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N Domae

Publications and source records attributed to N Domae.

At least 37 records · Page 2Linked to original sources
PubMed1994

Characteristics and partial purification of a novel cytosolic, magnesium-independent, neutral sphingomyelinase activated in the early signal transduction of 1 alpha,25-dihydroxyvitamin D3-induced HL-60 cell differentiation.

Treatment of HL-60 cells with a 1 alpha,25-dihydroxyvitamin D3 induces activation of a neutral sphingomyelinase (SMase), resulting in a decrease in sphingomyelin (SM) levels and an increase in ceramide levels in a proposed "sphingomyelin cycle" of cell regulation (Okazaki, T., Bell, R., and Hannun, Y. (1989) J. Biol. Chem. 264, 19076-19080). Cell-permeable synthetic ceramides induce HL-60 cell differentiation toward a monocytic lineage without conversion to sphingosine, suggesting that ceramide is a lipid mediator of cell differentiation (Okazaki, T., Bielawska, A., Bell, R., and Hannun, Y. (1990) J. Biol. Chem. 265, 15823-15831). In this study, we investigated a novel SMase that was activated 2-2.5 h after treatment of cells with 1 alpha,25-dihydroxyvitamin D3. The activated SMase was localized to the cytosolic fraction. It was inhibited by copper, ferric iron, and zinc and showed optimal activity at pH 7.5. A mixed micellar assay was developed for the enzyme, with optimal activity achieved at 12 mol% SM in Triton X-100 mixed micelles and at 20 mol% SM in deoxycholate micelles. The activity was modestly enhanced by phosphatidic acid, phosphatidylserine, or phosphatidylinositol, but not by other major phospholipids. Purification was performed by chromatography on DEAE anion-exchange, Q-Sepharose Fast Flow, hydroxylapatite, sphingosylphosphocholine affinity, and Superose 12 gel filtration columns. Two peaks of activity with molecular masses of 45 and 95 kDa were resolved by gel filtration chromatography on Superose 12. The specific activities of the purified 45- and 95-kDa enzymes were 2780 and 2790 nmol/mg/h, respectively. These data identify a novel cytosolic, magnesium-independent, neutral SMase(s) that is activated during cell differentiation.

Calcitriol↗
PubMed1994

Increased processing of lymphocyte function-associated antigen-1 in human natural killer cells stimulated with IL-2.

Previously we reported that surface expression of lymphocyte function-associated antigen-1 (LFA-1), the primary leukocyte integrin on human natural killer (NK) and lymphokine-activated killer (LAK) cells, does not differ between NK and LAK cells. In contrast to surface expression, we now report that much higher levels of both precursor and mature forms of LFA-1 molecules were found relative to MHC class I, another membrane glycoprotein, with metabolic labeling of IL-2-stimulated LAK cells compared with native NK cells. An 85-90 kDa glycoprotein, found in much higher quantities in LAK compared with NK cells, appeared to be a precursor of the 95 kDa beta chain of the beta 2 integrin family in human LAK cells because: (i) pulse-chase experiments using LAK cells demonstrated decreased 35S-labeling of the 85-90 kDa molecule with a concomitant increase in the radioactivity of the mature 95 kDa LFA-1 beta chain, (ii) results of protease treatment revealed that the two molecules share virtually identical peptide maps, and (iii) endoglycosaminidase F treatment of LAK cell lysates immunoprecipitated with antibody against LFA-1 beta resulted in the disappearance of both the 85-90 and 96 kDa LFA-1 beta signals, and appearance of a signal at approximately 76 kDa. Digestion of the same immunoprecipitates with neuraminidase resulted in the disappearance of the 95 kDa signal and revealed a single molecular weight signal corresponding to 85-90 kDa. These data suggest that a core protein of approximately 76 kDa becomes N-glycosylated, perhaps terminally with sialic acid residues, to mature into the 95 kDa form. Moreover, the rate of maturation of LFA-1 was more rapid in LAK than NK cells, with half times of 0.8 versus 1.5 h for the alpha chain and 3.7 versus 4.9 h for the beta chain for LAK versus NK cells respectively. IL-2 treatment of NK cells therefore alters the processing of LFA-1 molecules during the transition to LAK cells, providing a larger intracellular reservoir with which to replenish the surface molecule. Together with our previous observation that LFA-1 is phosphorylated and transduces signal more effectively in LAK than NK cells, the findings support the notion that adhesion molecules contribute to the increased function of LAK cells.

Cells, Cultured↗
PubMed1992

[Five cases of hematological disorders associated with acute myocardial infarction in thrombocytopenia].

Case of hematological disorders associated with acute myocardial infarction had been found in five of forty five autopsy cases which had hematological disorders during the past seven years. The five cases of hematological disorders consisted of two cases of myelodysplastic syndrome, a case of aplastic anemia, a case of primary myelofibrosis in blast transformation, and a case of acute myelogenous leukemia. All the patients were over 60 years old. Four patients had coronary artery stenosis and extensive myocardial infarction. Fibrinogen degradation products were elevated in four patients. DIC was recognized in two and suspected in two others. In all cases, platelet counts markedly decreased to less than 2.5 x 10(10)/L. Since no chest pain was noted by any patient, it was difficult to diagnose acute myocardial infarction without autopsy, except in one case. It is important to recognize the possibility of severe cardiac dysfunction due to myocardial infarction in thrombocytopenia, especially in the aged with DIC.

Aged↗
PubMed1990

[Clinical effect and pharmacokinetics of intermediate dose Ara-C therapy in a patient with acute non-lymphocytic leukemia with two CNS recurrences].

A case of two repeated CNS recurrences of acute non-lymphocytic leukemia (M2) was treated with intermediate dose Ara-C therapy and achieved 2 complete remissions. The clinical effect and pharmacokinetics of intermediate dose Ara-C therapy in this patient were discussed. A 55-year-old male with acute non-lymphocytic leukemia (M2) achieved complete remission by combination chemotherapy of Behenoyl-ara-C, Daunorubicin, 6-Mercaptopurine and Prednisolone in July, 1985. He subsequently received consolidation and intensification therapy with periodical intrathecal injection of Methotrexate (MTX), but 13 months later he developed his first CNS recurrence which was resistant to the intrathecal administration of Ara-C and MTX. As he also relapsed systemically, Ara-C was administered in intermediate dose (1 g/m2 every 12 hrs for 5 days) and he achieved complete remission both in the CNS and systemic manifestations. Six months later he was diagnosed as having a second CNS recurrence and another systemic relapse. Intermediate dose Ara-C was administered again, and he achieved complete remission in the CNS and partial remission in systemic manifestations. Pharmacokinetic study revealed high peaks of Ara-C concentration in plasma (6.2 microM immediately after the end of the infusion) and high degree of its penetration into the CNS (5.6 microM at 3 hr after the end of the infusion) suggesting the effective and perhaps a uniform level of Ara-C is achieved throughout the CNS by this therapy. In 3 other patients without CNS involvement 0.88 +/- 0.44 microM of Ara-C, which is enough concentrations for its cytostatic effect, was detected at 3 hr after the end of infusion, suggesting the efficacy of the therapy for CNS prophylaxis. In this case the relapse occurred after repeated administration of antileukemic drugs, including Behenoyl-ara-C, an analog of Ara-C, and was resistant to the intrathecal administration of Ara-C. These findings suggest that intermediate dose Ara-C therapy was effective to overcome a resistance to antileukemic drugs, including Ara-C, and also, in some cases, more effective than intrathecal injection of antileukemic drugs for the treatment of CNS leukemia.

Cytarabine↗
PubMed1990

[Idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia (IPL) accompanied with severe thrombocytopenia and interstitial pneumonitis].

A case of generalized lymphadenopathy with severe thrombocytopenia and marked polyclonal hypergammaglobulinemia is reported. A 51-year-old man was admitted to the hospital because of nasal bleeding and generalized lymphadenopathy. Laboratory examination revealed a platelet count of 6,000/microliters, a total protein level of 11.6 g/dl, and a gammaglobulin level of 8.7 g/dl including 6,726 mg/dl IgG, 1,119 mg/dl IgA, 265 mg/dl IgM, 265 mg/dl IgD and 226 IU/ml IgE. Neither definite evidence suggesting viral infection nor an autoimmune disease was found except slightly elevated titers of anti-microsome and anti-thyroglobulin antibodies. The chest X-ray revealed diffuse reticular shadowing suggesting interstitial pneumonitis. The cervical lymph node biopsy revealed massive infiltration by IgG-, IgA-, and IgM-positive plasmocytoid cells in the paracortical T cell areas, but no destruction of normal architecture of lymph node. The treatment with prednisolone resulted in a decrease in the severity of the lymphadenopathy, thrombocytopenia and polyclonal hypergammopathy. He is still well; however, interstitial pneumonitis, mild thrombocytopenia, and polyclonal hypergammopathy have persisted for 4 years. The histological findings in this case are similar to those in the case of Castleman lymphoma of a plasma cell type. Thus, considering the clinical data and clinical course, the diagnosis in this case is likely to be idiopathic plasmacytic lymphadenopathy with polyclonal hyperglobulinemia as a subtype of the plasma cell type of Castleman lymphoma. However, the accompanying interstitial pneumonitis and the severe thrombocytopenia, which was caused by excessive platelet destruction or by the suppression of megakaryocytes by proliferated plasma cells, are unique and are not found in any of the previously reported cases.

Humans↗
PubMed1989

Clinical pharmacology of N4-palmitoyl-1-beta-D-arabinofuranosylcytosine in patients with hematologic malignancies.

The pharmacokinetics of oral N4-palmitoyl-1-beta-D-arabinofuranosylcytosine (PLAC), a lipophilic and deaminase-resistant derivative of 1-beta-D-arabinofuranosylcytosine (ara-C), were determined in patients with hematologic malignancies. The concentration of ara-C and 1-beta-D-arabinofuranosyluracil (ara-U), metabolites of PLAC, were measured by radioimmunoassay and gas chromatography-mass spectrometry-mass fragmentography, respectively. The concentration of PLAC was determined by measuring ara-C, which was derived from PLAC by hydrolyzation. In six patients given an oral bolus of PLAC (300 mg/m2), the plasma-disappearance curve of PLAC corresponded to a one-compartment open model, including first-order absorption. The peak plasma level was 22.9 +/- 6.4 ng/ml, and the predicted time to reach the peak level was 2.5 +/- 1.0 h. The elimination half-life was 3.8 +/- 2.7 h. The plasma ara-C level increased slowly to 6.9 ng/ml during the 1st 2-3 h after administration and remained over 1.0 ng/ml for 12 h. Plasma ara-U was detectable for at least 24 h, with a peak concentration of 376 ng/ml at 6 h. Urinary PLAC excretion was below the limit of detection (5 ng/ml) in all cases. Prolonged urinary ara-C and ara-U excretion was detected, but the total recovery rate was low (6.7% in 24 h) and varied between patients. In spite of the lipophilic nature of the drug, the PLAC concentration in the cerebrospinal fluid, measured at 3 or 6 h, was below the limit of detection in all four patients with no meningeal involvement. This study showed low but persistent levels of PLAC in plasma and tissues, with a continuous release of small amounts of ara-C, which demonstrated antitumor activity in patients with hematologic malignancies.

Adult↗
PubMed1988

The concentration of serum lipids in Zen monks and control males in Japan.

The concentrations of total, low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol, triglyceride and apoprotein B have been examined in Zen monks whose intake of animal products was almost negligible for 2 to 8 years, and in age-matched (24 to 35 years) control Japanese males who eat Western style food. The mean levels of total, LDL- and HDL-cholesterol, and apoprotein B were 135.1 +/- 16.7, 73.0 +/- 11.6, 50.4 +/- 9.6, and 70.6 +/- 15.6 mg/dl, respectively in Zen monks. These levels were 28.5, 32.8, 18.8, and 23.9% lower in Zen monks than in control Japanese males. These values are statistically significant compared to those of the controls (p less than 0.01). There were no significant changes in the level of triglyceride in both groups.

Adult↗
PubMed1983

Purification and partial characterization of ring-shaped miniparticles.

Small ring-shaped miniparticles, found in the nucleus nucleolus and cytoplasm of a variety of normal and malignant cells, have been purified by a procedure involving differential and gradient centrifugation, hydroxylapatite chromatography and preparative electrophoresis. They are multisubunit proteins comprised of at least six polypeptide chains of Mr 20,000-30,000 Daltons (by one-D SDS-PAGE which present a series of 20-30 spots on two-D IEF/SDS gels. They can be reversibly dissociated in EDTA containing buffers. They are not membrane associated and contain no carbohydrate. They have an S20,W of 21S on sucrose gradients. They are immunologically similar in several human cell lines.

Cell Fractionation↗