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Biomedical subjects

T Shibuya

Publications and source records attributed to T Shibuya.

At least 415 records · Page 23Linked to original sources

Host control of susceptibility to erythroleukemia and to the types of leukemia induced by Friend murine leukemia virus: initial and late stages.

The genetic control of the susceptibility to early erythroleukemic induction by helper-independent Friend murine leukemia virus was determined to be due to the presence of a single dominant resistant locus. This locus, (termed Fv6), however, governs only resistance to early erythroleukemia, since other types of leukemias developed late in the resistant mice: myelomonocytic leukemia (approximately 70%), T-lymphoid leukemia (approximately 25%) and late erythroleukemia (approximately 10%). Data also indicated that mice with higher DBA/2 (resistant strain) genetic background had an increased frequency of myelomonocytic leukemias. Studies of the hemopoietic modulations indicated that mice that developed early or late erythroleukemia had dramatic increases in erythroid bursts, suggesting that the leukemic blocks are at the level of BFU-E or earlier. High levels of the granulocytic progenitor colonies were also found in mice with late erythroleukemia and myelomonocytic leukemia. Analysis of these leukemias indicate that they are multistage diseases.

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Mutagenicity and dominant lethal test of kojic acid--Ames test, forward mutation test in cultured Chinese hamster cells and dominant lethal test in mice.

The mutagenicity of kojic acid was studied by means of reversion mutation test in bacteria (Ames test), forward mutation test in cultured Chinese hamster cells and dominant lethal test in mice. A positive result was obtained only in Ames test (TA 98, 1535 and 100) which was not modified by the presence of S-9 fraction. Thus, it is concluded that although kojic acid is a weak mutagen in bacteria, it is nonmutagenic in eukaryotic systems either in vivo or in vitro.

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Behavioral pharmacologic studies in the monkey with DD-3480.

A comparative study has been made of the catalepsy-inducing and antiapomorphine effects of DD-3480, a new butyrophenone derivative, and haloperidol in monkeys. DD-3480 exhibited catalepsy-inducing effects in a dose-dependent manner at oral doses of 2.5-10 mg/kg. This effect was comparable to that of haloperidol, but its duration was shorter in DD-3480 than in haloperidol. An evident anti-apomorphine effect was observed at 2.5 mg/kg of DD-3480 (p.o.); it was slightly stronger than that of haloperidol.

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Morphological, immunological, and biochemical analyses of chicken spleen cells transformed in vitro by reticuloendotheliosis virus strain T.

Reticuloendotheliosis virus strain T (REV-T) is a highly oncogenic avian retrovirus which causes a rapid neoplastic disease of the lymphoreticular system. We derived six cell lines (1-3, 1-5, 2-10, 2-14, 2-16, and 2-20) from chicken spleen cells infected with REV-T. These cells can produce both the REV-T and its associated reticuloendotheliosis helper virus, REV-A. Histochemical analyses of these cells indicate that, while they are not stained by benzidine, peroxidase, beta-glucuronidase or acid alpha-naphthyl acetate esterase, they contain a high proportion (95%) of cells positive for acid phosphatase. Light and electron microscopic studies of these cells also revealed morphologies of lymphoblasts or activated lymphocytes with irregular nuclei and dispersed chromatin. Immunochemical analyses indicate that essentially all (90 to 100%) of the cells contain the surface marker Ia, but no cytoplasmic immunoglobulin M and immunoglobulin G could be detected by immunofluorescence staining. Results also show that some of these cell lines contain a low level of terminal transferase (0.02 to 0.17 unit/10(9) cells), and a proportion (3 to 35%) of these cells can be stained by an antiserum directed against chicken bursa cells. These results are consistent with the conclusion that the cells transformed by the highly oncogenic REV-T are lymphoid in nature. In addition, at least some of these cell clones may contain features characteristic of activated B-lymphocytes. Analysis of these cell clones indicates that some cell lines contain an adherent and nonadherent population with some differences in morphologies. In addition, electron microscopic examination revealed that, while the non-adherent cells are actively producing type C viruses, type C viruses are either absent or very rare in the adherent cell populations. These results support the conclusion that some of these cell lines are heterogeneous and contain subpopulations of cells with differences in their ability to produce viruses.

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Simultaneous measurement of biogenic amines and related compounds by high performance liquid chromatography (HPLC).

Simultaneous measurement by HPLC was used to determine brain dopamine (DA), noradrenaline (NA), and serotonin (5-HT), and their metabolites, vanillylmandelic acid (VMA), homovanillic acid (HVA), and 5-hydroxyindole acetic acid (5-HIAA). Brain tissues were homogenized with 0.025 N HCl and 0.1 M EDTA. Following extraction with n-butanol, amines were dissolved in acid solution, and the metabolites in alkaline solution; then 5-10 microliters of each was injected into the HPLC simultaneously. The injected samples were detected in the following order at 280 nm: VMA, NA, DA, 5-HIAA, HVA, 5-HT at a flow rate of 2 ml/min within about 20 min. Amines and the metabolites could be separated completely and measured at lower limits of approximately 5-10 ng.

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Canine-effective plasma concentrations of antiarrhythmic drugs on the two-stage coronary ligation arrhythmia.

Seven drugs were tested for their antiarrhythmic effects on ventricular arrhythmias 24 and 48 hr after two-stage coronary ligation in conscious beagles. Venous blood samples were drawn for plasma drug assays. Minimum effective plasma concentrations of drugs were calculated from derived concentration-time curves. Effective drugs and their minimum effective concentrations for the suppression of arrhythmias 24 and 48 hr after coronary ligation were: disopyramide, 4.2 and 2.3 micrograms/ml; procainamide, 26.4 and 27.0 micrograms/ml; phenytoin, 8.4 and 6.4 micrograms/ml; and a new beta-blocker, N-696, 7.6 and 8.7 micrograms/ml. The concentrations of disopyramide and phenytoin were almost the same as those reported for human antiarrhythmic concentrations, but those of procainamide were higher than those reported for man. Lidocaine, verapamil and a new beta-blocker, OPC-1427, were ineffective. Membrane-stabilizing effects seem to be important in suppressing the canine two-stage coronary ligation arrhythmia.

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Clonal analysis of early and late stages of erythroleukemia induced by molecular clones of integrated spleen focus-forming virus.

The integrated proviral DNA of the polycythemia-inducing isolate of Friend spleen focus-forming virus (SFFVp) has been identified in rat cell clones nonproductively infected with this replication-defective erythroleukemia virus and cloned in phage lambda vectors. These lambda SFFVp recombinants, lambda SFFVp502 and lambda SFFVp542, contain endonuclease EcoRI inserts of size 7.4 and 8.2 kilobases, respectively, and include full copies of the SFFVp genome, along with host flanking sequences. Infectivity of the cloned SFFVp genomes was tested by a two-step DNA transfer procedure involving transfection of the cloned DNA into 3T3 mouse fibroblasts or cotransfer of the cloned DNA into thymidine kinase-deficient 3T3 cells together with the cloned thymidine kinase gene of herpes simplex virus, followed by rescue of the transferred DNA by superinfection with a helper virus. Inoculation of the rescued virus into adult mice resulted in the appearance of spleen foci, rapid splenomegaly, and polycythemia. Early after infection, spleen cell populations contained large numbers of cells capable of forming small erythroid colonies in vitro (CFU-E) in the absence of erythropoietin. Late after infection, these mice contained cells capable of forming macroscopic colonies (CFU-FV) in vitro. These data indicate that molecular clones of SFFVp, in conjunction with a helper virus, induce the appearance of hemopoietic colony-forming cells characteristic of both the early and late stages of Friend leukemia.

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