Biomedical subjects
Publications and source records attributed to S Tashiro.
We described a patient with isolated duodenal varices of the third portion, preoperatively diagnosed by hypotonic duodenography and endoscopy. These varices seemed to be caused by portal hypertension due to liver cirrhosis. The third to the fourth portion of duodenum should be examined carefully in patients with liver cirrhosis, especially with gastrointestinal bleedings of unknown origin.
A clinical evaluation of arterial infusion of high-molecular-weight antitumor agent SMANCS dissolved in lipid lymphographic agent (thiodol) in 44 patients with mostly unresectable hepatoma is described. The treatment regimen demonstrated significant merits both therapeutically and diagnostically. Marked antitumor effects were shown in the decreased serum alpha-fetoprotein levels (86% of cases) and tumor size (95% of cases), and in survival period and histological findings. Furthermore, there was increased diagnostic sensitivity using CT scan, plain X-rays or ultrasound. The procedure of selective arterial administration of 3-4 mg of SMANCS in 3-4 ml of ethiodol per dose was simple to perform and was required only once every 3-4 weeks. Both ethiodol and the drug accumulated more selectively in tumor than in any other tissues and their activity remained for more than 3 weeks. Only minimal side-effects were associated with SMANCS and ethiodol during this study.
The catalysis by phosphatidylethanolamine methyltransferase (PEMT) of phosphatidylcholine (PC) synthesis by the successive methylation of phosphatidylethanolamine in the presence of S-adenosylmethionine (AdoMet) as methyl donor, was detected in actively myelinating mouse brains. PEMT activity in the microsome fraction of fetal mouse brain at 17 days of gestation was 253 mu u/mg protein and that of adult brain after 7 days of remyelination following 6 weeks cuprizone administration was 148 mu u/mg. These figures are much higher than found in normal adult brains (1.7 mu u/mg). An increase in PEMT activity was observed in the brains of genetically transmitted diabetic mice, C57BL/KsJ-db/db, and streptozotocin-induced diabetic mice; 16.3 and 9.2 mu u/mg, respectively. The methyl group of mecobalamin was transferred to homocysteine producing AdoMet and was further metabolized into choline and acetylcholine in brain slices. These results suggest that in the diabetic state, an increase in PC synthesis is probably required in order to replace damaged myelin or to supply choline or acetylcholine essential to for nerve functions. Mecobalamin might serve as the source of the methyl group utilized for PC synthesis.
A lymphographic agent, Ethiodol, injected via the hepatic artery was found to remain selectively in the tumor vessels of hepatoma for a long time in our clinic. Taking advantage of this selective continuous peripheral embolization, a lipophilic high molecular anticancer agent, SMANCS (Copolymer of styrene maleic acid conjugated to Neocarzinostatin) dissolved in Ethiodol was administered via the celiac axis or the hepatic artery with Seldinger's method. Anticancer effect was examined by histological findings of specimens removed using hepatic resection (13 cases) and autopsy (1 case) in 14 patients receiving this treatment. Anticancer effect of this treatment became clear through histological findings. In the patients administered SMANCS more than 0.26 mg per 1 cm2 of maximum cut-surface area, complete or widespread necrosis of the tumor occurred, whereas non-cancerous liver tissue remained unaffected.
Between September, 1981 and August, 1982, the IAP serum levels were measured in 151 patients to evaluate the correlation between these levels and the clinical spectrum. Pre- and postoperative IAP levels were also compared with the hospital course. Abnormally high IAP levels (greater than 450 micrograms/ml) were observed in malignant diseases, especially in patients with cancer of the pancreas, choledochus, gall-bladder, and esophagus. Of 193 patients, 81 revealed abnormal levels; 28 of these (34.6%) died during this study. The average of their survival time was 2.7 months. Nine of 81 patients (11.1%) experienced severe complications, but recovered. On the other hand, 112 patients with normal IAP levels had a relatively good hospital course; 9 (8%) died. None of the 112 patients experienced any complications. These results suggest that the IAP level may be a good tool in predicting clinical features and prognoses.
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Clinical records of 2567 patients (1717 female and 850 male) with primary carcinoma of the gallbladder in Japan, during the past 19 years, were collected by questionnaires sent out to the main 100 surgical institutes in Japan. Eighty-seven per cent of the patients were over fifty years of age. Gallstones were found in 58.8% of 1496 patients. About 50% of the patients with gallstones had cholesterol group stones. Of the 2269 patients who underwent surgical interventions, radical operations were performed in 467 patients (20.6%). Of the 467 patients, a correct preoperative diagnosis was made in only 77 patients (16.3%). Patients in Nevin's Stages I and II, whose lesions had been confined to the muscle layer, showed a good survival rate with only simple cholecystectomy or extended cholecystectomy, while the patients in Stages III, IV and V, whose lesions had spread beyond the muscle layer, showed poor results even with more aggressive surgical approaches. The poor prognosis of the lesions in Stages III, IV and V might be due to inappropriate aggressive procedures. For the lesions involving all the layers of the gallbladder wall, radical resection, such as extended cholecystectomy plus pancreatoduodenectomy, or extended right lobectomy plus pancreatoduodenectomy, might be recommended.
The insulin binding to hepatic plasma membranes, erythrocytes and adipocytes of 1-, 2-, and 9-month-old rats was measured by using [125I]insulin. When rats were fed a fat-free diet, the capacities of the insulin bindings significantly decreased with aging, whereas the dissociation constants were not altered. The capacities of 9-month-old rats were decreased to about half those of 1-month-old rats for plasma membranes, and about one-third for erythrocytes and adipocytes. On the other hand, the plasma insulin levels tended to be high with increasing age at 9-10 a.m., while the levels were even more elevated at 8-9 p.m. and not altered by aging. The insulin binding capacities were increased by feeding the fat-free diet to rats adapted to a stock diet and the increases were reduced with aging. The insulin binding capacities correlated well with the magnitudes of induction of lipogenic enzymes as reported previously [Iritani, N., Fukuda, H., & Fukuda, E. (1981) Biochim. Biophys. Acta 665, 636]. Therefore, it is suggested that insulin binding is implicated in age-dependent alterations of lipogenic enzyme induction.
Two advantages of the present therapeutic approach were described. Firstly, a selective deposition of lipiodol in tumor tissue was verified, thus more precise and accurate diagnosis by X-rays was possible either by CT or plain X-ray film. Secondly, pronounced accumulation of smancs in tumor tissue was observed, which established highly effective chemotherapy of unresectable hepatoma of 22 cases and 12 other cases based on (a) decrease in alpha-fetoprotein (86%), (b) tumor size (95%) and histology. Drug was given via the hepatic artery mostly 3-4 mg in 3-4 ml of lipiodol once every 3 to 4 weeks. Most patients have experienced a total dose of 6-8 mg in two cycles, but drug activity lasted more than 3 weeks. Neither hematosuppression nor anaphylaxis was observed. Major side effect was transient fever (38-39 degrees C) in about 50% of the cases which lasted no more than one week. Other minor side effect was abdominal pain during or after arterial infusion which lasted for about 20 min. Liver function was affected very slightly if any. Mild leukocytosis was observed in 65% of the patients.
A 69-year-old man with a large hepatoma of the right lobe extending in part to the medial segment of the left lobe was treated by ligation of the right hepatic artery combined with continuous infusion of a total dose of 5500 mg og 5-fluorouracil (5-FU) into the left hepatic artery. Postoperative celiac arteriogram and liver scintigram revealed a marked regression of the tumor size. After four weeks he was discharged in a satisfactory condition. Seven years and two months after the initial treatment he was readmitted because of a concomitant cancer of the cardia. Total gastrectomy was performed with a favorable result. A second look for the previous hepatic tumor during total gastrectomy revealed a fibrous tissue containing scattered nodules of hepatocellular carcinoma on the right lateral surface of the liver instead of the previous large tumor in the right hepatic lobe. He survived for eight ears after the first operation.
Cellular retinoic acid-binding protein (cRABP) was detected in the cytosol of virus-induced papilloma (Shope) of rabbit skin. The Shope papilloma cRABP showed the same ligand specificity and sedimentation value (2S) as was found in other animal species. The level of cRABP in the papillomatous tissue was significantly higher than that in the normal rabbit skin and increased in accordance with the growth and development of the tumor, reaching a peak about 40 days after the inoculation of the Shope papilloma virus. Although this binding capacity was about 15 times greater than in the normal skin, the level of cRABP in the transplantable carcinomas Vx2 and Vx7, both originating from the virus-induced papillomas over 20 years ago, was much the same as in normal rabbit skin.
When rats were fed for 2 weeks on 3% fat diets containing 0.5 or 1%corbicula (Corbicula japonica PRIME), clam (Tapes japonica) or oyster (Callocorchina) triglycerides, serum and liver triglyceride levels were significantly lowered. The activities of hepatic glucose-6-phosphate dehydrogenase, malic enzyme and acetyl-CoA carboxylase were markedly reduced in the rats. Cholesterol synthesis by liver slices was also reduced. The results of immunochemical titrations and Ouchterlony double-diffusion analysis indicated that the decreases in the activities of acetyl-CoA carboxylase and glucose-6-phosphate dehydrogenase were due to decreases in the enzyme quantities. The shellfish triglycerides include a high percentage of long chain and polyunsaturated fatty acids, which are common to and characteristic of the three kinds of shellfish. They would be effective components in these observations.
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Studies have been made on the subcellular localization of two long-chain acyl-coenzyme-A synthetases as well as glycerolphosphate acyltransferase and the acyl-CoA-oxidizing system in Candida lipolytica grown on oleic acid. Acyl-CoA synthetase I is distributed among different subcellular fractions, including microsomes and mitochondria where glycerolphosphate acyltransferase is located. On the other hand, acyl-CoA synthetase II is localized in microbodies where the acyl-CoA-oxidizing system is located. These results support our previous conclusion that acyl-CoA synthetase I is responsible for the production of acyl-CoA to be utilized for the synthesis of cellular lipids, while acyl-CoA synthetase II provides acyl-CoA that is exclusively degraded via beta-oxidation.
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The metabolic fate of trans-nonachlor and heptachlor in rats was studied in vivo and in vitro by using microsomal preparations of the liver. During in vivo studies the rate of excretion into urine and feces was monitored. The major metabolic products were collected from the feces and their chemical structures were determined by using various chromatographic and spectroscopic techniques. The immediate major metabolic product of transnonachlor is trans-chlordane which is further converted to 1,2-dichlorochlordene and to oxychlordane. From the latter metabolite, two major stable products, 1-hydroxy-2-chlorochlordene and 1-hydroxy-2-chloro-2,3-epoxy-chlordene are formed. Another route of metabolism is a direct formation of chlordene chlorohydrin which acts as a precursor for 1,2-trans-dihydroxydi-hydrochlordene. The major metabolic products of heptachlor were heptachlor epoxide, 1-exo-hydroxyheptachlor epoxide and 1,2-dihydroxy-dihydrochlordene.
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