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Biomedical subjects

T Taki

Publications and source records attributed to T Taki.

At least 217 records · Page 12Linked to original sources

Glycolipids of metastatic tissue in liver from colon cancer: appearance of sialylated Le(x) and Le(x) lipids.

Glycolipids of metastatic tissue in liver from colon cancer were separated by HPLC and their structures were analyzed. Neutral glycolipid was composed of five major components. Four of them showed similar mobilities to GlcCer, LacCer, Gb3Cer, and nLc4Cer on TLC. The structure of the fifth major component was analyzed by exo-glycosidase treatments, 400 mHz proton NMR spectrometry, gas chromatography-mass spectrometry of the methylated sugars, and immunostaining on a TLC-plate, and concluded to be (Formula: see text). Ganglioside was composed of two major components. One of them was identical with GM3. The structure of the second ganglioside was analyzed by exo-glycosidase treatment, immunostaining on a TLC-plate, and gas chromatography-mass spectrometry of methylated sugars, and concluded to be (Formula: see text). These Le(x) and sialyl-Le(x) structure-containing lipids accounted for about 12% of the neutral glycolipid fraction and 42% of the ganglioside fraction, respectively. From these results, it appears that the biosynthetic pathway for Le(x) structure-containing lipids is activated in colon cancer.

Chromatography, High Pressure Liquid↗

Developmental changes in ganglioside composition and synthesis in embryonic rat brain.

Developmental changes in ganglioside composition and biosynthesis was studied in rat brain between embryonic day (E) 14 and birth. In E14 brains, GM3 and GD3 were predominant. At E16, "b" series gangliosides, such as GD1b, GT1b, and GQ1b, increased in content. After E18, "a" series gangliosides such as GM1, GD1a, and GT1a increased in content, and the content of GM3 and GD3 markedly decreased. Because of these changes in composition, we determined the activities, in homogenates of embryonic brains, of two key enzymes of ganglioside synthesis: sialyltransferase for the synthesis of GD3 from GM3 and N-acetylgalactosaminyltransferase for GM2 synthesis from GM3. The sialyltransferase activity (GM3----GD3) was constant between E14 and E18 but decreased rapidly from E18 to birth. In contrast, the N-acetylgalactosaminyltransferase activity (GM3----GM2) increased between E14 and E18 but was constant from E18 to birth. These changes in ganglioside composition and enzymatic activities indicate that during development there is a shift from synthesis of the simplest gangliosides of the "a" and "b" pathways to synthesis of the more complex gangliosides.

Animals↗

Ganglioside GM3 as a modulator of differentiation of mouse myeloid leukemia cells (M1-T22).

The effects of exogenously added glycosphingolipids on the differentiation of mouse myeloid leukemia cells (M1-T22) have been studied. Eight gangliosides and ten neutral glycosphingolipids were tested in terms of their induction of phagocytic activities on the leukemia cells. N-Acetyl-neuraminosyllactosylceramide (NAc-GM3) was the most effective glycolipid for inducing the activity. By the addition of 25 micrograms/ml of NAc-GM3, about 70 percent of the cells acquired phagocytic activity within 20 h incubation. GM1a showed about half the activity of the GM3. In the case of the neutral glycosphingolipids, lactosylceramide (CDH) and globotriaosylceramide (CTH) showed significant effects on the induction of phagocytic activity. Preincubation of the cells with the NAc-GM3 enhanced the effect of dexamethasone as a differentiation inducer on M1-T22 cells. When a human promyelocytic leukemia cell line, HL-60, was preincubated with the NAc-GM3 ganglioside, induction of the phagocytic activity, together with inhibition of the cell growth by phorbol ester (TPA), were markedly enhanced. From these observations, the NAc-GM3 ganglioside seems to act as a modulator of differentiation of mouse myeloid leukemia cells and also of HL-60 cells.

Animals↗

Appearance of a novel type of ganglioside (GD1 alpha) in a differentiation-resistant clone of mouse myeloid leukemia cells, M1-R1.

Glycolipid compositions of three mouse myeloid leukemia cell clones, two that are sensitive to differentiation inducers (M1-T22 and M1-S1) and one that is differentiation-resistant (M1-R1), have been compared. The T22 and S1 clones contained glucosylceramide (GlcCer), lactosylceramide (LacCer) and gangliotriaosylceramide (Gg3Cer) as the major neutral glycolipids. The differentiation resistant clone, R1, was characterized by the appearance of globotriaosylceramide (Gb3Cer) and a decrease of Gg3Cer. There was a distinct difference in the ganglioside profile between the differentiation-inducible and -resistant clones: T22 and S1 cells contained no detectable amounts of ganglioside, whereas six different gangliosides were detected in the R1 clone. These gangliosides were isolated and identified as GM3, GM2, GM1a, GD1a, GM1b, and a unique disialoganglioside, GD1 alpha, having the following structure: (formula; see text) Based on these comparative studies, the relationship between the glycolipid composition and the differentiation potential of leukemia cells is discussed.

Animals↗

[Treatment of malignant gliomas with high-dose ACNU and autologous bone marrow transplantation].

Two patients with malignant gliomas located in the frontal lobe were treated by supraophthalmic intracarotid infusion of high-dose ACNU 15 mg/kg (ca. 600 mg/m2) combined with a total 60 Gy of irradiation after surgery. Irradiation therapy was started 13 days (case 1) and 10 days (case 2) after surgery, and single chemotherapy with ACNU 1,020 mg (case 1) and 1,100 mg (case 2) was performed when 36 Gy of whole brain irradiation was done. Chemotherapy was followed by autologous bone marrow transplantation containing 6.8 X 10(9) and 8.9 X 10(8) nucleated cells, respectively. Nadirs of white cell counts on 9 days in case 1 and 14 days in case 2 after chemotherapy were 280 cells and 240 cells/mm3, respectively, and the white cell counts less than 1,000/mm3 continued for 7 and 12 days, respectively. Local irradiation was started again when the number of white cells became more than 1,000/mm3 and 24 Gy was completed in each case. CT scanning carried out on discharge demonstrated no apparent abnormal high density area by contrast medium in both cases. These two patients did not show severe side effects at 10 months in case 1 and at 3 months in case 2 after high dose ACNU therapy, and remained progression-free at that time. Dose 15 mg/kg of ACNU may be the maximum tolerable dose patients can recover from severe myelosuppression, caused by high dose ACNU therapy combined with irradiation therapy, by marrow rescue.

Antineoplastic Agents↗

[Successful treatment of cerebral cysticercosis with praziquantel].

A case of a 56-year-old Korean man with cerebral cysticercosis was reported. This case demonstrated the first successful treatment with praziquantel in Japan and also the usefulness of a low-dose regime in the treatment of cerebral cysticercosis. The patient was admitted to our hospital with a 7 years history of generalized seizure and a 6 months history of gait disturbance. He had 6 subcutaneous nodules. A CT scan of the brain showed multiple cysts containing a small calcification and the largest lesion measured 5 cm in diameter in the cerebellar vermis. Posterior fossa craniectomy was performed and the cyst was pathologically confirmed as cysticercosis. A month postoperatively the patient was given praziquantel 50 mg/kg body weight in 3 divided doses per day. But medication with praziquantel was stopped on the 5th day because of severe headache, nausea and vomiting. He was readmitted 6 months later with appearance of gait disturbance, left facial paresis and dysphagia. A CT scan revealed enlargement of some of the residual cysts. The patient was then given smaller doses of praziquantel 8 mg/kg body weight in 3 divided doses with steroid cover for 48 days. He experienced no side effect during the therapy and became free from the neurological symptoms. A CT scan showed complete disappearance and only numerous small calcifications of the cysts.

Brain Diseases↗

[Effect of MX-2, a morpholino anthracycline derivative, against human and rat glioma cells and experimental leptomeningeal tumors in rats].

MX-2, a new morpholino anthracycline derivative, showed broad anti-neoplastic activity against experimental tumors. Molecular weight of MX-2 is 622.07, and it can cross blood-brain barrier because of its high lipid solubility. In this report, we described its in vitro and in vivo effects on brain tumors. The growth of rat 9L and human KNS-42 glioma cells were markedly inhibited by the medium containing more than 1 ng/ml of MX-2. The inhibitory concentration of MX-2 for 50% cell kill was 1.8 ng/ml for 9L cell and 18 ng/ml for KNS-42, respectively. These values were the almost same as those reported with P388 leukemia. In rats with meningeal carcinomatosis induced by intracisternal inoculation of Walker 256 carcinosarcoma cells, the median survival time was significantly prolonged. The increased life span was 40, 40, 40 (p less than 0.01), and 20% (p less than 0.05) in the animals given intravenous MX-2 of 1.5, 1.0, 0.75, and 0.375 mg/kg on day 1, 5, and 9 after tumor inoculation respectively. These results indicate that MX-2 may be a promising new antineoplastic agent for the treatment of malignant brain tumor.

Animals↗

Synthesis of 7'-(3-hydroxypropyl)fortimicin A and 6'-epifortimicin A.

1,10-Di-0-acetyl-2,3,4,6,7,8,9-heptadeoxy-2,6-bis(2, 4-dinitrophenylamino)-L-lyxo-decopyranose (7) and -D-ribo-decopyranose (8) have been prepared from methyl 2-acetamido-2,3,4,6-tetradeoxy-6-nitro-alpha-D-erythro-hexopyranoside via a nitro aldol reaction with 4-[(tetrahydropyranyl)oxy]butanal in the presence of cesium fluoride, and their configurations at C-6 have been established by conversion of the precursor of 8, namely, methyl 2,6-diacetamido-10-O-acetyl-2,3,4,6,7,8,9-heptadeoxy-alpha-D - ribo-decopyranoside, into the known methyl 2,6-diacetamido-2,3,4,6,7,8,9,10-octadeoxy-alpha-D-ribo-d ecopyranoside. The title fortimicin A derivatives, 7'-(3-hydroxypropyl)fortimicin A and 6'-epifortimicin A, have been synthesized by condensation of compound 7 and 8, respectively, with 2,5-di-O-benzoyl-1,4-bis[N-(methoxycarbonyl)]fortamine B, followed by deprotection and introduction of a glycyl group. Their antimicrobial activities have been found to be weak compared to that of fortimicin A.

Aminoglycosides↗

Time course of dolichol and dolichyl phosphate during chemical carcinogenesis in rat liver.

Hyperplastic liver nodules were induced in rats by administration of an initiator (diethylnitrosamine or 3'-methyl-4-dimethylaminoazobenzene) and/or a promoter (phenobarbital) by the method reported by Tatematsu et al. (1983, Carcinogenesis 4, 381-386). The dolichol content in the liver and liver microsomes of the rats treated with the initiator were approx. 1.5-times higher than that of the control and rats treated with only the promoter. However, the composition of dolichols was not changed. The time course of the dolichyl phosphate concentration in the rat liver treated with both initiator and promoter showed a pattern different from that in the control liver, the initiator-treated liver or the promoter-treated liver. The main component of dolichyl phosphate in liver treated with both the initiator and promoter changed from that with 18 isoprene units to that with 19. It is suggested that the changes in liver dolichols and dolichyl phosphates may be related to the formation of hyperplastic liver nodules.

Acyl Coenzyme A↗

Alpha-fetoprotein and human chorionic gonadotropin-producing lung cancer.

A 73-year-old man had primary lung cancer that produced both alphafetoprotein (AFP) and human chorionic gonadotropin (HCG). The preoperative serum AFP level of 1039 ng/ml decreased to the normal range 8 weeks after surgery. The preoperative serum HCG level of 11 mIU/ml, which temporarily decreased to the normal range after operation, soon increased thereafter. The serum HCG level decreased, however, to the normal range after postoperative mediastinal radiation therapy. During relapse, only the serum HCG level increased gradually to 26,000 mIU/ml 7 weeks before his death. The lung cancer was classified histologically as poorly differentiated adenocarcinoma. Immunohistochemically, AFP was detected in the mononuclear tumor cells of the primary tumor in the lung, and HCG was found in the giant cells of the subcarinal metastatic lymph node. The concanavalin A non-reactive fraction rate for AFP was 81.3%, and appeared to differ from those of hepatocellular carcinoma and yolk sac tumor.

Adenocarcinoma↗

A ganglioside of rat ascites hepatoma AH 7974F cells. Occurrence of a novel disialoganglioside (GD1 alpha) with a unique N-acetylneuraminosyl (alpha 2-6)-N-acetylgalactosamine structure.

A novel disialoganglioside has been isolated from rat ascites hepatoma AH 7974F cells. Based on the results of sequential enzymatic hydrolysis and gas chromatography-mass spectrometry analysis of the methylated sugars, the structure was concluded to be (Formula: see text) Proton magnetic resonance spectra of the ganglioside have been obtained and peaks of protons were assigned based on the analytical results. This is the first report on the occurrence in mammalian cells of an example of this new series of gangliosides which has NeuAc linked to the C6 position of GalNAc of the gangliotetraosyl backbone. The present ganglioside was named GD1 alpha.

Animals↗