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Biomedical subjects

H Kaneko

Publications and source records attributed to H Kaneko.

At least 199 records · Page 11Linked to original sources
PubMed1998

Mutational analysis of the N-ras gene in acute lymphoblastic leukemia: a study of 125 Japanese pediatric cases.

A point mutation of the N-ras gene is one of the known genetic alterations identified in patients with acute lymphoblastic leukemia (ALL), but its clinical importance is still controversial. Using polymerase chain reactions, we examined codons 12, 13 and 61 of this gene in 125 Japanese childhood ALL patients (64 common-ALL, 22 pre-B-ALL, 33 T-ALL, 2 B-ALL, 3 undifferentiated ALL, and 1 unclassified ALL) including 9 relapsed patients. An N-ras point mutation was observed in 14 (11%) patients (9 common-ALL, 3 T-ALL, and 2 undifferentiated ALL; 13 patients at diagnosis and 1 at relapse). The patients with undifferentiated ALL harbored an N-ras mutation at a significantly higher rate. However, no correlation was found between the presence of an N-ras mutation and sex, age, or white blood count. There was no significant difference in the event-free survival rate between 13 fresh patients with an N-ras mutation and 103 patients with a wild-type configuration. The N-ras mutation was present in about 10% of childhood ALL cases but it did not have a prognostic impact. The sequence analyses revealed that the majority of the patients (13/14) had an N-ras mutation of a G to A transition. This finding was consistent with previous reports on N-ras mutations in acute leukemias in which the incidence of a G to A mutation was significantly higher in ALL than in myeloid malignancies.

Child↗
PubMed1998

Human cord blood-derived primitive progenitors are enriched in CD34+c-kit- cells: correlation between long-term culture-initiating cells and telomerase expression.

We studied the functional characteristics of subpopulations of cord blood-derived CD34+ cells expressing different levels of CD38 and c-kit antigens, using clonal cell culture and long-term culture with allogeneic bone marrow stromal cells or the MS-5 murine stromal cell line to assay long-term culture-initiating cells (LTC-IC) in each subpopulation. To investigate the capacity for replication, proliferation, and differentiation of each subpopulation of CD34+ cells, we also studied the correlation between LTC-IC and telomerase activity. After 5 weeks of coculture, LTC-IC accounted for one out of 32 CD34+CD38- cells and one out of 33 CD34+c-kit- cells. In contrast, the frequency of LTC-IC was low in their antigen-positive counterparts (one per 84 CD34+CD38+ cells, one per 90 CD34+c-kit(low) cells, and very low among CD34+c-kit(high) cells). It was noteworthy that some LTC-IC derived from CD34+CD38- as well as CD34+c-kit- cells generated colony-forming cells (CFCs) after up to 9 weeks of coculture. Telomerase activity was consistently low in CD34+CD38- and CD34+c-kit- cells compared to CD38+ or c-kit(high or low) cells, suggesting that CD34+CD38- or c-kit- cells are likely to be more quiescent. These results suggest that the CD34+CD38- and CD34+c-kit- cell populations are primitive stem/progenitor cells, and that the telomerase activity of these cells correlates with their proliferative capacity as well as their stage of differentiation.

Animals↗
PubMed1998

Serum IgE level is negatively correlated with the ability of peripheral mononuclear cells to produce interferon gamma (IFNgamma): evidence of reduced expression of IFNgamma mRNA in atopic patients.

BACKGROUND: In patients with atopic diseases such as bronchial asthma and atopic dermatitis, an elevated serum IgE level is common. Several studies showed that interleukin-4(IL-4) and interferon-gamma (IFNgamma) are important for regulation of IgE production. OBJECTIVES: The study was designed to examine the pathogenesis of an elevated serum IgE level at the production levels of TH1-type and TH2-type cytokines. METHODS: The production of interleukin-2 (IL-2), IL-4, interleukin-5 (IL-5) and IFNgamma by peripheral blood mononuclear cells (PBMCs) stimulated with phytohemagglutinin (PHA) was analysed in 20 individuals with various serum IgE levels. The amount of IFNgamma mRNA in the stimulated PBMCs was analysed using a quantitative polymerase chain reaction method. RESULTS: Cytokine production was analysed simply as a function of serum IgE level. The serum IgE level was negatively correlated with the amount of IFNgamma secreted by PBMCs (n = 20, R = -0.724, P<0.005) when logarithmically transformed data were analysed, but were not or were only weakly correlated with those of IL-4, IL-2, or IL-5 secreted by these cells (n = 20). For investigation of the cause of reduced IFNgamma production in individuals whose serum IgE level are high, the amount of IFNgamma mRNA was determined. The levels of IFNgamma mRNA expression in the stimulated PBMCs correlated well with the amount of IFNgamma secreted by the PBMCs (n = 8, R = 0.947, P < 0.001). CONCLUSIONS: Reduced IFNgamma production ability due to reduced IFNgamma mRNA expression in PBMCs is associated with an elevated serum IgE level in atopic patients.

Adolescent↗
PubMed1998

Reduced interferon gamma production by antigen-stimulated cord blood mononuclear cells is a risk factor of allergic disorders--6-year follow-up study.

BACKGROUND: It is not sufficient to predict 'high allergic risk newborns' on the basis of increased IgE concentrations of cord blood alone, because a raised cord blood IgE concentration is specific but not sensitive in the prediction of the development of allergic disorders. Warner et al. have reported that interferon gamma (IFN-gamma) production by allergen-triggered cord blood cells is a predictor of atopic eczema, based on the 1-year follow-up study. OBJECTIVE: We examined whether IFN-gamma production by antigen-stimulated cord blood mononuclear cells (CBMCs) is a risk factor of allergic disorders, based on the 6-year follow-up study. METHODS: The relationships among cord blood IgE concentrations, IFN-gamma and interleukin-2 (IL-2) productions by antigen-stimulated CBMCs, and the development of allergic disorders in 21 infants for 6 years were investigated. RESULTS: Atopic dermatitis, atopic dermatitis and allergic rhinitis, or atopic dermatitis and bronchial asthma developed in seven of 21 subjects. The maximal IFN-gamma concentration in culture supernatants of ovalbumin (OA) or bovine serum albumin (BSA) stimulated CBMCs in infants who developed allergic disorders was significantly lower (P < 0.01) than that in infants who did not develop any allergic disorders. In contrast, the maximal IL-2 concentration in culture supernatants of OA- or BSA-stimulated CBMCs in infants who developed allergic disorders was not lower than in infants who did not develop any allergic disorders. Moreover, the IFN-gamma concentrations were negatively correlated with cord blood IgE concentrations. CONCLUSION: Reduced IFN-gamma production by antigen-stimulated CBMCs is a risk factor of allergic disorders.

Antigens↗
PubMed1998

Expression of Pax5 gene in human haematopoietic cells and tissues: comparison with immunodeficient donors.

In mice, Pax5 gene is indispensable for B cell development. Pax5-deficient mice fail to produce mature B cells owing to complete arrest of B cell development at a precursor stage. However, the lineage and stage of human Pax5 gene expression have remained elusive. In this investigation expression of the human Pax5 gene was studied. Pax5 gene expression was detected in B cell lines but not in myeloma cell lines. CD19 expression was correlated with Pax5 gene expression. Adult spleen and bone marrow and fetal spleen and liver showed strong Pax5 gene expression, as did the corresponding mouse tissues, as reported previously. In common variable immunodeficiency (CVID) peripheral blood lymphocytes (PBL) with a decreased number of B cells, no Pax5 gene expression was detected. Some CVID PBL stimulated with IL-2, IL-10 and anti-CD40 monoclonal antibody, expressed the Pax5 gene. Defect of Pax5 gene expression in CVID may be caused by regulatory T cell disorder.

Adolescent↗
PubMed1998

Binding of HIV-2 envelope glycoprotein to CD8 molecules and related chemokine production.

We recently found that human immunodeficiency virus (HIV)-2 envelope glycoprotein, but not that of HIV-1, could bind to CD4 and CD8 molecules on T cells, and that the binding site of HIV-2 envelope glycoprotein was located on the alpha-chain (but not the beta-chain) of CD8. This study showed that the binding of HIV-2 envelope glycoprotein could induce phosphorylation of protein tyrosine kinase p56lck in CD8+ T cells. We also found that production of beta-chemokines in response to HIV-2 envelope glycoprotein was significantly higher than that in response to HIV-1 envelope glycoprotein, and that CD8+ T cells were the main source of beta-chemokines production among the T-cell population. These findings indicate the possibility that the binding of envelope glycoprotein to CD8 molecules are related to signal transduction into CD8+ T cells and the resultant beta-chemokine production in HIV-2 infection. Our results may help to explain the differences in disease manifestations between HIV-1 and HIV-2, including the lower virulence of HIV-2 and the longer survival of HIV-2-infected individuals.

CD8 Antigens↗
PubMed1998

Coelomic pouch formation in reconstructing embryos of the starfish Asterina pectinifera.

The morphogenetic processes of coelomic pouch (CP) formation in starfish embryos that were experimentally dissociated and induced to undergo reconstruction were studied. An analysis of these embryos randomly chosen from several cultures showed that CP always form on either side of the esophagus, even though the CP formation can differ in timing of initiation and duration, and can vary in number and size from embryo to embryo. Successive observations of CP formation in living embryos revealed two distinct sequences of CP development that were accompanied by different appearances of the blastocoele. These processes were named 'enterocoelic-like' and 'schizocoelic-like' CP formation. The former resembled normal development and occurred in embryos with a transparent blastocoele. The latter was characterized by the aggregation and epithelialization of mesenchyme-like cells on either side of the esophagus and was observed in embryos possessing a cloudy blastocoele. In a few embryos, both types of CP formation were seen in the same individual ('mosaic type' CP formation). Thick sections of embryos possessing a cloudy blastocoele revealed that aggregates of mesenchyme-like cells undergoing CP formation directly contact the developing esophagus. Together, these data demonstrate flexibility in the morphogenetic processes that regulate CP formation, and suggest that positional cues in the esophagus regulate the placement of CP.

Animals↗
PubMed1998

Implications of gastric topical bioactive peptides in ammonia-induced acute gastric mucosal lesions in rats.

BACKGROUND: Ammonia, one of the pathogenic factors in Helicobacter pylori-induced mucosal injury, induces acute mucosal lesions in the rat glandular stomach. METHODS: The effect of ammonia administered intragastrically on gastric peptides was investigated in urethane-anesthetized rats. RESULTS: Gastric mucosal lesions were observed 5 min after 0.3% ammonia (4 ml/kg, intragastrically). Immunoreactive endothelin-1 (ET-1) and immunoreactive thyrotropin-releasing hormone (TRH) concentrations in the gastric wall decreased significantly 2 min and 5 min after ammonia, respectively. A significant increase in gastric juice immunoreactive ET-1 and TRH levels was reciprocally observed. The severity of gastric mucosal injury and changes in gastric immunoreactive ET-1 and TRH concentrations were shown to be concentration-dependent 30 min after ammonia. Atropine (5 mg/kg, intraperitoneally, -20 min) prevented ammonia-induced injury accompanied by a block of changes in gastric immunoreactive ET-1 and TRH concentrations. BQ-485 (ET(A) receptor antagonist; 2 mg/kg, subcutaneously) also abolished ammonia-induced lesions and gastric immunoreactive TRH changes. CONCLUSIONS: These findings suggested that gastric ET-1 and TRH play a role in ammonia-induced gastric mucosal injury mediated via a muscarine and an ET(A) receptor.

Ammonia↗
PubMed1998

Prolactin-induced expression of TATA-less cyclin D3 gene is mediated by Sp1 and AP2.

The TATA-less cyclin D3 gene is stimulated by prolactin (PRL) in rat Nb2 T-lymphocytes. DNA mobility shift assay and luciferase transfection analysis revealed that the gene has a potential promoter region, two enhancer domanins and a silencer region. The promoter region possessed three Sp1 sites and two AP2 sites, and both enhancer regions had one AP2 binding site each. Analysis using oligonucleotide probes and purified AP2 protein has suggested that the expression of rat cyclin D3 gene is promoted by Sp1 and AP2 factors.

Animals↗
PubMed1998

Cooperative and differential effects of estrogen, prolactin, 22K and 20K human growth hormones on cyclin D1/PRAD1 gene expression in T-47D human breast cancer cells.

The cyclin D1/PRAD1 gene is correlated with carcinogenesis of human breast cancer. In this study, we have analyzed effects of breast cancer-related hormones on the cyclin D1 gene expression in T-47D human breast cancer cells. Estradiol (E2) and human prolactin (hPRL) equally enhanced the cyclin D1 gene expression in the cells, and 22 and 20 kDa human growth hormones (22K and 20K hGHs) showed less stimulatory effects. In the presence of E2, however, hPRL or 22K hGH showed additive stimulations of the cyclin D1 gene expression to that by E2 alone, while 20K hGH did not show any additive stimulation of the gene expression. The results suggest that the signal pathways through estrogen and hPRL receptors are important for cyclin D1 gene expression in breast cancer cells, and that 20K hGH has little effect on the cyclin D1 gene expression in these cells because of its lower affinity to PRL receptor.

Blotting, Northern↗
PubMed1998

Inverse effects of 20K and 22K human growth hormones on the growth of T-47D human breast cancer cells in culture and in nude mice.

The major form of human growth hormone (22K hGH) stimulates the growth of T-47D human breast cancer cells in culture and in nude mice by binding to their receptors for growth hormone and prolactin. Another isoform of hGH having a smaller molecular mass (20K hGH) is known to show different binding affinities to these receptors. In this study, we have analyzed the effects of 20K hGH on the growth of T-47D cells in vitro and in vivo. 20K hGH (50 ng/ml) inhibited the proliferation and DNA synthesis of T-47D cells cultured in the presence and absence of 17 beta-estradiol (100 ng/ml), while 22K hGH (50 ng/ml) promoted the cellular growth. In estradiol-treated nude mice, 22K hGH (100 micrograms) remarkably promoted the growth of T-47D tumor, but 20K hGH again suppressed the tumor growth significantly. The results suggest the presence of different signal pathways for these two hGH isoforms and imply a possible clinical application for 20K hGH.

Animals↗
PubMed1998

Circulating interleukin-16 in systemic lupus erythematosus.

OBJECTIVE: To investigate the relationship between interleukin (IL)-16 and systemic lupus erythematosus (SLE). METHODS: Serum levels of IL-16 were examined in SLE patients using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The serum level of IL-16 in the patients was much higher than that in healthy volunteers (P < 0.001). An increase in IL-16 was observed in proportion to the activity of SLE assessed by the SLE Disease Activity Index (SLEDAI) score (P < 0.0001). CONCLUSIONS: Our observations suggest an interaction between disease activity and the production of IL-16 in SLE, and reveal that IL-16 is a useful indicator of disease activity. This is the first report describing the relationship between IL-16 and SLE.

Adolescent↗
PubMed1998

Vagal mechanisms underlying gastric protection induced by chemical activation of raphe pallidus in rats.

Peripheral mechanisms involved in kainic acid injected into the raphe pallidus (Rpa)-induced gastric protection were investigated in urethan-anesthetized rats. Gastric mucosal blood flow (GMBF), acid secretion, and gastric injury induced by intragastric ethanol (60%) were measured in response to kainic acid (25 pg) injected into the Rpa. Kainic acid reduced ethanol-induced gastric lesions by 57%. The protective effect was blocked by vagotomy, capsaicin deafferentation, and intravenous injection of the calcitonin gene-related peptide (CGRP) antagonist CGRP-(8-37) and NG-nitro-L-arginine methyl ester (L-NAME). L- but not D-arginine reversed the L-NAME action. Kainic acid injected into the Rpa, unlike outside sites, increased basal GMBF but not acid secretion. Indomethacin unmasked an acid secretory response to kainic acid. These results show that kainic acid injected into the Rpa at a dose that did not stimulate acid secretion, due to the inhibitory effect of prostaglandins, protects against ethanol-induced gastric injury through vagal-dependent activation of CGRP contained in capsaicin-sensitive afferents and nitric oxide-mediated gastric vasodilatory mechanisms.

Afferent Pathways↗
PubMed1998

Central action of adrenomedullin to prevent ethanol-induced gastric injury through vagal pathways in rats.

Adrenomedullin (AM), belongs to the calcitonin gene-related peptide (CGRP) family and interacts with AM and CGRP1 receptors. Specific AM receptors and immunoreactivity are present in the rat brain. The effect of intracisternal injection of rat AM on ethanol-induced gastric lesions was studied in conscious Wistar rats. The peptide was injected intracisternally or intravenously under short anesthesia 20 min before intragastric injection of 70% ethanol. Corpus lesions were determined 1 h after ethanol. Intracisternal AM (75, 150, and 300 pmol) dose-dependently inhibited ethanol-induced gastric lesions by 40-72% and rat alpha-CGRP (150 pmol ic) by 76%. Intravenous AM (300 pmol) had no effect. The CGRP1 receptor antagonist CGRP-(8-37) (9.6-19.2 nmol ic) dose-dependently inhibited the protective effect of intracisternal alpha-CGRP but not that of AM. Subdiaphragmatic vagotomy and peripheral injection of atropine, indomethacin, or NG-nitro-L-arginine methyl ester (L-NAME) prevented AM protective action. L-Arginine but not D-arginine blocked L-NAME action. These data suggest that both AM and CGRP act in the brain to prevent ethanol-induced gastric lesions through interaction with their specific receptors. AM action may involve vagal cholinergic-dependent modulation of prostaglandins and nitric oxide protective mechanisms.

Adrenomedullin↗
PubMed1998

Bopindolol: a slowly dissociating antagonist from the beta-adrenoceptors in guinea pig atria.

The dissociating and/or residual inhibitory effects of bopindolol from beta-adrenoceptors of atria strips pretreated with this drug which was then washed out with buffers on the responses to isoprenaline were determined and compared with those of propranolol, pindolol, atenolol, and the two active metabolites of bopindolol: 18-502 and 20-785. Low concentrations of bopindolol (10(-9) to 10(-8) mol/l) and the active metabolite 18-502 (10(-9) mol/l) produced rightward shifts of the concentration-response curves. On the other hand, high concentrations of bopindolol (10(-7) mol/l) and metabolite 18-502 (10(-8) and 10(-7) mol/l) produced a reduced maximum response by isoprenaline, suggesting that these nonparallel rightward shifts have pD2 values of 7.57 (bopindolol) and 7.67 (18-502), respectively, at 0 min after washout with buffers. Pindolol (10(-7) mol/l) and propranolol (10(-7) and 10(-8) mol/l) also produced a rightward shift of isoprenaline response curves, and these concentration-response curves in guinea pig atria strips pretreated with pindolol (10(-7) mol/l) and propranolol (10(-6) mol/l) recovered to control levels. Neither of these drugs, however, reduced the maximum response by isoprenaline. A high concentration (10(-5) mol/l) of atenolol was required for a rightward shift of the isoprenaline concentration-response curve, and this drug also did not reduce the maximum response. Thus, we conclude that bopindolol and metabolite 18-502 slowly dissociate and act as noncompetitive beta-antagonists rather than easily reversible beta-adrenoceptor antagonists.

Adrenergic beta-Agonists↗
PubMed1998

Rare alteration of genomic structure or expression of the DPC4 gene in myelogenous leukemias.

We examined homozygous deletion, point mutation and expression of DPC4 gene, a recently isolated candidate pancreatic tumor suppressor gene, in 53 patients with myelogenous leukemias and 5 cell lines. The patients consisted of 34 cases of chronic myelogenous leukemia including 22 in the chronic phase, 3 in the accelerated phase, and 9 in blastic crisis, and 19 with acute myelogenous leukemia including 9 at the initial presentation and 10 at relapse. Polymerase chain reaction (PCR)-based deletion analysis for DPC4 exon 8 and PCR-single strand conformation polymorphism study for the entire coding region were carried out. Homozygous deletion or subtle mutation was not detected in any of the samples examined. However, 3 patients with various clinical phases showed a decrease of DPC4 expression. These results suggest that DPC4 alteration is not a crucial event in the development or the progression of myelogenous leukemias.

DNA-Binding Proteins↗