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Biomedical subjects

T Inui

Publications and source records attributed to T Inui.

At least 217 records · Page 12Linked to original sources
PubMed1979

Reduction of anthracycline glycoside by NADPH--cytochrome P-450 reductase.

The in vitro degradation of the new antitumor anthracycline antibiotic, aclacinomycin-A, was studied using rat liver homogenate. In the presence of NADH or NADPH, the glycosidic bond at C-7 position of aclacinomycin-A was reductively cleaved to produce 7-deoxyaklavinone and 7-deoxyaklavinone dimer, MA144 E1. Subcellular fractionation indicated that most of the enzyme activity was present in the microsomal fraction and required anaerobic condition and NADPH. The purified enzyme reduced the glycosidic metabolites, MA144 M1 and MA144 N1, as well as aclacinomycin-A. The optimum pH for the anthracycline glycoside reductase reaction using aclacinomycin-A as substrate was 7.4. The enzyme was sigmoidally saturated with aclacinomycin-A and showed the concentration of 1.2 x 10(-4) M required for half maximal activity, and Km value of 7.7 x 10(-5) M for NADPH. The degradative pathway of aclacinomycin-A and its glycosidic metabolites was discussed.

Anaerobiosis↗
PubMed1978

Effect of guanosine 5'-diphosphate 3'-diphosphate and related nucleoside polyphosphates on induction of tryptophanase and beta-galactosidase in permeabilized cells of Escherichia coli.

Exogenous addition of guanosine and adenosine 5'-(mono, di and tri) phosphate 3'-diphosphates (pppGpp, ppGpp, pGpp, pppApp, ppApp and pApp) stimulated the synthesis of tryptophanase and beta-galactosidase in permeabilized cells of Escherichia coli. From the results obtained with ppGpp and pppApp, this effect appeared to be at a transcriptional level and depended greatly on the growth condition; the largest effect was observed in cells under shiftdown or grown on poor enrgy source. ppGpp and pppApp, unlike cyclic AMP, did not act to overcome the inhibition of enzyme induction by glucose, but in combination with cyclic AMP caused a synergistic stimulation effect. In the shiftdown cells, ppGpp and pppApp gave 30% or more stimulation effect on tryptophanase induction while cyclic AMP did not stimulate induction. There was therefore a pronounced difference between cyclic AMP and ppGpp or pppApp in stimulatory function.

Adenine Nucleotides↗
PubMed1977

Antitumor activity of new anthracycline antibiotics, aclacinomycin-A and its analogs, and their toxicity.

New anthracycline antibiotics have been isolated from the culture of Streptomyces galilaeus MA144-M1. Among 14 anthracycline compounds, aclacinomycin-A showed the strongest activity in inhibiting leukemia L-1210 and had lower toxicity than others. Antitumor activity of aclacinomycin-A against leukemia L-1210 and P-388, solid sarcoma-180, and lymphosarcoma 6C3HED was examined in comparison with adriamycin and daunomycin. Aclacinomycin-A showed the same degree of activity against leukemia L-1210 and P-388, when administered intraperitoneally, as daunomycin and somewhat less than adriamycin. In oral administration, aclacinomycin-A also exhibited a significant activity on leukemia L-1210. The degree of inhibition of the growth of sarcoma-180 and 6C3HED lymphosarcoma transplanted subcutaneously by aclacinomycin-A was almost the same as that of adriamycin and daunomycin, although the optimal dose was about twice more than adriamycin. Acute cardiotoxicity of aclacinomycin-A by a test using hamsters was more than 10 times lower than that of adriamycin.

Aclarubicin↗
PubMedDate not supplied

Solution synthesis of human midkine, a novel heparin-binding neurotrophic factor consisting of 121 amino acid residues with five disulphide bonds.

Human midkine (hMK), a novel heparin-binding neurotrophic factor consisting of 121 amino acid residues with five intramolecular disulphide bonds, was synthesized by solution procedure in order to demonstrate the usefulness of our newly developed solvent system, a mixture of dichloromethane or chloroform and trifluoroethanol. The final protected 121-residue peptide was assembled from two large fully protected intermediates, Boc-(1-59)-OH and H-(60-121)-OBzl, in CHL/TFE(3:1, v/v) using water-soluble carbodiimide in the presence of HOOBt as coupling reagents. After removal of the protecting groups by HF followed by treatment with Hg(OAc)2 in 50% acetic acid, the fully deprotected peptide was subjected to the oxidative folding reaction. The final product was confirmed to have the correct disulphide structure from its tryptic peptide mapping and to possess the same biological activities as those of the natural product. In order to clarify the active region of the hMK molecule, the N-terminal half domains [(1-59) and (60-121)] were also synthesized by the same procedure used for the hMK synthesis. The C-half domain was confirmed to show the full pattern of bioactivities except for the neuronal cell survival activity, while the N-half one showed much less activity in general.

Amino Acid Sequence↗
PubMedDate not supplied

Loss of basal cell phenotype with acquisition of lung-colonizing capability in mouse mammary tumors.

A transplantable pregnancy-dependent mouse mammary tumor, TPDMT-4, and its ovarian-dependent (T4-OR26) and autonomous (T4-OI96, T4-OI145, T4-OI165, T4-OI320 and T4-OI320CY) sublines were examined immunohistochemically for the expression of keratin 14 and type IV collagen. T4-OI96, T4-OI145, and T4-OI165, but not T4-OR26, T4-OI320, or T4-OI320CY, formed lung colonies (metastasis) after intravenous injection as a single-cell suspension. Despite the similar morphology of TPDMT-4 and its six sublines, only TPDMT-4 and the nonmetastatic sublines revealed a basal cell phenotype as defined by keratin 14 expression. Staining for type IV collagen was complete at the peripheries of the glandular structures in TPDMT-4 and nonmetastatic sublines but was patchy in the metastatic tumors.

Animals↗
PubMedDate not supplied

HTLV-I-associated myelopathy (HAM) in Tokushima Prefecture--geographical and clinical studies in an area between endemic and non-endemic areas of HTLV-I infection.

The geographic distribution and clinical features of patients with HTLV-I-associated myelopathy (HAM) in Tokushima prefecture were investigated. Nine patients were found prior to December 1990. The minimal prevalence was estimated as 1.1 per 100,000 in the general population, and 1 per 1,309 in HTLV-I-seropositive persons. Seven patients were found in the southern district facing the Pacific Ocean, but only 1 patient each was found in the northern and western districts. The age at disease onset ranged from 15 to 53 yr (average 33 yr). The ratio of male to female patients was 1:8. Adult T cell leukemia was associated with HAM in 1 patient, and Hashimoto's disease in 2 patients. These cases have not been reported previously. The route of transmission of HTLV-I was concluded to be vertical in 4 patients and horizontal in 4 patients, but was uncertain in 1 patient. No evidence of transmission by blood transfusion was found in these patients.

Adult↗