 alpha-hydroxylated bile acids were excreted into urine in the nonsulfate-nonglucuronide form. The amounts in the urine were greater than those found in the bile, portal and peripheral venous sera, and liver specimens. The biliary excretion and hepatic extraction of 1 beta-hydroxylated metabolites were more impaired and less efficient than for cholic acid. These findings suggested that hepatic 1 beta- or 6 alpha-hydroxylation of bile acids occurred concurrently in the patients with liver disease and that the resulting hydroxylated metabolites were efficiently excreted in the nonsulfate-nonglucuronide form into urine rather than into bile.

Adult↗
PubMed1990

[A recurrent gastric carcinoma found by metastasis to the scrotum].

Reported is a case of 67-year-old man with a recurrent gastric carcinoma that was associated with a possible lymphatic metastasis to the scrotum. Seven years earlier (October, 1980), since an adenocarcinoma of the stomach was present, a subtotal gastrectomy was performed. At that time, a IIc-like advanced tumor with a ul-III, measuring 32 x 28 mm in size, was noted on the anterior wall of the corpus near the greater curvature of the stomach, on macroscopical examination of the resected specimen. Microscopic findings showed a poorly differentiated adenocarcinoma with an involvement of the serosa but without a lymph node metastasis (H0, P0, n0, se, stage III). In July 1987, a tumor in the right scrotum was found and the patient underwent surgery. The resected specimen revealed a histologically cancerous involvement of the testis, the epididymis, the tunica vaginalis testis, and the spermatic cord. The cancerous cells showed the same poorly differentiated adenocarcinoma which had been observed in the primary locus of the stomach. Judging from these findings, this case was diagnosed as a recurrent gastric carcinoma with a lymphatic metastasis to the scrotum.

Adenocarcinoma↗
PubMed1989

Immunohistochemical localization of human liver glutathione S-transferase (GST) isozymes with special reference to polymorphic GST1.

The products of three human glutathione S-transferase (RX:glutathione R-transferase, EC 2.5.1.18) (GST) loci (GST 1, GST 2 and GST 3) were purified and their immunohistochemical localization in liver was studied with special attention to the polymorphism of GST1 (neutral isozyme). The GST1 was homogeneously stained in cytoplasm of hepatocytes throughout the lobule of liver showing GST1 1, GST1 2 and GST1 2-1 phenotypes. However, none of the hepatic tissue showing GST1 0 phenotype was stained. Immunohistochemical staining of GST2 (basic isozyme) was distributed in the cytoplasm of hepatocytes homogeneously throughout the hepatic lobule in all cases and the strong staining intensity was also demonstrated in nucleus. GST3 (acidic isozyme) was strongly stained in biliary epithelium, while staining of hepatocytes was not apparent. These results indicate that the human liver GST isozymes exhibit significant difference in their inter-individual, specific cellular and organellar distribution.

Animals↗
PubMed1989

Altered metabolism of bile acids in cholestasis: determination of 1 beta- and 6 alpha-hydroxylated metabolites.

Trihydroxy and tetrahydroxy bile acid metabolites substituted at the C-1 or C-6 position were studied using the urine, serum and liver tissue from sixteen patients with cholestatic liver diseases. Following extraction, isolation and hydrolysis, bile acids were converted into the dimethylethylsilyl derivatives and assayed by capillary gas chromatography-mass spectrometry. Five 1 beta-hydroxylated bile acids, viz. 1 beta,3 alpha,12 alpha-trihydroxy-, 1 beta,3 alpha,7 alpha-trihydroxy-, 1 beta,3 alpha,7 beta-trihydroxy-, 1 beta,3 alpha,7 alpha,12 alpha-tetrahydroxy-5 beta-cholanoic acids and an epimer of the first compound, and two 6 alpha-hydroxylated bile acids, viz. 3 alpha,6 alpha,7 alpha-trihydroxy-, 3 alpha,6 alpha,7 alpha,12 alpha-tetrahydroxy-5 beta-cholanoic acids, were completely or partially identified. Large amounts of 1 beta-hydroxylated and 6 alpha-hydroxylated bile acids were found in the urine, whereas only trace amounts were detected in the serum and liver tissue. These findings indicate that altered metabolism, such as 1 beta- or 6 alpha-hydroxylation of bile acids, is enhanced in cholestasis, and that the resulting hydroxylated metabolites are eliminated in the urine.

Bile Acids and Salts↗
PubMed1989

Lymphokine-activated suppressor (LAS) cells in patients with gastric carcinoma.

T-cell-growth-factor (TCGF) activate peripheral blood lymphocytes (PBL), cultured for 14 days, showed killer cell activities against natural-killer resistant Daudi cells in a 4 h 51Cr-release assay. However, the effector cells obtained from patients with nonresectable carcinoma exhibited very much lower cytotoxicity to tumor cells. To analyze the mechanism of depression, we have attempted to examine suppressor cell activities of the TCGF-activated PBL. The assay for the suppressor cell activities was made by in vitro inhibition of cell-mediated cytotoxicity by incubating radiolabeled target tumor cells with lymphokine-activated killer (LAK) cells and TCGF-activated PBL. LAK cells were induced by cultivation with recombinant interleukin-2. TCGF-activated PBL, obtained from four out of ten patients with resectable carcinoma and nine out of ten patients with nonresectable carcinoma, significantly suppressed the LAK cell activities. However, this suppression was not observed in TCGF-activated PBL from ten normal healthy control subjects. TCGF-activated PBL with immunosuppressive reactivity were named lymphokine-activated suppressor (LAS) cells. To investigate the phenotypic characterization of TCGF-activated PBL, the cells were analyzed by two-color flow cytometry. TCGF preferentially expanded CD8+CD11- cells and decreased the growth of CD8+CD11+ cells in both normal healthy control subjects and gastric cancer (resectable and nonresectable) patients. Dominantly expressed CD8+CD11- cells on TCGF-activated PBL in patients--especially those with nonresectable gastric carcinoma--showed strong LAS cell activity, irrespective of the presence of killer cell activities of CD8+CD11- cells in TCGF-activated PBL from normal healthy control subjects. The results suggested the generation of CD8+CD11- LAS cells from cancer patients, and revealed that CD8+CD11- T-cells contained killer and/or suppressor cell function. In addition, it was found that the TCGF-activated PBL from gastric cancer patients were associated with an increased proportion of CD4+ Leu8+, HLA-DR+CD8+ and HLA-DR+CD25+ cells.

Adult↗