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Biomedical subjects

K Akashi

Publications and source records attributed to K Akashi.

At least 145 records · Page 8Linked to original sources

Acute 'bilineal-biphenotypic' leukaemia.

We describe a unique case of hybrid leukaemia with bilineal and biphenotypic features. The coexistence of lymphoblasts and monoblasts was determined morphologically and cytochemically. Immunofluorescence and immunohistochemical analysis revealed that each blast population had both T lymphoid (CD2, cytoplasmic CD3) and myeloid (CD11, CD13, CD15) markers. Southern blot analysis of DNA extracted from the lymph node biopsy demonstrated the presence of monoclonal rearrangement of the TcR-C beta gene. Cytogenetic analysis of the bone marrow cells showed a karyotype of 48, XY, 7q+ in all of the metaphases examined. These observations are suggestive of a monoclonal origin for these two distinct blast populations.

Acute Disease↗

Effect of N-methionine-free, bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor in a primate model.

We demonstrate the in vivo effects of bacterially synthesized, N-methionine-free recombinant human granulocyte-macrophage colony stimulating factor (rh GM-CSF) using a crab-eating monkey model. Monkeys were treated with cyclophosphamide (60 mg/kg) and administered with rh GM-CSF (30 micrograms/kg/d) subcutaneously (s.c.) for 7 days. Within 12 h, a transient increase of neutrophils (greater than 15.0 x 10(9)/l) was observed, and complete recovery of WBC counts was obtained by d 9 (d 16 in control monkeys). Neutrophils and eosinophils were absolutely increased (greater than 8 x 10(9)/l) on d 10. Readministration of rh GM-CSF (30 micrograms/kg/d, s.c.) for 3 d (including control monkeys) revealed absolute increases of neutrophils, eosinophils, monocytes and platelets. A two-fold increase of granulocyte/macrophage colony-forming units was also seen in the bone marrow, while the number of burst-forming units-erythroid was not affected. These data indicate that rh GM-CSF of this type stimulates granulopoiesis and thrombopoiesis in vivo.

Animals↗

Granulocyte-macrophage colony-stimulating factor suppresses induction of neutrophil alkaline phosphatase synthesis by granulocyte colony-stimulating factor.

We evaluated the in vitro effects of recombinant human (rh) granulocyte colony-stimulating factor (G-CSF) and rh granulocyte-macrophage CSF (GM-CSF) on neutrophil alkaline phosphatase (NAP) activity and the incorporation of amino acids into polymorphonuclear leukocytes (PMN) from normal individuals and patients with chronic myelogenous leukemia (CML). Both the NAP activity and incorporation of amino acids into PMN were enhanced by the addition of G-CSF in a dose-dependent manner. NAP activity induced by G-CSF in PMN from CML patients showed a greater increase than that in PMN from normal controls. In contrast to G-CSF, GM-CSF did not affect the NAP activity in PMN in spite of the enhanced incorporation of amino acids into PMN by GM-CSF. Interestingly, both the NAP-inducing ability of G-CSF and its enhancing ability for amino acid incorporation were suppressed by GM-CSF in a dose-dependent manner when PMN were incubated with various concentrations of GM-CSF in addition to 100 ng/ml of G-CSF. These observations suggest that G-CSF and GM-CSF act differently: G-CSF induces NAP synthesis in PMN, whereas GM-CSF negatively modulates the effect of G-CSF. Further, it is suggested that protein synthesis induced by G-CSF is negatively modulated by GM-CSF in a general fashion.

Alkaline Phosphatase↗

Detection of fatty tissue in the myocardium by using computerized tomography in a patient with arrhythmogenic right ventricular dysplasia.

A case with arrhythmogenic right ventricular dysplasia involving the left ventricle as well as the right ventricle was presented. Right ventricular endomyocardial biopsy and computerized tomography were useful in detecting fatty tissue in the myocardium. This case deserves to be reported in reference to detecting fatty tissue in arrhythmogenic right ventricular dysplasia by using computerized tomography.

Adipose Tissue↗

Successful treatment of refractory systemic lupus erythematosus with intravenous immunoglobulins.

Two cases of refractory systemic lupus erythematosus (SLE) were successfully treated with intravenous immunoglobulins (IVIg). In Case 1, the immediate recovery from severe pancytopenia and the improvement of proteinuria were observed, following IVIg therapy in high doses (450 mg/kg) for 5 consecutive days. In Case 2, 3 courses of IVIg therapy (100 mg/kg) for 6 to 8 days resulted in a significant reduction of massive proteinuria. In both cases, the improvement of immunological variables was also seen.

Adolescent↗

An ATP-driven Cl- pump in the brain.

EDTA-treated microsomes prepared from rat brain mainly consisted of sealed membrane vesicles 200-500 nm in diameter and were rich in both Cl- -ATPase and Na+,K+-ATPase activities. Such Cl- -ATPase-rich membrane vesicles accumulated Cl- in an ATP-dependent and osmotically reactive manner in the presence of 1 nM ouabain. The Cl- uptake was maximally stimulated by ATP with a Km value of 1.5 mM; GTP, ITP, and UTP partially stimulated Cl- uptake, but CTP, beta, gamma-methylene ATP, ADP, and AMP did not. The ATP-dependent Cl- uptake was accelerated by an increase in the medium Cl- concentration with a Km value of 7.4 mM. Such stimulation of Cl- uptake by ATP was dependent on the pH of the medium, with an optimal pH of 7.4, and also on the temperature of the medium, with an optimal range of 37-42 degrees C. Ethacrynic acid dose dependently inhibited the ATP-dependent Cl- uptake with a concentration for half-maximal inhibition at 57 microM. N-ethylmaleimide (0.1 mM) completely inhibited and sodium vanadate (1 mM) partially inhibited the ATP-dependent Cl- uptake. The membrane vesicles did not accumulate H+ in the Cl- uptake assay medium. The ATP-dependent Cl- uptake profile agreed with that of Cl- -ATPase activity reported previously (Inagaki, C., Tanaka, T., Hara, M., and Ishiko, J. (1985) Biochem. Pharmacol. 34, 1705-1712), and this strongly supports the idea that Cl- -ATPase in the brain actively transports Cl-.

Adenosine Triphosphatases↗

Herpes simplex virus in oral mucosal ulcers in patients with hematological malignancy.

Developments of oral mucosal ulcers induced by herpes simplex virus (HSV) were studied in patients with hematologic malignancy. Herpes simplex virus type-1 (HSV-1) was identified by immunological staining using virus-specific monoclonal antibodies in the epithelial cells of such ulcers from two patients with malignant lymphoma (ML), three with acute myeloblastic leukemia (AML), one with refractomy anemia with excess blasts, two with chronic myelocytic leukemia (CML), one with acute lymphoblastic leukemia (ALL) and one with aplastic anemia (AA). Herpes simplex virus type-2 (HSV-2) was also identified in an ulcer from a patient with AML. Isolation of HSV-1 was successful in the two patients with ML, one with CML, one with AML, the one with ALL and the one with AA. The ulcers developed on the tongue (four cases), buccal membrane (five cases), hard palate (one case), soft palate (one case), soft palate (one case) and gingiva (two cases). Only one patient with CML and one with AML had accompanying labial vesicular lesions. All patients except the one with AA had previously been given combination chemotherapy with anti-neoplastic agents. The results indicate that HSV may have an important role to play in the development of chemotherapy-related oral mucosal ulcers in patients with hematological malignancy.

Adult↗

Frequent infection with human T-cell lymphotropic virus type I in patients with AIDS but not in carriers of human immunodeficiency virus type 1.

Antibody to human T-cell lymphotropic virus type I (HTLV-I) was measured in 49 Japanese patients (48 with hemophilia) infected with human immunodeficiency virus type 1 (HIV-1) and in 18 hemophiliacs who were not infected with HIV-1, by use of an enzyme-linked immunosorbent assay (ELISA). The antigen used was a gag-env hybrid protein constructed in vitro and expressed in Escherichia coli. This assay detected a specific antibody against HTLV-I. Four of the 18 HIV-1-negative hemophiliacs (22%) were positive for anti-HTLV-I antibody; their geometric mean titer was 951 U/ml. Seven of the 12 patients (58%) with acquired immune deficiency syndrome (AIDS) were positive for anti-HTLV-I antibody, and 8 of 35 HIV-1 + AIDS-free carriers (23%) were positive. The difference between the prevalence of HTLV-I infection in the two groups was statistically significant (p less than 0.0297). The geometric mean titer of antibody in the patients with AIDS was 318 U/ml and that for the HIV-1 + AIDS-free carriers was 1,496 U/ml. These findings suggest that HTLV-I infection could be one of the factors in the development of AIDS in individuals infected with HIV-I.

AIDS-Related Complex↗

2',5'-Oligoadenylate synthetase activity in peripheral blood lymphocytes as a clinical marker in interferon therapy for chronic hepatitis B.

Treatment of chronic hepatitis B (CHB) with human leukocyte interferon (IFN-alpha) was studied in terms of increase of 2',5'-oligoadenylate (2-5A) synthetase activity in peripheral blood lymphocytes (PBL) after IFN-alpha administration. The 2-5A synthetase activity in PBL increased to a maximum 16-24 h after IFN-alpha injection and then gradually decreased, while serum HB virus DNA polymerase (HBV-DNAP) activity, which corresponds to the amount of HBV virions in the serum, decreased to a minimum after about 48 h. Increase in 2-5A synthetase activity was followed about 1 day later by decrease in DNAP activity. Furthermore, of 9 patients treated with IFN for at least 22 weeks and observed for over 1 year after IFN treatment, the effective 5 cases in which HBeAg disappeared during IFN therapy and did not reappear showed rather high increases in 2-5A synthetase activity, whereas the ineffective 4 cases in which HBeAg remained positive at the end of IFN therapy showed little increases in enzyme activity. The present study suggests that prescreening by 2-5A synthetase assay before IFN therapy should be useful for obtaining better results in IFN treatment of CHB patients.

2',5'-Oligoadenylate Synthetase↗

Thyroid antigen-antibody nephritis: possible involvement of fucosyl-GM1 as the antigen.

Hyperthyroidism, microscopic hematuria, and proteinuria developed in an 11-year-old girl. Proteinuria decreased during treatment of hyperthyroidism with an antithyroid drug. On admission, serum anti-thyroglobulin antibody, antimicrosomal antibody, and immune complex were present. The thyrotropin binding inhibitory immunoglobulin (TBII) level was low. On the other hand, an antibody to the ganglioside component (fucosyl-GM1) was detected by an enzyme linked immunosolvent assay (ELISA). A thyroid biopsy specimen showed massive lymphocytic infiltration and interstitial fibrosis. A renal biopsy specimen showed marked proliferation of mesangial cells and increased mesangial matrix with focal segmental capillary wall abnormality. Electron microscopec studies demonstrated mild paramesangial dense deposits. By indirect immunofluorescence, granular glomerular basement membrane and mesangial staining were not detected with rabbit antibody to thyroglobulin, but were detected with rabbit antibody to fucosyl GM1. Fucosyl GM1 was also seen along the basilar aspect of the thyroid follicular epithelial cells. These observation suggests the development of glomerulonephritis mediated by thyroid antigen, particularly ganglioside component.

Antigen-Antibody Complex↗

Similarity of kinetics of three types of myeloperoxidase from human leukocytes and four types from HL-60 cells.

Km values for H2O2 and Vmax values for three types of myeloperoxidase (MPO) from human leukocytes (MPO-I, -II, and -III) and four types from human myeloid leukemia HL-60 cells (MPO-IA, -IB, -II, and -III) were determined. Km values of human leukocyte MPOs decreased with increasing pH from 4.4 to 6.2 and increased with increasing NaCl concentration from 0.025 to 0.14 M. There was no significant difference among Km values of leukocyte MPO-I, -II, and -III. NaBr also showed a tendency similar to that of NaCl with regard to the effects of pH and halide concentration on Km values. However, Km values in the presence of NaBr were lower than those in the presence of NaCl. Effects of pH and NaCl concentration on Vmax values of MPO-I, -II, and -III were also examined. Vmax values of MPO-I, -II, and -III were higher at pH 4.9 and 5.4 and increased with increasing NaCl concentration. In addition, no difference was observed between Km values of leukocyte and those of HL-60 cells. MPO-IB, the half-molecular-weight enzyme of HL-60 cells, also had the same Km values as the others. Furthermore, inhibition of the activities of seven MPOs of leukocytes and HL-60 cells by H2O2 was similarly observed at concentrations above 1 mM at pH 5.4 but not at pH 4.4. These results indicate that there is no difference in the affinity to H2O2 among leukocyte MPO-I, -II, and -III and HL-60 cell MPO-IA, -IB, -II, and -III.

Bromides↗

HVJ (Sendai virus) stimulates release of interferon from leukocytes used once for interferon production.

Leukocytes, subjected once to interferon (IFN) induction by HVJ (Sendai virus), were studied for their capability to produce IFN after a second similar stimulus. Substantial amounts of IFN (about 30 000 IU/ml) were recovered. Experiments using cycloheximide or actinomycin D and kinetic studies showed that this IFN originated mainly in IFN which resided within the cell as a result of the first induction and was released after the second stimulation. Increasing amounts of HVJ used for the second stimulus resulted in proportionally increased yields of IFN, reaching a plateau at the same dose of HVJ (1000 HAU/ml) as that which gave optimal yields after the first stimulation. Evidence is presented that the capacity of HVJ to trigger the production of a second IFN harvest is closely associated with its infectivity.

Cells, Cultured↗