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Biomedical subjects

M Gotoh

Publications and source records attributed to M Gotoh.

At least 289 records · Page 16Linked to original sources
PubMed1993

[Adoptive immunotherapy in patients with multiple hepatic cancers using lymphokine activated killer cells (LAK) and interleukin-2].

Tumor infiltrating lymphocytes (TIL) and peripheral blood lymphocytes (PBL) were isolated from 5 patients with multiple hepatocellular carcinoma (HCC) and with metastatic liver tumor. Proliferation of lymphocytes was observed following addition of interleukin-2 (700 JRU/ml) into the culture media. After analysis of LAK cells by FACS, the antitumor activities were examined. Higher levels of cytotoxic activity against tumor cells (K 562 and Daudi) have continued during the culture period ranging from 2 to 5 weeks. Adoptive immunotherapy was performed using TIL-LAK and PBL-LAK via hepatic artery for three patients with HCC and one patient with metastatic tumor. The average number of administered lymphocytes was 1 x 10(9). Reduction of tumor size was observed after this therapy, which caused no severe side effects exclusive of high fever and pleural effusion. Our results indicate that the treatment using lymphokine activated killer cells and interleukin-2 may be a promising modality for patients with multiple HCC.

Carcinoma, Hepatocellular↗
PubMed1993

[Efficacy of transarterial immuno-embolization therapy (TIE) in operable patients with hepatocellular carcinoma].

The efficacy of transarterial immuno-embolization therapy (TIE) was examined in six operable patients with hepatocellular carcinoma (HCC). We administered OK-432, fibrinogen (30 mg/ml) and thrombin (1 U/ml) through a catheter which was inserted into the tumor-feeding artery. In all patients with a high level of tumor markers (AFP and PIVKA-II), the level decreased promptly to less than the pretreatment level after TIE therapy. The therapy has not caused any serious side effects. No disturbance of the coagulation-fibrinolysis system due to TIE was observed in any patient. Histological examination of resected specimens following TIE showed massive infiltration of mononuclear cells around tumor cell nests, and lytic necrosis as well as coagulation necrosis of the main tumor and the intrahepatic metastases. Our results indicate that TIE may be an effective and promising modality for HCC patients.

Aged↗
PubMed1993

Protective effect of platelet-activating factor antagonist on ischemia-induced liver injury in rats.

Platelet-activating factor (PAF), one of the chemical mediators related to inflammation reaction, is also involved in the pathologic state induced by endotoxin or ischemia. PAF antagonist has been reported to block the action of PAF and protect cells from its deleterious effects. The effects of a PAF antagonist, CV-6209, were evaluated in this study by means of a partial liver ischemia model, in which ischemia was induced by clamping only part of the liver without causing intestinal congestion. This model allowed the study of ischemic liver injury without influence from other organs. After 30, 60, and 90 minutes of ischemia, the bile flow, ATP level, and energy charge of the ischemic lobes were compared for the effects with and without CV-6209. After 60 minutes of ischemia, those that had received CV-6209 showed more bile production and higher ATP level and energy charge, with values of 0.25 +/- 0.05 ml/hr, 3.9 +/- 0.9 nmol/mg dry liver weight, and 0.61 +/- 0.02, respectively. In contrast, the values for the control group were 0.05 +/- 0.05 ml/hr, 1.7 +/- 0.8 nmol/mg dry liver weight, and 0.43 +/- 0.08, respectively. Other liver function tests (aspartate aminotransferase and lactate dehydrogenase levels) could also be improved if an appropriate dose of PAF antagonist were administered. The results imply that PAF, as has been suggested in other studies on ischemic injury, plays a role in liver ischemia and that its deleterious effects can be blocked by PAF antagonist. We conclude that the PAF antagonist offers promise in the field of liver surgery, including liver transplantation, as a means of protecting the liver from ischemic injury.

Adenosine Triphosphate↗
PubMed1992

Cadherin dysfunction in a human cancer cell line: possible involvement of loss of alpha-catenin expression in reduced cell-cell adhesiveness.

A human lung cancer cell line, PC 9, was analyzed to elucidate the molecular mechanisms of dysfunction of cadherin-mediated cell-cell adhesion in cancer. Although PC 9 cells strongly expressed E-cadherin at the cell membrane, which was indistinguishable immunochemically from functional E-cadherin, they did not show tight cell-cell adhesion and had reduced E-cadherin-mediated aggregation activity. Immunoprecipitation with E-cadherin and Western blot analysis revealed that PC 9 cells did not express alpha-catenin, a cadherin-associated protein, suggesting that this was the cause of the cadherin dysfunction in the cell line. In addition, Northern and Southern blot analyses disclosed homozygous deletion of part of the alpha-catenin gene, which might have resulted in the loss of alpha-catenin expression in PC 9 cells.

Blotting, Northern↗
PubMed1992

Effects of intracerebroventricularly administered neostigmine on hypothalamic monoaminergic neuronal activities in awake rats.

Hypothalamic neuronal activities of noradrenaline, dopamine and serotonin as well as serum glucose concentrations were simultaneously monitored 60 min after the third cerebroventricular injection of neostigmine, a cholinesterase inhibitor, in rats. Each neuronal activity was assessed from a ratio of the concentration of the major metabolite to that of its precursor monoamine itself by using the technique of gas chromatography-mass spectrometry. Neostigmine caused significant increases in serum glucose concentrations, hypothalamic noradrenergic and dopaminergic neuronal activities, and significantly suppressed hypothalamic serotonergic neuronal activity. All these responses to neostigmine were completely inhibited by the co-administration of atropine. These observations emphasize the important role of the interactions between cholinergic (muscarinic) and monoaminergic neurons in the brain.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Both the anaerobic pathway and aerobic desaturation are involved in the synthesis of unsaturated fatty acids in Vibrio sp. strain ABE-1.

Vibrio sp. strain ABE-1 is a unique marine bacterium in terms of its ability to synthesize delta 9-trans-hexadecenoic acid and delta 7-cis-tetradecenoic acid (14:1(7c); Okuyama, H., Sasaki, S., Higashi, S. and Murata, N. (1990) J. Bacteriol. 172, 3515-3518). The present study, involving labeling with [1-14C]acetate, demonstrated that 14:1 is synthesized by the anaerobic pathway. When cells of this bacterium were grown in the presence of [1-14C]myristic acid (14:0), this compound was converted to palmitic (16:0) and hexadecenoic (16:1) acids but not to 14:1, under aerobic conditions. These results suggest that the incorporated 14:0 was elongated to 16:0 and then converted to 16:1 by the aerobic desaturation of 16:0. It appears that the anaerobic pathway and aerobic desaturation are both involved in the synthesis of unsaturated fatty acids during aerobic growth of Vibrio sp. strain ABE-1.

Acetates↗
PubMed1992

Intraoperative irradiation in resected carcinoma of the pancreas and portal vein.

We developed a new method that provides a wide retroperitoneal irradiation field for patients with cancer of the pancreas in whom a long invaded portal vein is resected during intraoperative radiotherapy. This method involves the use of a venous bypass with a heparinized catheter that does not require systemic anticoagulation or a pump. Anastomosis is completed after intraoperative radiotherapy. Mean (+/- SD) duration of the venous bypass was 3.0 +/- 1.5 hours (range, 2.0 to 6.6 hours), during which no abnormalities of systemic blood pressure, heart rate, and electrocardiographic activity and no signs of congestion of the intestines were observed. Eleven patients were treated with this method, and no complications ascribed to intraoperative radiotherapy or venous bypass were found. We recommend this method as safe and simple for expanding the irradiation field for intraoperative radiotherapy in patients with pancreatic cancer in whom the portal vein is resected.

Adult↗
PubMed1992

Genetic linkage between copper accumulation and hepatitis/hepatoma development in LEC rats.

The concentration of copper in the livers of Long-Evans rats with cinnamon-like coat color (LEC), in which hepatitis and then hepatomas develop spontaneously, was recently found to be abnormally high. Therefore, we examined the copper concentrations in the livers of LEC F1 backcrosses (LEC F1 x LEC) to determine the linkage of copper accumulation with development of hepatitis. Consistent with a previously reported ratio of rats with hepatitis to rats without hepatitis of about 1:1, hepatitis developed in 14 of 30 F1 backcrosses. The copper concentrations in the livers of all LEC F1 backcrosses with hepatitis were abnormally high and comparable to those of LEC rats. In contrast, the concentrations in all backcrosses without hepatitis were similar to those in normal Long-Evans with agouti coat color or Brown-Norway rats. Copper accumulation was shown to be closely linked with the development of hepatitis in LEC rats and appeared to be a possible cause of hepatitis. The concentrations of copper in the livers of Fischer 344 rats after carbon tetrachloride treatment were in the range for normal liver, indicating that a high copper concentration in the liver is specific to LEC rats and not a specific characteristic of hepatitis. Furthermore, we found that the size and level of ceruloplasmin mRNA in the livers of LEC rats were the same as those in LEA rats and that the size and level of ceruloplasmin polypeptide in their livers and plasma were almost the same as those in LEA rats. Therefore, these results suggest that the copper accumulation is not due to alteration of expression or to gross alteration of the ceruloplasmin gene.

Animals↗
PubMed1992

Synthesis in vitro of very long chain fatty acids in Vibrio sp. strain ABE-1.

The activity of fatty acid synthetase (FAS) from Vibrio sp. strain ABE-1 required the presence of acyl carrier protein and was completely inhibited by thiolactomycin, an inhibitor specific for a type II FAS. These observations indicate that this enzyme is a type II FAS. Analysis by gas-liquid chromatography of the reaction products synthesized in vitro from [2-14C]malonyl-CoA by the partially purified FAS revealed, in addition to 16- and 18-carbon fatty acids which are normal constituents of this bacterium, the presence of fatty acids with very long chains. These fatty acids were identified as saturated and mono-unsaturated fatty acids with 20 up to as many as 30 carbon atoms. The longest fatty acids normally found in this bacterium contain 18-carbon atoms. These results suggest that the FAS from Vibrio sp. strain ABE-1 has potentially the ability to synthesize fatty acids with very long chains.

Acyl Carrier Protein↗
PubMed1992

Selection of therapeutic modalities for hepatocellular carcinoma in patients with multiple hepatic lesions.

In the present study, we compared the survival of patients with multi tumor hepatocellular carcinoma (HCC) following their treatment with liver resection versus TAE. A total of 336 HCC patients were treated at Osaka University Hospital between 1980 and 1989. Of these, 140 patients underwent liver resection in the presence or absence of TAE and 173 subjects were treated with TAE alone. Our TAE protocol consisted of 50 mg Adriamycin, 3-5 ml lipiodol, and Gelfoam. The 1-, 3-, and 5-year survival values found for the liver resection group were 87.4%, 66.0%, and 47.4%, respectively, whereas the values calculated for the TAE group were 64.6%, 29.9%, and 15.8%, respectively. The survival of patients in the resection group was clearly better than that of subjects in the TAE group. Of the 140 patients who underwent resection, 36 cases were proven to have multiple lesions by histopathological examination. The 1- and 3-year survival values determined for this special group were 67.9% and 33.3%, respectively. Of the TAE cases, 113 were diagnosed as having multiple lesions by imaging examination, and their 1- and 3-year survival values were 59.7% and 24.9%, respectively. No significant differences in survival was found between these two different treatment modalities for these multiple-lesion cases. The results of this study indicate that it is unlikely that surgical resection is superior to TAE alone for the treatment of HCC patients with multiple lesions.

Adult↗
PubMed1992

Relationship between pathologic prognostic factors and abnormal levels of des-gamma-carboxy prothrombin and alpha-fetoprotein in hepatocellular carcinoma.

The relationship between pathologic prognostic factors and abnormal levels of des-gamma-carboxy prothrombin and alpha-fetoprotein was investigated in 42 patients with resectable hepatocellular carcinoma. The frequencies of macroscopic massive type, intrahepatic metastasis, and portal vein tumor thrombus were significantly higher in patients with positive des-gamma-carboxy prothrombin (p less than 0.05) but not with alpha-fetoprotein. Other histologic factors in tumorous and nontumorous tissues were not significantly different irrespective of the positivity of these markers. In patients with tumors not more than 6 cm in diameter, the frequency of intrahepatic metastasis was positively correlated with the positivity of des-gamma-carboxy prothrombin (p less than 0.05) and inversely with that of alpha-fetoprotein (p less than 0.05). Furthermore, intrahepatic metastasis was most frequently observed in patients with positive des-gamma-carboxy prothrombin and negative alpha-fetoprotein (eight of nine) and least frequently in cases with negative des-gamma-carboxy prothrombin and positive alpha-fetoprotein (one of eight). These findings indicated that both des-gamma-carboxy prothrombin and alpha-fetoprotein might be useful markers for the prediction of intrahepatic spread of hepatocellular carcinoma.

Biomarkers↗
PubMed1992

Relationship between hypothalamic noradrenergic activity and the sympathetic activity in interscapular brown adipose tissue after cold-swim stress in rats.

Noradrenaline (NA) activities in both hypothalamus and interscapular brown adipose tissue (IBAT) were simultaneously assessed before and after cold-swim stress in rats. The technique of gas chromatography-mass spectrometry was employed for the analysis of NA and its primary neuronal metabolite, 3,4-dehydroxy-phenylethylenglycol (DHPG), and the ratio of DHPG to NA was used as an index of NA activity. The ratios of DHPG/NA in both hypothalamus and IBAT were significantly elevated 5 and 20 min after cold-swim stress. Moreover, we found that there is a highly significant positive relationship between the hypothalamic DHPG/NA ratio and the ratio of DHPG/NA in IBAT (r = 0.872, p less than 0.0001). This observation strongly supports the concept in which hypothalamic NA neurons play an important role in modulating the sympathetic outflow.

Adipose Tissue, Brown↗
PubMed1992

Effects of adrenergic blockers on central nervous system-mediated hyperglycemia in fed rats.

We studied the effect of adrenergic blockade on hepatic venous hyperglycemia and the activation of a hepatic glycogenolytic enzyme, phosphorylase-a, in response to cerebral cholinergic activation. Neostigmine was injected into the third cerebral ventricle of bilaterally adrenodemedullectomized (ADMX) rats, while somatostatin and insulin were administered intravenously. Hepatic venous plasma glucose concentrations and hepatic phosphorylase-a activity were measured. Intracerebroventricular injection of neostigmine (5 x 10(-8) mol) caused increases in hepatic venous glucose concentrations and hepatic phosphorylase-a activity. Both of these changes were prevented by intraperitoneal (IB) pretreatment with phentolamine (5 x 10(-7), 1 x 10(-6) mol) without the intervention of insulin secretion, but not by pretreatment with the alpha-adrenoreceptor antagonist phenoxybenzamine (1 x 10(-6) mol), the beta-adrenoreceptor antagonist propranolol (1 x 10(-6) mol), the alpha 1-antagonists prazosin or bunazosin (1 x 10(-6) mol), the alpha 2-antagonist yohimbine (1 x 10(-6) mol), or prazosin (5 x 10(-7) mol) plus yohimbine (5 x 10(-7) mol). These results suggest that phentolamine prevented brain-mediated hepatic glycogenolysis by a mechanism that may not be classified pharmacologically as involving either alpha 1- or alpha 2-receptors.

Adrenalectomy↗
PubMed1992

Quantification of antimyosin uptake and infarct size at various stages of myocardial infarction.

We studied with quantitative techniques the clinical efficacy of indium-111 antimyosin at a later stage of myocardial infarction in 18 patients at various stages after infarction. Antimyosin accumulation was detected irrespective of infarct age and size and quantified as an infarct weight with a tomographic technique. Higher intensities in a planar image were observed in anterior Q wave infarct group (36 +/- 5 g) but not in inferior and non-Q wave anterior infarct groups because of the smaller infarct weights (8 +/- 3 g, 13 +/- 6 g, respectively). Infarct area calculated from thallium-201 tomography significantly correlated with left ventricular ejection fraction in both recent (less than 2 weeks) and older (2-week- to 6-month-old) infarct groups (r = -0.969, P less than 0.001; r = -0.860, P less than 0.001, respectively), whereas there was a significant negative correlation between infarct weight and left ventricular ejection fraction in the recent infarct group (r = -0.731, P less than 0.05) but not in the older infarct group. Thus, antimyosin tomography can detect myocardial necrosis with a high sensitivity regardless of infarct age, size, and location. However, the accumulation might be affected by infarct age and correspond to necrotic mass but not necessarily to infarct volume itself at a later stage probably because of the presence of necrosed and scarred tissues in infarcted myocardium.

Aged↗