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H Kageyama

Publications and source records attributed to H Kageyama.

At least 19 recordsLinked to original sources
PubMed2006

Bcl-2 is a key regulator for the retinoic acid-induced apoptotic cell death in neuroblastoma.

Retinoic acid (RA) has been shown to induce neuronal differentiation and/or apoptosis, and is widely used as a chemotherapeutic agent for treating the patients with neuroblastoma. However, the therapeutic effect of RA is still limited. To unveil the molecular mechanism(s) inducing differentiation and apoptosis in neuroblastoma cells, we compared CHP134 and NB-39-nu cell lines, in which all-trans-RA (ATRA) induces apoptosis, with LA-N-5 and RTBM1 cell lines, in which it induces neuronal differentiation. Here, we found that Bcl-2 was strongly downregulated in CHP134 and NB-39-nu cells, whereas it was abundantly expressed in LA-N-5 and RTBM1 cells. ATRA-mediated apoptosis in CHP134 and NB-39-nu cells was associated with a significant activation of caspase-9 and caspase-3 as well as cytoplasmic release of cytochrome c from mitochondria in a p53-independent manner. Enforced expression of Bcl-2 significantly inhibited ATRA-mediated apoptosis in CHP134 cells. In addition, treatment of RTBM1 cells with a Bcl-2 inhibitor, HA14-1, enhanced apoptotic response induced by ATRA. Of note, two out of 10 sporadic neuroblastomas expressed bcl-2 at undetectable levels and underwent cell death in response to ATRA in primary cultures. Thus, our present results suggest that overexpression of Bcl-2 is one of the key mechanisms to give neuroblastoma cells the resistance against ATRA-mediated apoptosis. This may provide a new therapeutic strategy against the ATRA-resistant and aggressive neuroblastomas by combining treatment with ATRA and a Bcl-2 inhibitor.

Apoptosis↗
PubMed2006

Adenosine A1 receptor antagonist improves intradialytic hypotension.

Intradialytic hypotension is a most frequent complication of hemodialysis and may contribute to cardiovascular events and high mortality. There is a hypothesis that an increase in adenosine generation during hemodialysis may cause vasodilation and a decrease in cardiac output, which results in systemic hypotension. We studied whether this can be blocked by an adenosine A1 receptor antagonist. We investigated the effects of an A1 antagonist, FK352, injection in 30 chronic hemodialysis patients with frequent intradialytic hypotension by a prospective, multicenter, double-blind placebo-controlled study for 4 weeks after 4 weeks of the observation period. Intradialytic hypotension was defined as systolic blood pressure (SBP) less than 110 mmHg, with SBP drop of more than 30 mmHg from the predialysis level. The efficacy of FK352 was primarily assessed by the reduction rate of dialysis hypotension between the FK352 and placebo groups. Incidence of emergency treatments caused by hypotension was evaluated. FK352 (50 mg, intravenous) or an equivalent placebo was injected into the dialysis circuit 1 h after starting dialysis. Blood pressure and heart rate were monitored every 30 min during dialysis. FK352 significantly improved intradialytic hypotension (P=0.046), in that the reduction rates of intradialytic hypotension in the FK352 and placebo groups were -12.8% (Q1 (first quantile), Q3 (third quantile): -27.5, -1.7), and +8.3% (Q1, Q3: -16.6, +16.7), respectively. The frequency of discontinuation of dialysis was significantly reduced by FK352. No apparent side effects were observed from treatment with FK352. In conclusion, the A1 antagonist FK352 may offer a novel therapeutic option for chronic dialysis patients associated with intradialytic hypotension.

Adenosine↗
PubMed2006

Galanin-like peptide promotes feeding behaviour via activation of orexinergic neurones in the rat lateral hypothalamus.

Galanin-like peptide (GALP) is produced in neurones in the hypothalamic arcuate nucleus and is implicated in the neural control of feeding behaviour. Previously, we have reported that GALP immunoreactive fibres were in direct contact with orexin/hypocretin immunoreactive neurones in the rat lateral hypothalamus using double-immunofluorescence. Centrally administered GALP is known to stimulate feeding behaviour. However, the target neurones of this action have not been clarified. The present study aimed to determine features of the GALP-mediated neuronal feeding pathway in rat. Accordingly, at the ultrastructural level, GALP-immunoreactive axon terminals were found to make synapses on orexin/hypocretin immunoreactive cell bodies and dendritic processes in the lateral hypothalamus. c-Fos immunoreactivity was expressed in orexin/hypocretin-immunoreactive neurones but not in melanin concentrating hormone-immunoreactive neurones in the lateral hypothalamus at 90 min after the application of GALP by i.c.v. infusion. Furthermore, to determine whether GALP regulates feeding behaviour via orexin/hypocretin neurones, the feeding behaviour of rats was studied following GALP i.c.v. injection with or without anti-orexin A and B immunoglobulin (IgG) pretreatment. The anti-orexin IgGs markedly inhibited GALP-induced hyperphagia. These results suggest that orexin/hypocretin-containing neurones in the lateral hypothalamus are targeted by GALP, and that GALP-induced hyperphagia is mediated via orexin/hypocretin neurones in the rat hypothalamus.

Animals↗
PubMed2006

Neuropeptide W is present in antral G cells of rat, mouse, and human stomach.

Neuropeptide W (NPW) is a 30-amino-acid peptide initially isolated from the porcine hypothalamus as an endogenous ligand for the G protein-coupled receptors GPR7 and GPR8. An intracerebroventricular administration of NPW increased serum prolactin and corticosterone concentrations, decreased dark-phase feeding, raised energy expenditure, and lowered body weight. Peripherally, GPR7 receptors are abundantly expressed throughout the gastrointestinal tract; the presence of NPW in the gastrointestinal endocrine system, however, remains unstudied. Using monoclonal and polyclonal antibodies raised against rat NPW, we studied the localization of NPW in the rat, mouse, and human stomach by light and electron microscopy. NPW-immunoreactive cells were identified within the gastric antral glands in all three species. Double immunohistochemistry and electron-microscopic immunohistochemistry studies in rats demonstrated that NPW is present in antral gastrin (G) cells. NPW immunoreactivity localized to round, intermediate-to-high-density granules in G cells. NPW-immunoreactive cells accounted for 90% chromagranin A- and 85% gastrin-immunoreactive endocrine cells in the rat gastric antral glands. Using reversed-phase HPLC coupled with enzyme immunoassays specific for NPW, we detected NPW30 and its C-terminally truncated form, NPW23, in the gastric mucosa. Plasma NPW concentration of the gastric antrum was significantly higher than that of the systemic vein, suggesting that circulating NPW is derived from the stomach. Plasma NPW concentration of the gastric antrum decreased significantly after 15-h fast and increased after refeeding. This is the first report to clarify the presence of NPW peptide in the stomachs of rats, mice, and humans. In conclusion, NPW is produced in gastric antral G cells; our findings will provide clues to additional mechanisms of the regulation of gastric function by this novel brain/gut peptide.

Animals↗
PubMed2006

[Metastatic lung tumor from uterine leiomyosarcoma].

We herein present 2 cases of metastatic lung tumor derived from uterine leiomyosarcoma. In the case 1, a 59-year-old woman was admitted to our hospital to examine abnormal shadow detected on chest X-ray. She had undergone hysterectomy and oophorectomy for uterine leiomyosarcoma 19 months previously. A round 3 cm mass in the right lung (S10) was seen on chest X-ray and computed tomography (CT). No other distant metastases or local recurrence were found, and the right lower lobectomy was perfomed under the clinical diagnosis of metastatic lung tumor. Postoperative pathologic examination revealed the tumor as a metastatic leiomyosarcoma. The patient recovered uneventfully, and there have been no signs of recurrence for 26 months after the pulmonary resection. In the case 2, a 58-year-old woman, who had undergone hysterectomy and oophorectomy for uterine leiomyosarcoma 7 months previously, was admitted to our hospital for further examination of pulmonary tumors on chest X-ray. Two tumors were recognized in the left lung (S8 and S10) on chest X-ray and CT. No other distant metastases or local recurrence were found, and the left lower lobectomy was performed under the clinical diagnosis of metastatic lung tumors. Pathological examinations revealed smooth muscle cells with nuclear pleomorphism and high mitotic indices. The tumors proved to be lung metastases derived from uterine leiomyosarcoma. Postoperative course was uneventful. However, brain metastasis was found 1 month after the pulmonary resection, and she underwent resection of brain metastasis. Two months after the brain metastasectomy, local recurrence of the brain tumor developed and re-resection followed by stereotactic radiotherapy was performed. Furthermore, intrapelvic recurrence was found 4 months after the pulmonary resection. Exploratory laparotomy revealed the tumor was unresectable, and she received 4 courses of chemotherapy (paclitaxel and carboplatin). For metastatic lung tumor from uterine leiomyosarcoma, surgery has been considered the best choice. However, for patients with uterine leiomyosarcoma who cannot be treated surgically because of multiple metastatic tumors or poor surgical risk chemotherapy (paclitaxel and carboplatin) or stereotactic radiotherapy can be strategies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Ventromedial hypothalamus lesions induce jejunal epithelial cell hyperplasia through an increase in gene expression of cyclooxygenase.

BACKGROUND: We demonstrated that ventromedial hypothalamus (VMH) lesions facilitate DNA synthesis, which reflects cell proliferation in abdominal organs, including the liver, pancreas, stomach, small intestine and large intestine, all of which are amply innervated by the vagal nerve. OBJECTIVE: To investigate which area DNA synthesis facilitates and what factors contribute to cell proliferation in the small intestine in VMH-lesioned rats. DESIGN: At 7 days after VMH lesions or sham operations, a segment of rat jejunum was taken for histological examination. A part of the jejunum was also removed from VMH-lesioned and sham-operated rats after 3 days and examined for 5-bromo-2'-deoxyuridine (BrdU) incorporation. At 6, 12 and 24 h after VMH lesions, the proximal intestine was removed from individual rats, from the pylorus to the mid-jejunum. Total RNA was extracted from these tissues of each rat, and the levels of epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha mRNA were determined using reverse-transcription polymerase chain reaction. Cyclooxygenase (COX)-1 and -2 mRNA levels were determined using Northern blotting. RESULTS: : Jejunal villi in VMH-lesioned rats were markedly enlarged compared to those of sham-operated rats and jejunal crypts in VMH-lesioned rats more markedly incorporated BrdU. Northern blot analysis revealed an increase in COX-1 mRNA after 6, 12 and 24 h in the jejunum of VMH-lesioned rats. COX-2 mRNA was decreased 6 and 12 h after VMH lesioning; however, it was significantly increased 24 h after VMH lesions in comparison to sham-operated rats. The levels of EGF and TGF-alpha mRNA were unchanged in VMH lesioned rats. CONCLUSION: VMH lesions induced enlargement of jejunal villi and increased the gene expression of COX-1 in the small intestine. Prostaglandins, probably E(2), induced by COX-1 may be one candidate factor responsible for the cell proliferation of the small intestinal epithelium in these rats.

Animals↗
PubMed2002

Magnetic superstructure in the two-dimensional quantum antiferromagnet SrCu2(BO3)2.

We report the observation of magnetic superstructure in a magnetization plateau state of SrCu2(BO3)2, a frustrated quasi-two-dimensional quantum spin system. The Cu and B nuclear magnetic resonance (NMR) spectra at 35 millikelvin indicate an apparently discontinuous phase transition from uniform magnetization to a modulated superstructure near 27 tesla, above which a magnetization plateau at 1/8 of the full saturation has been observed. Comparison of the Cu NMR spectrum and the theoretical analysis of a Heisenberg spin model demonstrates the crystallization of itinerant triplets in the plateau phase within a large rhomboid unit cell (16 spins per layer) showing oscillations of the spin polarization. Thus, we are now in possession of an interesting model system to study a localization transition of strongly interacting quantum particles.

Journal Article↗
PubMed2001

Dzyaloshinski-Moriya interaction in the 2D spin gap system SrCu(2)(BO(3))(2).

The Dzyaloshinski-Moriya interaction partially lifts the magnetic frustration of the spin-1/2 oxide SrCu(2)(BO(3))(2). It explains the fine structure of the excited triplet state and its unusual magnetic field dependence, as observed in previous ESR and new neutron inelastic scattering experiments. We claim that it is mainly responsible for the dispersion. We propose also a new mechanism for the observed ESR transitions forbidden by standard selection rules, which relies on an instantaneous Dzyaloshinski-Moriya interaction induced by spin-phonon couplings.

Journal Article↗
PubMed2001

Strong damping of phononic heat current by magnetic excitations in SrCu2(BO3)(2).

Measurements of the thermal conductivity as a function of temperature and magnetic field in the 2D dimer spin system SrCu2(BO3)(2) are presented. In zero magnetic field the thermal conductivity along and perpendicular to the magnetic planes shows a pronounced double-peak structure as a function of temperature. The low-temperature maximum is drastically suppressed with increasing magnetic field. Our quantitative analysis reveals that the heat current is due to phonons and that the double-peak structure arises from pronounced resonant scattering of phonons by magnetic excitations.

Journal Article↗
PubMed2001

Soft acoustic modes in the two-dimensional spin system SrCu2(BO3)(2).

SrCu2(BO3)(2) is a two-dimensional dimerized quantum spin system which is close to a quantum critical point. The sound velocity for the longitudinal and transverse acoustic modes shows strong spin-lattice effects. The shear c(66) mode exhibits a pronounced softening of 4.5% as a function of temperature and softens more than 25% in fields up to 50 T. This huge effect occurs in the vicinity of the magnetization plateaus m/m(0) = 1/4 and 1/3. We can analyze quantitatively the temperature dependence of all measured elastic modes c(11), c(44), and c(66) with an exchange striction mechanism. The soft c(66) mode with B(2g) symmetry enables us to predict the possible symmetry of the condensed triplets in some plateaus.

Journal Article↗
PubMed2001

XAFS study of LiCo1-xFexO2 cathode for rechargeable lithium battery by laboratory XAFS spectrometer.

The change of local structure in layered-rock-salt-type iron doped lithium cobaltate LiCo(1-x)Fe(x)O2 under electrochemical Li de-intercalation (charge) /re-intercalation (discharge) was studied by a laboratory type XAFS spectrometer. In Co K-XANES and Fe K-XANES of LiCo0.85Fe0.15O2 the absorption peak shifted to higher energy by 1.5-2eV for Co K-edge and by 2-2.5eV for Fe K-edge, respectively, after the first charge. The spectra returned close to initial position and had almost original shape after the first discharge. In Co K- and Fe K-EXAFS of LiCo0.85Fe0.15O2 during the first charge and discharge the reversible change of the local structure was observed mainly around the Co atoms although the partly irreversible change of the local structure was found around the Fe atoms. The variation of local structure occurred in similar manner for the samples with x=0.05 and 0.25. This indicates that both Co3+/Co4+ and Fe3+/Fe4+ redox reactions occur reversibly during the first charge and discharge.

Journal Article↗
PubMed2001

Genetic analysis of p73 localized at chromosome 1p36.3 in primary neuroblastomas.

BACKGROUND: Human p73, a novel homolog of p53, has recently been cloned and mapped at chromosome 1p36.3, the locus for putative tumor suppressor gene(s) of neuroblastoma (NBL) and other cancers. p73, like p53, inhibits growth and induces apoptosis in neuroblastoma and osteosarcoma cell lines. PROCEDURE: To test the hypothesis that p73 is a NBL suppressor gene, we examined expression, allelo-typing, and mutation of the p73 gene in primary human neuroblastomas. Loss of heterozygosity (LOH) for p73 was performed in 272 primary NBLs using a CT repeat polymorphic marker, which we found in intron 9 of the p73 gene. RESULTS: p73 LOH was observed in 28 out of 151 (19%) informative cases. The high frequency of p73 LOH was significantly associated with sporadic neuroblastomas (P< 0.001), MYCN amplification (P< 0.001), and advanced stages (P< 0.05). Mutational analyses by PCR-SSCP (single strand conformation polymorphism) revealed two mis-sense mutations in 140 NBLs, one somatic and one germline. CONCLUSION: Thus, the present results have shown that mutation of p73 is infrequent in NBLs, although the p73 locus is frequently lost in advanced stage tumors. These suggest that p73 may not be a tumor suppressor in the classic Knudson manner.

Amino Acid Substitution↗
PubMed2001

Different origin of hypertriglyceridemia induced by a high-fat and a high-sucrose diet in ventromedial hypothalamic-lesioned obese and normal rats.

OBJECTIVE: To clarify the mechanism by which plasma triacylglycerol is affected by a high fat or a sucrose diet. DESIGN: Two sets of six groups each having six rats were prepared-(1) ventromedial hypothalamic (VMH)-lesioned rats fed a standard diet; (2) sham VMH-lesioned rats fed a standard diet; (3) VMH-lesioned rats fed a high-fat diet; (4) sham VMH-lesioned rats fed a high-fat diet; (5) VMH-lesioned rats fed a high-sucrose diet; and (6) sham VMH-lesioned rats fed a high-sucrose diet. After VMH lesions and sham operations, the rats were provided standard, high-fat and high sucrose diets for 2 weeks. Two weeks later, blood samples were collected after overnight fast to determine plasma triacylglycerol (TAG), hepatic triacylglycerol secretion rate (TGSR), fractional catabolic rate (FCR) of triacylglycerol and postheparin plasma lipoprotein lipase (LPL), plasma glucose, insulin and leptin. RESULTS: Values of TAG, TGSR, FCR and LPL in VMH-lesioned obese rats were all greater than those in sham-operated rats, regardless of the diet fed. In sham-operated rats, high-fat diet fed rats showed higher TAG with similar TGSR, higher LPL and lower FCR than those of standard diet fed rats. High-sucrose diet fed rats showed significantly higher TAG with higher TGSR, higher LPL and lower FCR than those of standard diet fed rats. Moreover, high-sucrose diet fed rats showed higher TAG with higher TGSR, lower LPL and higher FCR than those of high-fat diet fed rats. In VMH-lesioned rats, high-fat diet fed rats showed higher TAG with similar TGSR, higher LPL and lower FCR than those of standard diet fed rats. High-sucrose diet fed rats showed markedly higher TAG with notably higher TGSR, higher LPL and lower FCR than those of standard diet fed rats. High-sucrose diet fed rats showed still higher TAG with markedly higher TGSR, similar LPL and higher FCR than those of high-fat diet fed rats. CONCLUSIONS: The mechanism by which TAG metabolism is affected by a high-fat or a high-sucrose diet differed; a high-fat diet increased plasma TAG level by lowering removal of TAG without increase in hepatic TAG secretion in sham-operated (normal) rats. A high-sucrose diet, in contrast, induced much higher plasma TAG levels by both increased hepatic TAG secretion and decreased removal of TAG. The effects of a high-fat or a high-sucrose diet were similar but exaggerated in VMH lesioned animals.

Animals↗
PubMed2000

Impaired reductive regeneration of ascorbic acid in the Goto-Kakizaki diabetic rat.

Ascorbic acid (AA) is a naturally occurring major antioxidant that is essential for the scavenging of toxic free radicals in both plasma and tissues. AA levels in plasma and tissues have been reported to be significantly lower than normal in diabetic animals and humans, and might contribute to the complications found at the late stages of diabetes. In this study, plasma and hepatic AA levels and AA regeneration were studied in the Goto-Kakizaki diabetic rat (GK rat) to elucidate the mechanism of decreasing plasma and hepatic AA levels in diabetes. AA concentrations in the plasma and liver were significantly lower in GK than in control rats. AA levels in primary cultured hepatocytes derived from GK rats were lower than those derived from control Wistar rats with or without dehydroascorbic acid (DHA) in the medium. Among various enzyme activities that reduce DHA to AA, the NADPH-dependent regeneration of AA in the liver was significantly suppressed in GK rats. Northern blot analysis revealed that only the expression of 3-alpha-hydroxysteroid dehydrogenase (AKR) was significantly suppressed in these rats. These results suggest that decreased AA-regenerating activity, probably through decreased expression of AKR, contributes to the decreased AA levels and increased oxidative stress in GK rats.

3-Hydroxysteroid Dehydrogenases↗
PubMed2000

Collective singlet excitations and evolution of raman spectral weights in the 2D spin dimer compound SrCu2(BO3)(2)

Raman light scattering of the two-dimensional quantum spin system SrCu2(BO3)(2) shows a rich structure in the magnetic excitation spectrum, including several well-defined bound state modes at low temperature, and a scattering continuum and quasielastic light scattering contributions at high temperature. The key to the understanding of the unique features of SrCu2(BO3)(2) is the presence of strong interactions between well-localized triplet excitations in the network of orthogonal spin dimers realized in this compound.

Journal Article↗
PubMed2000

Identification and characterization of a 500-kb homozygously deleted region at 1p36.2-p36.3 in a neuroblastoma cell line.

Loss of heterozygosity of the distal region of chromosome 1p where tumor suppressor gene(s) might harbor is frequently observed in many human cancers including neuroblastoma (NBL) with MYCN amplification and poor prognosis. We have identified for the first time a homozygously deleted region at the marker D1S244 within the smallest region of overlap at 1p36.2-p36.3 in two NBL cell lines, NB-1 and NB-C201 (MASS-NB-SCH1), although our genotyping has suggested the possibility that both lines are derived from the same origin. The 800-kb PAC contig covering the entire region of homozygous deletion was made and partially sequenced (about 60%). The estimated length of the deleted region was 500 kb. We have, thus far, identified six genes within the region which include three known genes (DFF45, PGD, and CORT) as well as three other genes which have been reported during processing our present project for the last 3(1/2) years (HDNB1/UFD2, KIAA0591F/KIF1B-beta, and PEX14). They include the genes related to apoptosis, glucose metabolism, ubiquitin-proteasome pathway, a neuronal microtubule-associated motor molecule and biogenesis of peroxisome. At least three genes (HDNB1/UFD2, KIAA0591F/KIF1B-beta, and PEX14) were differentially expressed at high levels in favorable and at low levels in unfavorable subsets of primary neuroblastoma. Since the 1p distal region is reported to be imprinted, those differentially expressed genes could be the new members of the candidate NBL suppressor, although RT-PCR-SSCP analysis has demonstrated infrequent mutation of the genes so far identified. Full-sequencing and gene prediction for the region of homozygous deletion would elucidate more detailed structure of this region and might lead to discovery of additional candidate genes. Oncogene (2000) 19, 4302 - 4307

Carrier Proteins↗
PubMed2000

Gene expression of neurotrophins and their receptors in lead nitrate-induced rat liver hyperplasia.

Neurotrophins including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) are known to play important roles in the survival, proliferation, differentiation, and/or maintenance of function in several tissues including neuronal tissues. The role of neurotrophins in liver tissue, however, has not yet been clarified. In the present study, we assessed the temporal change in gene expression of neurotrophins, NGF, BDNF, and NT-3, and their receptors, low affinity neurotrophin receptor (p75NTR) and Trks A, B, and C, by RT-PCR technique in the liver of rats treated with lead nitrate (LN; 0.1 mmol/kg body weight), an inducer of liver hyperplasia. The mRNAs for NGF, BDNF with exon 4, NT-3, p75NTR, and all Trk members were detected in the LN-untreated liver. LN treatment resulted in increases in the levels of NGF, BDNF with exon 4, NT-3, p75NTR, and TrkA mRNAs and further led to expression of BDNF mRNA with exon 3. The increase in gene expression of neurotrophins and their receptors was closely correlated with those in liver weight. In this report, we propose for the first time that neurotrophins may play crucial roles in LN-induced liver hyperplasia.

Animals↗