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Biomedical subjects

Y Hashimoto

Publications and source records attributed to Y Hashimoto.

At least 1,405 records · Page 78Linked to original sources
PubMed1985

Chemical modification of DNA with muta-carcinogens. I. 3-Amino-1-methyl-5H-pyrido[4,3-b]indole and 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole: metabolic activation and structure of the DNA adducts.

3-Amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) are potent mutagen/carcinogens isolated from pyrolyzates of tryptophan and glutamic acid, respectively, and they have been found to exist in many cooked foods. Trp-P-2 and Glu-P-1 bind to DNA covalently after metabolic activations. The compounds are oxidized to the corresponding hydroxylamines (N-OH-Trp-P-2 and N-OH-Glu-P-1) by microsomes. N-OH-Trp-P-2 and N-OH-Glu-P-1 are the proximate forms of Trp-P-2 and Glu-P-1, respectively. They are further activated by cytosol to the O-acyl derivatives, which bind covalently with DNA. The structures of the 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). These initial events caused by Trp-P-2 and Glu-P-1 were established chemically, both in vitro and in vivo.

Animals↗
PubMed1985

Chemical modification of DNA with muta-carcinogens. II. Base sequence-specific binding to DNA of 2-amino-6-methyl-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1).

2-Amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) binds covalently to DNA after metabolic activation to give 2-(C8-guanyl)amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Gua-Glu-P-1). The importance of the intercalative ability of the Glu-P-1 skeleton into DNA base pairs for this reaction is emphasized. The reactive form of Glu-P-1, N-acetoxy-Glu-P-1 (N-OAc-Glu-P-1), reacts preferentially at the C8 position of guanine residues in G-C-rich regions of DNA.

Base Sequence↗
PubMed1985

Chemical modification of DNA with muta-carcinogens. III. Reductive alkylation of DNA with mitomycin C.

Mitomycin C (MMC) binds to DNA after its reductive activation by catalytic hydrogenation with Pd on charcoal. Three modified nucleotides, named MG-1, MG-2, and MA, were isolated from the modified DNA after enzymatic hydrolysis to 5'-nucleotides. The structures of these modified nucleotides were deduced from their 1H-NMR and UV spectra, and from studies of the chemically transformed derivatives (hydrolysis, methylation, diazotization, and thioketonization). These three modified nucleotides were concluded to be 1,2-trans-2,7-diamino-1-(N2-deoxyguanylyl)mitosene (MG-1), 2,7-diamino-1-(O6-deoxyguanylyl)mitosene (MG-2) and 2,7-diamino-1-(N6-deoxyadenylyl)mitosene (MA). The same modified nucleotides were identified in DNA extracted from the livers of rats treated with MMC.

Alkylation↗
PubMed1985

Effect of sinomenine on antibody responses in mice.

Sinomenine, an epimorphinan alkaloid, was tested for the immunosuppressive effect in mice. This compound produced a decrease of plaque-forming cells (PFC) to a T cell-dependent antigen, sheep red blood cells, in vivo. The depression of the PFC response induced with sinomenine was dose and time dependent. On the other hand, it failed to suppress the PFC response to a T cell-independent antigen, lipopolysaccharide. The immunosuppressive dose of sinomenine did not alter the cellularity of spleen, thymus, bone marrow and peripheral blood leucocytes, the DNA synthesis activity of bone marrow cells nor the proliferative responses of spleen cells induced by T cell and B cell mitogens in unprimed mice. These data suggest a selective effect of sinomenine on lymphoid cells. This compound has a potential for use in studies of immuno-deficiencies or clarifying some aspect of immunity.

Animals↗
PubMed1985

Two bases are eliminated from DNA by treatment with bleomycin or with hemin-intercalators.

A hemin-intercalator, H4G-His, which possesses 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) as an intercalator moiety and histidine as an intramolecular ligand of the ferrous ion of the hemin ring, cleaves DNA very efficiently, and acts at guanine-pyrimidine sequences preferentially. Bleomycin (BLM) also cleaves DNA with the same base-sequence selectivity shown by H4G-His. The 5'-terminal of the DNA fragments cleaved by H4G-His or by BLM bears a phosphoryl group, while the 3'-terminal of the cleaved DNA fragments does not possess a 3'-phosphoryl group. There are three (or more) kinds of structures of the 3'-terminals. One of the structures of the 3'-terminals of the cleaved DNA fragments is a free 3'-hydroxy group. We propose that there exist plural mechanisms for DNA cleavage by H4G-His or by BLM, one of which involves elimination of two bases from DNA.

Base Sequence↗
PubMed1985

Stimulated rat T cell-derived inhibitory factor for cellular DNA synthesis (STIF). II. Kinetics of the production and characterization of the producer.

Kinetics of the production of a stimulated T cell-derived inhibitory factor for cellular DNA synthesis (STIF) (1) from Con A-stimulated SD rat spleen cells, and the cells involved in the production of the factor, were examined comparatively with those of interleukin 2 (IL 2) and interferon (IFN). STIF activity in the culture supernatants reached a plateau 24 hr after the culture, and the plateau level was maintained during an additional culture for 72 hr. Characterization of the cells involved in STIF production by means of negative selection of unfractionated or nylon-fractionated spleen cells with anti-rat T cell serum or monoclonal antibodies plus complement revealed that the cells are nylon-nonadherent T cells bearing a suppressor T cell marker. The nylon-nonadherent T cell population did not require additional macrophages for STIF production. In vivo pretreatment of rats with cyclophosphamide (25 to 100 mg/kg) reduced or abolished the production of STIF from the Con A-stimulated spleen cells of the rats. The STIF production from Con A-stimulated spleen cells was inhibited by the addition of indomethacin at 10 ng/ml, indicating a regulatory role of prostaglandin(s) in STIF production. The above characteristics distinguish a T cell subset for STIF production from those for IL 2 and IFN production.

Animals↗
PubMed1985

Stimulated rat T cell-derived inhibitory factor for cellular DNA synthesis (STIF). III. Effect on cell proliferation and immune responses.

Stimulated T cell-derived inhibitory factor for cellular DNA synthesis (STIF), a lymphokine produced from concanavalin A (Con A)-stimulated rat suppressor T cells, was examined for its inhibitory effect on various cultured cells and on in vitro immune reactions. STIF could inhibit the DNA synthesis of a variety of normal and neoplastic cells from rats, mice, and humans in a dose-dependent fashion. Kinetics studies revealed that STIF selectively inhibited cellular DNA synthesis after incubation for 12 hr, but after 36 hr, it also inhibited RNA and protein syntheses. The inhibited cellular DNA synthesis by 12-hr incubation with STIF was recovered after culturing the cells in STIF-free medium. The inhibitory effect of STIF on the DNA synthesis was not blocked by addition of a sugar (alpha-methyl-D-mannoside, N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, L-fucose, or L-rhamnose) in culture, as determined by using rat bone marrow cells. STIF inhibited proliferative responses of rat lymphocytes to T cell mitogens, Con A and phytohemagglutinin, and a B cell mitogen, lipopolysaccharide, as well as IL 2-dependent growth of cloned T572 cells. It could also inhibit both blastogenesis and cytotoxic T cell generation in allogeneic mixed lymphocyte reaction. The release of IL 2 from Con A-stimulated T cells was also inhibited by the added STIF in culture, as demonstrated from the finding that IL 2 activity was not detected in the supernatants even after an anion-exchange column chromatography. These results indicate that STIF could inhibit cellular DNA synthesis in a species-unrestricted manner and thus inhibits the proliferation of various normal and neoplastic cells, and that it could also inhibit lectin- or IL 2-dependent T cell proliferation as well as IL 2 production from T cells in in vitro immune reactions.

Animals↗
PubMed1985

[Aortic dissection presenting aortic regurgitation induced by diastolic prolapse of an intimal flap into the left ventricle: a case report].

A case of aortic dissection associated with aortic regurgitation which was induced by diastolic prolapse of an intimal flap into the left ventricular outflow tract was reported. This 57-year-old man, referred for evaluation of sudden onset of chest oppression and a heart murmur, was hypertensive for several years. His admission blood pressure was 184/44 mmHg, and a systolic ejection murmur and a diastolic decrescendo murmur were audible along the left sternal border. Two-dimensional echocardiography revealed an intimal flap in the markedly enlarged aortic root. The intimal flap moved posteriorly in systole and anteriorly in diastole, and prolapsed into the left ventricular outflow tract during diastole. Associated with the movement of the intimal flap, an aortic cusp was shifted from its original position to the left ventricular outflow tract in diastole. Aortography disclosed type I aortic dissection and severe aortic regurgitation. After medical treatment for four months, the patient underwent a Bentall surgical procedure and recovered. Impaired coaptation of the aortic valve induced by diastolic prolapse of the intimal flap into the left ventricular outflow tract is a newly encountered echocardiographic finding in proximal aortic dissection.

Aortic Dissection↗