Search PubMed⌕ Search

Biomedical subjects

S Furusawa

Publications and source records attributed to S Furusawa.

At least 145 records · Page 8Linked to original sources
PubMed1989

Production of interleukin-1-alpha and -beta by human peripheral polymorphonuclear neutrophils.

The mechanism of the production of interleukin-1 (IL-1) by human peripheral polymorphonuclear neutrophils (PMN) was investigated. Supernatants of PMN stimulated with 30 micrograms/ml lipopolysaccharide (LPS) were used as extracellular IL-1 and supernatants of their lysate as intracellular IL-1 source. IL-1 activity was measured by the C3H/HeJ thymocyte co-mitogenic assay. The supernatants from PMN stimulated with LPS for 72 h showed IL-1 activity which had an apparent molecular weight of 15-20 kilodaltons and pI of 5.0 and more than 8.5. It was neutralized with anti-IL-1 antibodies and it lacked IL-2 activity. Our time course study of the IL-1 assay with neutralization by anti-IL-1-alpha and -beta antibodies indicated that the extracellular IL-1-beta activity appeared predominantly in the early incubation periods, whereas alpha activity appeared predominantly in the late periods. Intracellular IL-1-alpha but not beta activity was detected mainly at the intermediate incubation periods. These data indicate that PMN stimulated with LPS produce both IL-1-alpha and -beta, and release IL-1-beta first and IL-1-alpha later.

Animals↗
PubMed1989

Potentiation of ifosfamide toxicity by chlordiazepoxide, diazepam and oxazepam.

The effects of chlordiazepoxide, diazepam and oxazepam on the lethal toxicity and metabolic activation of ifosfamide were investigated in mice. Ifosfamide was administered 24 h after the final injection of chlordiazepoxide, diazepam or oxazepam (100 mg/kg/d for 3 d, i.p.). The prior administration of chlordiazepoxide, diazepam or oxazepam enhanced the toxicity of ifosfamide (778 mg/kg, i.p.) during observation for 6 d after the administration of ifosfamide. In chlordiazepoxide-, diazepam- or oxazepam-treated mice, a higher concentration of active metabolite in the plasma after the administration of ifosfamide (200 or 600 mg/kg, i.p.) was observed as compared with that in mice treated with ifosfamide alone. On the other hand, chlordizepoxide, diazepam or oxazepam markedly enhanced the activity of ifosfamide oxidase in the liver microsomes. These results suggest that the potentiation of ifosfamide toxicity is due to stimulation of the metabolic activation of ifosfamide by chlordizepoxide, diazepam and oxazepam.

Animals↗
PubMed1989

Effect of human recombinant interleukin 4 on in vitro granulopoiesis of human bone marrow cells.

Utilizing in vitro colony assay, we investigated the effect of human recombinant interleukin 4 (hIL-4) on granulopoiesis of normal human bone marrow cells. Though hIL-4 itself did not possess any colony-stimulating activity, the number of neutrophil (N) colonies, particularly the number of small colonies, supported by human recombinant G-CSF (hG-CSF) was significantly increased when hIL-4 was used as a costimulant. In contrast, the number of eosinophil (Eo) colonies supported by hIL-5 was decreased when hIL-4 was used as a costimulant. Also, the numbers of N and Eo colonies supported by hIL-3 or hGM-CSF were both significantly decreased when hIL-4 was added. These data suggest that hIL-4 has diverse positive and negative regulatory effects on human neutro- and eosinophilopoiesis as a cofactor of various CSFs.

Adult↗
PubMed1989

[CD8+ agranular lymphocyte proliferative disorder with T-cell receptor beta-chain gene rearrangement associated with thymoma and neutropenia].

A 58-year-old male with a 10-years history of thymoma was admitted to our hospital because of the respiratory infection. Hepatosplenomegaly and systemic lymphadenopathy were revealed on physical examination. Chest roentgenogram showed a large anterior mediastinal tumor and a right pleural effusion. Blood examination showed Hb 11.5 g/dl, leucocyte count 1,600/microliters (1% neutrophils, 34% monocytes, 65% lymphocytes) and platelet count 11.2 x 10(4)/microliters. The lymphocytes in the peripheral blood and pleural fluid were mostly small agranular mature lymphocytes and CD2+ 3+ 4- 8+. A monoclonal rearrangement of TCR beta chain gene was found using Southern blot analysis of the lymphocytes in the peripheral blood and pleural fluid. The CFU-GM colony formation by bone marrow cells was normal, and not suppressed by the patient's serum or peripheral blood lymphocytes. Neutrophil-associated IgG was increased with a direct immunofluorescence test. Serum IgG level was slightly decreased. Radiation therapy for thymoma exerted no effect. Treatment with prednisolone 60 mg daily resulted in complete disappearance of the pleural effusion and partial improvement of hepatosplenomegaly, thymoma and neutropenia. Histological examination of the thymoma revealed predominantly spindle cell type. He is still in good condition 21 months after diagnosis. This case seems to represent neoplastic proliferation of mature CD8+ T cells associated with thymoma.

Agranulocytosis↗
PubMed1989

[Spontaneous differentiation from myeloperoxidase-negative acute nonlymphocytic leukemia to acute myelomonocytic leukemia].

We reported a 68-year-old woman with acute nonlymphocytic leukemia, in whom the leukemia transformed from poorly differentiated myeloperoxidase (MPO)-negative type into myelomonocytic type during the observation without chemotherapy. Hematological findings on admission revealed a leukocyte count of 3,500/microliters with 48% blasts and a platelet count of 9.2 x 10(4)/microliters. Bone marrow aspiration showed 68.2% infiltration of blasts negative for MPO. Sudan black B and esterase stains. By electron microscopy MPO was detected in the endoplasmic reticulum and nucleoenvelope of the blasts. Large vacuole-like granules were MPO-negative. She was observed without administration of any antileukemic agent or an immunopotentiator. The leukocyte count rose gradually, in association with increases in the relative and absolute counts of mature neutrophils and monocytic cells, and the platelet count. Twenty-six months after the initial diagnosis, a blood examination showed a leukocyte count of 74,300/microliters with 20.5% mature neutrophils and 15.5% monocytic and a platelet count of 31.4 x 10(4)/microliters. Cytological, cytochemical, ultrastructural and immunological studies of the bone marrow cells showed features compatible with acute myelomonocytic leukemia (FAB M4). This case is unusual in respect that poorly differentiated ANLL transformed spontaneously into moderately differentiated ANLL.

Aged↗
PubMed1989

[Neutrophil-associated IgG and neutrophil-binding IgG in autoimmune neutropenia].

Neutrophil-associated IgG (NAIgG) and neutrophil-binding IgG in sara (NBIgG) of 77 patients with neutropenia suspected to be caused by autoimmune mechanisms (group A) and 31 patients with aplastic anemia or myelodysplastic syndrome (group B) were assayed by flow cytometry. Auto-NBIgG was elevated in 32% of the patients in group A, particularly in about 70% of those with collagen diseases or ITP, but the level was normal in group B. Elevated NAIgG with normal auto-NBIgG levels was found in 27% of the patients in group A and in 64% of the patients in group B. The assay of auto-NBIgG was useful for detection of anti-neutrophil autoantibodies and for the diagnosis of autoimmune neutropenia. In addition, the level of NAIgG may be non-specifically elevated in non-immune neutropenia.

Agranulocytosis↗
PubMed1988

Effect of human recombinant interleukin 5 and G-CSF on eosinophil colony formation.

Human recombinant (r) IL-5 was shown to have the activity to stimulate eosinophil (Eo) colony formation from human non-T, non-adherent bone marrow cells. The majority of these colonies were found to contain a small number of basophils, macrophages or neutrophils. Human rG-CSF, which alone did not stimulate Eo colony formation, showed an enhancing effect on Eo colony formation when added with IL-5. IL-5 seems to stimulate the proliferation and differentiation of CFU-Eo, while G-CSF acts on the early stage of eosinophilopoiesis.

Cell Differentiation↗
PubMed1988

Interleukin 2 stimulates the T-cells from patients with eosinophilia to produce CFU-Eo growth stimulating factor.

To explore the mechanism of eosinophilopoiesis in patients with reactive eosinophilia, we studied the effect of interleukin 2 (IL-2) on the production of CSFs, especially CFU-eosinophil growth stimulating factor (CFU-Eo GSF) from T-lymphocytes in patients with reactive eosinophilia. Conditioned media (CM) prepared from patients' E rosette forming cells (ERFC) with or without IL-2 was assayed for CFU-Eo, CFU-monocyte, macrophage (CFU-M) and CFU-neutrophil (CFU-N) GSF. The addition of IL-2 to the ERFC significantly stimulated the production of CFU-Eo and CFU-M GSF while only CFU-M GSF increased in normals. Serial testing of the CFU-Eo GSF in ERFC-CM demonstrated that the ability of ERFC to produce CFU-Eo GSF with IL-2 stimulation was retained even when the eosinophilia had disappeared. These results suggest that CFU-Eo GSF is produced from T-cells with IL-2 stimulation and that the T-cells from patients produce IL-2 stimulation and that the T-cells from patients produce CFU-Eo GSF with IL-2 stimulation after the disappearance of eosinophilia.

Colony-Forming Units Assay↗
PubMed1988

Heterogeneity of in vitro growth pattern of megakaryocyte progenitors (CFU-M) in myeloproliferative disorders.

In groups of 26 patients with myeloproliferative disorders (MPD), 8 with chronic myelogenous leukaemia (CML); 8 with polycythaemia vera (PV); 10 with essential thrombocythaemia (ET); and 6 patients with reactive thrombocytosis (RT), we studied the growth characteristics of bone marrow CFU-M in agar culture. The bone marrows from all the patients with MPD formed so called endogenous CFU-M colonies, in the absence of PHA-LCM, that increased in a dose-dependent manner with the addition of increasing concentrations of normal human AB-citrated plasma (NH-ABCP), while the bone marrows from all the patients with RT and from healthy controls formed few or no endogenous CFU-M colonies. In MPD, the endogenous CFU-M growth was enhanced by normal T cells in a dose-dependent fashion, and was decreased with the depletion of T cells from the marrow cells. These results suggest that the formation of endogenous CFU-M colonies is caused by hypersensitivity of CFU-M in MPD to NH-ABCP, which may contain a small amount of Meg-CSF, and/or by in vitro T cell stimulation. Among MPD, the endogenous CFU-M growth in ET was significantly lower than that of other MPD patients; however, the total number of ET CFU-M grown in the presence of PHA-LCM was the highest. These data show that the bone marrow CFU-M in MPD are heterogeneous with respect to in vitro growth pattern or sensitivity to exogenous Meg-CSF.

Clone Cells↗
PubMed1988

Effect of pretazettine and viva-natural, a dietary seaweed extract, on spontaneous AKR leukemia in comparison with standard drugs.

Antileukemic activity of pretazettine hydrochloride (PTZ: a narcissus alkaloid) and Viva-Natural (a seaweed extract) has been confirmed against spontaneous AKR T cell leukemia in mice containing 20% of advanced leukemia. The activity of both agents has been compared with selected standard cytotoxic drugs, vincristine (VCR), methotrexate (MTX), 6-thioguanine (6-TG), and adriamycin (ADR), and immunomodulators, pyran copolymer (MVE-2), isoprinosine, levamisole and tilorone. PTZ activity seems to be superior (90% increase in life span, ILS) to those of MTX (71% ILS), 6-TG (60%), and ADR (49%), and inferior to VCR (114% ILS). Viva-Natural has been found to be the only immunomodulator (61%) active against AKR T cell leukemia, while all standard immunomodulators tested were not active. Combination treatment of PTZ with VCR, or 6-TG, or ADR, or Viva-Natural were synergistic, but combination of PTZ with MTX was not beneficial. PTZ or VCR has been found to be therapeutically very effective (323 or 347% ILS, respectively) against mice in advanced stage of leukemia, and induced complete clinical remissions. Also, PTZ has been found to reverse the leukemia-enhancing effect of ciclosporin in AKR mice at preleukemic stage.

AKR murine leukemia virus↗
PubMed1988

Heteroclitic antibodies: differences in fine specificities between monoclonal antibodies directed against dinitrophenyl and trinitrophenyl haptens.

The inhibition of binding of monoclonal antibodies by different haptens was studied using the 50% antibody binding assay. The binding of antidinitrophenyl and antitrinitrophenyl antibodies to dinitrophenylated or trinitrophenylated bovine serum albumin could be inhibited by monovalent dinitrophenyl or trinitrophenyl epsilon-aminocaproic acid. Some of the antibodies could be inhibited to a greater degree with the cross-reacting haptens than with the haptens homologous to the immunizing antigen, therefore these antibodies were heteroclitic.

Animals↗
PubMed1988

The suppressive effect of histamine on anti-DNP antibody production in mice.

To clarify the effect of histamine on antibody production, histamine was injected intravenously into DNP-KLH immunized C3H/HeN female mice. The number of anti-DNP plaque-forming splenic cells decreased in immunized and histamine-injected mice. Decreased PFC responses similarly occurred in recipient mice into which Lyt-2.1 T cells obtained from histamine-injected mice were transferred before immunization. The effect of histamine is not due to inhibition on plaque formation. The results indicated that histamine induced the augmentation of suppressor T cell (Ts) function and caused the decrease of antibody production in histamine-injected mice. The maximum activity of Ts in recipient mice was obtained from mice injected with histamine 3 days before the cell transfer. The suppressive activity of histamine was not antigen specific because Ts was induced in histamine-injected, nonimmunized mice. The treatment of histamine type 2 (H2) agonist showed decreased PFC responses in the mouse as well as histamine did. When mice were treated with an H2 antagonist followed by histamine, antibody production was not reduced. The above results indicated that histamine seemed to regulate antibody production through H2 receptors on lymphocyte membranes.

Adjuvants, Immunologic↗
PubMed1988

Reduction of cyclophosphamide-induced toxicity by diethyldithiocarbamate and carbon disulfide and its possible mechanism.

The mechanism of reduction in cyclophosphamide (CPA)-induced toxicity by diethyldithiocarbamate (DTC) and carbon disulfide (CS2) was examined in relation to CPA metabolism in mice. Pretreatment with DTC (100 mg/kg) or CS2 (50 mg/kg), p.o. decreased the acute toxicity of CPA. Active metabolites of CPA in the plasma after the administration of CPA (100 or 450 mg/kg, i.p.) was lowered by DTC or CS2 treatment. The liver microsomal CPA oxidase activity decreased 1 h after the administration of DTC (25-100 mg/kg, p.o.) or CS2 (12.5-50 mg/kg, p.o.). These results suggested that the reduction of CPA-induced toxicity in mice pretreated with DTC or CS2 was due to the inhibition of activation of CPA and reduced formation of alkylating metabolites.

Alkylation↗
PubMed1988

Studies on murine IgE with monoclonal antibodies. I. Characterization of rat monoclonal anti-IgE antibodies and the use of these antibodies for determinations of serum IgE levels and for anaphylactic reactions.

Rat monoclonal antibodies were constructed by fusion of immunized rat spleen cells with a nonsecreting mouse myeloma cell. Two monoclonal antibodies (6HD5 and HMK-12) were selected for further study. Both reacted with various IgE molecules of different specificities and different allotypes, but did not react with immunoglobulins of other isotypes and with light chains. These antibodies were therefore anti-isotypic (IgE) and not anti-allotypic or anti-idiotypic. It was shown by competition studies that these antibodies recognize different epitopes on the FcR epsilon fragment. A sensitive ELISA for the quantitation of murine IgE was developed with these monoclonal antibodies; the sensitivity was between 2 and 250 ng/ml for detection of serum IgE levels. Good correlation was obtained with protein amounts as determined by enzyme-linked immunosorbent assay (ELISA) and passive cutaneous anaphylaxis (PCA) activities. Both monoclonal antibodies were used to study anaphylactic reactions elicited by IgE antibodies. Both could inhibit PCA reactions and both could elicit reverse PCA reactions.

Animals↗