Biomedical subjects

K Miyake

Publications and source records attributed to K Miyake.

At least 19 recordsLinked to original sources

PubMed2006

Erythropoiesis in the Rps19 disrupted mouse: Analysis of erythropoietin response and biochemical markers for Diamond-Blackfan anemia.

The human ribosomal protein S19 gene (RPS19) is mutated in approximately 20% of patients with Diamond-Blackfan anemia (DBA), a congenital disease with a specific defect in erythropoiesis. The clinical expression of DBA is highly variable, and subclinical phenotypes may be revealed by elevated erythrocyte deaminase (eADA) activity only. In mice, complete loss of Rps19 results in early embryonic lethality whereas Rps19+/- mice are viable and without major abnormalities including the hematopoietic system. We have performed a detailed analysis of the Rps19+/- mice. We estimated the Rps19 levels in hematopoietic tissues and we analyzed erythrocyte deaminase activity and globin isoforms which are used as markers for DBA. The effect of a disrupted Rps19 allele on a different genetic background was investigated as well as the response to erythropoietin (EPO). From our results, we argue that the loss of one Rps19 allele in mice is fully compensated for at the transcriptional level with preservation of erythropoiesis.

Anemia, Diamond-Blackfan↗

PubMed2006

Disruption-induced mucus secretion: repair and protection.

When a cell suffers a plasma membrane disruption, extracellular Ca(2+) rapidly diffuses into its cytosol, triggering there local homotypic and exocytotic membrane fusion events. One role of this emergency exocytotic response is to promote cell survival: the internal membrane thus added to the plasma membrane acts as a reparative "patch." Another, unexplored consequence of disruption-induced exocytosis is secretion. Many of the cells lining the gastrointestinal tract secrete mucus via a compound exocytotic mechanism, and these and other epithelial cell types lining the digestive tract are normally subject to plasma membrane disruption injury in vivo. Here we show that plasma membrane disruption triggers a potent mucus secretory response from stomach mucous cells wounded in vitro by shear stress or by laser irradiation. This disruption-induced secretory response is Ca(2+) dependent, and coupled to cell resealing: disruption in the absence of Ca(2+) does not trigger mucus release, but results instead in cell death due to failure to reseal. Ca(2+)-dependent, disruption-induced mucus secretion and resealing were also demonstrable in segments of intact rat large intestine. We propose that, in addition to promoting cell survival of membrane disruptions, disruption-induced exocytosis serves also the important protective function of liberating lubricating mucus at sites of mechanical wear and tear. This mode of mechanotransduction can, we propose, explain how lubrication in the gastrointestinal tract is rapidly and precisely adjusted to widely fluctuating, diet-dependent levels of mechanical stress.

Animals↗

PubMed2005

Undressing the Kondo effect near the antiferromagnetic quantum critical point.

The problem of a spin-1/2 magnetic impurity near an antiferromagnetic transition of the host lattice is shown to transform to a multichannel problem. A variety of fixed points is discovered asymptotically near the antiferromagnetic critical point. Among these is a new variety of stable fixed point of a multichannel Kondo problem which does not require channel isotropy. At this point Kondo screening disappears but coupling to spin fluctuations remains. In addition to its intrinsic interest, the problem is an essential ingredient in the problem of quantum critical points in heavy fermions.

Journal Article↗

PubMed2005

The linkage and association of the gene encoding upstream stimulatory factor 1 with type 2 diabetes and metabolic syndrome in the Chinese population.

AIMS/HYPOTHESIS: The transcription factor upstream stimulatory factor 1 (USF1) regulates the expression of genes involved in glucose and lipid metabolism and has been associated with familial combined hyperlipidaemia. USF1 is located on chromosome 1q22-23, a region with evidence for linkage to type 2 diabetes and various traits of the metabolic syndrome in Chinese and other populations. The aim of this study was to investigate the linkage and association of USF1 with type 2 diabetes and the metabolic syndrome in Chinese individuals. MATERIALS AND METHODS: We genotyped three haplotype-tagging single nucleotide polymorphisms (SNPs) (rs3737787, rs2516841 and rs2516839) at USF1 in three samples of the Hong Kong Chinese population, including members of 179 families from the Hong Kong Family Diabetes Study, 1,383 hospital cases with type 2 diabetes and/or the metabolic syndrome and 454 normal control subjects. RESULTS: We found significant association of individual polymorphisms and haplotypes with type 2 diabetes and/or metabolic syndrome-related traits in the family samples using either family-based or unrelated normal control subjects. However, these variants could not explain much of the evidence for linkage in this region. Moreover, they were not associated with type 2 diabetes and/or the metabolic syndrome in the hospital cases. CONCLUSIONS/INTERPRETATION: The results are consistent with the hypothesis that variation at USF1 contributes to the risk of type 2 diabetes and the metabolic syndrome in families with strong evidence for linkage in the chromosome 1q region. However, they provide little support for USF1 as the susceptibility locus that generates the observed evidence for linkage at 1q21-25 for type 2 diabetes and/or the metabolic syndrome, and USF1 does not appear to have a major contribution to these phenotypes in the general Chinese population.

Adult↗

PubMed2005

A phase I-II trial of autologous peripheral blood stem cell transplantation in the treatment of refractory autoimmune disease.

OBJECTIVES: To carry out a phase I-II trial to elucidate the feasibility and efficacy of high dose cyclophosphamide (CY) supported by autologous peripheral blood stem cell transplantation (PBSCT) in the treatment of severe and refractory autoimmune disease (AD). METHODS: Peripheral blood stem cells (PBSCs) were mobilised during haematological recovery after relatively high dose CY (2 g/m2) for 2 days, followed by administration of granulocyte colony stimulating factor. After collecting PBSCs--more than 2x10(6) CD34+ cells/kg--by apheresis, CD34+ cells were immunologically selected and cryopreserved. Eight patients were enrolled--five had systemic sclerosis (SSc) alone, one had SSc with systemic lupus erythematosus, one amyopathic dermatomyositis (ADM), and one Wegener's granulomatosis (WG). All of the patients were treated with high dose CY (50 mg/kg) for 4 days and autologous PBSCT. RESULTS: Haematopoietic reconstitution was rapid and sustained. Toxicity due to the regimen included various infections such as pneumonia, sepsis, cystitis, herpes zoster, and acute heart failure. However, there was no treatment related mortality. Encouraging results were obtained after autologous PBSCT. Sclerosis of the skin was markedly improved in all of the patients with SSc. Interstitial pneumonia (IP), evaluated by PaO2, serum KL-6 levels, and pulmonary high resolution computed tomography, improved significantly. In a patient with ADM, severe and progressive IP also improved markedly. In a patient with WG, the size of the left orbital granuloma decreased substantially, resulting in reduction of the exophthalmos. CONCLUSIONS: These observations suggest that high dose CY with autologous PBSCT is feasible and may be effective in the treatment of severe and refractory AD.

Adult↗

PubMed2005

Implications of corpus gastritis, atrophy and cyclooxygenase in the development of gastric erosions after curing Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori eradication decreases recurrence of peptic ulcers with marked improvement in histological inflammation, but gastric mucosal injuries may be developed even after eradication. PURPOSE: To investigate the mechanisms responsible for the development of gastric erosions after eradication, we analysed the relationship between clinicopathological risk factors and the occurrence of gastric erosion after curing H. pylori infection. PATIENTS: Sixty patients underwent endoscopy before, and 3, 6 and 12 months after the completion of H. pylori eradication. METHODS: Risk factors associated with the development of gastric erosions after eradication were assessed by multivariate analysis, and cyclooxygenase-1 and -2 immunoreactivity was histologically examined in the gastric mucosa before and after eradication. RESULTS: The cumulative prevalence of gastric erosions after H. pylori eradication was 38.3% within 1 year. Using multivariate analysis, corpus gastritis scores (inflammation score+activity score), corpus atrophy scores and an age of more than 50 years were found to be independent factors associated with the development of gastric erosion after eradication with odds ratios of 7.39, 0.13 and 5.00, respectively. Cyclooxygenase-2 immunoreactivity of the corpus was decreased for the non-erosion group after eradication, but not for the erosion group. CONCLUSIONS: Severe gastritis or less severe atrophy in oxyntic glands but not in pyloric glands before eradication may be involved in the development of gastric erosions after curing H. pylori infection.

Age Factors↗

PubMed2005

Antiangiogenic gene therapy of myeloproliferative disease developed in transgenic mice expressing P230 bcr/abl.

Antiangiogenic gene therapy offers an attractive approach to the treatment of a variety of malignancies, including those of the hematological system. However, evaluation of this approach has been hampered by the lack of appropriate animal models. We have recently produced transgenic mice expressing P230 bcr/abl that develop myeloproliferative disease (MPD) closely resembling human chronic myelogenous leukemia. Using this MPD murine model, we examined the feasibility of systemic antiangiogenic gene therapy for hematological malignancy. An adenoviral vector containing the secretable endostatin gene was injected into the right quadriceps muscle of the MPD mice. The increased endostatin level was detected for at least 6 months. Hematological parameters including platelet counts, granulocyte counts, and the hemoglobin concentration were improved by this gene therapy. Infiltration of megakaryocytes was also significantly inhibited in treated MPD mice. Reduction of the microvessel density was confirmed by histological examination. These results demonstrated, for the first time, that antiangiogenic gene therapy is effective to inhibit leukemogenesis caused by expression of the chimeric bcr/abl gene.

Adenoviridae↗

PubMed2005

Preventive therapy for non-steroidal anti-inflammatory drug-induced ulcers in Japanese patients with rheumatoid arthritis: the current situation and a prospective controlled-study of the preventive effects of lansoprazole or famotidine.

BACKGROUND: There is a lack of evidence for the efficacy of preventive medications for peptic ulcers (PUs) among long-term users of non-steroidal anti-inflammatory drugs (NSAIDs) in Japan. AIM: To estimate the preventive effect by normal dose, not high-dose histamine-H2 receptor antagonists (H2RA) for NSAID-induced ulcers. METHODS: We designed two different studies to assess the efficacy of anti-ulcer agents in rheumatoid arthritis (RA) in patients treated over a long term with NSAIDs. An investigative survey divided patients into those not taking anti-ulcer agents (non-medication group); those taking mucosal protective agents (mucosal protectant group), H2RA (H2RA group), proton pump inhibitors (PPI group), or a prostaglandin E1 analog (PG) (PG group). The second study compared prospectively the preventive effects of either famotidine 20 mg bd (famotidine group) or lansoprazole 15 mg daily (lansoprazole group) in patients with PU scars. RESULTS: The prevalence of PU in the H2RA group was significantly lower compared to the mucosal protectant group (P < 0.05), and the mucosal protectant group was not significantly different to the non-medication group. The prospective study revealed that the PU onset rate of the famotidine group was 8% (1/13), and lansoprazole group was 15% (2/13), indicating no significant differences between the two. CONCLUSIONS: In Japan, normal-dose H2RA is expected to be a new PU preventive treatment strategy in patients requiring long-term NSAID therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2004

Anti-monocyte chemoattractant protein-1 gene therapy attenuates nephritis in MRL/lpr mice.

OBJECTIVE: Monocyte chemoattractant protein-1 (MCP-1) is up-regulated and recruits and activates inflammatory cells in human diffuse proliferative lupus nephritis (DPLN) and in nephritis of lupus model MRL/lpr mice. The aim of this study was to examine whether anti-MCP-1 gene therapy inhibits the progression of nephritis in MRL/lpr mice. METHOD: An NH(2)-terminal deletion mutant of the MCP-1 gene, 7ND, was injected into skeletal muscles of MRL/lpr mice with advanced stage nephritis to blockade MCP-1 and its receptor (CCR2) signalling pathway. RESULT: Histological findings of kidneys in treated mice, which received more than four injections of 7ND, showed that protection against renal injury resulted from reduced infiltration of leucocytes. Therefore, this therapy has been shown to prolong the life span of MRL/lpr mice. CONCLUSION: Anti-MCP-1 gene therapy is specifically effective in the localized inflammatory region. The data presented here indicate that this anti-MCP-1 gene therapy may be effective adjunct in the management of DPLN.

Animals↗

PubMed2004

Real-space observation of current-driven domain wall motion in submicron magnetic wires.

We report direct observation of current-driven magnetic domain wall (DW) displacement by using a well-defined single DW in a microfabricated magnetic wire with submicron width. Magnetic force microscopy visualizes that a single DW introduced in a wire is displaced back and forth by positive and negative pulsed current, respectively. The direct observation gives quantitative information on the DW displacement as a function of the intensity and the duration of the pulsed current. The result is discussed in terms of the spin-transfer mechanism.

Journal Article↗

PubMed2004

Absence of association between the MCP-1 gene polymorphism and histological phenotype of lupus nephritis.

Lupus nephritis presents two polar histological patterns, diffuse proliferative glomerulonephritis (DPGN) and membranous glomerulonephritis (MGN). In the kidney tissue of DPGN, numerous mononuclear cells were seen in the interstitium and glomeruli; on the other hand in MGN, infiltrating cells were less frequent. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemoattractant for monocytes, T-cells, and natural killer cells. In this study we assessed the significance of the MCP-1 gene in determination of the histological phenotype in lupus nephritis. There was no association between the risk of DPGN and the MCP-1 gene genotype.

Adolescent↗

PubMed2003

Monocyte chemoattractant protein 1 (MCP-1) released from Helicobacter pylori stimulated gastric epithelial cells induces cyclooxygenase 2 expression and activation in T cells.

BACKGROUND: and aims: To clarify the interaction between gastric epithelial and mucosal T cells, we examined the role of cytokines released from epithelial cells in response to Helicobacter pylori water extract protein (HPWEP) in regulating T cell cyclooxygenase 2 (COX-2) expression and activation. METHODS: Media from MKN-28 cells incubated with HPWEP for 48 hours were added to Jurkat T cells and human peripheral T cells. C-C and CXC chemokine concentrations in MKN-28 cell media, and COX-2 expression, interferon gamma (IFN-gamma), and interleukin (IL)-4 secretions in T cells were determined by western blot analysis and ELISA methods. Distributions of COX-2 positive T cells and monocyte chemoattractant protein 1 (MCP-1) in tissue specimens with H pylori associated gastritis were determined as single or double labelling by immunohistochemistry. RESULTS: MCP-1, IL-7, IL-8, and RANTES were detected in media from MKN-28 cells incubated with HPWEP. Media as a whole, and MCP-1 alone, stimulated COX-2 expression and peripheral T cell proliferation. Anti-MCP-1 antibody inhibited media stimulated COX-2 mRNA expression in Jurkat T cells. Media stimulated IFN-gamma but not IL-4 secretion from peripheral T cells, while MCP-1 stimulated IL-4 but not IFN-gamma secretion. Both stimulated cytokine release, and peripheral T cell proliferation was partially inhibited by NS-398, a specific COX-2 inhibitor. In mucosa with gastritis, COX-2 was expressed in T cells and MCP-1 was localised mainly in epithelial and mononuclear cells. MCP-1 levels and the intensity of COX-2 expression in tissue samples were closely related. CONCLUSIONS: Cytokines such as MCP-1, released from gastric epithelial cells in response to HPWEP, seem to modulate T cell immune responses, at least in part via COX-2 expression.

Blotting, Western↗

PubMed2002

Singular effects of impurities near the ferromagnetic quantum-critical point.

Systematic theoretical results for the effects of a dilute concentration of magnetic impurities on the thermodynamic and transport properties in the region around the quantum critical point of a ferromagnetic transition are obtained. In the quasiclassical regime, the dynamical spin fluctuations enhance the Kondo temperature. This energy scale decreases rapidly in the quantum fluctuation regime, where the properties are those of a line of critical points of the multichannel Kondo problem with the number of channels increasing as the critical point is approached, except at unattainably low temperatures where a single channel wins out.

Journal Article↗

PubMed2002

Association between IL-4 genotype and IL-4 production in the Japanese population.

We have identified that there are only two IL-4 gene haplotypes (I and II) in the Japanese population. There are significant differences among three genotypes (I/I, I/II and II/II) in the IL-4 producing proportion of peripheral Th cells using intracellular cytokine detection assay. These results make it likely that IL-4 genotype could influence the type of immune response.

Cells, Cultured↗

PubMed2002

Effect of acid suppression therapy on development of gastric erosions after cure of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori eradication markedly improves histological inflammation and decreases peptic ulcer recurrence, but little is known about the subsequent development of gastric mucosal injury. AIM: To investigate whether acid suppression treatment after eradication influences the development of gastric erosions. METHODS: Eighty-one patients (gastritis or peptic ulcer) after successful H. pylori eradication were divided into two groups: 40 received an H2-blocker for 6 months (H2-blocker-positive) and 41 received no treatment (H2-blocker-negative). Endoscopy was performed before, and at 3 and 6 months after completion of eradication. RESULTS: Cumulative prevalence of gastric erosions in the H2-blocker-positive group was significantly lower than in the H2-blocker-negative group, 25% vs. 42%, respectively. In the H2-blocker-negative group but not the H2-blocker-positive group, the cumulative prevalence of gastric erosions after eradication was higher in patients with less severe corpus atrophy or more severe corpus gastritis. CONCLUSIONS: Development of gastric erosions after H. pylori eradication may be controlled by acid suppression treatment. Less severe atrophy or more severe gastritis in oxyntic glands before eradication may be involved in the development of gastric erosions. These results support the idea that recovery of acid secretion may be one of factors for development of gastric mucosal erosions after successful eradication.

Biopsy↗

PubMed2002

Inhibition of Helicobacter pylori-induced cyclo-oxygenase-2 aggravates NSAID-caused gastric damage in Mongolian gerbils.

BACKGROUND: The effect of Helicobacter pylori infection on non-steroidal anti-inflammatory drug-induced gastric mucosal injury is controversial. AIM: To examine the effect of the interaction between H. pylori and non-steroidal anti-inflammatory drugs on gastric mucosal injury. METHODS: Mongolian gerbils infected with H. pylori were treated with indometacin at 8 mg/kg for 2 days or 7 days. Mucosal damage was assessed by macroscopic and histological examination, and myeloperoxidase activity was measured as an index of neutrophil infiltration. The expression levels of cyclo-oxygenase proteins were determined by Western blot analysis and cyclo-oxygenase activity. RESULTS: A 2-day course of indometacin did not cause an increase in gastric damage in H. pylori-infected Mongolian gerbils compared to uninfected gerbils, while a 7-day course of indometacin caused additive gastric damage in H. pylori-infected animals. H. pylori infection induced cyclo-oxygenase-2 expression in the stomach. Treatment with indometacin for 2 days did not significantly affect cyclo-oxygenase activity in H. pylori-infected animals, while treatment for 7 days inhibited both cyclo-oxygenase-1 and cyclo-oxygenase-2 activities. Pre-treatment with a selective cyclo-oxygenase-2 inhibitor aggravated mucosal injury in H. pylori-infected animals treated or not treated with indometacin for 2 days. CONCLUSIONS: Our results suggest that cyclo-oxygenase-2 protein induced by H. pylori infection may be involved in the defence of the gastric mucosa against damage caused by non-steroidal anti-inflammatory drugs. Therefore, inhibition of cyclo-oxygenase-2 activity may enhance non-steroidal anti-inflammatory drug-caused gastric damage in H. pylori-infected animals.

Animals↗

PubMed2002

Genetically determined interferon-gamma production influences the histological phenotype of lupus nephritis.

OBJECTIVE: To clarify whether the interferon-gamma (IFN-gamma) gene (IFNG) is associated with the histological phenotype of lupus nephritis. METHOD: We analysed microsatellite polymorphisms located within the first intron of the IFNG gene to determine the genotypes of patients with lupus nephritis WHO class IV (n=24), patients with WHO class V (n=12) and healthy controls (n=61). We used flow cytometric detection of intracellular cytokines to identify CD4(+) T cells producing IFN-gamma. Production of IFN-gamma by peripheral blood mononuclear cells after stimulation with phytohaemagglutinin was evaluated with an enzyme-linked immunosorbent assay. RESULT: The frequency of the IFNG allele 114 was significantly greater in WHO class V patients than in WHO class IV patients. Furthermore, the IFNG 114 +/+ genotype was more frequent in WHO class V than in WHO class IV patients. The level of IFN-gamma and the percentage of IFN-gamma-producing CD4(+) T cells were lower in individuals with genotype 114 +/+ than in individuals with genotype 114 -/-. CONCLUSION: The IFN-gamma gene is associated with the histological phenotype in lupus nephritis.

Adult↗

PubMed2001

Molecular genetic analysis of an endotoxin nonresponder mutant cell line: a point mutation in a conserved region of MD-2 abolishes endotoxin-induced signaling.

Somatic cell mutagenesis is a powerful tool for characterizing receptor systems. We reported previously two complementation groups of mutant cell lines derived from CD14-transfected Chinese hamster ovary--K1 fibroblasts defective in responses to bacterial endotoxin. Both classes of mutants expressed a normal gene product for Toll-like receptor (TLR)4, and fully responded to stimulation by tumor necrosis factor (TNF)-alpha or interleukin (IL)-1 beta. We identified the lesion in one of the complementation groups in the gene for MD-2, a putative TLR4 coreceptor. The nonresponder phenotype of this mutant was reversed by transfection with MD-2. Cloning of MD-2 from the nonresponder cell line revealed a point mutation in a highly conserved region resulting in a C95Y amino acid exchange. Both forms of MD-2 colocalized with TLR4 on the cell surface after transfection, but only the wild-type cDNA reverted the lipopolysaccharide (LPS) nonresponder phenotype. Furthermore, soluble MD-2, but not soluble MD-2(C95Y), functioned to enable LPS responses in cells that expressed TLR4. Thus, MD-2 is a required component of the LPS signaling complex and can function as a soluble receptor for cells that do not otherwise express it. We hypothesize that MD-2 conformationally affects the extracellular domain of TLR4, perhaps resulting in a change in affinity for LPS or functioning as a portion of the true ligand for TLR4.

Animals↗