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Biomedical subjects

T Higashi

Publications and source records attributed to T Higashi.

At least 379 records · Page 21Linked to original sources

[Role of oral administration of 1-hexyl-carbamoyl-5-fluorouracil (HCFU) for multimodal treatment of inoperable cirrhotics with hepatocellular carcinoma].

1-Hexylcarbamoyl-5-fluorouracil (HCFU) was orally administered at doses of 300-600 mg daily for 7-360 days to 27 inoperable cirrhotics with hepatocellular carcinoma. They were simultaneously treated with transcatheter arterial embolization (TAE), and mitomycin C (MMC) injected into the hepatic artery and/or subcutaneous injection of OK-432. Efficient treatment according to the Koyama and Saito (PR and MR) and Karnofsky classification (I -A and I -B) was obtained in 40.7 and 29.6%, respectively, of all the patients; 81.8 and 54.5%, respectively, in the patients treated with TAE and intraarterial MMC injection and 25.0 and 12.5%, respectively, in those given MMC therapy. However, the total doses of HCFU administered (3-216 g) were not related to either efficient or inefficient treatment. Survival rate obtained 1 year following diagnosis of HCC was much better in the patients treated with TAE and/or MMC therapy (greater than 70%) than in those without these treatments (20%). TAE intervals in HCC patients given repeated TAE and intrahepatic MMC injection were slightly prolonged by oral administration of HCFU (more than 12 g). The results suggest that HCFU might be effective for prevention of HCC recurrence following TAE.

Administration, Oral↗

[Preparation of conjugates of adriamycin with antibodies to alpha-fetoprotein and their properties].

For its selective accumulation into tumor cells, the antitumor drug adriamycin (ADM) was attached to specific antibodies reactive against alpha-fetoprotein, a carcinoembryonic protein, and the antibody and antitumor activities of the resulting conjugate were investigated. Using the glutaraldehyde or carbodiimide binding methods, preparations containing 4-5 moles of ADM per mole of antibody were obtained. They retained 60-75% of the original antibody activity. Upon incubation of AH-66 ascites hepatoma cells with the conjugates, an increased number of dead cells and inhibited uptake of 3H-thymidine by the cells were observed. The conjugates were more effective against tumor cells than the free drug, and it was further presumed that the cytotoxic action of ADM on normal cells could be reduced by binding it to a macromolecular protein.

Animals↗

Oxidation of acetylpolyamines by extracellular polyamine oxidase produced by Penicillium sp. No. PO-1.

The oxidation of acetylpolyamines by an extracellular polyamine oxidase of Penicillium sp. No. PO-1 was investigated. The optimal pH value for oxidation of acetylpolyamines was 6.0. The purified enzyme oxidized spermidine, spermine, N1-acetylspermidine, N8-acetylspermidine, N1,8-diacetylspermidine, N1-acetylspermine and N1,12-diacetylspermine. The relative velocities for oxidation of acetylpolyamines were lower than those of spermidine and spermine. The Km values for oxidation of acetylpolyamines were higher than those of spermidine and spermine. The enzyme split N1-acetylspermidine and N8-acetylspermidine at the same position of the linkage as in spermidine oxidation. N1-Acetylspermine was changed to N1-acetylspermidine. This oxidation mechanism was different from that of rat liver polyamine oxidase. N1-Acetylspermine inhibited the oxidation of spermine. Putrescine, N8-acetylspermidine and N1,12-diacetylspermine also inhibited the N1-acetylspermidine oxidation by the enzyme.

Animals↗

Alterations in neutral amino acid transport across the blood-brain barrier in hepatic failure.

The accelerated transport of the blood neutral amino acids into the brain in encephalopathic patients with fulminant hepatitis and advanced liver cirrhosis was demonstrated not only by determining the cerebrospinal fluid (CSF) aminogram but also by calculating the predicted velocity of the amino acid transport through the blood-brain barrier. Significant elevation in CSF aromatic amino acid (AAA) and methionine levels was observed in the encephalopathic patients. Arousal from hepatic encephalopathy by drip infusion of a branched chain amino acid (BCAA)-enriched solution was obtained coincidentally with the elevated BCAA levels and diminished concentrations of AAA and methionine in CSF. These clinical observations were confirmed experimentally in rats treated with carbon tetrachloride (CCl4) and D-galactosamine by obtaining the elevation of neutral amino acid contents in the brain and the slight increase in the brain uptake index (BUI) of a radiolabeled amino acid.

Amino Acids↗

Potassium-verapamil cardioplegia for myocardial protection: an experimental evaluation through preservation and transplantation.

The efficacy of potassium-verapamil cardioplegia for myocardial protection was studied using the canine heart preservation and transplantation system. Coronary vascular washout of the grafts was performed via the aortic root both in Group I (n=8) with 4 degrees C high potassium cardioplegic solution and in Group II (n=8) with 4 degrees C high potassium and 1 mg/L verapamil solution. The heart were immersed into the same solution as used for washout and stored at 4 degrees C for 6 hours, without oxygenation and perfusion. The grafts were transplanted orthotopically under conditions of cardiopulmonary (CP) bypass. Adequate hemodynamics without the support of CP bypass was obtained in all the grafts of Group II during a 2-hour observation period. In contrast, only five out of eight grafts in Group I were able to support the recipient circulation. Contraction bands were more prominently and frequently observed in the histology in Group I. Thus, the combination of coronary vascular washout with cold potassium-verapamil cardioplegia and storage at 4 degrees C with the same solution seems to be effective for myocardial protection of the canine heart in cases of orthotopic transplantation.

Animals↗

Organ-specific difference in the sugar chains of gamma-glutamyltranspeptidase.

Sugar chains of gamma-glutamyltranspeptidase purified from neonatal mouse liver and adult mouse kidney were quantitatively released as oligosaccharides from the polypeptide backbone by hydrazinolysis. A comparative study of the structures of the oligosaccharides has revealed that the GlcNAc beta 1 leads to 4Man beta 1 leads to group is found in the sugar chains of kidney enzyme but not in those of liver enzyme. This is considered as an organ-specific difference common to mammals because the same phenomenon was found in bovine and rat enzymes.

Acyltransferases↗

New intraoral x-ray fluorographic imaging for dentistry.

A new dental x-ray fluorographic unit has been developed. This unit is composed of small intraoral x-ray tube, a compact x-ray image intensifier, and a high-resolution TV system. The purposes for developing this equipment were to (1) directly observe the tooth during endodontic procedures and (2) reduce x-ray exposure to the patient and the dentist. The radiation exposure can be reduced to about 1/600 the exposure used with conventional dental film. In clinical trials, a satisfactory fluorographic dental image for endodontic treatment was obtained with this new device.

Humans↗

Purification and properties of bovine liver gamma-glutamyltransferase.

gamma-Glutamyltransferase [EC 2.3.2.2] (gamma-GTP) was purified to a homogeneous state from bovine liver. It had an apparent molecular weight of about 110,000, as judged by polyacrylamide gel electrophoresis, and consisted of two non-identical glycopeptides with molecular weights of 68,000 and 27,000. The amino acid composition of the bovine liver enzyme was similar to those of other gamma-GTPs. The enzyme contained large amounts of neutral sugars, amino sugars and sialic acid, although the sialic acid content varied in different preparations. The Michaelis constant of the enzyme was estimated to be 0.8 mM for gamma-L-glutamyl-p-nitroanilide in the presence of glycylglycine and 1.25 mM in the absence of glycylglycine. Glutathione competitively inhibited the release of p-nitroaniline from gamma-L-glutamyl-p-nitroanilide with a Ki value of 0.3 mM. The specific activities of the enzyme for gamma-L-glutamyl-p-nitroanilide in the presence of glycylglycine (pH 8.6) and for glutathione, a natural substrate (pH 7.4), were comparable to those reported for gamma-GTPs from other mammalian sources. The bovine liver enzyme showed the same gamma-glutamyl group acceptor specificity as other gamma-GTPs from normal mammalian tissues. The phosphate-independent glutaminase activity of the enzyme was much lower than that of the rat kidney enzyme both in the presence and absence of maleate.

Amino Acids↗