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Biomedical subjects

T Osuga

Publications and source records attributed to T Osuga.

At least 91 records · Page 5Linked to original sources
PubMed1989

Effect of ursodeoxycholic acid in chronic hepatitis and primary biliary cirrhosis.

Clinical and experimental investigations have suggested that ursodeoxycholic acid (ursodiol) may have cytoprotective or choleretic action and therefore be beneficial in patients with intrahepatic cholestasis or chronic liver disease. In an open-label study, we treated 45 patients with chronic hepatitis with 300 mg of ursodiol three times daily for six months. At four months, gamma-glutamyl transpeptidase (gamma-GTP) and leucine aminopeptidase levels had decreased. SGOT and SGPT levels also decreased significantly. Evaluation of histologic changes has not yet been completed. No significant differences in improvement of liver function tests were found in a comparison with 19 historical controls. We also studied eight patients with primary biliary cirrhosis, treated for more than one and a half years with 600 mg of ursodiol per day. At one month, itching diminished in five patients who had pruritus. ALPase and gamma-GTP levels decreased significantly, and GOT and GPT levels were also reduced. IgM levels did not change, but the titer of antimitochondrial body decreased by half in two patients. Levels of glycoursodeoxycholic acid increased, and in three patients follow-up liver biopsy showed marked improvement. These preliminary results suggest that ursodiol is safe and effective for the treatment of chronic hepatitis and primary biliary cirrhosis, but a large-scale, controlled trial is needed.

Alanine Transaminase↗
PubMed1989

Differential activation of lymphokine-activated killer cells with different surface phenotypes by cultivation with recombinant interleukin 2 or T-cell growth factor in gastric cancer patients.

Fourteen days' culture of human peripheral blood lymphocytes (PBL) with recombinant interleukin 2 (rIL 2) or T cell growth factor (TCGF) results in the generation of lymphokine-activated killer (LAK) effector cells which have the unique property of lysing natural killer (NK)-resistant human tumor cells, Daudi, as well as NK-sensitive, K562 cells. LAK cells were generated from both normal and gastric cancer patients' PBL. However, LAK cell activities induced by rIL 2 or TCGF decreased with the progress of the tumor growth. In addition, TCGF-induced LAK cell activities were found to be lower than the rIL 2-induced LAK cell activities. Different mechanisms may be involved in the decreases of the rIL 2-induced and TCGF-induced LAK cell activities. This study further demonstrates that the cell types involved are also heterogeneous, as determined by phenotypic characteristics. The LAK-effector cell type was analyzed by two-color flow cytometry. RIL 2-induced LAK cells showed increased proportions of CD4+Leu 8- and Leu 7+CD16-, and a decreased proportion of CD8+CD11- cells, which are believed to be associated with killer T cell functions. In contrast, TCGF-induced LAK cells revealed significantly increased proportions of CD8+CD11- and CD4+Leu8- cells, and a decreased proportion of Leu 7+CD16- cells. Thus, LAK cells with different surface phenotypes were induced by the cultivations with rIL 2 and with TCGF.

Adult↗
PubMed1989

[Immunochemical properties and immunohistological localization of human liver glutathione S-transferase isozymes].

The products of three human glutathione S-transferase (GST) loci (GST1, GST2 and GST3) were purified and their immunochemical properties as well as immunohistological localization in liver were studied. Three group of isozymes were different in molecular weight, substrate specificities and antigenicity. Two homodimers (type 1 and type 2) of GST1 which shows genetic polymorphism, were similar in immunochemical properties other than isoelectric point. Inactivity of GST1 0 was due to impaired protein synthesis. Immunohistologically, GST1 isozyme was homogeneously stained in cytoplasm of hepatocytes throught the lobule of liver showing GST1 1, GST1 2 and GST1 2-1 phenotypes. On the other hand, GST2 isozyme was stained in the cytoplasm as well as the nucleus of hepatocytes throughout the hepatic lobule in all cases. GST3 isozyme was strongly stained in biliary epithelium. These results indicate that the human liver GSTs are composed of three immunochemically distinct isozymes, which exhibit significant difference in inter-individual, specific cellular and organellar distribution.

Glutathione Transferase↗
PubMed1989

[A case of superficial esophageal cancer with an intramural metastasis to the gastric wall].

Reported is a case of 61-year-old man with a superficial esophageal cancer that was associated with an intramural metastasis to the stomach. Examination of the upper G.I. tract revealed a slightly elevated lesion with an irregular surface at the left wall of the lower esophagus, and a large submucosal tumor with an ulcerous formation that had developed and had increased rapidly within a month. Thus a resection of the lower esophagus and a total gastrectomy were performed. Histopathologically, the tumor of the lower esophagus was determined as being a moderately differentiated squamous cell carcinoma with a deep invasion to the submucosal tissue. The submucosal tumor of the stomach also was found to be a moderately differentiated squamous carcinoma. Neither provided evidence, however, of a direct involvement of the gastric serosa may have metastasized from the neighboring lymph nodes or from other organs, nor of any continuous mucosal metastasis between the primary lesion of the esophagus and the submucosal tumor of the stomach. Judging from these findings, the case was diagnosed as an esophageal cancer with an intramural metastasis to the stomach.

Carcinoma, Squamous Cell↗
PubMed1989

Concurrent occurrence of 3 beta,12 alpha-dihydroxy-5-cholenoic acid associated with 3 beta-hydroxy-5-cholenoic acid and their preferential urinary excretion in liver diseases.

3 beta-Hydroxy-(delta 5-3 beta-ol), 3 beta,12 alpha-dihydroxy-(delta 5-3 beta,12 alpha-ol), 3 beta,7 alpha-dihydroxy-(delta 5-3 beta,7 alpha-ol) and 3 beta,7 beta-dihydroxy-(delta 5-3 beta,7 beta-ol) 5-cholenoic acids were identified in patients with liver diseases by gas-liquid chromatography-mass spectrometry (GLC-MS). Of these unusual 3 beta-hydroxy-5-en-metabolites, delta 5-3 beta-ol and delta 5-3 beta,12 alpha-ol were found as major components in the urine of patients with liver diseases (cholestasis, liver cirrhosis, chronic hepatitis, acute hepatitis). Other 3 beta-dihydroxy-5-en-metabolites, delta 5-3 beta,7 alpha-ol and delta 5-3 beta,7 beta-ol, were found as minor components in the urine. The levels of delta 5-3 beta-ol and delta 5-3 beta,12 alpha-ol in urine were correlated with their levels in serum, with total bile acids in the urine, and with liver function, implying that the degree of their increment correlated well with the severity of liver diseases. The most abundant amounts of delta 5-3 beta-ol and delta 5-3 beta,12 alpha-ol were found in the urine as sulfate conjugates in comparison with bile, portal and hepatic venous sera, and liver tissue of the patients. The biliary excretion and hepatic extraction of these 3 beta-hydroxy-5-en-unsaturated bile acids were more impaired and inefficient than those of cholic and chenodeoxycholic acids.

Adult↗
PubMed1989

[A case of superficial squamous cell carcinoma of the esophagus showing multicentric development].

A 43-year-old male was admitted to the hospital with a complaint of mild dysphagia. A barium esophagogram showed an annular narrowing in the lower esophagus. Further, an endoscopic examination revealed erosive mucosa of the esophagus about 35 cm anal to the incisor. Lugol staining also revealed a geographical unstained lesion. The histologic diagnosis of a biopsy specimen indicated a squamous cell carcinoma and a total resection of the esophagus was performed. The operated material macroscopically showed a tumor of a superficially mixed type (IIa + IIc + IIb). The resected specimen histologically consisted of 18 squamous carcinomas that were separated with the normal squamous epithelium from each other. The major part of these lesions were limited to the epithelium, and only a few specimens microscopically showed an invasion of cancer nests in the propria mucosae. Great permeation of cancer cells into lymph vessels and the metastasis of one regional lymph node also were noted. Taken together, these findings indicated that the squamous cell carcinomas of this case seemed to have multicentrically developed from the normal esophageal mucosa.

Adult↗
PubMed1988

Analysis of integrated hepatitis B virus DNA and cellular flanking sequences cloned from a hepatocellular carcinoma.

By digestion with HindIII restriction enzyme, a human hepatocellular carcinoma was shown to contain only 2 hepatitis B virus (HBV) DNA inserts. Both HindIII fragments (8 and 16 kb) were molecularly cloned and the structures of HBV DNA and adjacent host sequences were analyzed. One clone (lambda YH 8) contained part of pre-S(I) through the entire S gene and the other (lambda YH 16) had the middle section of the S to the end of X gene of HBV DNA. No gross rearrangements were observed in either HBV or cellular DNA sequences in lambda YH 16 clone. However, the 8 kb HindIII fragment was considered to be amplified together with flanking cellular sequences. Furthermore, the HBV DNA was integrated into cellular genome at the Alu repeated sequences in lambda YH 8.

Bacteriophage lambda↗
PubMed1988

Immunochemical and immunohistological analyses of tumor-associated antigens defined by murine monoclonal antibodies against human pancreatic carcinoma cells.

Two murine monoclonal antibodies, SK-930 (isotype IgG2a) and SK-117 (isotype IgG1), were produced from spleen cells of mice immunized against human pancreatic carcinoma cell lines, MIA-PaCa 2 and Panc-1. With the use of the avidin-biotin-immunoperoxidase technique, the SK-930 and SK-117 antibodies detected an antigen found in 24 and 23 formalin-fixed tissue sections, respectively, of tumors obtained from 30 different patients with pancreatic carcinoma. Reactivity was also frequently found with tumors of the gallbladder, bile duct, stomach, colon and esophagus, while a large panel of normal human tissues, including normal pancreatic tissues, displayed little reactivity. These observations suggest that SK-930 and SK-117 are of value in identifying tumor-associated antigen (TAA) expressed in pancreatic carcinoma and other carcinomas of the digestive system. SK-930 antibody immunoprecipitated a 134 kilodalton molecule from extracts of 125I- or [35S]methionine- or [3H]glucosamine-labeled tumor cells. The SK-117-defined antigen corresponds to 152/137 kilodalton molecules. Moreover, cytofluorometric analyses showed that cells treated with periodic acid exhibited greatly decreased reactivity to the two antibodies, but cells treated with neuraminidase, trypsin or pronase showed unchanged reactivity. The findings suggest that the epitopes of the novel TAA expressed on pancreatic carcinoma cells are carbohydrate moieties.

Animals↗
PubMed1988

[Two-color flow cytometry analyses of peripheral blood lymphocytes (PBL) and lymphokine-activated PBL in gastric cancer patients].

A two-color flow cytometric analyses of the PBL of 51 patients (24 resectable, and 27 nonresectable), and of 30 healthy controls has been completed. The proportion of antigens, on the PBLs, defined by combinations of anti-Leu 2a and anti-Leu 15, anti-Leu 3a and anti-Leu 8, anti-Leu 3a and anti-HLA-DR, anti-HLA-DR and anti-Leu 2a and, anti-HLA-DR and anti-IL 2R, was not significantly different among the three groups. TCGF increased the proportion of Leu 2a+ Leu 15-, Leu 3a+ Leu 8-, HLA-DR+ Leu 2a+, Leu 3a+ HLA-DR+ and, HLA-DR+ IL 2R+ cells and reduced the proportion of Leu 2a+ Leu 15+ cells in gastric cancer patients, while the cultivation by IL 2 (2 weeks) increased the proportion of Leu 3a+ Leu 8-, HLA-DR+ IL 2R+ and Leu 3a+ HLA-DR+ cells, and did not change the proportion of Leu 2a+ Leu 15- and Leu 3a+ Leu 8+ cells, and decreased the proportion of Leu 2a+ Leu 15+ cells. These results, taken together with our previously published studies, suggest that the TCGF-activated Leu 2a+ Leu 15- subset but not the Leu 2a+ Leu 15+ subset serves as a phenotypic marker of suppressor-effector T cells, and that the IL 2-activated Leu 3a+ Leu 8- subset contained killer T cells against tumor cells in our experimental systems.

Antibodies, Monoclonal↗
PubMed1988

[A case of leiomyosarcoma of the stomach treated effectively by tegafur and absolute curative resection].

A 51-year-old woman with leiomyosarcoma of the stomach treated effectively with FT 600 mg/day p.o., is reported. Leiomyosarcoma of the stomach was found in the greater curvature on the fornix by examinations involving X-ray and gastrofiberscopy with biopsy. She was subsequently treated with MMC 6 mg/2 alpha/w x 5 weeks and FT 600 mg/day continuously on account of liver metastasis determined by liver scintigram and CT. After one year, both gastrofiberscopy and X-ray pictures showed a decrease in the size of the SMT. An evaluation of the treatment showed partial response (PR), and the state of PR was maintained for more than 5 years. Six years and 9 months after chemotherapy, however, unresponsiveness to the therapy appeared and regrowth of the SMT followed. Furthermore, intrahepatic SOL was definitely diagnosed to be cavernous hemangioma of the liver. Consequently, proximal gastrectomy was performed using R1-absolute curative resection, after confirming that the histology of the SMT was leiomyosarcoma of the stomach by endoscopic partial tumorectomy.

Combined Modality Therapy↗
PubMed1988

[An autopsy case of esophageal cancer with brain metastasis].

A rare case of esophageal cancer with brain metastasis is reported. A 54-year-old man complaining of dysphagia was admitted to our hospital. Endoscopic and radiographic examinations revealed an advanced esophageal cancer with supraclavicular lymph node metastasis. Five months later, muscle weakness of right upper extremities developed. A brain CT scan revealed a low density area with a ring enhancement in the left front parietal region. The patient developed right hemiplegia and delirium, and died seven months later. Autopsy findings showed a hematogenous metastasis of the left precentral gyrus, measuring 3.0 x 2.5 x 2.5 cm.

Brain Neoplasms↗
PubMed1988

Similarity of unusual bile acids in human umbilical cord blood and amniotic fluid from newborns and in sera and urine from adult patients with cholestatic liver diseases.

Unusual bile acids in umbilical cord blood and amniotic fluid of term newborns and in sera and urine from adult patients with cholestatic liver diseases were analyzed by use of gas-liquid chromatography-mass spectrometry. These bile acids were compared in order to elucidate possible similarities of bile acid metabolism between fetal and cholestatic liver. In both umbilical cord blood and amniotic fluid, 14 unusual bile acids were found in addition to normal bile acids (cholic, chenodeoxycholic, deoxycholic, and lithocholic acids), and 15, excluding ursodeoxycholic acid, were found in sera and urine from patients with cholestatic liver diseases. Of the unusual bile acids detected, 12 were common to both samples. Six unusual bile acids, 3 beta-hydroxy- and 3 beta,12 alpha-dihydroxy-5-cholenoic acids, 3 alpha,6 alpha,7 alpha-trihydroxy-5 beta-cholanoic acid, 1 beta,3 alpha,12 alpha-trihydroxy-1 beta,3 alpha,7 alpha-trihydroxy-, and 1 beta,3 alpha,7 alpha,12 alpha-tetrahydroxy-5 beta-cholanoic acids were more abundant than others. They could be classified into three groups, i.e., unsaturated, 6-hydroxylated, and 1 beta-hydroxylated bile acids. 1 beta-Hydroxylated bile acids, which were not found in serum specimens, were detected in sera from umbilical cord blood and from patients with cholestatic liver diseases. The presence of these unusual bile acids suggested similarities between the altered metabolic states of the two groups examined.

Adult↗
PubMed1987

Monoclonal antibody against human gallbladder carcinoma-associated antigen.

Monoclonal antibody HI-531 of immunoglobulin G2b subclass was produced against a human gallbladder carcinoma cell line. HI-531 was investigated for reactivity with a panel comprising ten types of different origin in fluorescence-activated cell sorter analysis. The antibody reacted with the gallbladder carcinoma cell line G-415 used for immunization and with four unrelated tumors. HI-531 was further shown, with the use of the avidin-biotin complex-immunoperoxidase technique and surgically resected tissues, to be strongly reactive with carcinoma of the gallbladder, pancreas, bile duct, and gastrointestinal tract. The antibody was reacted with several types of normal epithelial cells but often more weakly expressed than on corresponding tumors. One of six fetal lung tissues was weakly stained. All other fetal organ tissues tested showed negative staining reactions. These observations suggest that HI-531 may be of value in identifying the tumor-associated antigen expressed in gallbladder carcinoma. HI-531 immunoprecipitated the Mr 43,000 molecule from extracts of Na125I- or [35S]methionine-labeled tumor cells, but not from those of [3H]glucosamine-labeled tumor cells. In addition, cytofluorometric analysis showed that cells treated with trypsin or protease greatly decreased a reactivity to the antibody. The findings suggest that the antibody recognizes a Mr 43,000 protein molecule. Sequential immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis studies and analyses by nonequilibrium pH gradient and polyacrylamide gel electrophoreses showed that the Mr 43,000 molecule defined by HI-531 was not a Mr 43,000 heavy chain of HLA-A,B,C antigens detected by monoclonal antibody W6/32.

Animals↗