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Masanori Nakamura

Publications and source records attributed to Masanori Nakamura.

At least 19 recordsLinked to original sources
PubMed2006

Contributions of matrix metalloproteinases toward Meckel's cartilage resorption in mice: immunohistochemical studies, including comparisons with developing endochondral bones.

The middle portion of Meckel's cartilage (one of four portions that disappear with unique fate) degrades via hypertrophy and the cell death of chondrocytes and via the resorption of cartilage by chondroclasts. We have examined the immunolocalization of matrix metalloproteinase-2 (MMP-2), MMP-9, MMP-13, and MMP-14 (members of the MMP activation cascade) and galectin-3 (an endogenous substrate for MMP-9 and an anti-apoptotic factor) during resorption of Meckel's cartilage in embryonic mice and have compared the results with those of developing endochondral bones in hind limbs. MMP immunoreactivity, except for MMP-2, is present in nearly all chondrocytes in the middle portion of Meckel's cartilage. On embryonic day 15 (E15), faint MMP-2-immunoreactive and intense MMP-13-immunoreactive signals occur in the periosteal bone matrix deposited by periosteal osteoblasts on the lateral surface, whereas MMP-9 and MMP-14 are immunolocalized in the peripheral chondrocytes of Meckel's cartilage. The activation cascade of MMPs by face-to-face cross-talk between cells may thus contribute to the initiation of Meckel's cartilage degradation. On E16, immunopositive signaling for MMP-13 is detectable in the ruffled border of chondroclasts at the resorption front, whereas immunostaining for galectin-3 is present at all stages of chondrocyte differentiation, especially in hypertrophic chondrocytes adjacent to chondroclasts. Galectin-3-positive hypertrophic chondrocytes may therefore coordinate the resorption of calcified cartilage through cell-to-cell contact with chondroclasts. In metatarsal specimens from E16, MMPs are detected in osteoblasts, young osteocytes, and the bone matrix of the periosteal envelope, whereas galectin-3 immunoreactivity is intense in young periosteal osteocytes. In addition, intense MMP-9 and MMP-14 immunostaining has been preferentially found in pre-hypertrophic chondrocytes, although galectin-3 immunoreactivity markedly decreases in hypertrophic chondrocytes. These results indicate that the degradation of Meckel's cartilage involves an activation cascade of MMPs that differs from that in endochondral bone formation.

Acid Phosphatase↗
PubMed2006

Influence of the opening mode of the mitral valve orifice on intraventricular hemodynamics.

We analyzed intraventricular blood flow numerically to study the influence of the mode of mitral valve opening on the flow field in the left ventricle. Four different types of opening mode were examined: gradually axisymmetric, gradually anteroposterior (anatomical), gradually bilateral (anti-anatomical), or instantaneous opening and closing. In these models, the shape of the valve orifice was the same when the mitral valve was opened fully. The results demonstrated that the framework of the velocity profile of transmitral flow was built during the phase of mitral valve opening, which was characterized by the mode of valve opening. After the mitral valve opened completely, the transmitral velocity profile developed while maintaining its topological features. Consequently, each mode of mitral valve opening had its own pattern of intraventricular flow, although mitral valve opening accounted for less than 4% of a cardiac cycle. Particle tracking in the resulting flow field revealed that ventricular ejection was more efficient in the anteroposterior and axisymmetric opening modes. These results addressed the importance of the mode of mitral valve opening in intraventricular flow dynamics.

Blood Flow Velocity↗
PubMed2006

Elevated extracellular calcium stimulates secretion of bone morphogenetic protein 2 by a macrophage cell line.

It has been suggested that macrophages and multinucleated giant cells are responsible for phagocytosis of resorbable calcium phosphate (CaP) compounds implanted in bone defects. However, function of macrophages around the CaP, if continuously exposed to various concentration of extracellular calcium ions ([Ca(2+)](o)), is still unknown. The present study showed that when resorbable octacalcium phosphate was implanted in mouse calvaria, macrophage-like cells were observed around the implant during bone formation. Then, experiments were designed to investigate whether secretion of bone morphogenetic protein 2 (BMP-2) is enhanced by [Ca(2+)](o) in a macrophage cell line (J774A.1) in vitro. The mRNA expression and the secretion of BMP-2 in J774A.1 cells were significantly increased when incubated in the medium with [Ca(2+)](o) up to 14mM. The promotion of mRNA expression was maintained even when incubated with a small amount of minute CaP crystals. The present results suggest that [Ca(2+)](o) above physiological concentration may stimulate macrophages to induce osteogenic cytokine, such as BMP-2, for bone formation by osteoblast.

Animals↗
PubMed2006

Bone formation enhanced by implanted octacalcium phosphate involving conversion into Ca-deficient hydroxyapatite.

The present study was designed to investigate whether hydrolysis of synthetic octacalcium phosphate (OCP) into hydroxyapatite affects bone formation. Mouse bone marrow stromal ST-2 cells and primary calvarial osteoblastic cells were cultured on the dishes pre-coated with OCP or its hydrolyzed Ca-deficient hydroxyapatite (OCP hydrolyzate; HL). The capacity of proliferation and differentiation was determined up to day 20. Granules of OCP and HL were implanted into critical-size rat calvaria defects for 4 and 12 weeks, and then bone formation was measured by histomorphometry. Structural changes of incubated and implanted OCP were determined by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The proliferation of both ST-2 and primary osteoblasts cultured on OCP or HL was initially inhibited, whereas their differentiation to osteoblasts was promoted at last. Implantation of OCP in bone defect more significantly enhanced bone formation than that of HL until 12 weeks. OCP tended to convert to apatite in vitro and in vivo. The conversion of the implanted OCP was ascertained to advance gradually with implantation periods. Taken together, these results suggest that OCP supports appositional bone formation and OCP-apatite conversion may be involved in this stimulatory capacity of OCP.

Animals↗
PubMed2006

Successful outcomes of a novel endoscopic treatment for GI tumors: endoscopic submucosal dissection with a mixture of high-molecular-weight hyaluronic acid, glycerin, and sugar.

BACKGROUND: Endoscopic submucosal dissection (ESD) has recently been developed for endoscopic treatment of GI tumors, which enables us to resect even large tumors en bloc. However, a considerable frequency of perforation has become another problem. The best way to prevent perforation is to create a sufficient submucosal fluid cushion (SFC). The aim of this study is to find out the feasibility of ESD by using a mixture of 1900 KDa hyaluronic acid (Suvenyl) and a 10% glycerin plus 5% fructose solution (Glyceol). METHODS: Sixty-seven consecutive GI tumors in 54 patients who met indication criteria of ESD were enrolled. The mixing ratios of Suvenyl and Glyceol were 1:3 for esophageal/colorectal tumors and stomach tumors with scar, and 1:7 for stomach tumors without scar. After creation of SFCs, mucosal incision around the tumors and submucosal dissection under the tumors were made by cutting devices. The clinical outcomes were investigated. RESULTS: Mean resected and tumor sizes were 38.6 and 25.6 mm, respectively. Perforation occurred in one colon tumor with severe fibrosis (1.5%), which was managed by endoscopic clipping without salvage surgery. No blood transfusion was performed. In one stomach and in one rectal tumor (3%), endoscopic hemostasis was necessary because of postoperative bleeding. Overall endoscopic and histologic en bloc resection rates were 94% (63/67) and 78% (52/67), respectively, and there was no recurrence after follow-up of 1 year. CONCLUSIONS: ESD when using a mixture of Suvenyl and Glyceol results in excellent outcomes, and this injection solution should be used for ESD.

Adjuvants, Immunologic↗
PubMed2006

Safety of argon plasma coagulation for hemostasis during endoscopic mucosal resection.

Showing the safety of argon plasma coagulation (APC) over mucosal defects during/after endoscopic mucosal resection (EMR), 2 studies using resected pig (ex vivo) and living minipig (in vivo) stomachs were performed. As an ex vivo study, APC was applied over mucosal defects in 2 groups; with prior submucosal saline injection and without injection. Only subtle tissue damage was observed in the injection group, whereas apparent damage was observed in the noninjection group. The damaged distances in depth significantly increased as the pulse duration increased and those at the pulse duration of 4 seconds, which might be maximal in clinical practice, were approximately 1 mm. As an in vivo study, APC was applied over mucosal defects immediately after EMR. Only subtle tissue damage was observed even at the pulse duration of 20 seconds as shown in the ex vivo study. APC can be performed safely over the mucosal defects during/after EMR.

Animals↗
PubMed2006

Submucosal injection of normal saline may prevent tissue damage from argon plasma coagulation: an experimental study using resected porcine esophagus, stomach, and colon.

Argon plasma coagulation (APC) is considered to be a safe thermocoagulation technique, but some reports show perforation and deformity during and after APC. In this study, we investigated the usefulness of prior submucosal injection for APC. APC over the mucosa was performed on fresh resected porcine esophagus, stomach, and colon with prior submucosal injection of normal saline (injection group) and without it (control group). The depth of tissue damage increased linearly with pulse duration up to the shallower submucosal layer in both groups. After that, tissue damage in the injection group remained confined to the shallower submucosal layer under any condition, whereas that in the control group continued to extend. The tissue damages of the injection groups were significantly (P<0.05) shallower than those of the control groups that reached the deeper submucosal layer in all the organs. Submucosal injection of normal saline before the application of APC may limit tissue damage and prevent perforation and deformity.

Animals↗
PubMed2006

Helicobacter pylori status and the extent of gastric atrophy do not affect ulcer healing after endoscopic submucosal dissection.

BACKGROUND: Eradication therapy for Helicobacter pylori is effective in preventing peptic ulcer recurrence, but its efficacy in ulcer healing is still controversial. The effect of H. pylori on artificial ulcers after endoscopic resection is not known. The purpose of the present study was therefore to evaluate the influence of H. pylori infection on ulcer healing after endoscopic submucosal dissection (ESD). METHODS: One hundred and 10 patients who underwent ESD for gastric tumors, and for whom the infection status of H. pylori was confirmed before treatment, were included. The healing stage was studied by endoscopy performed at 8 weeks after ESD. In addition, 73 patients whose serum pepsinogen (PG) was evaluated before ESD, were divided into three groups: PG positive (PGI<or=70 ng/mL and I/II<or=3 ng/mL), strongly positive (PGI<or=30 ng/mL and I/II<or=2 ng/mL) and negative, to study the influence of atrophic gastritis on ulcer healing. RESULTS: Ulcer healing was observed in 85 patients (93%) who were H. pylori positive, and in 19 patients (100%) in whom H. pylori had been eradicated previously. Serum PG level had no influence on the healing process. Among 15 patients with ulceration or ulcer scar with the lesion, ulcer healing was observed in nine patients (60%), which was significantly low. CONCLUSIONS: Infection status of H. pylori and the extent of gastric atrophy do not affect ulcer healing after ESD. Preoperative existence of fibrotic change in the submucosal layer may delay the healing process.

Female↗
PubMed2006

Computational analysis of blood flow in an integrated model of the left ventricle and the aorta.

To study the effects of intraventricular flow dynamics on the aortic flow, we created an integrated model of the left ventricle and aorta and conducted a computer simulation of diastolic and systolic blood flow within this model. The results demonstrated that the velocity profile at the aortic annulus changed dynamically, and was influenced by the intraventricular flow dynamics. The profile was almost flat in early systole but became nonuniform as systole progressed, and was skewed toward the posterior side in midsystole and toward the anterior side in later systole. At a distance from the aortic annulus, a different velocity profile was induced by the twisting and torsion of the aorta. In the ascending aorta, the fastest flow was initially located in the posteromedial sector, and it moved to the posterior section along the circumference as systole progressed. The nonuniformity of the aortic inflow gave rise to a complex wall shear stress (WSS) distribution in the aorta. A comparison of the WSS distribution obtained in this integrated analysis with that obtained in flow calculations using an isolated aorta model with Poiseuille and flat inlet conditions showed that intraventricular flow affected the WSS distribution in the ascending aorta. These results address the importance of an integrated analysis of flow in the left ventricle and aorta.

Animals↗
PubMed2005

Interleukin-1beta induces death in chondrocyte-like ATDC5 cells through mitochondrial dysfunction and energy depletion in a reactive nitrogen and oxygen species-dependent manner.

IL-1 (interleukin-1) acts as a key mediator of the degeneration of articular cartilage in RA (rheumatoid arthritis) and OA (osteoarthritis),where chondrocyte death is observed. It is still controversial, however, whether IL-1 induces chondrocyte death. In the present study, the viability of mouse chondrocyte-like ATDC5 cells was reduced by the treatment with IL-1beta for 48 h or longer. IL-1beta augmented the expression of the catalytic gp91 subunit of NADPH oxidase, gp91phox, as well as inducible NO synthase in ATDC5 cells. Generation of nitrated guanosine and tyrosine suggested the formation of reactive nitrogen species including ONOO- (peroxynitrite), a reaction product of NO and O2-, in ATDC5 cells and rat primary chondrocytes treated with IL-1beta. Death of ATDC5 cells after IL-1beta treatment was prevented by an NADPH-oxidase inhibitor, AEBSF[4-(2-aminoethyl)benzene-sulphonyl fluoride], an NO synthase inhibitor, L-NAME (NG-nitro-L-arginine methyl ester), and a ONOO- scavenger, uric acid. The viability of ATDC5 cells was reduced by the ONOO(-)-generator 3-(4-morpholinyl)sydnonimine hydrochloride, but not by either the NO-donor 1-hydroxy-2-oxo-3-(N-methyl-2-aminopropyl)-3-methyl-1-triazene or S-nitrosoglutathione. Disruption of mitochondrial membrane potential and ATP deprivation were observed in IL-1beta-treated ATDC5 cells, both of which were restored by L-NAME, AEBSF or uric acid. On the other hand, no morphological or biochemical signs indicating apoptosis were observed in these cells. These results suggest that the death of chondrocyte-like ATDC5 cells was mediated at least in part by mitochondrial dysfunction and energy depletion through ONOO- formation after IL-1beta treatment.

Adenosine Triphosphate↗
PubMed2005

Heparin-binding EGF-like growth factor accelerates keratinocyte migration and skin wound healing.

Members of the epidermal growth factor (EGF) family are the most important growth factors involved in epithelialization during cutaneous wound healing. Heparin-binding EGF-like growth factor (HB-EGF), a member of the EGF family, is thought to play an important role in skin wound healing. To investigate the in vivo function of HB-EGF in skin wound healing, we generated keratinocyte-specific HB-EGF-deficient mice using Cre/loxP technology in combination with the keratin 5 promoter. Studies of wound healing revealed that wound closure was markedly impaired in keratinocyte-specific HB-EGF-deficient mice. HB-EGF mRNA was upregulated at the migrating epidermal edge, although cell growth was not altered. Of the members of the EGF family, HB-EGF mRNA expression was induced the most rapidly and dramatically as a result of scraping in vitro. Combined, these findings clearly demonstrate, for the first time, that HB-EGF is the predominant growth factor involved in epithelialization in skin wound healing in vivo and that it functions by accelerating keratinocyte migration, rather than proliferation.

Animals↗
PubMed2005

Distributions of magnesium and sulphur in defect layers of incisor dentine in magnesium-deficient rats.

This study examined the mechanism governing the occurrence of defect layers of incisor dentine in Mg-deficient rats by X-ray microanalysis. Young (5 weeks of age) Wistar male rats were pair-fed semi-synthetic diets containing either control (0.05% Mg) (N = 8) or Mg-deficient (0.001% Mg) (N = 8) ingredients for 17 days. All animals were time marked with a combination of 0.1 mol nitrilotriacetato lead and 0.1 mol nitrilotriacetato zinc (2mg Pb/kg body weight) on days 0, 7 and 14 into incisor dentine. Blood samples were obtained on days 10 and 17 in order to measure Ca, Mg, P and alkaline phosphatase activity levels in serum; moreover, hypomagnesaemia and hypercalcaemia were confirmed. After the 17th day, rats were sacrificed humanely under anaesthesia and mandibular incisors were removed. Dentine formation of right mandibular incisors was assessed (time marking lines); furthermore, Ca, P, Mg and sulphur (S) concentrations as well as Ca/P molar ratio were determined in left mandibular incisors based on contiguous measurement points at 2 microm intervals from dentine pulp to dentine of the lingual aspect via X-ray analysis. Additionally, proteoglycan distribution was observed in other Mg-deficient rat dentine. These findings demonstrated decreases in body weight, incisor formation and incisor length in Mg-deficient rats. Mg and S levels increased in the defect layers, whereas proteoglycan decreased. This phenomenon was possibly attributable to condensation of Mg and S contents consequent to decreased dentine formation during Mg-deficiency and a transient increase in Mg due to transport of Mg as a result of inhibition of cell proliferation in soft tissues.

Alkaline Phosphatase↗
PubMed2005

Uniformly sized molecularly imprinted polymer for atropine and its application to the determination of atropine and scopolamine in pharmaceutical preparations containing Scopolia extract.

A uniformly sized molecularly imprinted polymer (MIP) for atropine has been prepared. The MIP was prepared using 2-(trifluoromethyl) acrylic acid and ethylene glycol dimethacrylate as a functional monomer and cross-linker, respectively, by a multi-step swelling and thermal polymerization method. The selectivity factor, which is defined as the ratio of the retention factors (k) on the molecularly imprinted and non-imprinted polymers, k(imprinted)/k(non-imprinted), was 2.2 for atropine on the MIP. The obtained MIP was applied for the determination of tropane alkaloids (atropine and scopolamine) in a commercial gastrointestinal drug by a column-switching HPLC system, consisting of an MIP material as a pre-column, and a conventional cation-exchange analytical column. An interference peak was observed at the retention time of atropine derived from pre-column. However, since the peak area was less than 0.5% the peak area of atropine of a standard solution under the analytical conditions of this study (0.2 microg of atropine was loaded), this interference was negligible in the determination of atropine. On the other hand, no interference peak was observed at the retention time of scopolamine. Calibration curves of atropine and scopolamine showed good linearity in the range of 0.02-0.9 microg/ml (r=0.9999) and 0.003-0.09 microg/ml (r=0.9998), respectively. The mean recoveries of atropine and scopolamine from a placebo pharmaceutical preparation sample were 98.9 and 99.9%, respectively. The intra-day precision (measured by relative standard deviation, R.S.D. (%)) of both ingredients was less than 2.0%. The optimized column-switching system was applied successfully to the determination of atropine and scopolamine in a commercial gastrointestinal drug.

Acrylates↗
PubMed2005

Cytogenetic abnormalities in hepatoblastoma: report of two new cases and review of the literature suggesting imbalance of chromosomal regions on chromosomes 1, 4, and 12.

Two cases of hepatoblastoma with unique karyotypic changes are described. One case was that of a 2-year-old boy with an unbalanced chromosomal translocation involving 4q35 as the sole chromosomal abnormality. The clonal karyotype of this tumor was 46,XY,add(4)(q35)[3]/46,XY[9]. In the other case, that of a 2-year-old boy, karyotypic analyses revealed the clonal karyotype as 57,XY,+del(1)(p22),+2,+5,+6,+7,+8,+del(12)(p12),+18,+19,+20,+22[4]/46,XY[12]. Review of these two cases, together with previous reports, underscored the significance of numerical and/or structural chromosomal abnormalities of 1q, 4q, 2, 8, and 20 in the development of hepatoblastoma. The present results show that imbalance of the terminal region of 4q could be the sole chromosomal abnormality in a hepatoblastoma. We also found that imbalance of chromosomal regions on chromosomes 1 and 12 may contribute to the development of hepatoblastoma.

Aneuploidy↗
PubMed2005

Molecular genetic alterations and gene expression profile of a malignant rhabdoid tumor of the kidney.

Malignant rhabdoid tumor of the kidney (MRTK) is a rare but highly aggressive tumor in children, and knowledge about the molecular signature of this tumor is limited. We report the molecular genetic alterations and gene expression profile of an MRTK tumor that arose in a 4-month-old Japanese girl. Fluorescence in situ hybridization and Southern blot analyses revealed a homozygous deletion of an approximately 0.29-Mb genomic region bordered by the Rgr and DDT genes in these tumor cells. This deleted region encodes SMARCB1, a candidate tumor suppressor gene for MRTK. Using a high-density oligonucleotide DNA array, we found increased expression of 25 genes, including genes involved in the cell cycle (10 genes), DNA replication (3 genes), cell growth (5 genes), and cell proliferation (5 genes), in this MRTK tumor sample, compared with a noncancerous kidney (NK) sample. On the other hand, 64 genes, including 4 genes regulating apoptosis, were found to show decreased expression in this MRTK tumor sample, compared with the NK sample. Among these alterations, we found alterations of expression of some genes, such as IGF2, MDK, TP53, and TNFSF10, in this MRTK tumor, as described previously. The molecular genetic alterations and altered pattern of gene expression found in this case may have contributed to the biological characteristics of the MRTK tumor that arose in our patient.

Apoptosis↗
PubMed2005

Tissue damage of different submucosal injection solutions for EMR.

BACKGROUND: When choosing submucosal injection solutions for EMR, tissue damage should be considered, as well as the lesion-lifting ability. The objective of the study was to find out the potential tissue damage of submucosal injection solutions. METHODS: The submucosal injection solutions examined were the following: normal saline solution (NS), 3.75% NaCl, 20% and 50% dextrose water (DW), a glycerin solution (Glyceol; 10% glycerin with 0.9% NaCl plus 5% fructose), and two hyaluronic acid (HA) solutions (0.25% 1900 kDa/NS solution and 0.125% 1900 kDa/ Glyceol solution). Furthermore, DW with different concentrations (5%, 10%, 15%, 30%, 40%) also was examined to find out the tolerable concentration without tissue damage. A total of 2 mL of each solution per stomach were injected by endoscopy into the submucosal layer at the separate sites of 4 living minipigs. Two minipigs were euthanized after 30 minutes of endoscopic observations, and the others were euthanized after additional endoscopic observations a week after injection. RESULTS: There was no apparent tissue damage in NS, 5% and 10% DW, Glyceol, or two solutions of HA, whereas, hypertonic solutions, except Glyceol and 10% DW, have more or less potency of tissue damage. In 3.75% NaCl and DW with concentrations of >or=20%, considerable tissue damage was observed, which might affect resected EMR specimens and ulcer healing. CONCLUSIONS: Use of hypertonic solutions except Glyceol is not recommended with respect to tissue damage. A combination of HA and Glyceol is the most favorable submucosal injection solution, considering tissue damage and lesion-lifting ability.

Animals↗