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S Kumakura

Publications and source records attributed to S Kumakura.

At least 19 recordsLinked to original sources
PubMed2005

IFN-alpha enhances TNF-alpha-induced apoptosis through down-regulation of c-Myc protein expression in HL-60 cells.

We examined the effect of interferon-alpha (IFN-alpha) in combination with tumor necrosis factor-a (TNF-alpha) on growth, differentiation and apoptosis in HL-60 human myeloid leukemia cells. IFN-alpha inhibited cell growth and induced apoptosis, but not differentiation, in HL-60 cells. IFN-alpha enhanced TNF-alpha-induced apoptosis. We also investigated the expression of c-Myc and Bcl-2 oncoproteins, which are implicated in the survival or death of a cell. The levels of c-Myc protein expression were not changed by IFN-alpha alone at 24hrs of treatment, but were down-regulated at 72 hrs, accompanied by the appearance of apoptotic cells. While, IFN-alpha did not affect the level of Bcl-2 protein expression during this cultivation time. Interestingly, a combination treatment of IFN-alpha with TNF-alpha showed a greater decrease of c-Myc expression than TNF-a alone at 24hrs. Whereas, IFN-alpha did not significantly modulate Bcl-2 expression levels which were down-regulated by TNF-alpha. Therefore, the enhancement of TNF-alpha-induced apoptosis by IFN-a might be closely associated with the greater down-regulation of c-Myc protein, rather than Bcl-2. In contrast, with rapid down-regulation of c-Myc expression caused by TNF-alpha, IFN-alpha down-regulated c-Myc rather late (at 72 hrs), suggesting that both cytokines have a distinct pathway regulating c-Myc protein expression. However, the enhancement of apoptosis in the combination treatment would suggest the presence of a common signaling pathway for induction of apoptosis at down-stream of c-Myc.

Apoptosis↗
PubMed2000

Cell cycle-independent down-regulation of BCL-2 protein expression in differentiating HL-60 cells.

To understand the relationship between bcl-2 protein expression and the cell cycle during the processes of differentiation, we examined bcl-2 protein levels expressed during cell cycle phases in differentiating HL-60 human leukemia cells by using a two-color flow cytometric method. In exponentially proliferating HL-60 cells bcl-2 protein was constitutively expressed throughout the cell cycle phases, but a small population of G0/G1 cells expressed decreased levels of protein as compared with other cell cycle phases. HL-60 cells can be induced to differentiate to granulocytic pathway by retinoic acid or dimethylsulfoxide, and to monocytic/macrophagic pathway by 1, 25 dihydroxyvitamin D3 or 12-O-tetradecanoylphorbol -13-acetate. During treatment with any of these inducing agents, bcl-2 protein expression was time-dependently down-regulated after 24 h. A two-color flow cytometric analysis revealed that this down-regulation occurred throughout cell cycle phases, indicating that bcl-2 protein expression was down-regulated in cell cycle-independent manner during induction of differentiation in HL-60 cells. To our knowledge, this is the first demonstration suggesting that the regulation of bcl-2 protein expression is not related to the cell cycle during induction of differentiation in HL-60 cells.

Cell Cycle↗
PubMed1999

Increased activity of membrane glycoprotein PC-1 in the fibroblasts from non-insulin-dependent diabetes mellitus patients with insulin resistance.

Although most of patients with non-insulin-dependent diabetes mellitus (NIDDM) have insulin resistance, it is unknown whether a molecule might interfere with insulin action. Membrane glycoprotein PC-1 (plasma cell antigen-1), which inhibits insulin receptor tyrosine kinase activity, was isolated from fibroblasts of NIDDM patients. Because PC-1 content in skeletal muscle and adipose tissue correlated with whole body insulin sensitivity, PC-1 might play a role in insulin resistance. In order to know whether PC-1 activity of fibroblasts is also elevated in Japanese NIDDM patients, and whether PC-1 activity correlates with the parameters of insulin resistance in vivo or not, we measured PC-1 activity of cultured fibroblasts from 17 patients with NIDDM and seven healthy controls. PC-1 activity of the NIDDM patients was 85.2 +/- 33.1 nmol/mg per min (mean +/- S.D.), and was higher than that of healthy controls (42.6 +/- 12.7 nmol/mg per min, P = 0.0002). Insulin sensitivity was measured in 11 of 17 NIDDM patients by the artificial pancreas. PC-1 activity of the patients with insulin resistance (glucose infusion rate < 3.0 mg/kg per min, n = 7) was elevated to 99.9 +/- 31.9 nmol/mg per min, while that of the other patients (n = 4) was 55.3 +/- 7.5 nmol/mg per min (P = 0.003). In conclusion, glycoprotein PC-1 activity of dermal fibroblasts is correlated with insulin resistance in patients with NIDDM.

Adult↗
PubMed1999

Biological activities of scyphostatin, a neutral sphingomyelinase inhibitor from a discomycete, Trichopeziza mollissima.

Scyphostatin is a specific inhibitor for mammalian neutral magnesium-dependent sphingomyelinase with a fifty percent inhibition concentration (IC50) value of 1.0 microM. When used to inhibit lysosomal acid sphingomyelinase, an approximately 50-fold greater concentration is required. In human peripheral monocytes, the compound inhibits bacterial lipopolysaccharide (LPS)-induced prostaglandin E2 production and LPS-induced interleukin-1beta production with IC50 values of 0.8 microM and 0.1 microM, respectively. In rat, p.o. administration of the compound has also been shown to inhibit carrageenin-induced paw edema. Thus, it is hoped that utility of scyphostatin as a pharmacological tool will contribute to our understanding of the role of ceramide in the cellular inflammation process.

Amides↗
PubMed1999

[Hematological manifestations].

Hematological manifestations as the clinicopathological features of connective tissue disease are described. Secondary anemia, so called anemia of chronic disorders (ACD), is one of the most common features of connective tissue disease. In addition, quantitative abnormalities of leukocytes or thrombocytes which reflect upon the pathophysiology of underlying connective tissue disease are variously observed. Patients with connective tissue disease sometimes develop hematological malignancies. Increased risk of lymphoma in Sjögren's syndrome has been known. The use of alkylating agents as immunosuppressive therapy is also associated with the risk of secondary or therapy-related myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Pancytopenia or bicytopenia can be caused by hemophagocytosis which is related to connective tissue disease itself. Such condition is recognized as autoimmune-associated hemophagocytic syndrome (AAHS). Possible mechanism inducing hemophagocytosis, clinical features, diagnosis and treatment of AAHS are discussed.

Alkylating Agents↗
PubMed1998

Overexpression of membrane glycoprotein PC-1 can influence insulin action at a post-receptor site.

An elevated content of membrane glycoprotein PC-1 has been observed in cells and tissues of insulin resistant patients. In addition, in vitro overexpression of PC-1 in cultured cells induces insulin resistance associated with diminished insulin receptor tyrosine kinase activity. We now find that PC-1 overexpression also influences insulin receptor signaling at a step downstream of insulin receptor tyrosine kinase, independent of insulin receptor tyrosine kinase. In the present studies, we employed Chinese hamster ovary cells that overexpress the human insulin receptor (CHO IR cells; approximately 10(6) receptors per cell), and transfected them with human PC-1 c-DNA (CHO IR PC-1). In CHO IR PC-1 cells, insulin receptor tyrosine kinase activity was unchanged, following insulin treatment of cells. However, several biological effects of insulin, including glucose and amino acid uptake, were decreased. In CHO IR PC-1 cells, insulin stimulation of mitogen-activated protein (MAP) kinase activity was normal, suggesting that PC-1 overexpression did not affect insulin receptor activation of Ras, which is upstream of MAP kinase. Also, insulin-stimulated phosphatidylinositol (PI)-3-kinase activity was normal, suggesting that PC-1 overexpression did not interfere with the activation of this enzyme by insulin receptor substrate-1. In these cells, however, insulin stimulation of p70 ribosomal S6 kinase activity was diminished. These studies suggest, therefore, that, in addition to blocking insulin receptor tyrosine kinase activation, PC-1 can also block insulin receptor signaling at a post-receptor site.

Animals↗
PubMed1998

Reactive hemophagocytosis in systemic lupus erythematosus.

A patient with systemic lupus erythematosus (SLE) developed reactive hemophagocytosis. This case did not show any underlying diseases such as infection or malignancy other than SLE itself. The mechanisms inducing hemophagocytosis in SLE seem to be heterogeneous and remain to be elucidated. Although an immune complex-mediated mechanism in cases with acute lupus hemophagocytic syndrome has been proposed, we suggest the possible involvement of IL-1beta as the pathogenesis of our case.

Adult↗
PubMed1997

Adult onset Still's disease associated hemophagocytosis.

Reactive hemophagocytosis is characterized by the activation of histiocytes with prominent hemophagocytosis in the reticuloendothelial system, and usually occurs in association with underlying disorders such as viral or bacterial infection and malignancy. We describe 3 cases of adult onset Still's disease (AOSD) who developed hemophagocytosis in bone marrow. Extensive studies could not identify any viral infection or other known underlying disorders for reactive hemophagocytosis except for active AOSD. Although the causative mechanisms of reactive hemophagocytosis in AOSD are not clear, our cases suggest the possibility of AOSD associated hemophagocytosis.

Adult↗