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Biomedical subjects

Y Hashimoto

Publications and source records attributed to Y Hashimoto.

At least 1,495 records · Page 83Linked to original sources
PubMed1983

Antitumor effect of actinomycin D entrapped in liposomes bearing subunits of tumor-specific monoclonal immunoglobulin M antibody.

Sonicated liposomes containing actinomycin D in the membranes were chemically coated with the subunits of monoclonal immunoglobulin M (IgM) antibody against a mouse mammary tumor-associated antigen (MM antigen) and examined for their in vitro and in vivo antitumor effects against MM46 (MM+) and MM48 (MM-) tumors of C3H/He mouse origin. The antibody-bearing, actinomycin D-containing liposomes (chemoimmunoliposomes) were selectively bound to MM+ tumor cells and showed much more in vitro cytotoxicity against the tumor cells than that shown by free actinomycin D. The in vivo antitumor effect of the chemoimmunoliposomes was tested on the mammary tumor cells (5 X 10(4) to 5 X 10(6) transplanted i.p. into syngeneic mice. A single i.p. injection of the chemoimmunoliposomes containing 0.3, 0.5, or 1 microgram of actinomycin D into MM46 tumor-bearing mice resulted in the cure of some mice and a prolonged survival time in the rest of the mice as compared to results in controls. In this test, free actinomycin D, anti-MM IgM antibody, and bovine serum albumin-coated liposomes containing actinomycin D were marginally effective or ineffective. To examine a systemic antitumor effect of chemoimmunoliposomes, mice were inoculated with MM46 tumor cells and then treated with a single i.v. injection of liposomes 4 days later. If the mice were pretreated with an i.v. injection of unmodified multilamellar liposomes, an injection of the chemoimmunoliposomes containing 1 microgram of actinomycin D resulted in a significant inhibition of tumor growth. Both free actinomycin D and bovine serum albumin-coated liposomes containing actinomycin D were ineffective against the s.c. tumor. These results indicate that an antitumor drug entrapped in the membranes of small sonicated liposomes bearing antitumor monoclonal antibodies can be delivered to antigenic tumor cells and exert more efficient antitumor activity than does the free drug.

Animals↗
PubMed1983

Cyclic peptides. XIII. Asymmetric synthesis of aromatic L-alpha-amino acids through hydrogenation of cyclic dehydrodipeptides.

Four cyclic dehydrodipeptides, cyclo (-delta aminoacyl-L-Ala-), in which aminoacyl is Phe, Apb (2-amino-4-phenylbutanoic acid), App (2-amino-5-phenylpentanoic acid) and Aph (2-amino-6-phenylhexanoic acid), were prepared by condensation of cyclo (-N-Ac-Gly-N-Ac-L-Ala-) with the corresponding aldehydes. Among them, the yield of cyclo (-delta Apb-L-Ala-) was exceptionally low. Each compound was hydrogenated in the presence of Pd black at various temperatures and chiral induction in hydrogenation was evaluated. Low chiral induction at high temperature (50 degrees) was observed in the case of cyclo (-delta Phe-L-Ala-). Optically pure L-Apb, L-App and L-Aph were obtained from the corresponding cyclic dehydrodipeptides, respectively, by hydrogenation and subsequent acid hydrolysis.

Amino Acids↗
PubMed1983

Effects of 12-O-tetradecanoylphorbol-13-acetate on the proliferation and differentiation of normal and leukemic myeloid progenitor cells.

The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA) on myeloid colony formation were investigated by initial and delayed addition of TPA to the cultures. In the human placental conditioned medium-stimulated cultures, TPA inhibited normal myeloid colony formation without any change in colony morphology when added at the beginning of culture. However, macrophage-like transformation of myeloid colonies by TPA was clearly observed after the delayed addition of TPA. Colonies and clusters already formed at the time of TPA addition wee exclusively neutrophilic. Two days after TPA addition, many colonies apparently contained macrophage-like cells. Within 4 days after TPA addition, almost all myeloid colonies transformed into the macrophage type. Parallel study of initial and delayed addition of TPA revealed that this macrophage-like transformation of neutrophilic colonies occurred at high concentrations of TPA that would fully inhibit colony formation if added initially. TPA caused similar effects on leukemic colony formation.

Bone Marrow↗
PubMed1982

Simultaneous determination of glyceryl trinitrate and its principal metabolites, 1,2- and 1,3-glyceryl dinitrate, in plasma by gas chromatography-negative ion chemical ionization-selected ion monitoring.

A specific and sensitive method for the quantitation of glyceryl trinitrate (GTN) and its principal metabolites, 1,2- and 1,3-glyceryl dinitrate (GDN) in dog plasma by capillary gas chromatography-negative ion chemical ionization-selected ion monitoring using dichloromethane as a reagent gas and the corresponding compounds labelled with stable isotopes as internal standards. The quantitation limits of the method for GTN and the GDNs were 0.1 and 1.0 ng/ml in plasma, respectively. When GTN was administered intravenously to four anaesthetized beagle dogs at a dose of 6 micrograms/kg . min for 30 min, the plasma levels of GTN and 1,2- and 1,3-GDN reached a maximum at the end-point of infusion and decreased with bi-exponential decay. The half-lives of the alpha- and beta-phases were 0.50 and 4.95 for GTN, 8.10 and 40.6 for 1,2-GDN and 8.50 and 48.5 for 1,3-GDN, respectively.

Animals↗
PubMed1982

Increased endothelial cell adherence, aggregation, and superoxide generation by neutrophils incubated in systemic lupus erythematosus and Felty's syndrome sera.

The ability of sera from patients with systemic lupus erythematosus (SLE) and Felty's syndrome to induce increased adhesiveness of normal human neutrophils (PMN) was investigated. PMN from normal healthy donors were incubated in sera from 19 patients with active SLE, 12 with inactive SLE, 20 with Felty's, 24 with rheumatoid arthritis, and 34 normal persons. After incubation, the degree of adherence of the PMN to human endothelial cells in culture, their aggregation, and superoxide (O2-) generation were determined. Sera from patients with both active SLE and Felty's syndrome induced significantly increased PMN adherence to endothelial cells and PMN aggregation in vitro, compared with normal sera. This increased adherence to endothelial cells was maintained after heat treatment (56 degrees C for 30 minutes) of the sera. In O2- generation experiments, sera from patients with active SLE induced significantly increased O2- release from normal PMN using both fresh and heat-treated sera. Sera from Felty's patients demonstrated the same effect with heat-treated sera but not ith fresh sera. When sera from patients with active SLE and Felty's syndrome were used, all three parameters correlated significantly with each other in individual patients. In contrast, sera from the 12 patients with inactive SLE and 24 rheumatoid arthritis patients without Felty's failed to induce significant differences in the three parameters studied when compared with 34 normal controls. Fractionation of 3 SLE sera and 1 Felty's serum on Sephadex G-200 demonstrated that the adherence enhancing factor was present in both IgG and IgG-excluded fractions. The observed increased adhesiveness of PMN induced by SLE and Felty's sera may, at least in part, contribute to the neutropenia which is common in these diseases. Increased O2- release associated with PMN adherence may contribute to endothelial cell damage and vascular injury, which is also a common manifestation of these diseases.

Adult↗
PubMed1982

Glycolytic activity of rat aorta after exercise.

Activities of glycolytic enzymes in the aorta were investigated in female Wistar rats. There were two groups of rats; one served as the control (sedentary rats), while the other group was forced to run on a treadmill for 10 weeks. In the control animals, the activities of hexokinase, phosphofructokinase and aldolase were relatively lower than those of the other glycolytic enzymes (phosphoglucose isomerase, lactate dehydrogenase and pyruvate kinase). After exercise, the activity of phosphofructokinase increased by 15%, whereas the other enzymatic activities were much the same as in the controls. Within the limits of the experiments, the increased percentage of phosphofructokinase was statistically significant (p less than 0.05). Since phosphofructokinase is a putative rate limiting enzyme, this enzymatic activation may indicate that glycolytic activity in the rat aorta is enhanced during and after running exercise.

Animals↗
PubMed1982

Studies on the mechanism of action of 1 alpha,24-dihydroxyvitamin D3. III. The specific binding of 1 alpha,24-dihydroxyvitamin D3 to the receptor of chick parathyroid gland.

Three protein fractions of the cytosol of the chick parathyroid glands, which had the sedimentation constants of 2.5 S, 3.7 S and 5.5 S, were found to bind with 1 alpha,25-dihydroxyvitamin D3. Among these proteins, the 3.7 S protein was assumed to be the specific receptor protein. The 3.7 S receptor protein was also capable of binding to 1 alpha,24-dihydroxyvitamin D3 but not 25-hydroxyvitamin D3. The binding affinity of 1 alpha,24(R)-dihydroxyvitamin D3 to the 3.7 S receptor protein was estimated to be 1.2 times greater than that of 1 alpha,25-dihydroxyvitamin D3, while 1 alpha,25-dihydroxyvitamin D3 bound to the receptor protein about 10 times stronger than 1 alpha,24(S)-dihydroxyvitamin D3. The dissociation constant for the receptor-1 alpha,25-dihydroxyvitamin D3 complex at 0 degrees C was 2.7 x 10(-11) M, the dissociation constants were calculated to be 2.2 x 10(-11) M and 2.6 x 10(-10) M for the complexes with 1 alpha,24(R)-dihydroxyvitamin D3 and 1 alpha,24(S)-dihydroxyvitamin D3.

Animals↗
PubMed1982

Modification of nucleic acids with muta-carcinogenic heteroaromatic amines in vivo. Identification of modified bases in DNA extracted from rats injected with 3-amino-1-methyl-5H-pyrido[4,3-b]indole and 2-amino-6-methyldipyrido[1,2-a3:3',2'-d]imidazole.

Potent muta-carcinogens isolated from amino-acid pyrolysates, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and 2-amino-1-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), were injected intraperitoneally into Male Wistar rats. DNA and rRNA modified with these muta-carcinogens were then extracted from the livers of the rats, and modified nucleic-acid bases were isolated and analysed by high-performance liquid chromatography (HPLC). These modified nucleic-acid bases were identified as 3-(C8-guanyl)amino-1-methyl-5H-pyrido[4,3-b]indole (Gua-Trp-P-2) and 2-(C8-guanyl)amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Gua-Glu-P-1) by comparison of their retention times on HPLC and UV spectra with those of authentic compounds.

Animals↗
PubMed1982

In vitro metabolism of o-aminoazotoluene and mutagenesis of Salmonella by the metabolites.

Incubation of hepatocarcinogenic aminoazo dye, o-aminoazotoluene (OAT) with rat liver microsomes together with NADPH and NADH yielded N-hydroxy-OAT (I), 4'-hydroxy-OAT (II) and a smaller amount of 2'-hydroxymethyl-3-methyl-4-aminoazobenzene (III). As an artifact 4,4'-bis(o-tolylazo)-2,2' -dimethylazoxybenzene (IV) was also detected in a small quantity. The mutagenicities of these metabolites were assayed by using Salmonella typhimurium TA98 and TA100 together with S-9 prepared from the livers of rats treated with polychlorinated biphenyl mixture (PCB). OAT and III were strongly mutagenic, but only when S-9 was present. In contrast, I was a strong mutagen regardless of the presence or absence of S-9. II and IV were non-mutagenic. The yields of I, II and III from OAT were pronouncedly reduced by addition of cytochrome P-450 inhibitors, especially by a cytochrome P-448 inhibitor 7,8-benzoflavone. Mutagenesis by OAT was also inhibited by addition of 7,8-benzoflavone. Activation of OAT for mutagenesis was enhanced by pretreatment of the donor rats with PCB or 3-methyl-cholanthrene and to a much lesser extent by phenobarbital. These findings suggest that N-hydroxylation of OAT mainly proceeds via catalysis by cytochrome P-448 and that this process is an obligatory step for the activation of OAT. Synthetic methods for the preparation of new azo compounds such as I, IV and 2',3-dimethyl-4-nitrosoazobenzene are described.

Animals↗
PubMed1982

The occurrence of GM4 and GM2 in erythrocytes from inbred strains of mice.

Glycolipids of erythrocytes from inbred mice, C3H/He and CDF1, were analyzed. Galactosylceramide, glucosylceramide, GM4 and GM2 were separated and their structures were established. Sialic acid of GM4 was exclusively N-acetylneuraminic acid, while GM2 contained only N-glycolylneuraminic acid. The fatty acid composition of GM4 was very similar to that of galactosylceramide, and a similarity was also found between that of GM2 and glucosylceramide. These results suggest that erythroid cells of mice have two separate biosynthetic pathways of gangliosides. One is the pathway to GM4 (NeuAc) from galactosylceramide, and the other is that for synthesizing GM2 (NeuGc) from glucosylceramide.

Animals↗