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T Muramatsu

Publications and source records attributed to T Muramatsu.

At least 19 recordsLinked to original sources

Osteopontin as biomarker in early invasion by squamous cell carcinoma in tongue.

BACKGROUND: Osteopontin (OPN) expression in squamous cell carcinoma (SCC) of the tongue has not been clearly elucidated. METHODS: We selected 46 cases of tongue SCC and investigated the expression of OPN by immunohistochemical staining. The immunopositive reaction and score for each case were semiquantitatively evaluated. RESULTS: Scores were significantly higher in carcinoma nests than in neighboring normal epithelium or epithelial dysplasia. The OPN was expressed clearly in the cytoplasm of carcinoma cells. In cases of early invasive carcinoma, in particular, expression of OPN showed a remarkable increase at the invasion front compared with the non-invaded regions. However, there was no significant correlation between expression of OPN in the primary tumor nest and lymphatic metastasis, recurrence, or survival rate. CONCLUSION: This suggests that OPN is a useful biomarker of early invasion by SCC in tongue.

Adult↗

GER1, a GDSL motif-encoding gene from rice is a novel early light- and jasmonate-induced gene.

The reaction of the rice mutant HEBIBA differs from that of wild-type rice in that the mutant responds inversely to red light and is defective in the light-triggered biosynthesis of jasmonic acid (JA). Using the wild type and the HEBIBA mutant of rice in a differential display screen, we attempted to identify genes that act in or near the convergence point of light and JA signalling. We isolated specifically regulated DNA fragments from approximately 10 000 displayed bands, and identified a new early light- and JA-induced gene. This gene encodes an enzyme containing a GDSL motif, showing 38 % identity at the amino acid level to lipase Arab-1 in Arabidopsis thaliana. The GDSL CONTAINING ENZYME RICE 1 gene (GER1) is rapidly induced by both red (R) and far-red (FR) light and by JA. The results are discussed with respect to a possible role for GER1 as a negative regulator of coleoptile elongation in the context of recent findings on the impact of JA on light signalling.

Amino Acid Motifs↗

Responses of rat pulp cells to heat stress in vitro.

Although heat stress can cause irritation in the dentin/pulp complex, little is known about the thermotolerance of pulp cells and their response to heat stress. We investigated cultured rat pulp cell responses to heat stress. Cells were subjected to a temperature of 42 degrees C for 30 minutes, and HSPs, alkaline phosphatase activity, and gap-junctional communication were determined at various time points. Although only low levels of HSP70 expression were detected before heat treatment, heat shock markedly induced HSP70 expression, with it gradually increasing at 1 hour after being heated. HSP25, however, showed no dramatic change. Gap junction protein connexin43 rapidly degraded after heat treatment, recovering to normal levels within the following 6 hours. Alkaline phosphatase activity decreased immediately after heat stress, recovering after 1 hour. These results indicate that dental pulp possesses protective factors, including HSPs, and that it can recover viability of intercellular communication and alkaline phosphatase activity after heat stress.

Alkaline Phosphatase↗

Correlation between reduction of syndecan-1 expression and clinico-pathological parameters in squamous cell carcinoma of tongue.

We examined expression of syndecan-1 in squamous cell carcinoma (SCC) of tongue using immunohistochemistry. Forty-three cases of SCC arising in lateral border of tongue were investigated. From the immunohistochemical staining pattern, the cases were divided into two groups based on expression of syndecan-1 at the supra-peripheral cells of the tumor nest: Group A, completely or mainly positive; Group B, sporadically positive or negative. Most poorly differentiated SCC cases were classified into Group B (81.8%). The number of Group B cases in T1-2 was different from that in T3-4. The number of cases where syndecan-1 expression was reduced was much greater in T3-4, and represented the majority of Group B (86.7%). More than 80% of Grade 4D cases were in Group B (83.3%) based on the Yamamoto-Kohama criteria. These results indicate that reduction of syndecan-1 correlates to histological grade, tumor size and mode of invasion in tongue SCC.

Adult↗

Anomalous pressure dependence of the superconducting transition temperature of beta-pyrochlore AOs2O6 oxides.

High-pressure effects on the superconducting transitions of beta-pyrochlore oxide superconductors AOs(2)O(6) (A = Cs,Rb,K) are studied by measuring resistivity under high pressures up to 10 GPa. The superconducting transition temperature T(c) first increases with increasing pressure in every compound and then exhibits a broad maximum at 7.6 K (6 GPa), 8.2 K (2 GPa), and 10 K (0.6 GPa) for A = Cs, Rb, and K, respectively. Finally, the superconductivity is suppressed completely at a critical pressure near 7 GPa and 6 GPa for A = Rb and K and probably above 10 GPa for A = Cs. Characteristic changes in the coefficient A of the T(2) term in resistivity and residual resistivity are observed, both of which are synchronized with the corresponding change in T(c).

Journal Article↗

Postischemic gene transfer of midkine, a neurotrophic factor, protects against focal brain ischemia.

Gene therapy may be a promising approach for treatment of brain ischemia. In this study, we examined the effect of postischemic gene transfer of midkine, a heparin-binding neurotrophic factor, using a focal brain ischemia model with the photothrombotic occlusion method. At 90 min after induction of brain ischemia in spontaneously hypertensive rats, a replication-deficient recombinant adenovirus encoding mouse midkine (AdMK, n=7) or a control vector encoding beta-galactosidase (Adbetagal, n=7) was injected into the lateral ventricle ipsilateral to ischemia. At 2 days after ischemia, we determined infarct volume by 2,3,5-triphenyltetrazolium chloride staining. There were no significant differences in cerebral blood flow 1 h after ischemia between AdMK and Adbetagal groups. Infarct volume of AdMK group was 51+/-27 mm3, which was significantly smaller than that of Adbetagal group (86+/-27 mm3, P<0.05). TUNEL-positive and cleaved caspase-3-positive cells in the periischemic area of AdMK-treated rats were significantly fewer than those in Adbetagal-treated rats, suggesting that the reduction of infarct volume by midkine was partly mediated by its antiapoptotic action. Thus, gene transfer of midkine to the ischemic brain may be effective in the treatment of brain ischemia.

Adenoviridae↗

Reduction of osteocalcin expression in aged human dental pulp.

AIM: To investigate the expression of osteocalcin mRNA in young and in aged human dental pulp tissue to determine the characteristics of osteocalcin expression. METHODOLOGY: Human dental pulp tissues of the third molars were obtained from healthy young (17-23 years) and aged (>50 years) subjects, and total RNA was extracted. Osteocalcin mRNA expression was determined by RT-PCR and by quantitative real-time RT-PCR (QRT-PCR). The threshold cycle (Ct) value, which reflects the amount of PCR, was calculated and the difference between the value in young and aged pulp was statistically analysed. RESULTS: Osteocalcin mRNA was detected in all samples of human dental pulp tissue homogenates by RT-PCR analysis. Osteocalcin mRNA was expressed in young adult dental pulp but was decreased in aged human dental pulp. QRT-PCR analysis also showed a reduced expression of osteocalcin mRNA in aged human pulp. Expression of osteocalcin in young human pulp was significantly higher (about sixfold) than in aged pulp (P<0.01, Mann-Whitney U-test). CONCLUSION: Reduction of osteocalcin expression may be associated with the loss of viability in human dental pulp tissue, and may be a characteristic of aged human dental pulps.

Adolescent↗

Lipoma and opthalmoplegia in mitochondrial diabetes associated with small heteroplasmy level of 3243 tRNA(Leu(UUR)) mutation.

We report a patient with mitochondrial diabetes mellitus associated with the A3243G mutation (MDM3243). The patient is a 77-year man with diabetes. At age 68, he noticed diplopia, due to superior rectus muscle palsy of the right eye. At age 70, he noticed lipoma on the right arm. The pathology of his muscle revealed some ragged-red fibers, and focal cytochrome c oxidase deficiency. Hence, he may have a pathogenetic mechanism in common with CPEO (chronic progressive external ophthalmoplegia) or mitochondria-related autoimmune disorder associated with mononeuropathy. He had the rate of 0.102% for heteroplasmy of 3243 mitochondrial DNA mutation in leukocytes. This case's heteroplasmy level is the smallest among the reported cases of MDM3243 in the literature. 3243 mitochondrial DNA mutation is known to induce a lack of uridine-modification in tRNA(Leu(UUR)) at the first letter of the anticodon, with which the third letter of the codon pairs, and decline of the pairing of the anticodon of tRNA with the codon of mRNA, suggesting the termination of polypeptide-elongation to generate premature proteins. Therefore, we speculate that these premature proteins may accumulate overtime, thereby affecting cells in target organs.

Aged↗

Meta-analysis of three diabetes population studies: association of inactive ALDH2 genotype with maternal inheritance of diabetes.

To date, there have been three population studies that examined the association of mitochondrial aldehyde dehydrogenase 2 (ALDH2) genotype with inheritance of diabetes. Here, we summarize the results by meta-analysis. The study 1 consisted of 212 type 2 diabetics who did not have renal failure. The study 2 consisted of 73 type 2 diabetics who had renal failure. The study 3 consisted of 230 type 1 diabetics. In total, 515 subjects were examined for the association of ALDH2 genotype with inheritance of diabetes. Out of 515 subjects, 307 (60%) had active ALDH2 (ALDH2*1/ALDH2*1) and 208 (40%) had inactive ALDH2 (175 had ALDH2*1/ALDH2*2 and 33 had ALDH2*2/ALDH2*2). As for family history, 25 subjects (8.1%) in the active ALDH2 group had a diabetic mother, compared with 43 (20.6%) in the inactive ALDH2 group. Twenty-nine subjects (9.4%) in the active ALDH2 group had a diabetic father, compared with 14 (6.7%) in the inactive ALDH2 group. The percentage of diabetic mother was higher in the inactive ALDH2 group, the differences were statistically significant (P < 0.0001). We hence speculate that diabetic patients with inactive ALDH2 genotype may have underlying background of mitochondria etiology, thereby showing maternal trait of diabetes inheritance. In conclusion, meta-analysis using three diabetes population studies strongly confirmed the association between ALDH2 inactivity and maternal inheritance.

Aldehyde Dehydrogenase↗

Midkine promoter-driven suicide gene expression and -mediated adenovirus replication produced cytotoxic effects to immortalised and tumour cells.

We examined possible application of a regulatory region of midkine (MK) gene, which is frequently upregulated in a number of human tumours but not in normal cells, to cancer gene therapy. We examined transcriptional activity of the MK genomic fragments in paired cell lines, immortalized cells and their parental normal fibroblasts, and found that the MK fragments activated a fused reporter or a suicide gene preferentially in the immortalized cells. Recombinant adenoviruses (Ad), in which the MK fragment was inserted upstream to the E1A gene (AdMK), replicated preferentially in the immortalized cells and were cytotoxie to them. Human hepatocellular carcinoma cells were significantly susceptible to AdMK compared with human normal fibroblasts in vitro and the replication of AdMK was less than that of wild-type Ad in the infected fibroblasts. Hepatocellular carcinoma cells infected with AdMK did not form tumours in immunocompromised mice and intratumoural injection of AdMK into the hepatocellular carcinoma developed in mice retarded the subsequent tumour growth. Expression of E1A and necrosis of tumours were detected in AdMK-injected but not control Ad-injected cases. The MK promoter-driven suicide gene therapy and -mediated replicative Ad can thereby produce cytotoxic effects to immortalized and tumour cells with minimal damage to normal cells.

Adenoviridae↗

Effect of peripheral blood progenitor cell dose on hematopoietic recovery: identification of minimal progenitor cell requirements for rapid engraftment.

Repeated high-dose chemotherapy (HDC) with stem cell support is advocated for curative treatment of epithelial ovarian cancer patients, requiring large quantities of progenitor cell harvest. Although the switchover to peripheral blood stem cell transplantation has generally made possible the harvest of large quantities of progenitor cells, the minimum threshold is still pertinent for planning the safe conduct of HDC. However, as the minimum threshold for safe peripheral blood stem cell transplantation (PBSCT) is not yet established, this study was designed to clarify the minimum amount of progenitor cells required for prompt recovery of hematopoietic. Retrospective analysis was performed on 52 HDCs administered in 37 ovarian cancer patients. After autologous bone marrow aspiration (10 patients) or peripheral blood stem cell harvest (27 patients), colony-forming unit granulocyte macrophage (CFU-GM) were enumerated prior to cryopreservation. Numbers of CFU-GM were again calculated before reinfusion and the patients were divided into eight groups: 0.13-<0.4, 0.4-<0.7, 0.7-<1.0, 1.0-<3.5, 3.5-<5.0, 5.0-<10.0, 10.0-<20.0 and >20.0 (x 10(5)/kg). The minimum CFU-GM threshold (x 10(5)/kg) was found to be 1.0-<3.5 for platelets and 3.5-<5.0 for white blood cells. Higher infusion doses did not lead to significant benefits in hematopoietic reconstruction. These results indicate that preservation of a minimum of 7-10 x 10(5)/kg CFU-GM is recommended for the safe conduct of tandem HDCs.

Female↗

Reduction of connexin 43 expression in aged human dental pulp.

AIM: To investigate the expression of connexin 43 (CX43) mRNA in young and old human dental pulp tissues to determine the characteristics of CX43 expression. METHODOLOGY: Samples were obtained from human dental pulp of healthy young (17-23 years) and aged (>50 years) subjects. CX43 expression was determined by RT-PCR and by quantitative real-time RT-PCR (QRT-PCR). The threshold cycle (Ct) value, which reflects the amount of PCR, was calculated and the difference between value in the young pulp and that in the aged pulp was statistically analysed. RESULTS: RT-PCR analysis of human dental pulp tissue detected CX43 mRNA in all the samples. CX43 was abundantly expressed in young adult dental pulp, but expression of CX43 mRNA was dramatically decreased in aged human dental pulp. QRT-PCR analysis also showed the reduced expression of CX43 in aged pulp, and expression of CX43 in young pulp was significantly higher (about 10-fold, P < 0.01, Mann-Whitney U-test). CONCLUSION: Reduction of CX43 expression may be associated with the loss of viability in human dental pulp, and is considered as one characteristic of aged pulp.

Adolescent↗

[Surgical treatment of left ventricular-right atrial communication complicated with aortic and mitral valves regurgitation: report of a case].

A 50-year-old man with a heart murmur from early childhood and a one year history of general fatigue was admitted. Cardiac examination showed a left ventricular-right atrial (LV-RA) communication, and aortic and mitral valve regurgitation (III/IV). At surgery, the LV-RA communication was located in the atrioventricular membranous portion 3 mm above the septal leaflet of the tricuspid valve. The etiology of the LV-RA communication was congenital and valvular diseases were acquired changes caused by sclerosis due to infected endocarditis or hypertension. The diameter of the LV-RA communication defect was 6 mm, and the fibrous tissue around the defect was closed directly. Next, double-valve replacement was performed safely. However, the day after surgery, the patient developed complete atrioventricular block and implantation of a DDD pacemaker was required. He was discharged without other complication. We recommend the careful closure of the LV-RA communication defect, if the defect is small and rich in fibrous tissue.

Aortic Valve Insufficiency↗

A promoter region of the midkine gene that is frequently expressed in human hepatocellular carcinoma can activate a suicide gene as effectively as the alpha-fetoprotein promoter.

We examined the expression of the midkine (MK) and alpha-fetoprotein (AFP) genes in 15 paired human specimens obtained from hepatocellular carcinoma (HCC) and the corresponding noncancerous regions of the same patients. A total of 14 HCC but none of the noncancerous specimens were positive for the MK mRNA. In contrast, three HCC specimens and one corresponding noncancerous sample out of the three AFP-positive HCC cases expressed the AFP gene. A 2.3-kb genomic fragment in the regulatory region of the MK gene could activate a fused reporter gene in both AFP-producing and -nonproducing HCC lines, and the MK fragment-mediated transcriptional activity was comparable to the AFP enhancer-linked AFP promoter in AFP-producing cell lines. The AFP-producing but not AFP-nonproducing HCC cell lines that were transfected with the MK promoter-linked herpes simplex virus-thymidine kinase (HSV-TK) gene became susceptible to a prodrug ganciclovir to a similar degree of the HCC transfected with the enhancer-linked AFP promoter-fused HSV-TK gene. These data suggest that the MK promoter can activate a therapeutic gene preferentially in HCC and is as useful as the AFP promoter in clinical settings.

Aged↗

Long-term implantation of zinc-releasing calcium phosphate ceramics in rabbit femora.

Zinc is an essential trace element that has stimulatory effects on bone formation. Recently, we developed zinc-releasing calcium phosphate ceramics in order to add the pharmacologic effect of zinc to calcium phosphate ceramics. In our previous study, we showed that the optimum zinc content for promoting bone formation was 0.316 wt %. Therefore a zinc composite ceramic of zinc-containing beta-tricalcium phosphate and hydroxyapatite, with a zinc content of 0.316 wt %, was chosen for long-term implantation. Cylindrical rods of the zinc composite ceramic were implanted in rabbit femora for 2 to 60 weeks. Using computer-aided image analysis, a histomorphometric study was carried out to investigate bone formation and resorption around the implants. The control was a composite ceramic of beta-tricalcium phosphate and hydroxyapatite without zinc. The addition of zinc to the implant demonstrated both favorable and unfavorable effects on bone remodeling. The favorable effect was enhanced bone apposition to the implant surface, demonstrated by a significant increase in intramedullary bone apposition rate at 6 weeks and in cortical bone apposition rate at 24 and 60 weeks (p < 0.05). The unfavorable effect was increased bone resorption, demonstrated by a significant increase in medullary cavity area at 60 weeks (p < 0.05). In order to utilize the favorable effect and avoid the unfavorable effect of zinc, either a reduction in zinc content in the zinc composite ceramic or the selection of implantation sites that do not have excessive exposure to bone marrow are required.

Animals↗

Correlation of elevated level of blood midkine with poor prognostic factors of human neuroblastomas.

The heparin-binding growth factor midkine (MK) is the product of a retinoic acid-responsive gene, and is implicated in neuronal survival and differentiation, and carcinogenesis. We previously reported that MK mRNA expression is elevated in neuroblastoma specimens at all stages, whereas pleiotrophin, the other member of the MK family, is expressed at high levels in favourable neuroblastomas. As MK is a secretory protein, it can be detected in the blood. Here, we show a significant correlation of the plasma MK level with prognostic factors of neuroblastomas. The plasma MK level was determined in 220 patients with neuroblastomas, and compared with that in children without malignant tumors (n=17, <500 pg ml(-1)). The plasma MK level became significantly elevated with advancing stages (stage 1: 445 pg ml(-1) (median), n=73; stage 2: 589, n=39; stage 3: 864, n=40; stage 4: 1445, n=56; and stage 4S: 2439, n=12). More importantly, a higher MK level was strongly correlated with poor prognostic factors: over 1 year of age (P=0.0299), MYCN amplification (P<0.0001), low TrkA expression (P=0.0005), nonmass screening, sporadic neuroblastomas (P<0.0001), and diploidy/tetraploidy (P=0.0007). Thus, these results demonstrate that the plasma MK level is a good marker for evaluating the progression of neuroblastomas. Moreover, considering the ability of antisense MK oligodeoxyribonucleotide to suppress tumour growth of colorectal carcinoma cells in nude mice, as recently reported, the present study suggests that MK is a possible candidate molecular target for therapy for neuroblastomas.

Animals↗