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Biomedical subjects

T Nishimura

Publications and source records attributed to T Nishimura.

At least 1,207 records · Page 67Linked to original sources

Heterogeneity of factor IX BM. Difference of cleavage sites by factor XIa and Ca2+ in factor IX Kashihara, factor IX Nagoya and factor IX Niigata.

Abnormal factor IX was isolated from the plasma of a patient with hemophilia B Kashihara and two patients with hemophilia BM. The F.IX was purified to homogeneity by using monoclonal anti-F.IX-Sephrose, heparin-Sepharose and DEAE-Sephadex A-50 affinity chromatography successively. The isolated proteins have the same molecular weight and the same mobility on crossed immunoelectrophoresis as normal F.IX. The limited proteolysis of purified proteins was induced by F.XIa/Ca2+ or by RVV-X/Ca2+. A time course study showed that F.IX Nagoya seemed to be cleaved by neither F.XIa nor RVV-X, F.IX Kashihara was cleaved partially by F.XIa but not by RVV-X, and that F.IX Niigata was cleaved completely at the rate similar to normal F.IX, though the resultant product of F.IX Niigata did not show any F.IXa activity. These results favored the view that hemophilia B+ or BM is a heterogeneous disorder.

Antigens, Heterophile↗

Adhesion behavior of rat lymphocytes to poly(ether)-poly(amino acid) block and graft copolymers.

Block and graft copolymers consisting of poly(ether) and poly(amino acid) were synthesized, and adhesion behavior of rat lymphocytes to the surface of the film made from these copolymers was analyzed by the microsphere column method. Poly(ethylene glycol) (PEG) and poly(benzyl L-glutamate) (PBLG) were used as poly(ether) and poly(amino acid), respectively. Adhesion behavior of lymphocytes was found to depend on the content and chain length of the components in these copolymers.

Animals↗

Augmentation of the therapeutic efficacy of adoptive tumor immunotherapy by in vivo administration of slowly released recombinant interleukin 2.

Immunization of C57BL/6 mice with MMC-treated syngeneic lymphoma cells, MBL-2, caused the generation of antitumor effector cells in vivo and the immunized mice permanently rejected viable MBL-2 lymphoma cells. Both plastic nonadherent T cells and plastic adherent M phi obtained from MBL-2 immunized mouse peritoneal exudate cells revealed strong cytotoxic activity against MBL-2 lymphoma cells, whereas immune spleen cells were not highly active against MBL-2 lymphoma cells in vitro. However, systemic adoptive transfer of immune spleen cells into the MBL-2-bearing mice by i.v. infusion in conjunction with i.p. cyclophosphamide (100 mg/kg) treatment cured the mice of tumor. This therapeutic efficacy of immune spleen cells was reflected by the number of transferred effector cells and over 5 X 10(7) immune spleen cells were required to cure the mice completely. The cells mediating in vivo rejection of MBL-2 lymphoma cells were Thy 1.2+ T cells. This ACIT was specific against MBL-2 lymphoma cells and had no effect on the growth of other syngeneic tumors, B16 melanoma or BMC6A fibrosarcoma. In vivo administration of recombinant interleukin 2 (r-IL2) combined with ACIT greatly modulated the cure rate of tumor-bearing mice. In addition, we found that slowly released r-IL 2 administratered from an ALZET miniosmotic pump was more effective in augmenting the therapeutic efficacy of immune spleen cells in ACIT than a single injection of the same total dose of r-IL 2.

Animals↗

Generation of lymphokine-activated killer (LAK) cells from tumor-infiltrating lymphocytes.

Culture of tumor-infiltrating lymphocytes (TIL) containing about 20% BMC2 tumor cells with recombinant human interleukin 2 (rIL-2) resulted in the diminish of tumor cells and the growth of lymphocytes. These IL-2-activated lymphocytes showed a strong cytotoxic activity against not only syngeneic tumor cells but also allogeneic tumor cells. Such broad-reactive killer cells, termed lymphokine-activated killer (LAK) cells, are also inducible from spleen cells by in vitro activation with IL-2. However, LAK cells generated from TIL (TIL-LAK) showed higher cytotoxic activity against BMC2 than LAK cells generated from spleen cells (S-LAK). Furthermore, it was demonstrated that TIL-LAK cells revealed marginal cytotoxic activity against normal Con A blasts and YAC-1 cells as opposed to S-LAK. Flow cytometric analysis of TIL-LAK indicated that TIL-LAK cells mainly consisted of Thy 1.2+, Ly 2+, asialo GM1+ cells. TIL-LAK cells displayed not only in vitro cytotoxicity but also in vivo anti-tumor activity. Furthermore, it was also confirmed that TIL-LAK cells could be induced in autochthonous mouse tumor systems and human gastric tumor systems.

Animals↗

Mutagenicity of the photochemical reaction products of pyrene with nitrogen dioxide.

The mutagenicity of the photochemical reaction products of pyrene with nitrogen dioxide (NO2) and the mutagens in them were investigated for the interpretation of their biological significance as genetoxic hazards of polycyclic aromatic hydrocarbons (PAHs) in airborne particles. Samples extracted from the photochemical reaction products of pyrene with NO2 diluted with air using a high-pressure mercury lamp were mutagenic for Salmonella typhimurium strains TA97 and TA98 in the absence of S9 mix, with a trend to detoxification in the presence of the metabolic system. The mutagens in the crude samples extracted from their products, which were fractionated by normal-phase high-performance liquid chromatography (HPLC) on a column of Nucleosil 100-30 with n-hexane-benzene as an eluting solution, were analyzed by HPLC, mass spectrometry and Fourier transform infrared (FT-IR) spectrometry. Based on these results, it was recognized that 1-nitropyrene (1-NP), 1,3-dinitropyrene (1,3-DNP), 1,6-dinitropyrene (1,6-DNP) and 1,8-dinitropyrene (1,8-DNP) was formed by the photochemical reaction of pyrene with NO2. The yield of DNPs peaked at 2-3 h irradiation.

Chromatography, High Pressure Liquid↗

Recombinant interleukin 2 allows the differentiation of Thy 1.2+ LAK cells from nude mouse spleen cells.

Culture of nude mouse spleen cells with recombinant human interleukin 2 (r-IL 2) resulted in the proliferation and generation of lymphokine-activated killer (LAK) cells which could lyse a variety of tumor cells. Flow cytometry study indicated that nude mouse spleen cells contained almost no Thy 1.2+ cells at the initial times of the culture, whereas LAK cells obtained from nude mouse spleen cells by culture with r-IL 2 (nude-LAK cells) expressed high intensity of Thy 1.2 antigen and lymphokine-activated cell-associated (LAA) antigen. The cytotoxic activity of nude-LAK cells was greatly reduced by treatment with anti-Thy 1.2 antibody plus complement but not with anti-Ly 1.2 or Ly 2.2 antibody plus complement treatment. Moreover, nude-LAK cells were resistant to the treatment with anti-asialo GM1 antibody plus complement, in contrast to resident nude natural killer (NK) cells. These data strongly suggested that r-IL 2 allowed the nude mouse spleen cells to differentiate into Thy 1.2+, Ly 1-,2-, asialo GM1- LAK cells which were distinct from Thy 1.2+, Ly 2+, asialo GM1- LAK cells induced from normal mouse spleen cells.

Animals↗

Serum haloperidol levels of schizophrenics receiving treatment for tuberculosis.

Serum haloperidol levels were studied in schizophrenic patients with and without antituberculosis therapy, and the effect of these agents on serum haloperidol level was evaluated. Rifampicin caused significant suppression of serum haloperidol levels in all cases studied (n = 7). The serum haloperidol clearance rate was accelerated in patients taking rifampicin, with a shortened half-life (4.9 h) compared with the control group (9.4 h). Among 18 schizophrenic patients receiving isoniazid, three showed significantly elevated serum haloperidol levels. It is possible that isoniazid can elevate haloperidol levels in some patients depending upon some unknown factors. The elevation of serum haloperidol level was though to be due to prolonged clearance of haloperidol secondary to isoniazid interaction with hepatic enzymes involved in drug metabolism. These observations suggest that haloperidol doses in schizophrenic patients receiving rifampicin or isoniazid must be carefully monitored.

Adult↗

Incidence, severity and clinical course of right ventricular involvement after acute inferior myocardial infarction; assessment by sequential 99Tcm-pyrophosphate scan and gated blood pool scan.

To evaluate the incidence, severity and clinical course of right ventricular (RV) involvement after acute inferior myocardial infarction (IMI), 78 patients (pts) with IMI were investigated by both 99Tcm-pyrophosphate (PYP) scan and gated blood pool scan (GBPS). GBPS was performed at admission and 10 days, whereas 99Tcm-PYP scan was performed at 3 to 6 days. RV uptake of PYP was demonstrated in 25 (32%) pts on 99Tcm-PYP scan and RV akinesis or moderate hypokinesis by GBPS was observed in 39 (50%) pts on the acute scan; 25 pts (Group A) with positive RV uptake and 14 pts (Group B) with no RV uptake. In the remaining 39 pts (Group C) had normal RV wall motion. Severely depressed RVEF improved nearly 10 points on the tenth day in Group A (from 30.8 +/- 12.3 to 40.9 +/- 6.7%, p less than 0.01) and Group B (from 35.6 +/- 8.2 to 44.5 +/- 10.5%, p less than 0.01), respectively. Group C showed normal RVEF (from 47.4 +/- 7.6 to 50.1 +/- 10.2%). Fourteen pts of 39 (Groups A and B) who had developed shock or hypotension improved strikingly after appropriate therapy except for one death during their hospital course. Our data demonstrated: some patients with RV dysfunction in IMI do not have severe necrosis as judged by PYP scanning, those with positive RV uptake and depressed RV function show a lower degree of recovery than those with no RV uptake, but start from a lower initial value of RV function, and the combination of 99Tcm-PYP scan and GBPS offers prognostic information in IMI with RV dysfunction.

Adult↗

Inhibition of DNA replication initiation by aminoglycoside antibiotics.

The reinitiation of DNA replication induced by a temperature shift in a dnaC(Ts) mutant of Escherichia coli was markedly inhibited by aminoglycoside antibiotics around the MIC in a short period. Protein synthesis continued for several minutes after the addition of aminoglycosides but was immediately blocked by chloramphenicol, suggesting that the inhibition of initiation of replication by aminoglycosides is not a secondary effect due to the interruption of protein synthesis. Aminoglycosides did not significantly affect RNA synthesis, suggesting that primer RNA synthesis for DNA initiation is not blocked by the agents. The lethal action of habekacin was observed simultaneously with the inhibition of DNA reinitiation. DNA elongation demonstrated with a dnaE(Ts) mutant or toluene-treated cells of a polA mutant was not significantly affected by aminoglycosides. The oriC-membrane complex formation was markedly interrupted by habekacin in the dnaC(Ts) mutant, and the in vitro reconstitution of the oriC-membrane complex was completely blocked by aminoglycosides. The present studies show that aminoglycosides block initiation of DNA replication and suggest that the inhibition is caused by the interruption of oriC-membrane attachment.

Aminoglycosides↗

Fusion of SV40-induced endocytotic vacuoles with the nuclear membrane.

The interaction between simian virus 40(SV40)-induced endocytotic vacuoles and the nuclear membrane was investigated using cationized ferritin (CF) and concanavalin A (Con A) as cell membrane markers. These markers bound to the cell surfaces of CV-1 cells together with SV40 at 4 degrees C. Following incubation of these modified cells at 37 degrees C in serum-free medium, the cell membranes showed many invaginations. After incubation for 60 min at 37 degrees C in the same medium, many various-sized vacuoles were present that contained membrane-bound CF, Con A and SV40. After 2 h of incubation at 37 degrees C, Con A was present in some areas of the perinuclear cisterna along the nuclear membrane. The control experiment, however, showed no localization of Con A-binding on the nuclear membrane. These results provide evidence that SV40-induced endocytotic vacuoles migrate toward the nucleus and fuse with its membrane.

Animals↗

[Effects of somatostatin and its analogue, des (Ala1, Gly2) [D-Trp8, D-Asu3,14]-somatostatin (SS-1), on gastric mucosal blood flow and gastric secretion].

The inhibitory effects of somatostatin and its analogue (SS-1) on gastric mucosal blood flow (MBF) and gastric secretion were studied using bethanechol and pentagastrin as stimulants in anesthetized rats. In the present study, the inhibitory action of SS-1 was particularly investigated, regarding somatostatin as the control compound. Pretreatment with SS-1 at 1, 10, 30, or 100 micrograms/kg, i.v. (single dosing), inhibited the increase of MBF and gastric secretion stimulated by bethanechol in a dose-dependent manner. SS-1 showed no marked difference from somatostatin in terms of the degree and manner of the inhibition until 30 min after treatment. At 90 min, however, SS-1 still showed an inhibitory action, which was more prominent in gastric secretion than in MBF. Thus, SS-1 had a longer duration of action than somatostatin. Generally, SS-1 and somatostatin inhibited MBF to the same degree, whereas SS-1 inhibited gastric secretion more strongly than somatostatin. When pentagastrin was used to stimulate MBF and gastric secretion, SS-1 inhibited MBF and gastric secretion to the same degree as did somatostatin, but again, SS-1 had a longer duration of action than somatostatin.

Animals↗