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Biomedical subjects

N Taniguchi

Publications and source records attributed to N Taniguchi.

At least 559 records · Page 31Linked to original sources

The effect of brief physical exercise on free radical scavenging enzyme systems in human red blood cells.

Eleven sedentary male students were studied, using a bicycle ergometer, for 30 min at about 75% of their maximal oxygen uptake, to observe the effects of brief physical exercise on free radical scavenging system enzymes of the erythrocytes. Of the enzymes examined, only total glutathione reductase activity showed a significant elevation immediately after exercise and appeared to remain high at 30 min after exercise. The results suggest that acute physical exercise has some effects on red blood cell glutathione reductase activity, which is related primarily to maintenance of reduced glutathione.

Adult↗

Plasma beta-thromboglobulin and platelet factor 4 concentrations in patients with atrial fibrillation.

The clinical significance of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF-4) levels were evaluated in 26 patients with atrial fibrillation (af) complicated by valvular heart disease (VHD), 73 patients with af but without valvular heart disease and 57 normal subjects. The beta-TG level was significantly higher in af patients without VHD than in normal subjects (49.4 +/- 35.8 ng/ml vs 31.2 +/- 14.0 ng/ml, p less than 0.01) and in af patients with VHD than in normals (64.1 +/- 52.8 ng/ml vs 31.2 +/- 14.0 ng/ml, p less than 0.01). Af patients with or without VHD tended to show high levels of PF4 compared with normals (af patients without VHD: 34.1 +/- 45.5 ng/ml, af patients with VHD: 18.6 +/- 27.2 ng/ml, normals: 11.6 +/- 8.2 ng/ml). There was no correlation between beta-TG levels and age in af patients without VHD or in normals. There was also no correlation between beta-TG levels and heart rate in af patients without VHD. The activation of platelets was suggested in patients with atrial fibrillation on the basis of increased levels of platelet releasing substances, especially in those with VHD. The high levels of beta-TG and PF4 in patients with atrial fibrillation may be one explanation for the high incidence of thromboembolism in these patients, indicating the necessity of antiplatelet therapy.

Adolescent↗

Leu 11+ T gamma cell chronic lymphocytic leukemia with partially activated natural killer function and its further activation by recombinant IL2 in vitro.

A patient with T gamma cell chronic lymphocytic leukemia with the Leu 11+ phenotype and novel function of activated natural killer cells is reported. The peripheral blood mononuclear cells of this patient showed large granular lymphocytes by May-Giemsa staining and lamellipodia by scanning electron micrography. Tests on reactivity with monoclonal antibodies showed that most cells were Leu 11+, OKT3-/Leu 1-, OKT4-, OKT8-, Leu 7-, OKM1-, and Tac-. Freshly collected cells lysed not only K562, which is highly sensitive to natural killer cells, but also Raji cells and Daudi cells, which are not. Leu 11+ cells were triggered by recombinant interleukin 2 (rIL2) to proliferate, produce gamma-interferon (gamma IFN), and show enhanced HLA-DR antigen expression, and 30% of the Leu 11+ cells became positive for IL2 receptor antigen (Tac). The spectrum of cytotoxic activity of these cells against target cells was extended by rIL2; after treatment with rIL2, the cells also lysed HeLa cells and even fresh cancer cells. This stimulation also increased the activities of acid phosphatase and tartrate-resistant acid phosphatase of the cells and resulted in the appearance of nonspecific esterase activity. The expanded cell population may represent a neoplasm, but these findings provide information on a novel differentiation stage of activated NK cells.

Aged↗

Malignant clonal expansion of large granular lymphocytes with a Leu-11+, Leu-7- surface phenotype: in vitro responsiveness of malignant cells to recombinant human interleukin 2.

A 14-year-old Japanese female with neutropenia showed malignant proliferation of the large granular lymphocytes (LGLs). These LGLs were E rosette+ and Fc(IgG) receptor+ and therefore are referred to as T gamma lymphocytes. They were also Leu-11+ and OKT11+; however, they were clearly negative for Leu-7, OKT3, OKT8, OKM1, and HNK-1 antigens as well as for terminal deoxynucleotidyl transferase activity. Karyotype analysis revealed 47, XXX. The LGLs showed no rearrangement of T cell receptor C beta genes. The natural killer (NK) cell activity against K562 target cells was low, but was significantly augmented after stimulation by recombinant human interleukin 2 (IL 2) in contrast to minimal NK boosting by recombinant human gamma-interferon (gamma-IFN). Such a unique responsive ability to lymphokines was quite similar to that noted in fetal and cord blood cells. These LGLs also demonstrated a considerable increase in antibody-dependent cell-mediated cytotoxicity (ADCC) and lymphokine-activated killer (LAK) activity after a short incubation with IL 2. Although in a resting stage they showed no IL 2 receptor expression as examined by anti-Tac antibody, Tac antigen appeared after IL 2 treatment followed by a marked increase in 3H-thymidine incorporation and a remarkable production of gamma-IFN. To investigate the mechanism of neutropenia, in vitro IL 2-stimulated coculture studies of these cells with normal bone marrow cells were performed. Colony formation of myeloid progenitors (CFU-C) was significantly suppressed. In addition, the conditioned medium from IL 2-stimulated LGLs indicated a remarkable suppression of CFU-C. These results suggest that these LGLs with a Leu-11+, Leu-7- surface phenotype might belong to a unique subset of pre-NK cells that are functionally and phenotypically similar to those represented at any early stage of human ontogeny and that they strongly express Tac antigen under the influence of IL 2 administration, followed by remarkable cell proliferation and gamma-IFN production.

Adolescent↗

Zinc metabolism in human blood during acute exposure to cold.

Effects of acute exposure to cold (10 degrees C for 60 min) on the concentrations of zinc and related proteins in red blood cells and in plasma were studied on seven male students. Lower concentrations of total zinc and of zinc derived from carbonic anhydrase I (CA-I) in red blood cells were found during cold exposure and 15 min after cold exposure, whereas no significant changes occurred in the concentration of zinc derived from carbonic anhydrase II (CA-II) or Cu2Zn2 superoxide dismutase (SOD1). The decrease in total zinc concentration in red blood cells was mostly due to that in CA-I concentration. On the other hand, there were not any changes in total zinc, albumin-bound zinc, and alpha 2-macroglobulin-bound zinc concentrations in plasma during the experimental period. These results, together with the marked hemoconcentration during cold exposure, suggest that cold stress induces an efflux of zinc from plasma.

Acclimatization↗

[Phase II study on oral administration of MCNU (ranomustine) tablet. Hanshin Cooperative Study Group on Hematological Disorders].

A phase II study of MCNU tablet has been performed on 70 patients with hematological disorders including mostly myeloproliferative disorders. MCNU tablet was given p.o. at a dose of 50 mg daily for 2-6 days (total 100-300mg) as one course with average intervals of 3 to 5 months or more for patients responding to this drug. The effective rates were 72% in 18 patients with chronic myelogenous leukemia, 88% in 25 patients with polycythemia vera and 68.5% in 19 patients with essential thrombocythemia. Side effects of MCNU tablet were nausea and vomiting (31%) which had a dose-dependent relationship, mild liver dysfunction (5%) and elevation of BUN and creatinine (2%) which were not serious. The results were almost comparable to those of the phase II study of MCNU given intravenously.

Administration, Oral↗

Monoclonal antibody which has the neutralizing activities for human IL-2.

Six monoclonal antibodies against recombinant human interleukin-2 (IL-2) were successfully prepared by fusing NS-1 with spleen cells of BALB/c mice immunized with human recombinant IL-2. The specificities of these monoclonal antibodies were confirmed. By enzyme linked immunosorbent assay (ELISA) method, the antibody concentrations of each ascitic fluid obtained from BALB/c-nu/nu transplanted with the established hybridoma clones were varied for 10(3) to 10(5) depending on the clone. By SDS-PAGE analysis with immunoprecipitates formed between monoclonal antibodies and recombinant human IL-2, all monoclonal antibodies reacted unequivocally with recombinant human IL-2. Two monoclonal antibodies (designated as KNT-1 and KNT-2) out of six established clones reacted with natural human IL-2 molecule obtained from cultured human peripheral blood lymphocytes (PBL) stimulated with PHA-P and TPA. KNT-1 and KNT-2 monoclonal antibodies have inhibitory effects on the proliferative response of natural killer (NK-7) cell (one of the IL-2 dependent cultured cell lines) elicited by recombinant, natural human, or natural rat IL-2. Monoclonal antibody, KNT-1, inhibited activities of both recombinant or natural human IL-2, but did not neutralize activities of IL-2, derived either from murine EL-4 or from rat spleen cells. Another monoclonal antibody, KNT-2, had neutralizing activity for either recombinant or natural human IL-2 and eliminated the activity of rat-derived IL-2, but did not interfere with the activity of murine IL-2. The remaining four monoclonal antibodies (designated as KNT-3, -4, -5 and -6) did not affect the proliferative response of NK-7 cells elicited by natural human, rat and murine IL-2. These observations indicate that functional portion(s) of IL-2 molecules from different species have somewhat different structures.

Animals↗

Establishment of four mouse hybridoma cell lines producing monoclonal antibodies reactive with ras oncogene product p21.

With the use of proteins derived from Escherichia coli cells expressing the v-H-ras gene product as immunogens and an enzyme-linked immunosorbent assay with whole cells for a screening method, 4 BALB/c mouse hybridoma cell lines (rp-12, rp-28, rp-35, and rp-38) were isolated that produced monoclonal antibodies (MoAbs) showing higher reactivity with murine ras gene-activated cell lines than with normal cell lines. All the MoAbs complexed p21ras from the ras gene-activated cell lines in Western immunoblot analysis and demonstrated a binding property of p21ras to guanine nucleotides. The indirect immunofluorescence assay revealed that MoAbs rp-12 and rp-28 stained the murine and human H- or K-ras-activated cell lines, and MoAbs rp-35 and rp-38 not only stained these cell lines but also weakly stained a human N-ras-activated cell line. All these MoAbs stained the murine fibroblast lines with lower intensity, but they did not stain a human fibroblast line. Further, positive reactions with MoAb rp-12 were seen against human melanomas, but there was no reaction against nevi. The rp-12, rp-28, rp-35, and rp-38 antibodies are useful additions to the MoAbs reacting with p21ras reported previously.

Animals↗

Effects of a new dihydropyridine calcium antagonist on vascular smooth muscles, cardiac muscles and [3H]-nitrendipine binding.

The effects of methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2- yl)-1,4- dihydropyridine 3-carboxylate (DHP-218), a new dihydropyridine calcium antagonist, on vascular smooth muscles, cardiac muscles and [3H]-nitrendipine binding to the cardiac muscle and brain membranes were investigated in vitro. Vascular smooth muscles: Calcium-induced contraction of the rat aorta in high K+ solution was inhibited by DHP-218 with the pA2 value of 9.11. The IC50 value for the inhibitory effects of this compound in high K+-induced and phenylephrine-induced contraction was 6.3 nmol/l and 66 nmol/l, respectively. Vasodilatory effects of this drug on various blood vessels of rabbits contracted by high K+ appeared to a similar extent. The onset of the vasodilatory effect was very slow and the recovery rate of vasodilatory response after washout with the bathing solution containing high K+ or phenylephrine was also very slow. Cardiac muscles: Negative chronotropic and inotropic actions were observed at concentrations more than 30 and 100 nmol/l, respectively. Duration of the plateau phase of normal action potential was shortened and the amplitude and duration of slow action potential were reduced at concentrations more than 1 mumol/l. Very high vasculoselectivity was observed. Displacement of [3H]-nitrendipine binding: The pattern of displacement of [3H]-nitrendipine binding by DHP-218 was very similar to that of other 1,4-dihydropyridines but this compound was about 70 times less potent than nifedipine in [3H]-nitrendipine displacement capacity. These results indicate that DHP-218 has specific vasodilatory action due to calcium antagonism, but association and dissociation rates with tissue and receptors were different from those of nifedipine.

Action Potentials↗

Association of specific tyrosine phosphorylation with stages of B-cell differentiation in human lymphoid leukemias.

In vitro protein phosphorylation in various types of human fresh lymphoid leukemic cells (C-ALL, B-CLL, HCL and PCL: B-cell lineage and T-ALL, ATL and T-CLL: T-cell lineage) were studied. In cases of B-CLL and HCL, tyrosine protein kinase (TPK) activity was at least 5-fold higher than that in other cases of B- and T-cell lineages. B-cell leukemic cells at various differentiation stages had different endogenous substrates in tyrosine phosphorylation as well as distinct TPK activity. The P-tyr-containing proteins of 68K, 59K and 56K were detected commonly in all the cases of B-cell lineage. The phosphorylated protein of 32K was present only in cases of PCL. On the other hand, in T-ALL and ATL, the major substrate in tyrosine phosphorylation was 58K. These results suggest that the characterization of in vitro tyrosine phosphorylation provides a new means not only to distinguish T- and B-lymphoid leukemia, but also to differentiate stages of lymphoid development.

B-Lymphocytes↗

Increased activity of 5-lipoxygenase in polymorphonuclear leukocytes from asthmatic patients.

The formation of 5-lipoxygenase products of arachidonic acid, 5-HETE and 5,12-diHETE, was determined in 100,000 X g supernatant of polymorphonuclear leukocytes from 17 healthy subjects, 17 patients with extrinsic asthma and 15 patients with intrinsic asthma. After the supernatant was incubated with 14C-arachidonic acid in the presence of calcium and indomethacin, the lipoxygenase products of arachidonic acid were separated by thin layer chromatography. The results were expressed as the percentage conversion of 14C-arachidonic acid into the product per 10(7) cells. The formation of 5,12-diHETE, but not of 5-HETE, was significantly increased in the cells from the group of patients with extrinsic asthma (4.38 +/- 0.78%, mean +/- S.E.; p less than 0.01) and intrinsic asthma (6.09 +/- 1.11%; p less than 0.01), when compared to normal subjects (1.74 +/- 0.30%). Both extrinsic and intrinsic asthmatics had significantly enhanced 5-lipoxygenase activity, which was expressed as the sum of percentage conversion of 14C-arachidonic acid into 5-HETE and 5,12-diHETE. The percentage conversion in normal subjects was 4.19 +/- 0.39%, 6.24 +/- 0.84% for 17 patients with extrinsic asthma (p less than 0.05), and 8.59 +/- 1.29% for 15 patients with intrinsic asthma (p less than 0.01). There was no significant difference between these asthmatic groups. These results indicate that 5-lipoxygenase activity is increased in patients with bronchial asthma.

Adult↗