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Biomedical subjects

Masao Tanaka

Publications and source records attributed to Masao Tanaka.

At least 37 records · Page 2Linked to original sources
PubMed2006

Hepatic ischemia/reperfusion injury is prevented by a novel matrix metalloproteinase inhibitor, ONO-4817.

BACKGROUND: Matrix metalloproteinases (MMPs) play an important role in inflammation and neoplastic invasion and metastasis. Little is known about the effects of MMP inhibitors on hepatic ischemia/reperfusion injury. The aim of this study is to examine the inhibitory effects of ONO-4817 (oral inhibitor of MMPs) in rats. METHODS: Hepatic ischemia/reperfusion was induced in male Wister rats by clamping the portal vein and hepatic artery. The animals were randomized into an ONO-4817 group (300 mg/kg body weight per/day) and a vehicle group by oral gavage of a test substance. Serum alanine aminotransferase, histologic changes, gelatinolytic activity, MMP-2 and MMP-9 activities, tissue inhibitor of metalloproteinase 2 (TIMP-2) messenger RNA (mRNA) levels, and mRNA and serum levels of tumor necrosis factor alpha (TNFalpha) and interleukin 1beta (IL-1beta) were measured in both groups. RESULTS: ONO-4817 prevented ischemia/reperfusion injury to the hepatocytes as shown by significant reductions of serum alanine aminotransferase and less severe histologic changes. Gelatinolytic activity was inhibited markedly in the liver of the ONO-4817 group as demonstrated by film in situ zymography. MMP-9 and MMP-2 activities also were inhibited in the ONO-4817 group as shown by gelatin zymography. TIMP-2 mRNA levels showed no significant differences between the 2 groups. TNFalpha mRNA showed no downregulation, but IL-1beta mRNA was downregulated in the liver of the ONO-4817 group 1 to 3 hours after reperfusion. Serum levels of TNFalpha and IL-1beta showed a significant decrease in the ONO-4817 group, compared with the vehicle group after reperfusion. CONCLUSIONS: Hepatic ischemia/reperfusion injury was improved by a novel MMP inhibitor, ONO-4817, not only by inhibition of gelatinolytic activity but also by a decrease in release of inflammatory cytokines.

Animals↗
PubMed2006

Strategy for prevention of local recurrence of pancreatic cancer after pancreatectomy: antitumor effect of gemcitabine mixed with fibrin glue in an orthotopic nude mouse model.

BACKGROUND: Pancreatic cancer frequently recurs after operative treatment, resulting in a poor prognosis. Inhibition of proliferation of residual cancer cells is important for improved survival of patients with pancreatic cancer. Fibrin glue (FG) is a biocompatible, adherent hemostat that can deliver high concentrations of anticancer drugs to residual cancer cells. The aim of this study was to evaluate the local antitumor effect of a mixture of gemcitabine (GEM) and FG on pancreatic cancer cells implanted orthotopically in nude mice. METHODS: SUIT-2 human pancreatic cells were injected into the tail of the pancreas of nude mice. Seven days later, groups of mice were treated with 80 mg/kg GEM mixed with 0.5 mL fibrin glue (GEM + FG), 0.5 mL FG alone (FG), single intraperitoneal (i.p.) injection of 80 mg/kg GEM (GEM1), i.p. injection of 80 mg/kg GEM weekly for 3 weeks (GEM1,2,3), GEM + FG followed by weekly GEM injections for 2 weeks (GEM + FG + GEM2,3), or i.p. injection of PBS weekly for 3 weeks (controls). RESULTS: Twenty-eight days after cell injections, tumor volumes of groups treated with GEM + FG + GEM2,3, GEM1,2,3, GEM + FG, GEM1, and FG were decreased by 84%, 70%, 62%, 37%, and 10%, respectively, compared to that of control mice. GEM + FG + GEM2,3 had the strongest anticancer effect compared to all other groups (P < .05). Additionally, GEM + FG showed a more potent antitumor effect compared to GEM1 (P < .05). Survival of mice treated with GEM + FG + GEM2,3 was longer than that of mice in all other groups (P < .05). CONCLUSIONS: A mixture of GEM and FG was effective in inhibiting the growth of orthotopically implanted pancreatic neoplasms in nude mice. This procedure may be useful clinically to prevent the local recurrence of pancreatic cancer after pancreatectomy.

Animals↗
PubMed2006

Anti-aminoacyl-tRNA synthetase antibodies in clinical course prediction of interstitial lung disease complicated with idiopathic inflammatory myopathies.

In the treatment of polymyositis and dermatomyositis (PM/DM), the complication of interstitial lung disease (ILD) is an important prognostic factor. It has been reported that autoantibodies against aminoacyl-tRNA synthetases (ARS) are strongly associated with ILD. The aim of this study is to examine the correlation between anti-ARS and the clinical course of ILD. We investigated 41 cases of PM/DM with ILD. The response of ILD to corticosteroids (CS) was determined according to the change in respiratory symptoms, image findings, and pulmonary function between, before and 2 months after the treatment. Anti-ARS (anti-Jo-1, PL-7, PL-12, EJ, OJ and KS) antibodies were screened with the RNA immunoprecipitation assay. In the stratification into ILD-preceding, simultaneous and myopathy-preceding types, anti-ARS antibodies were significantly frequent in the ILD-preceding type (p < 0.05). In the stratification into anti-ARS-positive and negative groups, the response of ILD to CS was significantly better in the positive group (p < 0.05). However, recurrence of ILD was significantly more frequent in the positive group (p < 0.01), and 2 year prognoses of pulmonary function (%VC and %DLCO) were not different between the two groups. In conclusion, screening of anti-ARS may be useful to predict late-onset myopathy in ILD-preceding patients and to predict the clinical course of ILD in PM/DM patients.

Adult↗
PubMed2006

Age-associated changes in viscoelastic properties of the bovine temporomandibular joint disc.

To test the hypothesis that compressive properties of the temporomandibular joint (TMJ) disc change with age, we investigated its viscoelastic properties and stress-relaxation behavior under compression. Compressive stress-relaxation tests were performed in different regions of bovine discs of various ages. For each disc, specimens were derived from three different regions (anterior, central, and posterior). For four strain levels (5, 10, 15, and 20%), a stress-relaxation test was conducted over a 5-min period. Values of the instantaneous modulus, E(0), appeared to be larger in the anterior than in the posterior region of the disc, irrespective of age. The E(0) value increased with age, especially in the central region. Values of the relaxed modulus, E(R), also increased significantly with age. There were no regional differences in values of the relaxed modulus. Under stress-relaxation, the relaxation time became longer with age, especially in the posterior region. The results suggest that the compressive properties, instantaneous and relaxed moduli, increase with age, while the relaxation time becomes longer. This implies that the TMJ disc becomes harder with age. Furthermore, the compressive properties of the TMJ disc are region-specific. As a result of the harder disc, it is likely that the TMJ becomes more vulnerable to secondary damage, such as fracture and tissue degradation.

Aging↗
PubMed2006

Three-dimensional finite-element model of the human temporomandibular joint disc during prolonged clenching.

In the temporomandibular joint (TMJ), overloading induced by prolonged clenching appears to be important in the cascade of events leading to disc displacement. In this study, the effect of disc displacement on joint stresses during prolonged clenching was studied. For this purpose, finite-element models of the TMJ, with and without disc displacement, were used. Muscle forces were used as a loading condition for stress analysis during a time-period of 10 min. The TMJ disc and connective tissue were characterized as a linear viscoelastic material. In the asymptomatic model, large stresses were found in the central and lateral part of the disc through clenching. In the retrodiscal tissue, stress relaxation occurred during the first 2 min of clenching. In the symptomatic model, large stresses were observed in the posterior part of the disc and in the retrodiscal tissue, and the stress level was kept constant through clenching. This indicates that during prolonged clenching the disc functions well in the asymptomatic joint, meanwhile the retrodiscal tissue in the symptomatic joint is subject to excessive stress. As this structure is less suitable for bearing large stresses, tissue damage may occur. In addition, storage of excessive strain energy might lead to breakage of the tissue.

Adult↗
PubMed2006

International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas.

Non-inflammatory cystic lesions of the pancreas are increasingly recognized. Two distinct entities have been defined, i.e., intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN). Ovarian-type stroma has been proposed as a requisite to distinguish MCN from IPMN. Some other distinct features to characterize IPMN and MCN have been identified, but there remain ambiguities between the two diseases. In view of the increasing frequency with which these neoplasms are being diagnosed worldwide, it would be helpful for physicians managing patients with cystic neoplasms of the pancreas to have guidelines for the diagnosis and treatment of IPMN and MCN. The proposed guidelines represent a consensus of the working group of the International Association of Pancreatology.

Endocrine Surgical Procedures↗
PubMed2006

Natural killer T-cells participate in rejection of islet allografts in the liver of mice.

A role of natural killer T (NKT) cells in transplant rejection remains unknown. Here, we determined whether NKT cells participate in rejection of islet allografts, using NKT cell-deficient mice. Survival of islet allografts in streptozotocin-induced diabetic CD1d(-/-) mice or Valpha14 NKT cell(-/-) mice was significantly prolonged without immunosuppression when grafted into the liver, but not beneath the kidney capsule, compared with wild-type mice. Acceptance of intrahepatic islet allografts was achieved in CD1d(-/-) mice by a subtherapeutic dose of rapamycin, which was abrogated in conjunction with the transfer of hepatic mononuclear cells from wild-type, but not from CD1d(-/-), mice at islet transplantation. The second islet grafts from a donor-specific, but not from a third-party, strain in CD1d(-/-) mice bearing functional islet allografts were accepted without immunosuppression at 120 days after the initial transplantation. These findings demonstrate that NKT cells play a significant role in rejection of islet allografts in the liver of mice, but that NKT cells are not essential for induction of donor-specific unresponsiveness in this model. The current study indicates that NKT cells might be considered as a target for intervention to prevent islet allograft rejection when the liver is the site of transplantation.

Adoptive Transfer↗
PubMed2006

Pancreatic pseudocyst after acute organophosphate poisoning.

Acute organophosphate poisoning (OP) shows several severe clinical symptoms due to its strong blocking effect on cholinesterase. Acute pancreatitis is one of the complications associated with acute OP, but this association still may not be widely recognized. We report here the case of a 73-year-old man who had repeated abdominal pain during and after the treatment of acute OP. Hyperamylasemia and a 7-cm pseudocyst in the pancreatic tail were noted on investigations. We diagnosed pancreatic pseudocyst that likely was secondary to an episode of acute pancreatitis following acute OP. He was initially treated with a long-term intravenous hyperalimentation, protease inhibitors and octerotide, but eventually required surgical intervention, a cystgastrostomy. Acute pancreatitis and hyperamylasemia are known to be possible complications of acute OP. It is necessary to examine and assess pancreatic damage in patients with acute OP.

Acute Disease↗
PubMed2005

The role of S100A6 in pancreatic cancer development and its clinical implication as a diagnostic marker and therapeutic target.

Recent microarray analyses showed that the S100 family contains members that are candidate diagnostic markers or therapeutic targets. In the present study, to evaluate the involvement of S100A6 in pancreatic cancer and its clinical usefulness for diagnosis, we examined S100A6 mRNA expression in pancreatic tissues and pancreatic juice from patients with different pancreatic diseases. To investigate the role of S100A6 in carcinogenesis of pancreatic cancer and the potential of S100A6 as a diagnostic marker for early detection of pancreatic cancer, we did immunohistochemistry and microdissection-based mRNA analysis of pancreatic normal ducts, pancreatic intraepithelial neoplasias, and invasive ductal carcinomas. We also used in vitro experiments and microarray analysis with RNA interference to evaluate the functional role of S100A6 and its potential as a therapeutic target for pancreatic cancer. S100A6 mRNA levels were significantly higher in carcinoma specimens than in nonneoplastic tissues. In pancreatic juice, there was a significant difference in S100A6 expression between patients with carcinoma and those with nonneoplastic disease. Receiver operating characteristic curves revealed that S100A6 might be a useful marker for diagnosis of pancreatic cancer. Immunohistochemistry and microdissection-based analysis showed differential expression of S100A6 among normal ducts, pancreatic intraepithelial neoplasias, and invasive ductal carcinomas. In vitro data showed that inhibition of S100A6 decreased proliferation and invasiveness of cancer cells, and these findings were supported by microarray data. Our present results suggest that quantitation of S100A6 mRNA is a promising tool for diagnosis of pancreatic cancer, and that S100A6 may be a promising therapeutic target for pancreatic cancer.

Biomarkers, Tumor↗
PubMed2005

Suppression of metastasis of human pancreatic cancer to the liver by transportal injection of recombinant adenoviral NK4 in nude mice.

NK4, a 4-kringle fragment of hepatocyte growth factor (HGF), is an HGF antagonist that also acts as an angiogenesis inhibitor. NK4 strongly inhibits the infiltration, metastasis, and tumor growth of pancreatic cancer. The aim of our study was to evaluate the antitumor effect of adenovirus-mediated NK4 gene transfer to the liver on hepatic metastasis of pancreatic cancer in vivo. We constructed recombinant adenoviral NK4 (Ad-NK4), which encodes a secreted form of human NK4. Intrasplenic injection of Ad-NK4 induced high and relatively maintained expression of NK4 protein in the liver and suppressed the number and growth of metastatic foci in the liver in a nude mouse model. Microscopically, central necrosis was found even in small metastatic foci in Ad-NK4 treated mice. Immunohistochemical analysis of metastatic tumors showed a remarkable decrease in microvessel density and an increase in the number of apoptotic tumor cells after treatment with Ad-NK4. These results indicate that intraportal injection of Ad-NK4 may be a useful therapeutic modality for the clinical control of hepatic metastasis in pancreatic cancer.

Adenocarcinoma↗
PubMed2005

Novel bactericidal surface: Catechin-loaded surface-erodible polymer prevents biofilm formation.

We developed a novel bactericidal surface based on a catechin-loaded surface-erodible polymer. (-)-Epigallocatechin-3-gallate (EGCg), which is the main constituent of tea catechins, showed a dose-dependent inhibitory effect on Escherichia coli biofilm formation and a dose-dependent enhanced destructive effect on biofilm. EGCg-immobilized surfaces were prepared by photopolymerization of liquid biodegradable polyesters. The releasing rate was enhanced with an increase in surface-erosion rate of photocured polymers. Polymers with high releasing capacity dose-dependently reduced biofilm formation on the surfaces. The confocal laser scanning microscopic and scanning electron microscopic observations revealed that EGCg induced biofilm-destructing activities, which include bacterial membrane damage, degradation of exopolysaccharides, and detachment of colonized cells. From these results, potential advantages of the clinical use of catechin-loaded polymer-coated implants or catheters are discussed in terms of a reduced occurrence of biomaterial-centered infections without substantial toxicity or adverse effects.

Anti-Infective Agents↗
PubMed2005

Valpha14 NK T cell-triggered IFN-gamma production by Gr-1+CD11b+ cells mediates early graft loss of syngeneic transplanted islets.

Pancreatic islet transplantation is a highly promising approach for the treatment of insulin-dependent diabetes mellitus. However, the procedure remains experimental for several reasons, including its low efficiency caused by the early graft loss of transplanted islets. We demonstrate that Gr-1+CD11b+ cells generated by transplantation and their IFN-gamma production triggered by Valpha14 NKT cells are an essential component and a major cause of early graft loss of pancreatic islet transplants. Gr-1+CD11b+ cells from Valpha14 NKT cell-deficient (Jalpha281-/-) mice failed to produce IFN-gamma, resulting in efficient islet graft acceptance. Early graft loss was successfully prevented through the repeated administration of alpha-galactosylceramide, a specific ligand for Valpha14 NKT cells, resulting in dramatically reduced IFN-gamma production by Gr-1+CD11b+ cells, as well as Valpha14 NKT cells. Our study elucidates, for the first time, the crucial role of Gr-1+CD11b+ cells and the IFN-gamma they produce in islet graft rejection and suggests a novel approach to improving transplantation efficiency through the modulation of Valpha14 NKT cell function.

Animals↗
PubMed2005

Novel serum tumor marker, RCAS1, in pancreatic diseases.

AIM: As tumor markers for pancreatic carcinoma, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 have been used, but the sensitivity and specificity are not enough for the diagnosis of pancreatic carcinoma. METHODS: A novel serum tumor marker, RCAS1, was compared with two conventional serum tumor markers, CEA (highly specific for pancreatic cancer) and CA 19-9 (highly sensitive for pancreatic cancer), in 48 patients with pancreatic exocrine tumors. RESULTS: When the diagnosis of benign or malignant conditions was examined by one tumor marker, the sensitivity of RCAS1 alone (55%) was higher than that of CEA alone (27%) and the specificity of RCAS1 alone (92%) was greater than that of CA19-9 alone (78%). When examined by a combination of two markers, the sensitivity of a combination of RCAS1 and CA19-9 (95%) was superior to those of CA19-9 alone (78%), RCAS1 alone (55%, P = 0.002), CEA alone (27%) (P<0.001), RCAS1 and CEA (59%) and CA19-9 and CEA (82%). CONCLUSION: These results suggest that the combination of RCAS1 and CA19-9 is highly sensitive for pancreatic carcinoma.

Adult↗
PubMed2005

Monochromatic synchrotron radiation muCT reveals disuse-mediated canal network rarefaction in cortical bone of growing rat tibiae.

The purpose of this study was to demonstrate the ability of computed microtomography based on monochromatic synchrotron radiation (SRmuCT) in microstructural analysis of cortical bone. Tibial diaphyses of growing rats (14 wk, n = 8) undergoing unilateral sciatic neurectomy 8 wk before study were imaged with spatial volume resolution of 5.83 x 5.83 x 5.83 microm3 by SRmuCT (20 keV) at the synchrotron radiation facility (SPring-8). Reconstructed image data were translated into local mineral densities by using a calibrated linear relationship between linear absorption coefficients and concentrations of homogeneous K2HPO4 solution. Pure bone three-dimensional images, produced by simple thresholding at a bone mineral density of 0.82 g/cm3, were analyzed for macro- and microscopic structural properties. In neurectomized hindlimbs, cortical canal network rarefaction as well as bone atrophy were found. The former was characterized by 30% smaller porosity, 11% smaller canal density in transverse section, and 38% smaller canal connectivity density than those in contralateral bone. On the other hand, no difference was found in bone mineral density between neurectomized and intact hindlimbs (1.37 vs. 1.36 g/cm3). In conclusion, SRmuCT is a promising method for the three-dimensional analysis of cortical microstructure and the degree of mineralization in small animals.

Absorptiometry, Photon↗