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S Irino

Publications and source records attributed to S Irino.

At least 19 recordsLinked to original sources
PubMed1995

Cell-to-cell interaction of cytokine-dependent myeloblastic line constitutively expressing membrane-bound stem cell factor abrogates cytokine dependency partially through granulocyte-macrophage colony-stimulating factor production.

Stem cell factor (SCF) is a cytokine for hematopoietic progenitor cells and plays an important role in megakaryocyte proliferation. The UT-7 cell line was established from a patient with megakaryoblastic leukemia, and its growth and survival are strictly dependent on interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (Epo), or IL-6. In this study, we showed that SCF also supported the growth of UT-7 in the absence of other cytokines and downregulated the cell surface c-kit receptors. Constitutive expression of SCF by introducing SCF expression vector made UT-7 grow factor-independently in liquid medium, but not in semisolid medium. This SCF-expressing factor-independent UT-7 (UT-7scf9) expressed the membrane bound form of SCF on their surface, but did not secrete detectable amounts of soluble SCF. UT-7scf9 formed aggregates as they grew in the absence of cytokines, and this aggregation was inhibited by adding soluble SCF into the medium. UT-7 cultured with SCF and UT-7scf9 cultured without cytokines expressed GM-CSF, and anti-GM-CSF neutralizing antibody partially inhibited their growth. These results suggest that SCF stimulated UT-7 proliferation partially through the autocrine-loop of GM-CSF, and UT-7scf9 expressed SCF mostly as a membrane-bound form, which transduces its growth signal through c-kit receptor as they aggregate by cell-to-cell interaction.

Base Sequence↗
PubMed1994

Antisense src expression inhibits proliferation and erythropoietin-induced erythroid differentiation of K562 human leukemia cells.

We constructed a recombinant plasmid which expresses antisense src RNA in human cells and used it as a tool for investigating the role of pp60c-src in proliferation and differentiation of K562 human leukemia cells. In erythropoietin (EPO)-responsive cells, EPO induces rapid tyrosine phosphorylation of several cellular proteins including EPO receptor (EPOR) although EPOR has no tyrosine kinase domain. Here we show that antisense src RNA expression suppresses pp60c-src synthesis in the recombinant plasmid-transfected K562 cells, reduces the proliferation and inhibits hemoglobin synthesis and glycophorin A expression promoted by EPO in K562 cells. These findings suggest that pp60c-src plays crucial roles in the proliferation and EPO-induced erythroid differentiation of K562 cells.

Cell Differentiation↗
PubMed1994

Antisense src expression inhibits U937 human leukemia cell proliferation in conjunction with reduction of c-myb expression.

To elucidate the role of pp60c-src in U937 human monoblastoid leukemia cell proliferation, recombinant plasmids containing the src gene or myb gene, which could produce antisense src or antisense myb RNA after dexamethasone treatment, were constructed and transfected into U937 cells (U937-ASRC, U937-AMYB). pp60c-src synthesis in U937-ASRC was diminished by the third day after induction of antisense src RNA and the cell proliferation was reduced, furthermore, the amount of p75c-myb was significantly decreased by the third day. p75c-myb synthesis in U937-AMYB was diminished by the second day after induction of antisense myb RNA and the cell growth was significantly inhibited but the amount of pp60c-src in U937-AMYB was not reduced. These results suggest that a decrease in the amount of pp60c-src leads to an inhibition of p75c-myb expression and subsequent reduction in the U937 cell proliferation.

Cell Division↗
PubMed1994

Characterization of unique human TCR V beta specificities for a family of streptococcal superantigens represented by rheumatogenic serotypes of M protein.

The M protein of Streptococcus pyogenes plays a major role in the virulence of these bacteria. Members of the M protein superfamily are characterized by the presence of tandem segments of repeated amino acid sequences. The NH2-terminal end of the M proteins is a hypervariable region that harbors the type-specific epitopes of the molecule. Pepsin cleaves the molecule into a highly conserved carboxyl terminal half and a variable amino terminal portion referred to as pep M. In some individuals, infection with certain serotypes of group A streptococci is followed by autoimmune disorders such as rheumatic fever and acute glomerulonephritis. The serotypes of M protein that show a high degree of association with acute rheumatic fever are referred to as rheumatogenic serotypes. We have reported that one such serotype, type 5, is a superantigen to human T cells, specifically stimulating T cells bearing V beta 2, V beta 4, and V beta 8 elements. Here we extend our studies by examining other rheumatogenic serotypes for superantigenic properties. Studies with types 6, 18, 19, and 24 M proteins revealed that they are all superantigens to human T cells. The specificity to V beta 4 was shared by the rheumatogenic M proteins tested; however, each pep M serotype has its unique characteristic set of V beta specificity and these are distinct from those reported for the streptococcal pyrogenic exotoxins. The non-rheumatogenic serotype, pep M2, only stimulated V beta 2-bearing T cells. This study establishes that the structurally related M proteins represent a family of streptococcal superantigens analogous to the structurally related family of staphylococcal enterotoxin superantigens.

Amino Acid Sequence↗
PubMed1994

Low-dose continuous subcutaneous infusion of granulocyte colony-stimulating factor for chemotherapy-induced neutropenia in acute myelogenous leukemia and its pharmacokinetics.

Granulocyte colony-stimulating factor (G-CSF) shortens the duration of chemotherapy-induced granulocytopenia in acute leukemia. G-CSF is administered by 30-min intravenous infusion at a dose of 200 micrograms/m2/day or 5 micrograms/kg/day in most studies. In this study, the efficacy of a reduced dose (33 micrograms/m2/day) of continuous subcutaneous infusion of G-CSF was compared with the effects achieved by 30-min intravenous infusion of the standard dose (200 micrograms/m2/day) in neutropenia after identical chemotherapy in seven patients with acute myelogenous leukemia who were in remission. The duration of granulocytopenia (< 0.5 x 10(9)/l), thrombocytopenia (< 50 x 10(9)/l); G-CSF administration and fever (> 38 degrees C) were 10.1 +/- 5.0 days, 16.5 +/- 9.3 days, 16.6 +/- 7.4 days and 3.1 +/- 5.4 days for 33 micrograms/m2/day continuous subcutaneous infusion, and 10.7 +/- 6.8 days, 16.7 +/- 9.9 days, 16.1 +/- 7.6 days and 2.0 +/- 2.5 days for 30-min intravenous infusion of the standard dose of G-CSF. In each parameter studied, there was no statistical difference between the two methods of G-CSF administration by paired t-test. The costs for G-CSF could be substantially reduced. In most patients, plasma G-CSF concentration rose to the highest level of 1.8-3.7 ng/ml 48-72 h after starting 33 micrograms/m2/day continuous subcutaneous infusion, and gradually decreased as the peripheral granulocyte count recovered, suggesting binding of G-CSF molecules to the specific receptors on the cells of granulocytic lineage.

Adult↗
PubMed1994

Effect of ubenimex on the proliferation and differentiation of U937 human histiocytic lymphoma cells.

We investigated the effect of ubenimex on the growth and differentiation of U937 cells, a histiocytic lymphoma cell line. Ubenimex is a dipeptide ((2S,3R)-3-amino-2-hydroxy-4-phenylbutyryl-L-leucine) and an inhibitor of aminopeptidase B produced by Streptomyces olivoreticuli. Ubenimex inhibited the proliferation of U937 cells in a dose-dependent manner. Ubenimex-treated U937 cells showed condensation of nuclear chromatin, increase of cytoplasmic vacuoles and more intense nonspecific esterase staining compared with untreated U937 cells. Expression of CD13 and CD68 detected by monoclonal antibodies My7 and EBM11, respectively, was enhanced by ubenimex, but the expression of CD4 detected by MT310 was significantly decreased. The effects of ubenimex on U937 cell growth inhibition and enhancement of monocytic cell surface marker expression on U937 cells were reversible when cultivated without ubenimex for more than 6 days. In addition, the bactericidal activity of U937 cells was increased by ubenimex treatment, and was further enhanced by treatment with macrophage colony-stimulating factor (M-CSF). Furthermore, ubenimex augmented the expression of M-CSF receptors by U937 cells and enhanced the tyrosine kinase activity of cellular pp60c-src. These findings indicated that ubenimex inhibited the proliferation of U937 cells and induced morphological, cytochemical and functional differentiation into monocyte/macrophages.

Aminopeptidases↗
PubMed1994

Effects of the antisense myb expression on hemin- and erythropoietin-induced erythroid differentiation of K562 cells.

In order to elucidate the role of c-myb gene in erythroid differentiation of K562 cell induced by hemin (Hm) and erythropoietin (Epo), we constructed recombinant plasmid that could produce antisense myb RNA after induction with dexamethasone. During treatment with Hm, K562 cells constitutively expressed c-myb mRNA, and 50% of them began to synthesize hemoglobin (Hb). Expression of antisense myb RNA reduced the amount of c-myb mRNA, and the percentage of Hb-synthesizing cells was decreased to 20%. In the presence of Epo, c-myb mRNA declined and 20% of K562 cells synthesized Hb regardless of antisense myb RNA expression. It is suggested that constitutive expression of c-myb mRNA is necessary for Hm-induced differentiation, and that a decrease in the amount of c-myb mRNA induced by antisense myb RNA expression suppresses Hm-induced differentiation. The amount of c-myb mRNA in K562 cells was reduced during the differentiation induced by Epo. Expression of GATA-1 mRNA was almost constant during Hm-induced differentiation, but increased during Epo treatment. It is supposed that the mechanism of Hm-induced differentiation is distinguished from that of Epo-induced differentiation in K562 cells.

Analysis of Variance↗
PubMed1994

PML-RAR alpha fusion transcripts by RNA PCR in acute promyelocytic leukemia in remission and its correlation with clinical outcome.

Molecularly defined specific chromosomal translocation in leukemia allows detection of minimal residual leukemia cells by the reverse transcription-polymerase chain reaction (RT-PCR). However, the positivity of the specific fusion transcripts in chronic myelogenous leukemia and acute myelogenous leukemia with t(8;21) is reportedly not directly correlated with the predictability of relapse. We analyzed seven patients with acute promyelocytic leukemia (APL) in hematological remission for PML-retinoic acid receptor alpha (PML-RAR alpha) fusion transcripts by RT-PCR with the sensitivity level of one APL cell in 10(5) bone marrow mononuclear cells. Two of the four patients with chemotherapy-induced remission had detectable PML-RAR alpha only before treatment. In the other two patients with chemotherapy-induced remission, the PML-RAR alpha was detectable when their remission was first confirmed and became negative after consolidation chemotherapy. Two patients were resistant to chemotherapy and achieved remission by all-trans-retinoic acid; PML-RAR alpha was detectable in them for a few months during consolidation chemotherapy. Two patients whose PML-RAR alpha had become continuously positive had relapse 2 and 8 months later, but the other five patients with continuously negative or only transiently positive PML-RAR alpha remained in remission during follow-up for 11 to 35 months. These findings suggest the relevance of detectable PML-RAR alpha by RT-PCR to the predictability of relapse in acute promyelocytic leukemia.

Adolescent↗
PubMed1994

[Establishment and characterization of a human small cell lung carcinoma cell line (MT-428) derived from the patient who showed neurological paraneoplastic syndrome].

A new human small cell lung carcinoma (SCLC) cell line, designated MT-428, was derived from a patient who showed neurological paraneoplastic syndrome (combined with subacute cerebellar degeneration and peripheral sensory neuropathy) and was established in tissue culture. This cell line exhibited small cell (variant type) morphology as observed by phase contrast and electron microscopy. The MT-428 cells had a doubling time of 72 hours. Chromosomal analysis showed complicated rearrangements at short and long chromosomes with a modal number of 68. Several tumor markers, NSE, TPA and CPK-BB, were detected in culture medium. This cell line had a cloning efficiency of 1.3% in 0.8% methylcellulose. Finally, it should be noticed that autoantibody against MT-428 cell was demonstrated in serum of the patient. We concluded that the MT-428 cell line may provide a suitable model for studies of neurological paraneoplastic syndrome.

Animals↗
PubMed1993

Alkaline phosphatase activity in the human promyelocytic leukemia cell line, HL-60, induced by retinoic acid and recombinant human granulocyte colony-stimulating factor.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) not only enhanced the growth of HL-60 cells, but also significantly increased NBT-reducing ability and alkaline phosphatase (ALP) activity of the cells, which were enhanced by the treatment with retinoic acid (RA). Protein kinase C inhibitors (H-7 and staurosporine) significantly suppressed this induction of ALP. The pretreatment with RA followed by rhG-CSF treatment showed almost the same degree of ALP activity as that induced by the simultaneous treatment with RA and rhG-CSF. This study suggests that RA and rhG-CSF are the potent inducers of ALP activity of HL-60 cells and protein kinase C is supposed to have a role in this induction of ALP.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Characterization, growth, and differentiation of a human myeloid leukemia cell line, TI-1 cell.

A cell line (TI-1) has been established from the peripheral blood of a patient with acute myeloid leukemia (M2). A typical TI-1 cell displayed many abnormalities of its chromosomes, but not the Philadelphia (Ph1) chromosome. Light and electron microscopic examination and histochemical analysis indicated that the TI-1 cells were undifferentiated blast cells, but immunologic marker studies suggested that these cells had myeloid characteristics. The proliferation of TI-1 cells was dependent on the concentration of fetal bovine serum (FBS). Their doubling time was 13.8 hours when they were cultured in a medium containing 10% FBS. Phorbol-12 myristate 13-acetate (PMA) induced the TI-1 cells to differentiate into monocyte-like cells, as judged by their morphologic similarity to monocytes, their adhesion to the culture dish, and their increase of both nitroblue tetrazolium (NBT)-reducing ability and nonspecific esterase (NSE)-activity. PMA significantly inhibited the proliferation and DNA synthesis of TI-1 cells in a dose-dependent manner. The PMA-induced differentiation was significantly inhibited by the protein kinase C inhibitors (H-7, staurosporine). Hemin induced the TI-1 cells to differentiate into erythroid cells. The number of hemoglobin-producing cells and hemoglobin production was increased by hemin treatment. Hemin also inhibited the proliferation of the TI-1 cells. Thus, the TI-1 cell represents a bipotent, granulo-monocytoid, and erythroid cell line. The TI-1 cell line will be a useful model for monocytoid and erythroid differentiation.

Aneuploidy↗
PubMed1992

Acute myelocytic leukemia associated with thrombocytosis and inv 3(q21.3; q26.2) in a case of Grönbland-Strandberg syndrome.

Grönbland-Strandberg syndrome is an inherited connective tissue disorder with cutaneous, ophthalmologic, and systemic manifestations. Here we report a case of AML with thrombocytosis arising in a patient with this syndrome. Karyotypic analysis of bone marrow cells revealed the inversion 3 (q21.3;q26.2). To our knowledge, this is the first report of the association of AML with thrombocytosis and Grönbland-Strandberg syndrome. This might be a coincidental association, but it suggests some interesting speculations regarding the pathogenesis of these diseases.

Chromosome Inversion↗
PubMed1992

Elevation of plasma truncated elastase alpha 1-proteinase inhibitor complexes in patients with inflammatory lung diseases.

Human neutrophil elastase plays an important role in the development of several inflammatory lung diseases; however, there have been relatively few investigations using plasma samples. In this report, we describe alterations in the plasma elastase:alpha 1-PI complex in patients with chronic obstructive pulmonary disease (COPD) (15 cases), COPD with infection (8), diffuse panbronchiolitis (DPB) (8), bronchiectasis (9), pneumonia (10), and the adult respiratory distress syndrome (ARDS) (14), and in 15 normal volunteers. The elastase:alpha 1-PI complex concentration was determined by an enzyme-linked immunosorbent assay. Western immunoblot analysis of the elastase:alpha 1-PI complex was also performed. Plasma elastase:alpha 1-PI complex was also performed. Plasma elastase:alpha 1-PI complex levels in patients with COPD with infection (504 micrograms/L +/- 93 micrograms/L) were significantly higher, as compared with those with COPD but without infection (118 micrograms/L +/- 9 micrograms/L) and normal volunteers (122 micrograms/L +/- 4 micrograms/L). Increased complex concentrations were also found in patients with DPB and bronchiectasis (643 micrograms/L +/- 222 micrograms/L and 558 micrograms/L +/- 198 micrograms/L, respectively) as compared with normal volunteers. Increased complex concentrations were also found in patients with pneumonia and ARDS (450 micrograms/L +/- 101 micrograms/L and 1,400 micrograms/L +/- 438 micrograms/L, respectively). Western immunoblot analysis using anti-alpha 1-PI antibody and antineutrophil elastase antibody showed two types of elastase:alpha 1-PI complexes, one with a molecular weight of 60,000 daltons (60 kilodaltons [KD]) and the other at 50,000 daltons (50 KD). Although the native 80-KD elastase:alpha 1-PI complex was detected in bronchoalveolar lavage fluid, it was not found in plasma. In summary, these results demonstrated that levels of the truncated complex were increased in patients with various inflammatory lung diseases. This truncated form may play an important role in the pathophysiology of inflammatory processes.

Adult↗