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H Kaneko

Publications and source records attributed to H Kaneko.

At least 289 records · Page 16Linked to original sources
PubMed1996

Metabolism of tetramethrin isomers in rat. III. Stereochemistry of reduced metabolites.

1. Three main urinary metabolites, two isomers of 3-hydroxycyclohexane-1,2-dicarboximide (3-OH-HPI-1 and 2) and 1,2-tetrahydrodicarboxylic acid (TCDA) were purified from rat treated with (1RS, trans)-tetramethrin [3,4,5,6-tetrahydrophthalimidomethyl (1RS, trans)-chrysanthemate]. 2. To elucidate the mechanism of formation of these reduced metabolites, the stereochemistry of 3-OH-HPI-1, 3-OH-HPI-2 and TCDA was clarified by chemical reactions, spectroanalysis (nmr) and X-ray analysis. 3. The sole difference in configuration between 3-OH-HPI-1 and 3-OH-HPI-2 was found to be the orientation of the hydroxyl group to the cyclohexane ring, and both of these reduced metabolites showed cis-addition of two hydrogens. In contrast, reduction resulted in the trans form with TCDA. 4. These findings indicate the existence of two different reduction reaction mechanisms in the rat.

Animals↗
PubMed1996

Lack of CD54 expression and mutation of p53 gene relate to the prognosis of childhood Burkitt's lymphoma.

Expression of the intercellular adhesion molecule-1 (CD54) as well as the mutations of p53 gene were studied in childhood Burkitt's lymphoma (BL). Expression of CD54 was identified in 6 of 15 fresh BL cases. Mutations of p53 gene, analyzed by polymerase chain reaction-single stranded chain polymorphism followed by sequencing, were found in 5 of 14 cases examined. Interestingly, all the cases with p53 mutation were CD54 negative. This high frequency of p53 mutation in the CD54 negative group prompted us to analyze the clinical features of these cases. Six of 15 cases died within 21 months after initiation of therapy and five of these were CD54 negative. In addition, four of these had p53 mutation. These results suggest that the lack of CD54 by BL cells may provide the background for the mutation of p53 gene to occur which could result in the transformation to a more aggressive phenotype.

Adolescent↗
PubMed1996

Alterations of CDKN2 gene structure in childhood acute lymphoblastic leukemia: mutations of CDKN2 are observed preferentially in T lineage.

We analyzed homozygous deletions and mutations of the CDKN2(p16(INK4A)/MTS1) gene, using polymerase chain reaction and Southern blot analysis, in 120 children with acute lymphoblastic leukemia (ALL). Homozygous deletion was found in 17 of 89 (19%) precursor B-ALL patients, in 11 of 24 (46%) T-ALL patients, and in 0 of 7 other phenotype ALL patients. After excluding 28 (23%) patients who showed a homozygous deletion of CDKN2, we found that three patients (3%) had mutation at exon 2 of CDKN2 using PCR-SSCP and sequencing strategy. One had a CGA to TGA nonsense mutation (Arg to stop) at codon 72, one had a 1-bp deletion at codon 117, and the third had a 2-bp deletion at codon 70, resulting in frameshifts in the two latter patients. All three of these patients were T phenotype ALL, and the incidence of mutation in the 24 T-ALL patients examined was 13%. In contrast, no mutation was detected in the remaining patients with precursor-B or other type ALL (0/96). Our results suggest that mutational inactivation of the CDKN2 gene may contribute to the leukemogenic growth, especially in some patients with T-ALL.

Adolescent↗
PubMed1996

Elevation of lymphocyte and hematopoietic stem cell numbers in mice transgenic for human granulocyte CSF.

Transgenic mice expressing human granulocyte colony stimulating factor (hG-CSF) were bred to establish an experimental model for studying the biologic function of hG-CSF. The mice produced approximately 1000 pg/ml of hG-CSF in sera and expressed hG-CSF mRNA in all of the tissues examined. Granulocytosis and elevation of hematopoietic precursor number were observed in hematopoietic tissues as expected, but lymphocytosis with 5-fold increase in peripheral blood and 2-fold increase in spleen was also evident. Hematopoietic stem cells capable of reconstituting lethally irradiated recipient mice were abundant in the circulation of these transgenic mice. No disadvantageous tissue damage was observed when various organs were analyzed. As shown in this study, G-CSF has a stimulating effect on lymphopoiesis when it is expressed in a certain condition. The lymphocytosis, as well as the high level of hematopoietic stem cell mobilization into circulation, indicates a wider range of potential G-CSF activity than expected. The mice transgenic for hG-CSF described herein will contribute greatly to the understanding of the regulatory mechanism in hematopoiesis.

Animals↗
PubMed1996

A species comparison of 14C-labeled 7-ethoxycoumarin metabolism in precision-cut liver slices from guinea pig and dog using a phosphor imaging system.

The metabolism of 14C-labeled 7-ethoxycoumarin (7EC) has been investigated in precision-cut liver slices from guinea pigs and dogs. 7EC was incubated with slices in 12-well plates (4 slices/well; n = 3) for up to 8 hr. In addition, a new simple method was established for analyzing 7EC and its metabolites simultaneously by using thin-layer chromatography-radioluminography (TLC-RLG). In both species, 7EC was taken up rapidly into the slices and metabolized extensively under the conditions used (no serum fraction supplemented), showing both phase I and phase II metabolism. In guinea pig medium samples, 4-ethoxy-2-hydroxyphenylacetic acid (EHPA) and 7-hydroxycoumarin (7HC) glucuronide were major metabolites. In dogs, conjugated 7HCs (with D-glucuronic acid and sulfate) were major products but EHPA was formed only to a small extent. These results suggest that deethylation in dogs occurs to a much greater extent than in guinea pigs. These results demonstrate the advantages of precision-cut liver slices as a powerful tool to investigate the species specific metabolism of xenobiotics, since the conditions employed enabled both phase I and phase II reactions in vitro.

Animals↗
PubMed1996

Abnormal B cell response of protein kinase C in some common variable immunodeficiency.

The localization of protein kinase C (PKC) was investigated in B cells or B cell lines derived from patients with common variable immunodeficiency (CVI) and healthy controls. Stimulation of the healthy control B cells by phorbol ester or anti-mu induced PKC activation and translocation to the plasma membrane after 10 min. In contrast, in the CVI-B cells, no apparent PKC translocation was induced by either phorbol ester or anti-mu stimulation. These results suggest that the pathogenesis in some CVI patients might involve defects in the pathway of PKC activation.

Adult↗
PubMed1996

Microsatellite instability is an early genetic event in myelodysplastic syndrome but is infrequent and not associated with TGF-beta receptor type II gene mutation.

We examined microsatellite instability (MSI) at 10 loci of dinucleotide repeats using the polymerase chain reaction (PCR) in patients with myelodysplastic syndrome (MDS). Bone marrow DNA was obtained from 45 patients repeatedly during the disease course and fibroblast DNA was also collected from 19 of them as a normal control. Three of the 19 patients showed an alteration at more than three loci, when the allele length was compared between their fibroblast DNA and the initial marrow DNA. On the other hand, none of the 45 patients showed an alteration when the initial sample was compared with the latest one. One of the three patients with MSI had refractory anemia and two refractory anemia with ring sideroblasts and none of them showed disease progression, complex chromosome abnormality, karyotypic evolution, or mutation of N-RAS or TP53. Moreover, a frameshift mutation within 10 repeating adenines of transforming growth factor beta type II receptor gene, which was recently recognized as a critical target of MSI, was not found in any of the patients including the three with MSI. These findings suggest that MSI is an early but infrequent genetic event and is independent of other critical genetic aberrations in the development of MDS.

Bone Marrow↗
PubMed1996

[A case report of Takayasu's arteritis with aortic pseudoaneurysm caused by aortic perforation].

A 47-year-old man presented with hemoptysis. From around June 20, 1995, he had symptoms of a common cold, but hemoptysis suddenly occurred on July 1 and he was brought to hospital. The chest X-ray film showed pleural effusion and enlargement of the mediastinum. CT scans showed calcification of the aorta, with a pseudoaneurysm 8 cm in diameter anterior to the descending aorta. When thoracotomy was performed under partial extracorporeal circulation, the thoracic cavity was found to be filled with bloody hydrothorax and hematoma, and the lower lobe of the left lung was adherent to the descending aorta. After a longitudinal incision was made in the aorta, a perforation 7 mm in diameter was identified in the posterior wall, and this was assumed to be the cause of the pseudoaneurysm. This part of the aorta was replaced with a Woven Dacron graft. Takayasu's arteritis was diagnosed by histological examination of the resected specimen, and the changes in the aortic wall at the site of perforation were considered to be chronic. About 30% of patients with this disease have aortic ectasia, but only a few pseudoaneurysms have been reported. Since the pseudoaneurysm occurred in our patient after reduction in the dose of medication, the development of perforation was suggested to be related to this change. In the future, this patient will require careful follow up for anastomotic aneurysm.

Aneurysm, False↗
PubMed1996

Internal tandem duplication of the flt3 gene found in acute myeloid leukemia.

We analyzed mRNA expression of the flt3 gene in 30 patients with acute myeloid leukemia (AML) and 50 with acute lymphoblastic leukemia (ALL). Using reverse transcriptase-polymerase chain reaction (RT-PCR), expression of flt3 was observed in 61 patients; 22 (73%) with AML and 39 (78%) with ALL. Among these, five patients with AML (one M2, two M4, and two M5) showed unexpected longer transcripts with a primer combination which could amplify the transmembrane (TM) domain through the juxtamembrane (JM) domain. For those patients who expressed flt3 mRNA, the extracellular domain of the flt3 gene was also examined by RT-PCR, but no length abnormality was seen in this region. We further analyzed the TM domain through the second tyrosine kinase domain by genomic amplifications. The five patients who showed aberrant flt3 transcripts exhibited abnormal longer PCR products in addition to the germline products at a region corresponding to the JM through the first TK (TK1) domains. Sequence analyses of the abnormal RT-PCR products demonstrated that partial sequences were tandemly duplicated. Because all these altered transcripts were in-frame, deduced protein products could be expected. Sequence analyses of the genomic DNA revealed that three of the five patients showed a simple internal duplication within exon 11; one had an internal duplication (26 bp) with a 4-bp insertion; and in the fifth patient, a 136-bp sequence from the 3' part of exon 11 to intron 11 and the first 16-bp sequence of exon 12 were each duplicated with 1-bp insertion. In order to confirm the tumor specificity of these alterations, DNA samples obtained at complete remission were also analyzed in the three patients harboring an flt3 duplication, but no abnormal PCR product other than germline was detected in any of the samples. Our results suggest that an internal tandem duplication at the JM/TK1 domains of the flt3 gene is a somatic change detected preferentially in AML, possibly containing a monocytic component.

Acute Disease↗
PubMed1995

TRH in the dorsal motor nucleus of vagus is involved in gastric erosion induced by excitation of raphe pallidus in rats.

The influence of excitation of the raphe pallidus neurons on gastric mucosal lesions was examined in urethane-anesthetized rats pretreated with indomethacin (5 mg/kg, i.p., -60 min). Kainic acid (12 ng/30 nl), delivered into the raphe pallidus, increased gastric acid secretion (94.8 +/- 15.9 mumol/60 min) and produced gastric lesions in 2.7 +/- 0.3% of the corpus mucosa. No gastric erosions were observed when kainic acid was injected nearby, but outside, of the raphe pallidus. The gastric lesions induced by microinjection of kainic acid into the raphe pallidus neurons were completely prevented by atropine (0.3 mg/kg, -30 min, s.c.) and bilateral microinjection of TRH antibody # 8964 (1.3 microgram/site) into the dorsal motor nucleus of the vagus (DMN). Microinjection of the TRH antibody into the hypoglossal nucleus or control antibody into the DMN did not modify the mucosal lesions induced by kainic acid into the raphe pallidus. These data suggest that activation of raphe pallidus induced vagal cholinergic mediated gastric erosion through TRH release in the DMN.

Animals↗
PubMed1995

Selective inhibition of gastrulation in the starfish embryo by albuside B, an inosine analogue.

External application of 0.2-100 micrograms/ml albuside B inhibits gastrulation of the starfish (Asterina pectinifera) embryo. Treated embryos retain the late blastula morphology with the vegetal plate. However, the vegetal plate is unreactive to soybean agglutinin, a probe for observing the progenitor cells of the archenteron (mesendoderm) in a normal embryo. The effective period of the treatment is limited from 4 to 6 h after fertilization, a period immediately before the onset of blastulation. RNA synthesis is unaffected during the period of sensitivity. The selectivity of the inhibition shows that albuside B may be a useful tool for studying the mechanisms of mesendoderm differentiation.

Animals↗
PubMed1995

Establishment and molecular characterization of a novel leukemic cell line with Philadelphia chromosome expressing p230 BCR/ABL fusion protein.

The cell line AR230 was established from the peripheral blood mononuclear cells of a patient with chronic myeloid leukemia and t(9;22) translocation bearing a variant type of BCR/ABL rearrangement. AR230 expresses a BCR/ABL fusion protein with a molecular mass of 230 kilodaltons (kDa) due to the insertion of 180 amino acids encoded by 3' exons of BCR (b4 to c3). An immune complex kinase assay showed that the 230-kDa BCR/ABL protein ahd autophosphorylation activity. Immunoprecipitation analysis revealed a stable complex of GRB2 and 230-kDa BCR/ABL proteins, indicating that the Ras activation pathway is involved in the process of transformation. AR230 expressed another short transcript consisting of a BCRc2/ABL junction, which is associated with a stop signal shortly after the junction. To our knowledge, this is the first cell line expressing a 230-kDa fusion product of BCR/ABL. AR230 will be useful for studying the biological function of divergent BCR/ABL proteins.

Amino Acid Sequence↗
PubMed1995

TP53 mutations emerge at early phase of myelodysplastic syndrome and are associated with complex chromosomal abnormalities.

We examined TP53 mutation in 57 patients with myelodysplastic syndrome (MDS) at either the MDS phase or at the terminal leukemic phase using polymerase chain reaction-mediated single-strand conformation polymorphism (PCR-SSCP) analysis. TP53 mutations within exons 5 through 8 were found in seven patients. All these mutations were detected at the presentation of MDS whether these patients showed leukemic transformation or not. TP53 mutations were frequently found in patients with loss of the short arm of chromosome 17 (17p-) (three of seven patients with 17p-, 43%) and complex karyotypic abnormalities (five of 14, 38%). Among the seven patients with the TP53 mutation, four patients progressed to acute leukemia within 7 months from the diagnosis of MDS, and the remaining three died within 7 months without leukemic transformation. These findings suggest that mutations of the TP53 can be implicated in leukemic transformation and a poor prognosis in MDS.

Acute Disease↗
PubMed1995

Molecular cloning and characterization of mouse HS1.

Here we report the cloning of a cDNA and a genomic DNA encoding the mouse homolog of human HS1, a hematopoietic cell-specific protein-substrate of non-receptor type protein-tyrosine kinase(s). Sequence analysis of the mouse HS1 cDNA revealed that it is highly homologous to human HS1 (total percent match = 84%) especially in the amino-terminal half, which contains unique repeating motifs, and in the carboxyl-terminal Src-homology 3 domain. As is the human counterpart, the mouse HS1 gene is expressed exclusively in hematopoietic cells. Genomic fragments covering most of the HS1 gene were isolated and used to map this gene to mouse chromosome 16.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Inhibitory effect of the immunosuppressant FK506 on apoptotic cell death induced by HIV-1 gp120.

Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 may play a central role in inducing immunoregulatory disorders after HIV infection. The apoptotic death of normal human peripheral blood mononuclear cells was induced by priming with gp120 followed by stimulation with an anti-T cell receptor (TCR) antibody. Tumor necrosis factor-alpha produced by gp120-binding macrophages may be important to induce this cell death. Treatment of gp120-primed cells with an immunosuppressant (FK506) before TCR signaling inhibited apoptotic cell death, and this blocking effect of FK506 was concentration dependent. FK506 did not have any influence on cell growth and viability over the range of concentrations tested. These findings suggest that FK506 is a potentially useful drug in delaying the onset of AIDS after HIV infection.

Antiviral Agents↗