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Biomedical subjects

M Takanashi

Publications and source records attributed to M Takanashi.

At least 91 records · Page 5Linked to original sources
PubMed1991

Correlation between the proliferative response to granulocyte colony-stimulating factor and the positivity of transferrin receptor in acute myeloblastic leukemia cells.

The use of granulocyte colony-stimulating factor (G-CSF) after chemotherapy for acute myeloblastic leukemia (AML) has been reported. However, there is a drawback in that G-CSF may stimulate the proliferation of AML progenitors. To determine the parameter(s) indicative of responsiveness of AML blasts to G-CSF, various surface phenotypes of blasts were examined in relation to the blast colony formation stimulated by G-CSF in 39 AML patients. A correlation was found only with transferrin receptor positivity among the various phenotypes studied. The population mean of percentages of transferrin receptor-positive blasts in the group responding to G-CSF in vitro was significantly higher than that of blasts in the group not responding to G-CSF. A further correlation was found between transferrin receptor positivity and the number of G-CSF receptors on the blasts; that is, blasts expressing more G-CSF receptors have greater transferrin receptor positivity. In our previous study, we observed that blasts with a large number of G-CSF receptors produce more colonies in response to G-CSF. These results indicated that blasts expressing more transferrin receptors have a larger number of G-CSF receptors and may show more active proliferation in response to G-CSF. Therefore, the proliferative response of blasts to G-CSF can be predicted by examining transferrin receptor positivity. The clinical use of G-CSF in AML patients may be recommended when the patient's blasts have a low level of transferrin receptor expression. The measurement of transferrin receptors on blasts, instead of the rather complicated G-CSF receptor determination, would be a useful indicator for the safer application of G-CSF in AML patients.

Antigens, CD↗
PubMed1991

Pharmacological characteristics of adenosine-induced inhibition of dog ventricular contractility: dependence on the pre-existing level of beta-adrenoceptor activation.

Experiments were carried out to characterize the adenosine-induced negative inotropic effect in relation to the extent of beta-adrenoceptor activation in the isolated dog left ventricular myocardium. Adenosine and R-N6-phenylisopropyladenosine inhibited the positive inotropic effect of isoprenaline (10(-7) mol/l and lower) about 20% of its maximal response, which was antagonized by an A1 adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine in a concentration-dependent manner. The negative inotropic effect of adenosine disappeared and that of R-N6-phenylisopropyl-adenosine decreased when the isoprenaline concentration was elevated to the level higher than 10(-7) mol/l. Adenosine deaminase (1.5 U/ml) that abolished the negative inotropic effect of adenosine enhanced the effect of R-N6-phenylisopropyladenosine, indicating that endogenous adenosine released by high isoprenaline concentration (10(-6) mol/l) modulates the interaction. The maximal response to adenosine and R-N6-phenylisopropyladenosine determined in the presence of 10(-7) mol/l isoprenaline was 50% of that of carbachol which elicited the maximal inhibition even in the presence of 10(-6) mol/l isoprenaline. The negative inotropic effects of R-N6-phenylisopropyladenosine and carbachol were additive to the maximal response equivalent to that of carbachol. The difference in the efficiency between the adenosine and muscarinic receptor agonists may be partly ascribed to the difference in densities of the respective receptors in the dog ventricular myocardium. The negative inotropic effect of R-N6-phenylisopropyladenosine in the presence of isoprenaline was associated with decrease in cyclic AMP levels elevated previously by isoprenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1991

Potent inhibitory action of chlorethylclonidine on the positive inotropic effect and phosphoinositide hydrolysis mediated via myocardial alpha 1-adrenoceptors in the rabbit ventricular myocardium.

The influence of the alpha 1b-adrenoceptor-selective antagonist chlorethylclonidine on the alpha 1-adrenergic positive inotropic effect and the phosphoinositide hydrolysis induced by phenylephrine was investigated in the rabbit ventricular myocardium. Pretreatment of membrane fractions derived from the rabbit ventricular muscle with 10(-5) mol/l chlorethylclonidine decreased the specific binding of [3H]prazosin (at a saturating concentration of 10(-9) mol/l) from the control value of 11.27 +/- 0.48 to 4.18 +/- 1.87 fmol/mg protein. The inhibition by adrenaline of the binding of [3H]prazosin (slope factor and affinity) was not affected by chlorethylclonidine. The positive inotropic effect of phenylephrine (in the presence of 3 x 10(-7) mol/l bupranolol) was inhibited by chlorethylclonidine in a concentration-dependent manner (10(-7)-10(-5) mol/l) and abolished by 10(-5) mol/l chlorethylclonidine. The concentration of chlorethylclonidine to inhibit the phenylephrine-induced maximum response to 50% was 2.4 x 10(-6) mol/l. The accumulation of [3H]inositol monophosphate and [3H]inositol trisphosphate induced by 10(-5) mol/l phenylephrine was inhibited by chlorethylclonidine in the same concentration range. These findings indicate that the myocardial alpha 1-adrenoceptors mediating a positive inotropic effect in the rabbit ventricular myocardium may belong to the chlorethylclonidine-sensitive alpha 1b-subtype, and that the subcellular mechanism of action involve phosphoinositide hydrolysis.

Adrenergic alpha-Antagonists↗
PubMed1991

Effects of interleukins 1-7 on the proliferation of T-lineage acute lymphoblastic leukemia cells.

We investigated the proliferative effects of interleukins 1-7 (IL-1 to -7) on leukemic cells from 10 patients with T-lineage acute lymphoblastic leukemia (T-ALL). Five patients had CD7+4-8-acute leukemia, one had CD5+ acute leukemia, and four had CD1+ acute leukemia. To examine the proliferative effect of each interleukin, 3H-TdR incorporation method was used. In the presence of IL-1, no increase in 3H-TdR incorporation was observed for any of the T-ALL cells. With IL-2, 3H-TdR incorporation increased in cells from 5 out of 10 T-ALL patients, including those with CD7+4-8-, CD5+, and CD1+ acute leukemia. In the presence of IL-3 or IL-6, 3H-TdR incorporation increased in cells from 2 out of 5 patients with CD7+4-8- acute leukemia. However, CD5+ or CD1+ acute leukemia cells were not stimulated by IL-3 or IL-6. With IL-4, 3H-TdR incorporation was increased in the cells from 2 out of 5 patients with CD7+4-8- acute leukemia and in the cells of 2 of those with CD1+ acute leukemia. IL-5 increased the 3H-TdR incorporation by cells from 2 out of 5 patients with CD7+4-8- acute leukemia and 1 patient with CD1+ acute leukemia. IL-7 increased 3H-TdR incorporation in cells from all five CD7+4-8- acute leukemia and 2 of those with CD5+ or CD1+ leukemia. No synergistic effect was found when IL-7 and other cytokines were added to cells from the 3 patients with CD7+4-8- acute leukemia who were tested.

Antigens, CD↗
PubMed1991

Differential inhibitory action of phorbol-12,13-dibutyrate on the positive inotropic effect of endothelin-1 and Bay K 8644 in the isolated rabbit papillary muscle.

Endothelin-1 (ET-1) elicited a concentration-dependent positive inotropic effect on the rabbit isolated papillary muscle (electrically driven at 1 Hz at 37 degrees C). The duration of isometric contractions was prolonged by ET-1 in a concentration-dependent manner mainly by prolongation of relaxation time. A tumor-promoting phorbol ester, i.e., phorbol-12,13-dibutyrate (PDBu), inhibited selectively the positive inotropic effect of ET-1 at the concentration that it did not (10 nmol/L) or only slightly (10-20% at 100 nmol/L) reduced the basal force of contraction and the positive inotropic effect of Bay K 8644. The positive inotropic effect of 10 mumol/L of phenylephrine mediated via myocardial alpha 1-adrenoceptors (in the presence of 0.3 mumol/L of bupranolol) was likewise inhibited by PDBu in the same concentration range as it suppressed the ET-1-induced positive inotropic effect. PDBu at concentrations higher than 100 nmol/L inhibited the positive inotropic effects of Bay K 8644 and isoproterenol, and decreased the basal force of contraction in a concentration-dependent manner to a similar extent. Thus, PDBu exhibited selective and potent inhibitory action on the ET-1-induced and alpha 1-adrenoceptor-mediated positive inotropic effect (compared with that on the effect of the Ca2+ channel agonist Bay K 8644 and a beta-adrenoceptor agonist). The present findings indicate that ET-1 elicits a positive inotropic effect on the rabbit ventricular myocardium, the characteristics of which are similar to those of myocardial alpha-adrenoceptor activation, which may involve the phosphoinositide hydrolysis.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Characterization of positive inotropic effect of endothelin on mammalian ventricular myocardium.

Endothelin-1 elicited a positive inotropic effect (PIE) on isolated rabbit, guinea pig, and rat but not on dog ventricular myocardium. Specific high-affinity binding of 125I-labeled endothelin-1 was detected in the ventricular membrane fraction of these species. Maximal binding capacity was the highest in the rabbit, lowest in the dog, and in between in the guinea pig and rat; this rank order corresponds roughly to the effectiveness of endothelin-1 in producing a PIE. There was no difference in the potency or efficacy for the PIE of the endothelin isoforms endothelin-1, -2, and -3 in the rabbit papillary muscle. A tumor-promoting phorbol ester, phorbol 12,13-dibutyrate, inhibited selectively the PIE and the accumulation of [3H]inositol monophosphate induced by endothelin-1 as well as those of myocardial alpha 1-adrenoceptor stimulation in a concentration that did not (10(-8) M) or only slightly (10(-7) M) reduced the PIE of BAY K 8644. Phorbol 12,13-dibutyrate did not affect the specific binding of 125I-labeled endothelin-1 in the ventricular membrane fraction of the rabbit. The present findings indicate that the characteristics of the endothelin-induced PIE in mammalian ventricular myocardium are similar to those of myocardial alpha 1-adrenoceptor activation that may involve phosphoinositide hydrolysis. The receptor density and the PIE of endothelin on mammalian cardiac muscle show a wide range of variation among species.

Animals↗
PubMed1991

Distribution of epithelial membrane antigen in eccrine poroma.

Using immunohistochemical methods, we investigated the distribution of epithelial membrane antigen (EMA) on the normal eccrine gland, eccrine poroma and hidroacanthoma simplex. Granular membrane-associated reaction of EMA was detected on the outer cells of both the intraepidermal and the upper portion of intradermal eccrine ducts, as well as on the luminal surfaces and intercellular canaliculi of eccrine glands. Clear immunolabeling was also present in the tumor cells of eccrine poroma and hidroacanthoma simplex. Thus, it is suggested that the constituent cells of these tumors originate from the outer cells of the intraepidermal and/or the upper portion of the intradermal eccrine ducts. There was no immunolabeling for EMA on the tumor cells of seborrheic keratosis and basal cell carcinoma. Immunohistochemical staining for EMA is a useful tool for the diagnosis of skin appendage tumors.

Adenoma, Sweat Gland↗
PubMed1991

Myocardial alpha 1-adrenoceptors mediate positive inotropic effect and changes in phosphatidylinositol metabolism. Species differences in receptor distribution and the intracellular coupling process in mammalian ventricular myocardium.

Species-dependent variations of myocardial alpha 1-adrenoceptor-mediated positive inotropic effects of epinephrine were assessed in relation to characteristics of alpha 1-receptor bindings and acceleration of phosphatidylinositol metabolism in the isolated rat, rabbit, and dog ventricular myocardium. Epinephrine in the presence of the beta-adrenoceptor antagonist bupranolol (10(-6) M) elicited a positive inotropic effect through activation of alpha 1-adrenoceptors in rat and rabbit, whereas in dog ventricular myocardium, bupranolol abolished the positive inotropic effect of epinephrine. [3H]Prazosin bound to membrane fractions derived from rat, rabbit, and dog ventricular muscle with high affinities in a saturable and reversible manner. In dog, Bmax and Kd values of alpha 1-adrenoceptor binding sites were identical to those in rabbit ventricular muscle. The Bmax value of alpha 1-adrenoceptors in rat ventricle was the highest, amounting to two to four times those in rabbit and dog. Epinephrine displacement curves for the specific binding of [3H]prazosin in the membrane fraction of these species showed high and low affinity sites with slope factors significantly less than unity, which were shifted to single low affinity sites with slope factors close to unity by addition of 5'-guanylylimidodiphosphate. Accumulation of [3H]inositol 1-phosphate [( 3H]IP1) in ventricular slices prelabeled with [3H]myo-inositol was increased by epinephrine in a time- and concentration-dependent manner in rat ventricular slices. [3H]IP1 accumulation likewise was facilitated by alpha 1-adrenoceptor stimulation in rabbit ventricular slices, whereas the extent of [3H]IP1 accumulation was much less than that in rat. In dog ventricular slices, [3H]IP1 was not accumulated by epinephrine. In rabbit papillary muscle, the time course of increase in contractile force induced by alpha-adrenoceptors coincided with the prolongation of the action potential duration with a similar time course, which is in strong contrast to previous findings in rat that the contractile response was dissociated from the electrophysiological response to alpha-adrenoceptor stimulation. The present results indicate that a wide range of variation of alpha 1-adrenoceptor-mediated regulation of myocardial contractility may be ascribed to different contributions of facilitatory as well as inhibitory regulatory processes that lead to intracellular Ca2+ mobilization subsequent to myocardial alpha 1-adrenoceptor activation among mammalian species.

Action Potentials↗
PubMed1991

[Increase in alpha-actin and basic fibroblast growth factor in angiofibromas in patients with tuberous sclerosis].

We examined alpha-actin and an angiogenic factor, basic fibroblast growth factor (bFGF), by immunohistochemistry and Western blot analysis in four angiofibromas (AFs) and a connective tissue nevus (CTN) obtained from two patients with tuberous sclerosis (TS). There was an increase of alpha-actin-positive microvessels in the papillary and the upper reticular dermis of AFs and a CTN as compared to those in normal skin. The main localization of alpha-actin in the microvessels of AFs was considered to be pericytes. Many microvessels and a few interstitial fibroblast-like cells in frozen sections of AFs and a CTN were positively stained for bFGF, and most of the bFGF-positive microvessels corresponded to those containing alpha-actin as determined by double immunostaining. These data suggested a possible role of increased bFGF in stimulating angiogenesis and/or mainitaining vessels in AFs, although augmentation of mitotic activity was not noted by staining with Ki-67. Further investigations on the identification of the bFGF-producing cells and biological function of bFGF in AFs may be a clue to elucidate pathomechanisms of AFs.

Actins↗
PubMed1991

Inotropic effects of endothelin on mammalian ventricular contractility.

Endothelin-1 elicited a concentration-dependent positive inotropic effect on the isolated rabbit, guinea pig, and rat, but not on the dog ventricular myocardium. The duration of isometric contractions was prolonged by endothelin-1 in a concentration-dependent manner, mainly by prolongation of relaxation time. Phorbol 12,13-dibutyrate (PDBu) (a tumor-promoting phorbol ester) inhibited the positive inotropic effect of endothelin-1, as well as myocardial alpha 1-adrenoceptor stimulation at low concentrations (10(-9) mol/l and above) without (10(-8) mol/l) or less (10(-7) mol/l) affecting the basal force of contraction, and the positive inotropic effect of beta-adrenoceptor stimulation. The present findings indicate that endothelin elicits a positive inotropic effect on mammalian ventricular myocardium, the characteristics of which are very similar to those of myocardial alpha-adrenoceptor stimulation.

Animals↗
PubMed1990

Modification of glycophorin A during oxidation of erythrocyte membrane.

Human erythrocyte ghosts were oxidized with tert-butyl hydroperoxide and subsequently treated with tritiated borohydride to label the membrane proteins modified during the membrane oxidation. From the ghosts, oxidized-and-tritiated glycophorin A was isolated and characterized. No intermolecular cross-links were observed as analyzed by sodium dodecylsulfate gel electrophoresis. But, the number of lysine residues was significantly reduced and susceptibility to proteinases such as trypsin, chymotrypsin and pronase was lower than that of control glycophorin A. Trypsinization of the oxidized-and-tritiated glycophorin A gave insoluble and soluble trypsin fragments. After dansylation, N-terminal amino acids of the trypsin-fragments were determined. Dansyl amino acids from the insoluble trypsin fragments were not identical with those from control insoluble counterparts in the membrane-spanning region of glycophorin A molecule. Fractionation by gel filtration of dansyl-soluble trypsin fragments, and the N-terminal amino acid analysis of the fractionated peptides indicated that the peptides derived from the glycosylated region located in the outside of the membrane matrix were identical with those from control soluble counterparts. The results suggest that the glycosylated outside region of glycophorin A was modified only slightly but the hydrophobic membrane-spanning region was extensively modified during membrane oxidation, most likely by oxidized lipids.

Amino Acids↗
PubMed1990

Induction of eosinophilic colonies by interleukin-5 on acute myeloblastic leukaemic cells.

The effect of interleukin-5 (IL-5) on blast colony formation of acute myeloblastic leukaemia (AML) cells was studied. IL-5 showed a weak but significant colony stimulatory effect in one out of six cases studied. IL-5 induced eosinophilic colony growth in this case, and chromosomal and histochemical analyses strongly suggested that these eosinophilic colonies were derived from leukaemic blast progenitor cells. To our knowledge, this is the first report that IL-5 induces eosinophilic colonies on fresh AML cells. A possible induction of differentiation of AML blast cells by IL-5 is suggested.

Adult↗
PubMed1990

Enhanced growth of clonogenic cells from acute myeloblastic leukaemia by erythropoietin.

The effect of erythropoietin (Epo) on colony formation by blast progenitors in acute myeloblastic leukaemia other than erythroleukaemia was studied using a blast colony assay. Epo alone did not induce colony formation, but when it was used together with phytohaemagglutinin-stimulated leucocyte-conditioned medium (PHA-LCM) the number of leukaemic colonies significantly increased in nine out of 12 cases studies. Preincubation of Epo with anti-Epo antibody completely abolished this enhancement, indicating that the increase in colony numbers was caused by Epo itself. Cell surface phenotype analysis of colonies produced by Epo plus PHA-LCM showed no increase in percentages of erythroid and megakaryocyte lineages. The addition of Epo also increased the self-renewal capacity of leukaemic blast cells. Fresh leukaemic cells did not express Epo receptors, but they were induced after incubation with PHA-LCM. The present study thus showed that the proliferative response to Epo is not restricted only to the erythroid lineage, but also extends to AML blast cells other than those in erythroleukaemia in the presence of colony stimulating factors.

Antibodies↗
PubMed1990

A new serum-free culture system for leukemic colony assay.

A new serum-free assay system for leukemic colony formation (leukemic colony-forming units, L-CFU) was established, and, utilizing this system, the colony-promoting activities of recombinant human colony-stimulating factors (rhCSFs) and the effectiveness of CSFs on cellular self-renewal capacity were investigated. The serum-free assay system included deionized bovine serum albumin (1%), cholesterol (7.8 micrograms/ml), and ASF 101 medium. The plating efficiencies obtained by culturing with phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM) ranged from 0.01% to 1.35% in this system. Spontaneous colonies were observed in 9 out of 13 cases studied. Recombinant human granulocyte CSF (rhG-CSF), rh granulocyte-macrophage CSF (rhGM-CSF), rh interleukin 3 (rhIL-3), and rh interleukin 1 (rhIL-1) stimulated colony formation in 10, 9, and 6 out of 13, and 5 out of 11 cases, respectively. The magnitude of stimulation by each CSF ranged from 6% to 145%, 21% to 200%, 0% to 1229%, and 14% to 182% of PHA-LCM, respectively. In eight cases, blast colony assays in serum-free and serum-containing cultures were simultaneously performed. The magnitudes of responsiveness of each CSF differed in the two assay systems; this indicated some effect of fetal calf serum. The value of self-renewal capacity was also examined and compared with that in serum-containing culture. Self-renewal capacity could be maintained with a serum-free culture system. It showed marked variation from case to case, and there was no correlation between the primary colony formation and the self-renewal capacity in both culture systems. Taken together, the development of a completely serum-free culture system was found to be efficient as evaluated by a L-CFU colony assay.

Blood↗
PubMed1989

Effect of recombinant interferons on hairy cell leukemia progenitors.

The effects of recombinant interferons (rIFNs) on colony formation by progenitor cells from the peripheral blood of patients with hairy cell leukemia (HCL) were examined. Results showed that both rIFN-alpha and -beta inhibited HCL colony formation in a dose-dependent manner, with the inhibitory effect of rIFN-alpha being similar in degree with that of rIFN-beta. The inhibitory effect of rIFN-gamma, however, was not uniform; of four patients, inhibition was observed in cells from two patients, but no effect was found in the cells of the other two. These results indicate that rIFN-alpha and -beta could be effective in the treatment of HCL, whereas rIFN-gamma may be of limited efficacy.

Blast Crisis↗
PubMed1989

Effect of recombinant GM-CSF and recombinant G-CSF on colony formation of blast progenitors in acute myeloblastic leukemia.

The colony-promoting activities of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) and recombinant granulocyte colony-stimulating factor (rG-CSF) on primary and secondary colony formation by blast progenitors (leukemic colony-forming units [L-CFU]) from 21 patients with acute myeloblastic leukemia (AML) were examined using blast colony assay and compared to colony promotion stimulated by phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM). Recombinant GM-CSF stimulated blast colonies in 13 out of 20 cases examined (1 case not done). The magnitude of stimulation by rGM-CSF varied significantly according to the type of AML, but in general was lower than that of PHA-LCM. Blast cells of type M1 did not form any colonies with rGM-CSF, although numerous colonies were produced with PHA-LCM. Type M4 blasts formed fairly large numbers of colonies, though slightly less than those stimulated by PHA-LCM. Blasts of type M2 and M5 formed colonies with the stimulation of rGM-CSF, but the numbers were considerably smaller than type M4 and those stimulated with PHA-LCM. Recombinant G-CSF stimulated blast colonies in only 5 out of 21 cases, 3 of them being type M2. The number of cases responding to rG-CSF was significantly smaller than that responding to rGM-CSF, and even in cases in which colonies were formed, the magnitude of stimulation was minimal. From these results it seems likely that blast cells of different types of AML require a different kind of CSF for their optimal growth; type M4 blasts responded to the stimulation of rGM-CSF well, but blasts of other types of AML responded poorly. Thus, except for type M4, CSF(s) other than rGM-CSF seems to be required for the sufficient growth of L-CFU. Recombinant G-CSF is not likely to play an essential role in the proliferation of leukemic blasts of most types. Previous exposure to rGM-CSF and rG-CSF did not alter the self-renewal capacity, cellular phenotype, and morphology of colony cells, indicating that the direction and degree of differentiation of L-CFU stimulated by rGM-CSF or rG-CSF were not different from those stimulated with PHA-LCM.

Colony-Stimulating Factors↗
PubMed1987

Effect of recombinant interferons on colony formation of blast progenitors in acute myeloblastic leukemia.

The effect of recombinant interferons (rIFNs) on primary and secondary colony formation by blast progenitors (leukemic colony-forming units, L-CFU) from the peripheral blood of patients with acute myeloblastic leukemia (AML) was examined. rIFN-alpha, rIFN-beta, and rIFN-gamma inhibited L-CFU in a dose-dependent manner. When 3000 U/ml rIFN-alpha, -beta, and -gamma were added, L-CFU were suppressed to 20%, 12%, and 40% of the control cultures, respectively. The concentrations of rIFN-alpha, -beta, and -gamma required for 50% inhibition of colony formation were 63, 29, and 250 U/ml, respectively. The self-renewal capacity of L-CFU was inhibited by rIFNs in a dose-dependent manner, the degree of inhibition being the same for all three rIFNs. These rIFNs also inhibited normal granulocyte-macrophage progenitors to a similar degree as L-CFU. Taken together, these in vitro studies indicate that these rIFNs may be efficacious in the treatment of AML, though development of granulocytopenia may be observed as a complication of IFN therapy.

Antibodies, Monoclonal↗