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Biomedical subjects

K Takatsuki

Publications and source records attributed to K Takatsuki.

At least 217 records · Page 12Linked to original sources
PubMed1992

[Expression of multidrug resistance 1 and correlation with clinical drug resistance in acute leukemia].

Expression of multidrug resistance (mdr 1) gene, which encodes a transmembrane efflux pump referred to P-glycoprotein, leads to the decreased intracellular accumulation of various lipophilic drugs, such as vinca alkaloids, anthracyclines and epipodophyllotoxins. As these drugs are commonly used in chemotherapy for acute leukemia, it is of importance to determine whether mdr 1/P-glycoprotein expression is associated with clinical resistance. In several reports, some leukemia cells from untreated patients have expression of mdr 1/P-glycoprotein. We quantitatively detected low levels of mdr 1 expression in all cases of untreated acute leukemia and normal hematopoietic cells, using the reverse transcriptase-polymerase chain reaction. Carefully designed clinical trials including mdr 1 reversing agents may have significant consequences for the treatment of acute leukemia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Increased plasma decay-accelerating factor levels in paroxysmal nocturnal hemoglobinuria.

Decay-accelerating factor (DAF) is a complement regulatory membrane protein that is often absent from the cell surface of blood cells in paroxysmal nocturnal hemoglobinuria (PNH). DAF has also recently been found in the body fluids of healthy individuals. However, its precise structure and biological significance are not yet clear. To clarify the clinical and pathological implications of free DAF, we measured plasma DAF levels in PNH patients, using a newly developed quantitative enzyme-linked immunosorbent assay (ELISA), with a measurable range between 0.2-12 ng, for soluble DAF. ELISA assays revealed significantly increased plasma DAF levels in PNH patients (258 +/- 150 ng/ml, mean +/- S.D., n = 9) as compared with healthy controls (80 +/- 41 ng/ml, n = 17) (p less than 0.01). Taken together with the finding that DAF is synthesized in and released extracellularly from affected PNH cells, plasma DAF levels would be useful for clinical diagnosis and for the quantitative evaluation of the clonal expansion of affected cells in PNH.

Adult↗
PubMed1992

Synergistic effects of interleukin 3 and interleukin 11 on murine megakaryopoiesis in serum-free culture.

We investigated the effects of interleukin 11 (IL-11) on murine megakaryopoiesis in serum-free cultures, using nonadherent, nonphagocytic, and T-cell-depleted bone marrow cells. IL-11 alone had no influence on megakaryocyte (Meg) colony formation in serum-free methylcellulose cultures, but it significantly enhanced the growth of Meg and granulocyte-macrophage-Meg colonies supported by optimal and suboptimal concentrations of interleukin 3 (IL-3). IL-11 also increased the size of IL-3-dependent Meg colonies as well as increasing the size and DNA content of constituent Meg. In liquid cultures, IL-11 alone did not increase the number of Meg, but it enhanced their size and acetylcholinesterase (AchE) levels. The addition of IL-11 to cultures containing suboptimal concentrations of IL-3 resulted in a synergistic increase of Meg AchE. These results suggest that IL-11, similarly to interleukin 6, has an effect on Meg and acts synergistically with IL-3 to augment murine megakaryopoiesis in vitro.

Acetylcholinesterase↗
PubMed1992

Altered expression of protein kinase C in adult T-cell leukemia cells.

Protein kinase C (PKC) has been shown to be involved in the mitogenic response and in oncogenic cell transformation in many experimental models. We analyzed the expression of PKC in both highly purified leukemic T cells freshly isolated from adult T-cell leukemia (ATL) patients and control T lymphocytes obtained from healthy volunteers. PKC activity was decreased in the ATL cells as compared with the control T cells. Cytosolic PKC activity in the ATL cells was remarkably decreased, whereas particulate membrane PKC activity was similar to the control level. The percentage of PKC activity in the particulate fraction was 34% in the ATL cells and 19% in the control cells. Regarding the altered subcellular localization of PKC activity, phorbol ester-induced translocation of cytosolic PKC was inhibited in some ATL cases. Similarly to the decrease in PKC activity, there was a decrease in the expression of the major PKC isozymes II(beta) and III(alpha) in ATL cells. These results suggest impaired regulation of PKC expression in ATL as well as in many experimental cancers.

Adult↗
PubMed1992

[Reactive histiocytosis during initial remission induction therapy for acute myeloblastic leukemia].

Six of 14 patients with acute myeloblastic leukemia (AML) complicated reactive histiocytosis during initial remission induction therapy. All six patients had a high fever without signs of infection during initial chemotherapy, and periods of myelosuppression were prolonged. Histiocytes with a mature appearance, some of which phagocyted erythrocytes, thrombocytes or neutrophils, increased in the bone marrow. All of 3 patients tested showed high serum levels of ferritin. Two of 3 patients treated with 125 mg/day methylprednisolone achieved complete remission. In the remaining 3 patients, one patient achieved complete remission, but the others died of fungal pneumonia or sepsis. Thus, reactive histiocytosis is one of the severe complications in patients with AML undergoing chemotherapy.

Adult↗
PubMed1992

Identification and characterization of specific receptors for the LD78 cytokine.

LD78 is a small secreted protein that has a sequence similar to a number of other polypeptides, including murine macrophage inflammatory protein 1 alpha (MIP-1 alpha), interleukin 8 (IL-8), Act-2, monocyte chemoattractant protein 1 (MCP-1), and others. These polypeptides are members of a novel cytokine superfamily that is involved in the inflammatory response, wound healing, hematopoiesis, and tumorigenesis. Specific receptors for purified clonal LD78 protein were measured using four cell lines (HL-60, U937, Jurkat, and MJ). 125I-labeled recombinant LD78 bound most efficiently to U937 cells. We therefore characterized the receptors as being on the surface of U937 cells. Binding reached an equilibrium after incubation for 60 min at 4 degrees C. Scatchard analysis showed that there were two classes of binding sites on U937 cells, high affinity sites (Kd = 5.3 x 10(-9) M) and low affinity sites (Kd = 9.3 x 10(-8) M), with the average number of binding sites per cell being approximately 30,000 and approximately 90,000, respectively. These receptors for LD78 were distinct from the receptors for gamma-IFN and for IL-8. SDS-PAGE analysis of chemically crosslinked 125I-labeled LD78 receptor complexes identified a single band of 52 kDa. The ability to detect specific LD78 receptors should prove valuable in efforts to molecularly clone these receptors and to dissect the biological actions of LD78.

Chemokine CCL3↗
PubMed1992

Possible mechanisms for the elevation of serum beta 2-microglobulin levels in adult T-cell leukemia.

In our previous study, we found that serum beta 2-microglobulin (beta 2M) levels were elevated in the active, but not in the inactive, phase of adult T-cell leukemia (ATL), suggesting a correlation between the beta 2M level and the clinical severity of this disease. In this study we examined the mechanisms underlying the elevation of serum beta 2M levels in ATL. First, the production of beta 2M by ATL cells was investigated in vitro. High levels of beta 2M were detected in the conditioned culture medium (CM) of ATL cells from seven out of nine patients. Second, we assessed the effects of the CM on the release of beta 2M by three human cell lines unrelated to ATL (NCTC 2544, Chang liver, and L 132; originating from the skin, the liver, and the fetal lung, respectively). Most of the CM definitely promoted beta 2M production by these cell lines. beta 2M production by the cell lines was markedly promoted by exogenous interferon-gamma (IFN-gamma), a well-known potent inducer of class I HLA antigen expression. We then investigated whether an antibody directed against IFN-gamma could attenuate the activity of three ATL CM. The anti-IFN-gamma antibody reduced the stimulatory activity of the CM to 28-65% of the original level, but did not affect basal beta 2M production by these cell lines. These data suggest that there are at least two mechanisms causing the elevation of serum beta 2M levels in ATL; direct production by tumor cells, and production by non-malignant cells that is mediated via humoral factors secreted by the ATL cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Rapid protein tyrosine phosphorylation selectively induced in murine responsive ELM-I-1 cells by erythropoietin.

We investigated whether protein tyrosine phosphorylation was induced by erythropoietin (Epo) in two murine Epo-responsive cell lines (ELM-I-1, which proliferates autonomously and is induced to differentiate by Epo, and DA-1ER, which grows in a manner dependent on Epo or interleukin-3 (IL-3) without differentiation). In ELM-I-1, Epo induced the tyrosine phosphorylation of a protein of about 80-85 kDa (py80) which appeared in the Triton-X soluble fraction of the cell lysate in a time- and concentration-dependent manner. Maximal levels of phosphorylation were obtained within 5-10 min at Epo concentrations above 0.1 U/ml. IL-3 is known to promote the proliferation of this cell line, but it did not induce py80 phosphorylation. In DA-1ER, tyrosine phosphorylation of py80 was not induced by either Epo or IL-3. These findings suggest that there are multiple pathways of Epo signaling and that one of them could be via tyrosine kinase activation. Furthermore, it is possible that the tyrosine phosphorylation of py80 is involved in the pathway leading only to erythroid differentiation but not to cellular proliferation.

Animals↗
PubMed1992

[Münchhausen syndrome with severe iron deficiency anemia].

A patient with Münchhausen syndrome who had severe iron deficiency anemia (IDA) is reported. A 31 year-old female presented with irregular genital bleeding. However, gynecological examination disclosed no evidence of specific disorders causing bleeding. Tests for bleeding tendency and hemolysis were all negative. Although massive bleeding was absent, she had three episodes of a rapid fall in Hb level associated with marked fatigue and weakness, and subsequently rapidly developed serious IDA afterwards. Factitious bleeding was strongly suspected. Blood transfusion performed when the patient was not being watched failed to increase Hb, while transfusions given while the patient was watched were effective. She was not cooperative throughout the hospital course and was discharged on her own request. In outpatient clinic, the diagnosis was confirmed by the evidence that she diluted her own blood samples.

Adult↗
PubMed1991

Hemolysis of human erythrocytes is a new bioactivity of gangliosides.

Using sheep erythrocytes and liposomes, an inhibitory effect of gangliosides has been shown on the activation of the alternative pathway of complement. However, in studies using human erythrocytes, we found that gangliosides had hemolytic activity that was possibly mediated through activation of the alternative pathway. Pretreatment of human erythrocytes obtained from healthy volunteers or paroxysmal nocturnal hemoglobinuria (PNH) patients with a ganglioside mixture purified from human erythrocytes enhanced their susceptibility to homologous human complement, and resulted in dose-dependent hemolysis. The enhancement was more marked in PNH erythrocytes than control cells. Protease treatment of the ganglioside mixture did not change its hemolytic activity, but sialidase treatment abolished the activity. Among the major erythrocyte gangliosides, II3NeuAc-LacCer (GM3) was the most potent hemolytic agent. Gangliosides purified from bovine brain were also active, while neither nonsialylated glycosphingolipids, the ceramide moiety, or sialic acid alone were active. Sialic acid residues in the ganglioside molecules were essential to this activity, but the amount of the residue or the source of the gangliosides seemed not to be important. Several treatments inhibiting the alternative but not classical complement pathway markedly reduced the ganglioside hemolytic activity. This novel bioactivity of gangliosides was thus suggested to be mediated partly by activation of the alternative pathway.

Chromatography, Thin Layer↗
PubMed1991

Discordant gene and surface expression of the T-cell receptor/CD3 complex in adult T-cell leukemia cells.

Cell surface expression of the T-cell receptor (TCR)/CD3 complex on the cells from 11 acute type adult T-cell leukemia (ATL) and 4 lymphoma type ATL patients was examined by flow cytometry. Cells from 10 of 11 acute ATL patients were TCR alpha beta+ and CD3+, and their mean fluorescence intensities were low (TCR alpha beta, 25.3-84.6; CD3, 22.8-87.8). Cells from two of four lymphoma type ATL did not express this complex, and the other two were CD3+, TCR alpha beta-. In contrast, the mean fluorescence intensity of the TCR/CD3 complex in cells from a patient with T4 chronic lymphocytic leukemia was not low (TCR alpha beta, 129.9; CD3, 117.1). mRNA expressions of the TCR alpha, beta, and CD3 gamma, delta, epsilon, and zeta chains were examined by Northern blots. ATL cells from two acute and two lymphoma types expressed amounts of this complex equal to or greater than those expressed by T4 chronic lymphocytic leukemia. CD3 delta and TCR beta mRNA in ATL and T4 chronic lymphocytic leukemia cells were equally stable to actinomycin D treatment. The synthesis of CD3 zeta protein by ATL cells was detected by Western blotting assay. On the basis of these findings, we discuss the possible involvement of the TCR/CD3 complex in activation of ATL cells.

Adult↗
PubMed1991

A principal neutralizing domain of human immunodeficiency virus type 1 interacts with proteinase-like molecule(s) at the surface of Molt-4 clone 8 cells.

A principal neutralizing domain (PND) of the major envelope glycoprotein (gp120) of the HTLV-III BH10 strain of human immunodeficiency virus type 1 (HIV-1) has significant amino acid similarities to a reactive site of Kunitz-type basic proteinase inhibitors. We therefore thought that the PND may interact with cellular proteinase-like molecule(s) upon HIV-1 infection and measured the cellular proteolytic activities at the surface of intact Molt-4 clone 8 cells, which are highly susceptible to HIV-1 infection. The cells preferentially cleaved succinyl-Leu-Leu-Val-Tyr-4-methylcoumaryl-7-amide, a good substrate of chymotrypsin, and the activity was strongly inhibited by N-tosyl-L-phenylalanyl chloromethyl ketone (IC50 = 11.5 microM) and chymostatin (IC50 = 4.8 microM). A synthetic peptide of 24 residues (amino acids 308-331) that correspond to the PND also inhibited the cellular proteolytic activity in a dose-dependent manner (IC50 = 79.2 microM). The inhibition was still observed at low temperature (IC50 = 42.7 microM) and even after the peptide-treated cells were washed. We therefore think that the peptide interacts with proteinase-like molecule(s) located at the surface of the cells. The synthetic peptides from four other strains of HIV-1 corresponding to the PND similarly inhibited the proteolytic activity. These results may be helpful to clarify the novel mechanism(s) for HIV-1 infection.

Amino Acid Sequence↗