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M Yamazaki

Publications and source records attributed to M Yamazaki.

At least 37 records · Page 2Linked to original sources
PubMed2004

Autoantibodies against phosphatidylserine-prothrombin complex in patients with systemic sclerosis.

OBJECTIVE: To determine the frequency and clinical association of antiphosphatidylserine-prothrombin complex (PS/PT) antibody (Ab) in systemic sclerosis (SSc). METHODS: Anti-PS/PT IgG Ab was examined by enzyme linked immunosorbent assay (ELISA) in 112 patients with SSc. Thirty three healthy volunteers and 30 patients with systemic lupus erythematosus (SLE) were also investigated as controls. RESULTS: Anti-PS/PT Ab was detected in 18/112 (16%) patients with SSc and 10/30 (33%) patients with SLE, whereas it was not detected in any normal controls. Anti-PS/PT Ab was more frequently detected in patients with SSc with peripheral ischaemia and lung disease (pulmonary fibrosis and pulmonary hypertension) than in patients with SSc without the Ab. However, anti-PS/PT Ab was not associated with the severity of skin sclerosis. Importantly, two patients were negative for both lupus anticoagulant and Ab against cardiolipin beta(2)-glycoprotein I complex among six anti-PS/PT Ab positive patients with SSc and a thromboembolic episode. CONCLUSIONS: Anti-PS/PT Ab is associated with thromboembolism, peripheral ischaemia, and lung involvement in some patients with SSc. Examination of this Ab may be useful to recognise the risk of thromboembolism in patients with SSc.

Adult↗
PubMed2003

Therapeutic effect of anti-OX40L and anti-TNF-alpha MAbs in a murine model of chronic colitis.

Interaction of OX40 (CD134) on T cells with its ligand (OX40L) on antigen-presenting cells has been implicated in pathogenic T cell activation. This study was performed to explore the involvement of OX40/OX40L in the development of T cell-mediated chronic colitis. We evaluated both the preventive and therapeutic effects of neutralizing anti-OX40L MAb on the development of chronic colitis in SCID mice induced by adoptive transfer of CD4(+)CD45RB(high) T cells as an animal model of Crohn's disease. We also assessed the combination of anti-OX40L and anti-TNF-alpha MAbs to improve the therapeutic effect. Administration of anti-OX40L MAb markedly ameliorated the clinical and histopathological disease in preventive and therapeutic protocols. In vivo treatment with anti-OX40L MAb decreased CD4(+) T cell infiltration in the colon and suppressed IFN-gamma, IL-2, and TNF-alpha production by lamina propria CD4(+) T cells. The combination with anti-TNF-alpha MAb further improved the therapeutic effect by abolishing IFN-gamma, IL-2, and TNF-alpha production by lamina propria CD4(+) T cells. Our present results suggested a pivotal role of OX40/OX40L in the pathogenesis of T cell-mediated chronic colitis. The OX40L blockade, especially in combination with the TNF-alpha blockade, may be a promising strategy for therapeutic intervention of Crohn's disease.

Animals↗
PubMed2003

The role of cryptopatch-derived intraepithelial lymphocytes in the development of chronic ileocecitis.

Lympho-haemopoietic progenitors residing in murine gut cryptopatches (CPs) have been shown to generate intestinal extrathymic intraepithelial lymphocytes (IELs). However, the role of CPs in the development of intestinal inflammation remains unclear. To investigate the role of CPs in the development of intestinal inflammation, we examined SAMP1/Yit mice, which spontaneously develop a chronic intestinal inflammation localized to the terminal ileum and cecum. Here, we showed the sharp correlation between the disease onset and the decreased number of CPs, resulting in decreased number of both thymus-independent IELs including T-cell receptor gammadelta+ (TCRgammadelta+) and CD8alphaalpha+TCRalphabeta+ cells but not thymus-dependent CD8alphabeta+TCRalphabeta+ and CD4+TCRalphabeta+ cells in SAMP1/Yit mice. These data provide the first suggestion that thymus-independent IELs derived from CP might play protective role against the onset and the development of intestinal inflammation.

Animals↗
PubMed2003

Stereoselective hepatic disposition of a diastereomeric pair of alphavbeta3 antagonists in rat.

1. The study investigated mechanisms underlying the stereoselective hepatic disposition observed in rats of a zwitterionic diastereomeric pair ((3S)-3-[(3R or 3S)-2-oxo-3-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl]pyrrolidin-1-yl]-3-quinolin-3-ylpropanoic acid) with different lipophilicities. 2. In a recirculating isolated rat liver system, the more hydrophilic diastereomer II possessed biliary clearance, CLb, and bile-to-liver concentration ratio higher (about 10-30-fold) than the lipophilic zwitterion I, whereas both I and II exhibited comparably high concentration ratios between liver and perfusate. Although MK-571, a known multidrug resistance protein (MRP) inhibitor, significantly inhibited the CLb of both compounds, it did not inhibit their canalicular transport, as evident by unchanged concentration ratios between bile and liver of either I or II. 3. Following an intravenous infusion of I or II to Sprague-Dawley rats, the biliary clearance calculated either based on plasma (CL(b,p)) or liver concentration (CL(b,l)), of II was much higher than that of I (about 5-50-fold). In rats lacking multidrug resistance protein 2 (Mrp2) (Eisai hyperbilirubinemic rat, EHBR), the biliary excretion rate and CL(b,p) of II were also higher than the corresponding values for I. However, both CL(b,p) or CL(b,l) of either I or II were not reduced in EHBR, as compared with control SD rats. 4. In the in vitro rat canalicular membrane vesicle study, I and II exhibited no differences in their inhibitory effect on the Mrp2 mediated ATP-dependent [3H]DNP-SG initial uptake (no inhibition at 10 microM and only about 40% inhibition at 100 microM). 5. Collectively, these results suggested that (1) the difference in the hepatic disposition between the two isomers was due primarily to the difference in their transport mechanism across the canalicular membrane and (2) Mrp2 did not play a major role in the observed differences in the biliary excretion of the diastereomers I and II in rats.

Animals↗
PubMed2003

Normal development of the gut-associated lymphoid tissue except Peyer's patch in MyD88-deficient mice.

MyD88 is a key adaptor molecule for signalling via Toll-like receptors (TLRs) and the response to gut commensal microbes. To investigate the role of TLRs/MyD88 pathway in the development of the gut-associated lymphoid tissue (GALT), we examined the development of Peyer's patches (PPs) and cryptopatch (CP), and also one of effector compartment, intraepithelial lymphocyte (IEL) in MyD88-/-, TLR2-/- and TLR4-/- mice. In MyD88-/- mice, the organogenesis of PPs was not disturbed. However, PPs in 2-week-old MyD88-/- mice were significantly smaller than those in MyD88+/- mice. Also, in 2-week-old TLR4-/-, but not TLR2-/- mice, PPs did not develop rapidly. The development of PPs in MyD88-/- and TLR4-/- mice was completely recovered in 10 weeks. PP cells from MyD88-/- mice showed significant decrease in proliferation when stimulated with lipopolysaccharide. The development of CP and IEL was also normal in 10-week-old MyD88-/- mice. These results suggest that the TLRs/MyD88 pathway might be involved in the development of PPs only at early postnatal stage, and TLRs/MyD88-independent signalling is critically involved in the development of GALT in adult mice.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Vascular endothelial growth factor and receptor interaction is a prerequisite for murine hepatic fibrogenesis.

BACKGROUND: It has been shown that expression of the potent angiogenic factor, vascular endothelial growth factor (VEGF), and its receptors, flt-1 (VEGFR-1) and KDR/Flk-1 (VEGFR-2), increased during the development of liver fibrosis. AIMS: To elucidate the in vivo role of interaction between VEGF and its receptors in liver fibrogenesis. METHODS: A model of CCl(4) induced hepatic fibrosis was used to assess the role of VEGFR-1 and VEGFR-2 by means of specific neutralising monoclonal antibodies (R-1mAb and R-2mAb, respectively). R-1mAb and R-2mAb were administered after two weeks of treatment with CCl(4), and indices of fibrosis were assessed at eight weeks. RESULTS: Hepatic VEGF mRNA expression significantly increased during the development of liver fibrosis. Both R-1mAb and R-2mAb treatments significantly attenuated the development of fibrosis associated with suppression of neovascularisation in the liver. Hepatic hydroxyproline and serum fibrosis markers were also suppressed. Furthermore, the number of alpha-smooth muscle actin positive cells and alpha1(I)-procollagen mRNA expression were significantly suppressed by R-1mAb and R-2mAb treatment. The inhibitory effect of R-2mAb was more potent than that of R-1mAb, and combination treatment with both mAbs almost completely attenuated fibrosis development. Our in vitro study showed that VEGF treatment significantly stimulated proliferation of both activated hepatic stellate cells (HSC) and sinusoidal endothelial cells (SEC). VEGF also significantly increased alpha1(I)-procollagen mRNA expression in activated HSC. CONCLUSIONS: These results suggest that the interaction of VEGF and its receptor, which reflected the combined effects of both on HSC and SEC, was a prerequisite for liver fibrosis development.

Animals↗
PubMed2003

Ameliorating effect of anti-Fas ligand MAb on wasting disease in murine model of chronic colitis.

Fas/Fas ligand (FasL) interaction has been implicated in the pathogenesis of various diseases. To clarify the involvement of Fas/FasL in the pathogenesis of intestinal inflammation, we investigated the preventive and therapeutic effects of neutralizing anti-FasL monoclonal antibody (MAb) on the development of chronic colitis induced by adaptive transfer of CD4+CD45RBhigh T cells to SCID mice. Administration of anti-FasL MAb from 1 day after T cell transfer (prevention study) resulted in a significant improvement of clinical manifestations such as wasting and diarrhea. However, histological examination showed that mucosal inflammation in the colon, such as infiltration of T cells and macrophages, was not improved by the anti-FasL MAb treatment. In vitro studies showed that anti-FasL MAb did not inhibit IFN-gamma production by anti-CD3/CD28-stimulated lamina propria CD4+ T cells but suppressed TNF-alpha and IL-1beta production by lamina propria mononuclear cells. Therapeutic administration of anti-FasL MAb from 3 wk after T cell transfer also improved ongoing wasting disease but not intestinal inflammation. These results suggest that the Fas/FasL interaction plays a critical role in regulating systemic wasting disease but not local intestinal inflammation.

Adoptive Transfer↗
PubMed2002

Heterogeneity of presenile dementia with bone cysts (Nasu-Hakola disease): three genetic forms.

Nasu-Hakola disease (NHD) is an autosomal recessive disorder characterized by presenile dementia and bone cysts. Finnish patients revealed a large deletion in DAP12 gene encoding a key element for transducing activation signal. The authors examined six Japanese cases for DAP12 alleles. Five of the six had loss-of-function mutation, either a single-base deletion or a novel point mutation. The single patient without mutation normally expressed DAP12 protein. Japanese NHD has at least three genetic forms regarding DAP12.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Differential display analysis of gene expression in plants.

This review deals with the application of differential display to investigate gene expression in plants. A substantial articles reports the isolation and profiling of various genes expressed in cells using this technique. Genes involved in physiological events, stress responses, signal transduction and secondary metabolism have been isolated and characterized. Some of the isolated genes encode transcription factors, membrane proteins and rare enzymes that were previously difficult to purify. These results suggest that differential display is a powerful tool used to investigate the rare genes involved in the plant life cycle without using information from proteins.

Anthocyanins↗
PubMed2002

Differential screening-selected gene aberrative in neuroblastoma protein modulates inflammatory pain in the spinal dorsal horn.

Differential screening-selected gene aberrative in neuroblastoma (DAN) belongs to a novel gene family that includes the Xenopus head-inducing factor, Cerberus and the dorsalizing factor, Gremlin. It has been suggested that members of this family control diverse processes in growth, development and the cell cycle.Here, we demonstrate that the DAN protein is produced in the small neurons of the dorsal root ganglion and is transported to the nerve terminals in the spinal dorsal horn in adult rats. Furthermore, intrathecal injection of an antibody to the DAN protein suppressed inflammatory pain caused by the introduction of complete Freund's adjuvant or carrageenan into the rat hindpaw. The amount of mRNA for DAN in dorsal root ganglion neurons and of its expressed protein in the spinal dorsal horn were both increased in inflammatory models.Together, these data suggest that the DAN protein may be a novel neuromodulator in primary nociceptive nerve fibers.

Afferent Pathways↗
PubMed2002

Glu274Lys/Gly309Arg mutation of the tissue-nonspecific alkaline phosphatase gene in neonatal hypophosphatasia associated with convulsions.

We describe a patient diagnosed with lethal perinatal hypophosphatasia with a unique clinical presentation of convulsions that responded to vitamin B6. Genomic DNA sequence analysis of the tissue-nonspecific alkaline phosphatase (TNSALP) gene revealed two missense mutations: a G-to-A transition resulting in a Glu to Lys at codon 274 (E274K), and a G-to-C transversion resulting in a Gly to Arg at codon 309 (G309R). The first mutation was maternally transmitted and was previously characterized as a moderate one, whereas the latter was paternally transmitted and has not been previously reported. Phenotype/genotype correlation indicates that G309R is a deleterious mutation that can lead to seizures and a lethal outcome, as was demonstrated in our patient.

Alkaline Phosphatase↗
PubMed2002

Effective gene therapy for medullary thyroid carcinoma using recombinant adenovirus inducing tumor-specific expression of interleukin-12.

No satisfactory treatment of metastatic medullary thyroid carcinoma (MTC) is available. Cell-specific gene therapy offers a new approach. We have constructed a recombinant replication-defective adenoviral vector expressing murine interleukin-12 (mIL-12), driven by a modified CALC-I promoter (TCP). This vector (AdTCPmIL-12) includes two separate cassettes encoding mIL-12 p35 or p40 subunit controlled by TCP inserted in the E1 region of adenovirus type 5. In vitro and in vivo reporter gene expression using TCP revealed its cell-specific activity. AdTCPmIL-12-infected rat MTC (rMTC) cells produced high amounts of functional mIL-12 cells in vitro, while other cell lines infected with AdTCPmIL-12 did not. AdTCPmIL-12-transduced rMTC cells completely lost their tumorigenicity in syngenic WAG/Rij rats. Direct injection of 1 x 10(9) plaque forming units of AdTCPmIL-12 into subcutaneous rMTC tumors in WAG/Rij rats caused tumor regression in over 60% of animals within 20 days. Rats cured of tumors did not develop tumors after re-injection of naive rMTC cells, demonstrating lasting immunity. Treatment with AdTCPmIL-12 of one tumor resulted in regression of an established tumor at a distant site. Moreover, intratumoral or intravenous injection of AdTCPmIL-12 did not induce evident toxicity. These results indicate AdTCPmIL-12 can contribute to effective and less toxic gene therapy of MTC.

Adenoviridae↗
PubMed2002

Regulational effect of ghrelin on growth hormone secretion from perifused rat anterior pituitary cells.

Ghrelin, a novel growth hormone (GH)-releasing peptide, was recently isolated from the rat stomach as an endogenous ligand to growth hormone secretagogue receptor (GHS-R). Ghrelin specifically stimulates the release of GH from the rat anterior pituitary gland, but the regulational effect of ghrelin on GH secretion has not yet been clarified. We used a perifusion system to examine the single effect and combined effects of ghrelin with growth hormone-releasing hormone (GHRH) and somatostatin on GH secretion from rat anterior pituitary cells. The increase in GH concentration due to ghrelin stimulation showed a transitory peak that was almost the same as that previously reported for GHS, but apparently distinct from that of GHRH. Ghrelin (10(-10) M to 10(-8) M) stimulated GH secretion from the rat anterior pituitary cells in a dose-dependent manner. Serial ghrelin stimulation of the dispersed cells at 1-h intervals decreased the GH response, but the response recovered with stimulation at 3-h intervals, indicating that ghrelin strongly desensitized cells. Costimulation with ghrelin and GHRH elicited neither a synergistic nor an additive GH response from the rat pituitary cells. Furthermore, pretreatment to anterior pituitary cells with somatostatin strongly abolished ghrelin- and/or GHRH-stimulated GH secretion. In this study, we demonstrated that ghrelin caused weaker GH secretion than that caused by GHRH, and we also showed that costimulation with GHRH had no additive or synergistic effect on GH secretion, suggesting that ghrelin indirectly affects coordinated GH release from pituitary gland, as found in vivo.

Animals↗
PubMed2002

Beneficial effect of JTV-803, a new synthetic inhibitor of activated factor X, against both lipopolysaccharide-induced and tissue factor-induced disseminated intravascular coagulation in rat models.

We examined whether JTV-803, a specific activated factor X inhibitor independent of antithrombin III (ATIII), is effective against disseminated intravascular coagulation (DIC) in rat models induced by tissue factor (TF) or lipopolysaccharides (LPS). In male Wistar rats, DIC was induced by a 4 h infusion of thromboplastin (3.75 U/kg) or LPS (50 mg/kg). The rats were given JTV-803 (0.3 or 3 mg/kg, bolus intravenously) (JTV-803 groups) or low molecular weight heparin (LMWH groups) (200 U/kg, bolus intravenously) prior to an injection of TF or LPS. The results showed that JTV-803 was dose-dependently effective against DIC in both TF-induced and LPS-induced rat models. This anti-DIC effect of JTV-803 at higher doses was almost equivalent to that of LMWH in both types of DIC. Plasma ATIII activity was more prominent in the group treated with JTV-803 than in that treated with LMWH. None of rats died in the TF-induced DIC model with or without drug administration. On the contrary, seven of 22 rats died (mortality rate, 31.8%) in the LPS-induced DIC model without drug administration. Although the mortality rate of rats induced with LPS and treated with LMWH was quite high (6/16, 37.5%), none of the LPS-induced rats treated with JTV-803 died. These findings suggested that JTV-803 can treat both TF-induced and LPS-induced DIC models, and that this drug has greater potential in preserving ATIII and in improving the prognosis of DIC.

Animals↗
PubMed2002

Epidemiological investigation of a fatal case of cholera in Japan by phenotypic techniques and pulsed-field gel electrophoresis.

A fatal case of cholera caused by Vibrio cholerae 01 El Tor serotype Ogawa occurred in Aichi Prefecture, Japan in 1995. The patient was identified locally, but the route of the infection was unknown. The causative isolate and 38 other domestic and imported V. cholerae O1 isolates, obtained between 1984 and 1997, were analysed by prophage typing, antimicrobial susceptibility testing and pulsed-field gel electrophoresis (PFGE). This was done to determine whether the isolate from this case differed from others associated with either mild cholera infections or asymptomatic carriage, and to elucidate the route of infection. Cholera toxin (CT) from 37 toxigenic isolates was assayed semi-quantitatively. The 39 isolates were divided into 12 temporary types in accordance with the results of the three typing techniques. The isolate from the fatal infection and nine other isolates were classified as temporary type IV. No difference in CT production was found between the isolate from the fatal case and the other 36 toxigenic isolates. Taken together, it is unlikely that a V. cholerae 01 isolate of distinguishable type was responsible for the fatal illness. Temporary type IV isolates were frequently present in both domestic and imported cases from 1994 to 1997 in Aichi, but they did not emerge before 1993. These results suggest that a new clone was introduced after 1993 from overseas and then disseminated into Aichi, and this may have been an important step in triggering the fatal case of cholera.

Adult↗
PubMed2002

Effects of dipyridamole and aspirin on shear-induced platelet aggregation in whole blood and platelet-rich plasma.

BACKGROUND: Shear-induced platelet aggregation (SIPA) is an important mechanism of thrombosis at arterial bifurcations or stenotic lesions. METHODS: We investigated the in vitro effects of dipyridamole (DP) and acetylsalicyclic acid (ASA) on SIPA in whole blood and platelet-rich plasma (PRP). RESULTS: In whole blood, DP 20 microM significantly inhibited SIPA, while DP 5 microM or ASA 5 or 20 microM did not. SIPA in whole blood was, however, significantly inhibited by the combination of 5 or 20 microM of DP and ASA. SIPA in PRP was not inhibited by any concentration of DP or ASA, alone or in combination. CONCLUSIONS: These results suggest that DP has an effect on red blood cells and that ASA enhances the inhibitory effect of DP on SIPA in whole blood. These effects may be related to the additive effect of combination therapy with DP and ASA on stroke prevention.

Adult↗
PubMed2002

Chromatin reprogramming of male somatic cell-derived XIST and TSIX in ES hybrid cells.

In mammalian somatic cells, the X chromosome is active in XY males, whereas one X chromosome is inactivated in XX females. On the active male X chromosome, the XIST and TSIX genes are transcribed in undifferentiated cells of pre-implantation embryos (undifferentiated state) and then down-regulated upon cell differentiation (differentiated state). To explore the epigenetic mechanism involved in the on-off switching of XIST and TSIX transcription in the active X chromosome, male somatic cells were hybridized with male embryonic stem (ES) cells. Fluorescence in situ hybridization analysis revealed that the XIST gene derived from somatic cells was derepressed, as shown by the advent of two pinpoint signals. This was confirmed by strand-specific RT-PCR of XIST and TSIX genes. To analyze changes in chromatin structure in the promoter regions of XIST and TSIX derived from somatic cells, histone tail modifications were studied by chromatin immunoprecipitation analysis. Histones H3 and H4, which were hypoacetylated in the somatic cells, were hyperacetylated in the hybrid cells, and histone H3 lysine 4, which was hypomethylated in the somatic cells, was hypermethylated in the hybrid cells, indicating that the reactivation of XIST and TSIX was linked with chromatin modifications. In the telomeric region of DXPAS34, acetylation of histones H3 and H4 was dependent on reactivation of XIST and TSIX, whereas histone H3 lysine 4 was constitutively methylated independent of the transcriptional activity of those genes. We propose that the chromatin reprogramming is linked with the resetting of the memory found in the process of choosing an active X chromosome.

Animals↗