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Biomedical subjects

A Ohsaka

Publications and source records attributed to A Ohsaka.

At least 37 records · Page 2Linked to original sources

Granulocyte colony-stimulating factor administration modulates the surface expression of effector cell molecules on human monocytes.

Granulocyte colony-stimulating factor (G-CSF) has been shown to stimulate human neutrophil functions, both in vitro and in vivo. We examined the effects of G-CSF administration on the surface expression of effector cell molecules on human neutrophils and monocytes. G-CSF (50 micrograms/m2/d) was administered subcutaneously to five healthy volunteers once a day for 7 d. Venous blood was obtained immediately before and after the completion of G-CSF administration and 1 week after the last G-CSF administration. The surface expression of complement receptors (CR), Fc receptors for IgG(FcR) and cellular adhesion molecules on human neutrophils and monocytes were determined by indirect immunofluorescence using flow cytometry and monoclonal antibodies. The expression of CR1, CR3, FcRI and FcRII on neutrophils increased significantly after G-CSF administration and then decreased after the last G-CSF administration. The expression of human leucocyte adhesion molecule-1 (LAM-1) on neutrophils reflected the above expression. On the other hand, the administration of G-CSF increased the expression of CR1, CR3, FcRI and FcRIII on monocytes. The expression of CR1, CR3 and FcRI on monocytes then decreased after the last G-CSF administration, whereas the expression of FcRIII remained at an increased level. These findings indicate that G-CSF administration modulates the expression of effector cell molecules on circulating monocytes as well as on neutrophils, resulting in enhanced defence against selected infections or in potentiation of the tumouricidal capacity of phagocytes in cancer patients.

Adult↗

Familial thrombocytosis.

Four cases of thrombocytosis in three successive generations of a family are described. High peripheral platelet count was found incidentally in the proband with cutaneous malignant lymphoma. Bone marrow examination showed megakaryocytic hyperplasia. Neither Philadelphia chromosome nor chimaeric bcr/abl junction was detected in marrow cells. In this family, thrombocytosis was thought to be transmitted by an autosomal dominant mode of inheritance.

Child, Preschool↗

Evolution of severe aplastic anemia to myelodysplasia with monosomy 7 following granulocyte colony-stimulating factor, erythropoietin and high-dose methylprednisolone combination therapy.

A 19-year-old man was diagnosed as having severe aplastic anemia and received high-dose methylprednisolone treatment without hematological response. A second course of high-dose mPSL treatment together with granulocyte colony-stimulating factor (G-CSF) plus erythropoietin (EPO) was then started and resulted in trilineage blood cell response. Ten months after the combination therapy thrombocytopenia developed and cytogenetic analysis showed 45,XX,-7, indicating an evolution to myelodysplastic syndrome (MDS) associated with monosomy 7.G-CSF and EPO treatment together with immunosuppression may be an effective therapy in SAA patients, but such a therapy may increase the risk of evolution to MDS.

Adult↗

[Acute lymphoblastic leukemia accompanied by severe hypercalcemia; successful treatment with bisphosphonate].

A 62-year-old woman was admitted to the hospital because of bone pain. Laboratory data showed blasts in the peripheral blood, hypercalcemia (corrected calcium 15.1 mg/dl) and an increased level of parathyroid hormone related-protein (PTHrP). Bone marrow aspiration revealed increased lymphoblasts (96.5%), indicating acute lymphoblastic leukemia (ALL, L1). Subsequent radiological examination disclosed bone infiltration of ALL. Although the hypercalcemia was successfully treated with bisphosphonate, the PTHrP level remained high. After chemotherapy, the blasts in the peripheral blood disappeared and the PTHrP level normalized. We hypothesize that in the present case the production of PTHrP by lymphoblasts resulted in the hypercalcemic state. Although ALL is rarely accompanied by hypercalcemia, this case might help us to understand the relationship between ALL and hypercalcemia.

Diphosphonates↗

Complement receptor type 1 (CR1) deficiency on neutrophils in myelodysplastic syndrome.

We present a patient with myelodysplastic syndromes (MDS) whose neutrophils exhibited defective expression of complement receptor type 1 (CR1). A 73-year-old man was admitted with an evolution of MDS from RA into RAEBT according to the FAB classification of MDS. The neutrophil alkaline phosphatase (NAP) score was zero. The surface expression of membrane effector molecules on neutrophils was determined by indirect immunofluorescence using flow cytometry and monoclonal antibodies. The expression of CR1 on neutrophils as identified by staining with CD35 was defective in the patient, and the expression of other complement receptors (CR3 and CR4), Fc receptors and adhesion molecules was normal. CR1 deficiency and defective NAP score on neutrophils in the patient might account for impairment of common storage pool, presumably novel intracellular secretory vesicles.

Aged↗

Local anesthetic lidocaine inhibits the effect of granulocyte colony-stimulating factor on human neutrophil functions.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) enhanced superoxide (O2-) release in human neutrophils stimulated by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) and inversely regulated the surface expression of cellular adhesion molecules, leukocyte adhesion molecule-1 (LAM-1) and CD11b/CD18 leukocyte integrin, on human neutrophils; that is, rhG-CSF downregulated the expression of LAM-1 and upregulated the expression of CD11b on neutrophils. The cationic local anesthetic lidocaine inhibited not only FMLP-induced O2- release in neutrophils but also FMLP-induced CD11b upregulation and LAM-1 downregulation on neutrophils in a dose-dependent manner. Lidocaine also abolished the priming effect of rhG-CSF for enhanced release of O2- in neutrophils and inhibited rhG-CSF-induced CD11b upregulation and LAM-1 downregulation on neutrophils in a dose-dependent manner. These findings suggest that lidocaine inhibits human neutrophil functions, such as adherence to endothelial cells, by interfering with the expression of cellular adhesion molecules on neutrophils, and that lidocaine might have anti-inflammatory properties by inhibiting the effect of inflammatory cytokines.

Anesthesia, Local↗

[G-CSF and G-CSF receptor].

Relationship between leucocytosis and G-CSF blood concentration were examined. Increase in blood concentration of G-CSF of surgical patient and dialysis patient with leucocytosis were noticed. Determination of G-CSF receptor on leucocyte was performed by the flow cytometry using biotinylated G-CSF. Modulation of G-CSF receptor on leucocyte at surgery and dialysis was identified in vivo. Studies of G-CSF blood concentration and modulation of G-CSF receptor are useful in analysis of dynamics of leucocyte and analysis of infectious disease.

Granulocyte Colony-Stimulating Factor↗

Granulocyte colony-stimulating factor down-regulates the surface expression of the human leucocyte adhesion molecule-1 on human neutrophils in vitro and in vivo.

The leucocyte adhesion molecule-1 (LAM-1) is the human homologue of the murine peripheral lymph node homing receptor, MEL-14, and might play a crucial role in neutrophil localization at inflammatory sites. We have reported previously that recombinant human granulocyte colony-stimulating factor (rhG-CSF) stimulates or enhances several neutrophil functions in vivo, as well as in vitro. To further explore the possible role of G-CSF in inflammation we studied the effect of rhG-CSF on the surface expression of LAM-1 on human neutrophils, both in vitro and in vivo. The expression of LAM-1 by human neutrophils was investigated by indirect immunofluorescence using flow cytometry and monoclonal antibodies anti-Leu-8 and TQ1. A whole blood analysis was performed to minimize in vitro manipulation. Most circulating human neutrophils expressed LAM-1 on the cell surface. Brief exposure of neutrophils to rhG-CSF in vitro decreased the surface expression of LAM-1. rhG-CSF down-regulated neutrophil LAM-1 expression in a time- and dose-dependent manner. Neutrophils from healthy volunteers and from patients who were receiving rhG-CSF exhibited a decreased expression of LAM-1 after rhG-CSF administration, and the expression thereafter returned or overshot the pretreatment level after stopping rhG-CSF administration. These findings indicate that rhG-CSF down-regulates the surface expression of LAM-1 on human neutrophils in vivo, as well as in vitro, and G-CSF might participate in neutrophil-endothelial cell interaction in inflamed tissue.

Antigens, CD↗

Effects of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor on respiratory burst activity of neutrophils in patients with myelodysplastic syndromes.

The superoxide (O2-)-releasing capacity in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) and the priming effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on FMLP-induced O2- release were investigated in neutrophils from 14 patients with myelodysplastic syndromes (MDS). The O2(-)-releasing capacity in MDS neutrophils varied from patient to patient. As compared with normal neutrophils, the O2(-)-releasing capacity in MDS neutrophils was increased in 9/14 patients, normal in three patients and decreased in two patients. There was no close relationship between the O2(-)-releasing capacity and the peripheral blood neutrophil count or the plasma concentration of C-reactive protein. The priming of neutrophils by rhG-CSF was not observed in five patients, whereas rhGM-CSF primed neutrophils from all patients. The priming effect of rhGM-CSF was consistently greater than that of rhG-CSF in each patient. The intravenous administration of rhG-CSF (300 micrograms/body) to two MDS patients showed an increase in the peripheral blood neutrophil count and enhancement of neutrophil O2- release. These findings demonstrate that the neutrophil O2(-)-releasing capacity in MDS varies from patient to patient and is not always impaired, and that rhGM-CSF is able to prime neutrophils which never respond to rhG-CSF.

Adult↗

[Effect of THP-CVP regimen for elderly patients with malignant lymphoma].

Between April 1990 and June 1992, a multicenter clinical trial of chemotherapy regimens was performed with patients, aged 65 years or more, suffering from malignant lymphoma. The total number of patients was 38 included 30 initial cases (median age: 72) and 8 relapsed cases (79). The chemotherapy regimen, administered every 3 weeks, included pirarubicin (30 mg/m2; day 1), cyclophosphamide (500 mg/m2; day 1), vindesine (1.5 mg/m2; day 1), and prednisolone (40 mg/m2; days 1-5) for the initial cases, and etoposide (100 mg/m2; days 1-5) in addition for relapse cases. The complete response and partial response rates were 50.0% and 40.0% in initial cases, respectively, and 50.0% and 0% in relapsed cases, respectively. The 50% survival period was 25.9 months in initial cases and 18.0 months in relapse cases. There were no serious side effects related to the regimens. Performance status deteriorated in only one case after chemotherapy. We concluded that the chemotherapy regimens were useful and safe for elderly patients with malignant lymphoma.

Aged↗

Clinicopathologic and therapeutic aspects of angioimmunoblastic lymphadenopathy-related lesions.

The clinicopathologic features of 14 patients with angioimmunoblastic lymphadenopathy (AIL)-related lesions were analyzed. Lymph node biopsy specimens from all the patients showed a diffuse obliteration of lymph node architecture, prominent vascular proliferation, a polymorphous cellular infiltrate, including immunoblasts, and varying degrees of clear cell proliferation. The patients were eight males and six females, with a median age of 58.5 years. All but one were in an advanced stage at the time of diagnosis. Bone marrow involvement was observed in eight patients. Thirteen patients had a negative serologic reaction for antibody to human T-cell leukemia virus type I (HTLV-I), and one patient was considered to be a HTLV-I carrier. Polyclonal hypergamma-globulinemia was observed in 6 patients, and 6 of the 12 patients showed elevated IgE levels. Immunophenotyping of the involved lymph nodes revealed a preponderance of T-cells in all the patients. Eleven of these patients showed a predominance of CD4+ over CD8+ T-cells, and only one patient showed a predominance of CD8+ over CD4+ T-cells. Two of five patients whose gene analysis was carried out showed clonal rearrangement of the T-cell receptor beta chain gene without rearrangement of the immunoglobulin heavy chain genes. Twelve patients received doxorubicin-containing combination chemotherapy; of these, 7 patients achieved complete response, and the other 5 had partial response. Nine patients are still alive with a median follow-up period of 21 months, and five patients died during the follow-up period. Progression to high-grade T-cell lymphoma with systemic infiltration was ascertained in two of three cases for which autopsy was performed. From our experience, we recommend doxorubicin-containing combination chemotherapy as initial therapy for AIL-related lesions.

Aged↗

Increased respiratory burst activity of neutrophils in patients with aplastic anemia: effects of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor.

The superoxide (O2-)-releasing capacity in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) and the priming effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on FMLP-induced O2-release were investigated in neutrophils from 13 patients with aplastic anemia (AA). The O2(-)-releasing capacity of AA neutrophils (0.85 +/- 0.36 nmol/5 min/1 x 10(5) cells, n = 13) was significantly (p < 0.01) increased as compared with that of normal neutrophils (0.24 +/- 0.12 nmol/5 min/1 x 10(5) cells, n = 17). There was no close relationship between the O2(-)-releasing capacity and the peripheral blood neutrophil count or the plasma concentration of C-reactive protein. The plasma concentrations of G-CSF and GM-CSF were not elevated to the detectable levels (< 0.1 ng/ml and < 0.2 ng/ml, respectively) in all patients tested. FMLP-induced O2(-)-release was further enhanced by pretreatment of cells with rhG-CSF or rhGM-CSF for 10 min at 37 degrees C, except that no significant priming by rhG-CSF was observed in five patients. The priming effect of rhGM-CSF was consistently greater than that of rhG-CSF in all patients. The i.v. administration of rhGM-CSF (6 micrograms/kg body weight/day) to one patient resulted in an increase in neutrophil O2(-)-release stimulated by FMLP. These findings indicate that neutrophils from AA patients are already primed in vivo for enhanced release of O2- and that these neutrophil functions are further potentiated by rhG-CSF or rhGM-CSF.

Adolescent↗

Morphometric analysis of myelofibrosis in agnogenic myeloid metaplasia and chronic myelogenous leukemia.

A morphometric analysis of bone marrow biopsy specimens from patients with myelofibrosis was made to determine the amount of lattice fiber and the number of megakaryocytes, to compare the degree of myelofibrosis in primary and secondary myelofibrosis, and to assess the relationship between the morphometric findings and other parameters. Eight patients with agnogenic myeloid metaplasia (AMM) and six with chronic myelogenous leukemia associated with frank myelofibrosis (CML-MF) were studied. When the main clinical, hematological, and laboratory features of both groups of patients were compared, the only significant difference was in the neutrophil alkaline phosphatase score. Morphometric study showed that the amount of lattice fiber and the number of megakaryocytes in AMM were not statistically different from those in CML-MF, and that neither the number of megakaryocytes nor the platelet count correlated with the amount of lattice fiber.

Aged↗

Enhanced neutrophil functions in a patient with colony-stimulating activity-producing lung cancer.

We studied neutrophil functions in a patient with colony-stimulating activity (CSA)-producing lung cancer. A 59-year-old man had an abnormal chest X-ray and leucocytosis, predominantly with neutrophils. Pneumonectomy was performed, and the histological diagnosis of the tumour was large-cell carcinoma of the lung. The tumour induced marked granulocytosis in tumour-transplanted nude mice, and the conditioned media of the tumour contained very strong human-active CSA. Superoxide release and membrane depolarization in neutrophils stimulated by the chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine, were markedly enhanced in the patient. These findings suggest that CSA produced by the tumour primed neutrophil functions in vivo in the patient.

Animals↗

Stimulation and priming of human neutrophils by granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor: qualitative and quantitative differences.

Granulocyte colony-stimulating factor(G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) increased neutrophil C3bi-receptor expression and adherence and rapidly (less than 10 min) primed neutrophils to enhanced O2- release and membrane depolarization stimulated by chemotactic peptide. Direct triggering of O2- release in suspended neutrophils was also provoked by GM-CSF but not by G-CSF. GM-CSF-induced O2- release was inhibited by cyclic AMP agonists and cytochalasin B. The biological activity was greater in non-glycosylated GM-CSF than in glycosylated GM-CSF, whereas it was identical in glycosylated and non-glycosylated G-CSFs. Direct stimulation and priming by GM-CSF were consistently greater than those by G-CSF and the combined addition of the optimal concentrations of G-CSF and GM-CSF resulted in the effects of GM-CSF alone. These findings indicate that the effects of G-CSF and GM-CSF on neutrophil functions are qualitatively and quantitatively different from each other.

Alprostadil↗

Application of 15N-nuclear magnetic resonance (N.M.R.) spectroscopy for the study of nitrogen metabolism of a parasite: transamination in Angiostrongylus cantonensis eggs.

In an attempt to study nitrogen metabolism in a parasite, we applied 15N-nuclear magnetic resonance (NMR) technology with a stable isotope, a 15N-labeled compound, for the study of the transamination system in A. cantonensis eggs, and demonstrated that 15N-aspartic acid can serve as an amino group donor for both the 2-oxoglutaric-glutamic acid and the pyruvic acid-alanine transamination systems in the eggs.

Angiostrongylus↗

Recombinant human granulocyte colony-stimulating factor as an activator of human granulocytes: potentiation of responses triggered by receptor-mediated agonists and stimulation of C3bi receptor expression and adherence.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) enhanced superoxide release and membrane depolarization in parallel in human granulocytes stimulated by the receptor-mediated agonists, N-formyl-methionyl-leucyl-phenylalanine and wheat germ agglutinin, but not by the Ca2+ ionophore ionomycin and phorbol myristate acetate, which bypass the receptors to stimulate the cells. The optimal effect was obtained by pretreatment of cells with 25 to 50 ng/mL (1.3 to 2.6 nmol/L) rhG-CSF for 10 minutes at 37 degrees C. rhG-CSF produced by bacteria and mammalian cells had identical biological effects on a molar basis. rhG-CSF neither affected stimulus-induced increase in cytoplasmic free Ca2+ nor changed the number and affinity of N-formyl-methionyl-leucyl-phenylalanine receptors. The priming effect of rhG-CSF was temperature dependent and did not require new protein synthesis. rhG-CSF increased the expression of C3bi receptors on human granulocytes and enhanced granulocyte adherence to nylon fiber. The optimal effect was obtained by pretreatment of cells with 25 to 50 ng/mL rhG-CSF for 30 minutes at 37 degrees C. rhG-CSF had no effect on human monocytes. These findings demonstrate that rhG-CSF can selectively stimulate mature granulocyte functions.

Calcium↗

Effects of the in vivo administration of recombinant human granulocyte colony-stimulating factor following cytotoxic chemotherapy on granulocytic precursors in patients with malignant lymphoma.

We examined the effects of the in vivo administration of recombinant granulocyte colony-stimulating factor (rhG-CSF) on granulocytic precursors in the bone marrow of 4 patients with malignant lymphoma who received chemotherapy. Patients were treated with rhG-CSF at doses of 100-800 micrograms/m2/day intravenously for 14 days only in the first course of chemotherapy (G-CSF course) followed by the second course of chemotherapy without rhG-CSF which was used as a control course. In the G-CSF course, white blood cell counts (WBCs) demonstrated a biphasic response consisting of a first peak observed within a few days after the initiation of rhG-CSF administration, and a second peak observed on the last day of rhG-CSF injection or the day after. In the second peak, the incidence of granulocyte-macrophage colony-forming units (CFU-GM) in mononucleated bone marrow cells did not change significantly after treatment with rhG-CSF as compared with a control. However, since the number of nucleated cells in the bone marrow increased, the absolute number of CFU-GM in the bone marrow increased. The number of mature and immature granulocytes in the bone marrow increased. These findings suggest that G-CSF stimulates the proliferation and differentiation of granulocytic precursors in the bone marrow in granulocytopenic patients who received cytotoxic drugs and causes mature granulocytes to be released from the bone marrow.

Adult↗