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Biomedical subjects

H Takano

Publications and source records attributed to H Takano.

At least 235 records · Page 13Linked to original sources
PubMed1998

Intraoperative spasm of coronary and peripheral artery--a case occurring after tourniquet deflation during sevoflurane anesthesia.

A 68-yr-old man with a 9-yr history of hypertension presented for hemiglossectomy, segmental resection of the mandible, and the radial forearm free flap grafting. Intraoperatively, facial artery spasm was observed during microvascular suturing of the radial artery to the facial artery. Simultaneously, systolic blood pressure decreased from 100 to 80 torr and the ST segment elevated to 15 mm from the base line. The possible mechanisms responsible for vasospasm in coronary as well as in peripheral arteries under sevoflurane anesthesia are discussed.

Aged↗
PubMed1998

Occult intestinal bleeding imaged by technetium-99m-HSA-D radionuclide angiography: a case report.

Radionuclide angiography (RNA) with 99mTc-diethylenetriamine pentaacetic acid human serum albumin (99mTc-HSA-D) is a sensitive screening method for diagnosing systemic perfusion abnormalities. Sometimes the results produce unexpected information. This information is helpful when considering the clinical perfusion pathophysiology. Recently, we were able to detect an intestinal bleeding lesion clearly for a patient by using RNA.

Aged↗
PubMed1998

[Incidence of mutation and deletion in topoisomerase II mRNA of etoposide and m-AMSA resistant cell lines].

The efficacy of all chemotherapeutic agents is limited by the occurrence of drug resistance. To further understand resistance to topoisomerase (topo) II inhibitors, 50 sublines were isolated as single clones from parental cells by exposure to ETP or m-AMSA. Subsequently, a population of cells from each subline was exposed to three-fold higher drug concentrations allowing 16 stable sublines to be established at higher extracellular drug concentration. The frequency and nature of mutations in topo II in the drug selected cell lines have been evaluated. In order to screen a large number of cell lines, an RNase protection assay was developed. Fragments covering the entire coding sequence of topo II was isolated after PCR amplification and subcloned in pGEM3Z vector. Using this approach, mismatches was observed in 13.6% of resistant cell lines (12% of resistant cell lines exposed to lower drug concentrations and 18.8% of resistant cell lines exposed to higher drug concentrations). Our findings suggest that mutations of topo II gene seem to be an important and frequent mechanism of resistance to topo II inhibitors.

Amsacrine↗
PubMed1998

Oral administration of L-arginine potentiates allergen-induced airway inflammation and expression of interleukin-5 in mice.

The role of nitric oxide in the airway hyperresponsiveness and inflammation of bronchial asthma has not yet been established. However, L-arginine, the substrate for nitric oxide synthases, reportedly alleviates airway hyperresponsiveness caused by parainfluenza virus and reduces granulocytic inflammation induced by ischemia-reperfusion. We investigated the effects of L-arginine on a murine model of allergic asthma that included airway hyperresponsiveness, eosinophilic inflammation and expression of interleukin (IL)-5 in the lung. The mice received drinking water with or without L-arginine for 9 weeks. Histologic evaluation and cellular profiles in bronchoalveolar lavage fluid showed that p.o. administration of L-arginine (72 micromol/kg/day) significantly enhanced eosinophilic airway inflammation and goblet cell proliferation that were associated with intratracheal instillation of ovalbumin. L-Arginine also increased protein levels of IL-5 and IL-2 in supernatants from the lung exposed to ovalbumin. The number of eosinophils in bronchoalveolar lavage fluid correlated significantly with the expression of IL-5. L-Arginine did not reverse ovalbumin-associated airway hyperresponsiveness to inhaled ACh. These results suggest that p.o. administration of L-arginine aggravates allergen-induced eosinophilic airway inflammation via expression of IL-5, and in this model it does not show therapeutic efficacy against airway hyperresponsiveness associated with allergen exposure. Oral administration of L-arginine, the precursor of nitric oxide, may not be an effective intervention in allergic asthma.

Animals↗
PubMed1998

[Autoimmune thrombocytopenia following syngeneic peripheral blood stem cell transplantation].

A 35-year-old man with non-Hodgkin's lymphoma (NHL) (follicular small cleaved, B cell, stage IVB) received double myeloablative chemotherapy with syngeneic peripheral blood stem cell transplantation (PBSCT). Although platelet recovery was delayed until day 29 after the second transplantation, thereafter trilineage hematopoietic reconstitution was achieved. The evaluation after PBSCT did not detect any residual tumor. The patient was in good health until day 138, when his platelet count suddenly began falling; on day 150, it had fallen to 1.5 x 10(4)/microliter, and the patient was re-admitted for treatment. The bone marrow was normocellular with a normal count and megakaryocyte structure. Other examinations, including serological tests and computed tomography of the neck, chest, abdomen, and retroperitoneum, did not indicate a recurrence of NHL or reveal the cause of thrombocytopenia. The patient's platelet-associated IgG (PAIgG) level was at 70.9 ng/10(7) platelets (normal range: 9-25 ng/10(7) platelets); a diagnosis of thrombocytopenia due to an autoimmune mechanism such as idiopathic thrombocytopenic purpura (ITP) was made. Prednisolone therapy increased the platelet count and reduced the PAIgG level. Thrombocytopenia with an ITP-like mechanism rarely occurs more than 100 days after autologous or syngeneic stem cell transplantation, and should be taken into consideration as a late complication of PBSCT.

Adult↗
PubMed1998

Impaired erythropoiesis in transgenic mice overexpressing a truncated erythropoietin receptor.

Erythropoietin (EPO), one of the pivotal regulators of erythrocyte production, transmits signals through the EPO receptor (EPOR). We have previously reported that human bone marrow (BM) cells express two dominant forms of the EPOR, one full-length and one truncated (EPOR-F and EPOR-T). Experiments with a cell line have shown that the EPOR-T acts as a dominant-negative regulator of EPOR-F-mediated signals. Its role in erythropoiesis in vivo, however, has yet to be clarified. Here we show the presence in mouse BM of a truncated form of the EPOR that is essentially the same as EPOR-T in humans. To investigate its role in vivo, we generated transgenic mice overexpressing mouse EPOR-T (EPOR-T-Tg mice). As a result, two independent EPOR-T-Tg lines were established. One line revealed mild anemia, but another line did not. When anemia was induced experimentally in these mice, however, both lines showed apparently poor recovery resulting in higher mortality than wild-type control mice. The impaired erythropoiesis found in these mice thus strongly suggests the EPOR-T's role as a negative regulator of erythropoiesis in vivo.

Anemia, Hemolytic↗
PubMed1998

In vitro expansion of CD34+/CD41+ cells from human peripheral blood CD34+/CD41- cells: role of cytokines for in vitro proliferation and differentiation of megakaryocytic progenitors.

The aim of this study is to clarify the transitional change of the proliferation and differentiation of human peripheral blood CD34+ cells to megakaryocytic lineage, focusing on its clinical application. We developed a rapid system to purify human peripheral blood CD34+ cells from healthy volunteers, which produced CD34+ cells with a 90% purity. The purified CD34+ cells predominantly consisted of CD41- cells, and the rate of coexpression of CD41 was 0.6% +/- 0.5%. When the purified cells were cultured in liquid phase for 10 days in the presence of recombinant human stem cell factor (rSCF: a ligand for c-kit), interleukin-3 (rIL-3), and thrombopoietin (rTPO: a ligand for Mpl), the number of CD34+/CD41+ cells increased to 19% +/- 7% of total expanded cells on day 4 (4 days of liquid culture) and then gradually decreased to 2.2% +/- 0.6% on day 10. The absolute number of CD34+/CD41+ cells increased and reached a plateau on day 6, and 1.7 +/- 0.6 x 10(5) CD34+/CD41+ cells were produced by 1 x 10(5) CD34+/CD41- day 0 cells. The CD34-/CD41+ cells appeared on day 6, continuously increased in number until day 10, and constituted the main population of expanded cells on day 10, with a value of 38% +/- 18%. On day 10, 19.5 +/- 10.6 x 10(5) of CD34-/CD41+ cells were produced by 1 x 10(5) CD34+/CD41- day 0 cells. The deletion of rTPO from this cytokine combination decreased the number of CD34+/CD41+ and CD34-/CD41+ cells, after days 6 and 8, respectively. Day 0 cells required rIL-3 for promoting colonies containing megakaryocytes, whereas rTPO alone promoted almost no megakaryocytic colonies from day 0 cells. Thus, a combination of IL-3 and SCF expands CD34+/CD41+ cells from CD34+/CD41- cells, and TPO mainly acts to increase CD34-/CD41+ cells. This study suggests that if the expansion of CD34+/CD41+ is performed in vitro, the 6 days' culture of peripheral blood CD34+/CD41- cells with a combination of IL-3 and SCF with TPO provides the most rapid and stable products of CD34+/CD41+ cells for the rapid recovery of platelets in patients with peripheral blood stem cell transplantation.

Adult↗
PubMed1997

Cellular adaptation to drug exposure: evolution of the drug-resistant phenotype.

The efficacy of all chemotherapeutic agents is limited by the occurrence of drug resistance. For etoposide (VP-16), increased expression of MDR-1 or MRP and alterations in topoisomerase IIalpha have been shown to confer tolerance. To further understand resistance to VP-16, three sublines, designated MCF-7-VP17, ZR-75B-VP13, and MDA-MB-231-VP7, were initially isolated as single clones from parental cells by exposure to VP-16. Subsequently, a population of cells from each subline was exposed to 3-fold higher drug concentrations, allowing stable sublines to be established at higher extracellular drug concentrations. Characterization of the resistant sublines demonstrates the adaptation that occurs with advancing drug concentrations during in vitro selections. Reduced topoisomerase II mRNA and protein levels were observed in the initial isolates. This reduction was accompanied by a decrease in topoisomerase II activity and cellular growth rate and was associated with 6-314-fold resistance to topoisomerase II poisons. With advancing resistance, MRP expression increased and VP-16 accumulation decreased. This adaptation allowed for partial restoration of topoisomerase II activity as a result of increased expression (MCF-7-VP17 and ZR-75B-VP13) or hyperphosphorylation (MDA-MB-231-VP7), with a resultant increase in growth rate. In MDA-MB-231-VP7 cells, hyperphosphorylation coincided with increased casein kinase II mRNA and protein levels, suggesting a role for this kinase in the acquired hyperphosphorylation. In this cell line, hyperphosphorylation mediated the increased activity despite a fall in topoisomerase IIalpha protein levels secondary to an acquired 600-bp deletion in one topoisomerase IIalpha allele, which resulted in reduced protein levels. In all three sublines, high levels of resistance were attained as a result of synergism between the reduced topoisomerase IIalpha levels and MRP overexpression. These studies demonstrate how cellular adaptation to increasing drug pressure occurs and how more than one mechanism can contribute to the resistant phenotype when increasing selecting pressure is applied. Reduced expression of topoisomerase II is sufficient to confer substantial resistance early in the selection process, with synergy from MRP overexpression helping to confer high levels of resistance.

Antineoplastic Agents, Phytogenic↗
PubMed1997

Murine strain differences in allergic airway inflammation and immunoglobulin production by a combination of antigen and diesel exhaust particles.

To clarify the relationship between the manifestations of allergic airway inflammation modulated by diesel exhaust particles (DEP) and immunoglobulin production in response to an antigen, airway inflammation characterized by the infiltration of eosinophils, goblet cell proliferation, and antigen-specific immunoglobulin (Ig) production was investigated in five strains of mice after immunization with ovalbumin (OA). Mice were injected intratracheally with OA (1 microg) or OA (1 microg) + DEP (50 microg) four times at 3-week intervals. The order of antigen-specific IgG1 production in plasma of mouse strains treated with OA alone was CBA/2N <BDF/1 <C57BL/6 < ICR <C3H/He. The adjuvant effect of DEP on IgG1 production was observed in CBA/2N, BDF/1, ICR, and C57BL/6 mice. The immune activity in BDF/1 mice was significantly elevated (P < 0.01). The OA-specific IgE in plasma was unaffected by antigen challenge with or without DEP in any strain. The degree of eosinophilic inflammation and goblet cell proliferation in the airway induced by OA alone or OA + DEP corresponded well with the antigen-specific IgG1 production. These results suggest that the manifestations of allergic airway inflammation modulated by DEP were closely related to the immunoglobulin production response to OA, especially with regard to enhanced IgG1 production.

Animals↗
PubMed1997

Expression of somatostatin receptor subtype 2 mRNA in human lymphoid cells.

We analyzed the mRNA expression of somatostatin receptor subtypes 1 to 5 (SSTR1-5) in human lymphoid cell lines, human peripheral blood lymphocytes (PBL), and human lymphatic leukemia cells, using the reverse transcription-polymerase chain reaction method. In human lymphoid cell lines, SSTR2 mRNA expression was clearly detectable, and there was no evidence of SSTR1 mRNA expression. SSTR2 mRNA was barely detectable in PBL from healthy individuals but was clearly detectable in EB virus-transformed lymphocytes. Lymphocytes from some of the leukemic patients showed elevated SSTR2 mRNA expression. SSTR2 mRNA expression in PBL was upregulated upon stimulation by PHA. SSTR3 mRNA was also observed in all the cell lines examined, although in one cell line, the expression was weak. Some cell lines showed little or no SSTR4 or 5 mRNA expression. The expression pattern of SSTR2 mRNA suggests that this receptor may have some important roles in lymphocyte activation, development, and/or tumorgenesis.

Cell Line↗
PubMed1997

Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene.

Familial adenomatous polyposis coli (FAP) is a disease characterized by the development of multiple colorectal adenomas, and affected individuals carry germline mutations in the APC gene. With the use of a conditional gene targeting system, a mouse model of FAP was created that circumvents the embryonic lethality of Apc deficiency and directs Apc inactivation specifically to the colorectal epithelium. loxP sites were inserted into the introns around Apc exon 14, and the resultant mutant allele (Apc580S) was introduced into the mouse germline. Mice homozygous for Apc580S were normal; however, upon infection of the colorectal region with an adenovirus encoding the Cre recombinase, the mice developed adenomas within 4 weeks. The adenomas showed deletion of Apc exon 14, indicating that the loss of Apc function was caused by Cre-loxP-mediated recombination.

Adenomatous Polyposis Coli↗
PubMed1997

Hematopoiesis in the fetal liver is impaired by targeted mutagenesis of a gene encoding a non-DNA binding subunit of the transcription factor, polyomavirus enhancer binding protein 2/core binding factor.

The Pebpb2 gene encodes a non-DNA binding subunit of the heterodimeric transcription factor, polyomavirus enhancer binding protein 2/core binding factor (PEBP2/CBF), and is rearranged in inversion of chromosome 16 associated with human acute myeloid leukemia. To investigate its physiological function, Pebpb2 was mutated by a targeting strategy to generate a null mutant. The homozygous mutation in mice proved lethal in embryos around embryonic day 12.5, apparently due to massive hemorrhaging in the central nervous system. In addition, definitive hematopoiesis in the liver was severely impaired. The observed phenotype was indistinguishable from that reported for homozygous disruption of AML1, which encodes a DNA binding subunit of PEBP2/CBF. Thus, the results indicate that the two subunits function together as a heterodimeric PEBP2/CBF in vivo and that PEBP2/CBF plays an essential role in the development of definitive hematopoiesis.

Animals↗
PubMed1997

Enhancement of estrogen receptor gene expression in the mediobasal hypothalamus during anestrus in the beagle bitch.

Estrogen receptor mRNA (ER mRNA) levels were measured in the mediobasal hypothalamus (MBH) of beagle bitches at different stages of the estrous cycle, and compared with levels in ovariectomized (OVX) estrogen-treated bitches. In cyclic bitches, the level of hypothalamic ER mRNA increased during the progression of anestrus and declined thereafter. Hypothalamic ER mRNA and plasma luteinizing hormone (LH) levels during anestrus and proestrus were positively correlated (r = 0.94, P < 0.001). In OVX bitches, levels of hypothalamic ER mRNA were low, and increased significantly after treatment with a low dose of estradiol benzoate. These results suggest that, during the course of anestrus in the bitch, hypothalamic ER mRNA expression increases, and may be up-regulated by estradiol.

Animals↗
PubMed1997

Effects of aminoguanidine on systemic inflammatory response syndrome induced by platelet activating factor and by lipopolysaccharide in rats.

We investigated the effects of aminoguanidine, a relatively selective inhibitor of inducible nitric oxide (NO) synthase, on the systemic inflammatory response syndrome induced by platelet activating factor (PAF) and by lipopolysaccharide in rats, with emphasis on NO production in vivo. Aminoguanidine treatment improved survival rates after lipopolysaccharide challenge, whereas it aggravated the lethality caused by PAF. Lipopolysaccharide induced a marked increase in the concentrations of nitrate and nitrite in plasma compared with vehicle administration, and the increase was prevented by aminoguanidine. In contrast, PAF challenge with or without aminoguanidine did not affect the concentrations of nitrate and nitrite in plasma compared with vehicle administration. These results suggest that NO derived from inducible NO synthase is not a major participant in the systemic inflammatory response syndrome induced by PAF. Aminoguanidine is not likely to provide beneficial effects in conditions where PAF is produced and the concentrations of nitrate and nitrite in plasma are not significantly increased.

Animals↗
PubMed1997

Norepinephrine induces the raf-1 kinase/mitogen-activated protein kinase cascade through both alpha 1- and beta-adrenoceptors.

BACKGROUND: Although norepinephrine induces cardiac hypertrophy by activating protein kinase A and C through beta- and alpha 1-adrenoceptors, respectively, protein kinase A has been reported to inhibit cell growth in many other cell types. METHODS AND RESULTS: To elucidate the molecular mechanism of norepinephrine-induced hypertrophic responses, we examined the effects of protein kinase A and protein kinase C on the activities of raf-1 kinase and mitogen-activated protein (MAP) kinases and on protein synthesis rates using cultured cardiomyocytes of neonatal rats. Norepinephrine-induced activation of MAP kinases was partially inhibited by either an alpha 1-adrenoceptor blocker (prazosin) or a beta-adrenoceptor blocker (propranolol) and was completely abolished by both blockers. Both a beta-adrenoceptor agonist, isoproterenol, and an alpha 1-adrenoceptor agonist, phenylephrine, increased the activities of raf-1 kinase and MAP kinases and phenylalanine incorporation into proteins. Furthermore, isoproterenol and phenylephrine synergistically activated these kinases and protein synthesis. Similar synergistic activation of MAP kinases was observed when other protein kinase A-activating agents such as forskolin, dibutyryl cAMP, and isobutyl-methylxanthine were used with a protein kinase C-activating agent at the same time. Chelation of extracellular Ca2+ completely abolished isoproterenol- and phenylephrine-evoked MAP kinase activation. CONCLUSIONS: Norepinephrine activates the raf-1 kinase/MAP kinase cascade through both alpha 1- and beta-adrenergic stimulation, and signaling pathways from the two receptors synergistically induce cardiomyocyte hypertrophy.

1-Methyl-3-isobutylxanthine↗
PubMed1997

No editing of mitochondrial plasmid transcripts in mitochondria of Physarum that have an RNA-editing system.

Two types of RNA editing have been reported in the mitochondria of Physarum; extensive insertions of nucleotides and single-base substitutions. In the Ng strain of P. polycephalum and its derivatives, mitochondria have a specific plasmid (mF) that promotes fusion of mitochondria. We examined the editing of transcripts derived from the mF plasmid. For analysis, we selected three regions of the plasmid, including a DNA fragment that corresponded to missing conserved domains of the RNA polymerase. In contrast to the mitochondrial DNA (mtDNA), no RNA editing of the transcripts of the mF plasmid was detected. Our results suggest that the mechanism of transcription of the mitochondrial plasmid is independent of that of mtDNA, indicating that the plasmid has a different evolutionary origin from the mtDNA.

Animals↗