Pitavastatin attenuates the upregulation of tissue factor in restraint-stressed mice.
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Animals↗
Biomedical subjects
T Matsushita
Publications and source records attributed to T Matsushita.
Abnormal hemostasis tests and bleeding in chronic liver disease: are they related? No, but they need a careful look.
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Blood Coagulation Tests↗
Identification of a novel autoantibody reactive with 155 and 140 kDa nuclear proteins in patients with dermatomyositis: an association with malignancy.
OBJECTIVE: Myositis-specific autoantibodies (MSAs) are a useful tool in diagnosis, defining clinical subsets and predicting prognosis of dermatomyositis (DM) and polymyositis (PM). In this study, we identified a novel MSA reactive with 155 and 140 kDa nuclear proteins [anti-155/140 antibody (Ab)] and determined the clinical feature of DM patients positive for this autoantibody (autoAb). METHODS: Sera from 52 Japanese patients with DM, 9 with PM, 48 with systemic lupus erythematosus (SLE), 126 with systemic sclerosis and 18 with idiopathic interstitial pneumonia were examined by immunoprecipitation assays. Positive sera were further characterized by immunodepletion and immunofluorescence staining. RESULTS: Seven of the 52 (13%) Japanese patients with DM immunoprecipitated 155 and 140 kDa proteins from 35S-labelled K562 leukaemia cell extract. No patients with SLE, systemic sclerosis or idiopathic interstitial pneumonia as well as healthy controls were positive for this autoAb. Patients with anti-155/140 Ab developed heliotrope rash, Gottron's papules or sign and flagellate erythema significantly more frequently than those negative. Notably, internal malignancy was found at significantly higher frequency in those positive than those negative (71 vs 11%; P < 0.005). In contrast, none of these patients positive for this autoAb had interstitial lung disease. CONCLUSIONS: This novel MSA is associated with cancer-associated DM and may serve as a diagnostic serological marker for this specific subset.
Adult↗
A novel neuronal cell line derived from the ventrolateral region of the suprachiasmatic nucleus.
The suprachiasmatic nucleus of the anterior hypothalamus is the center of an internal biological clock in mammals. Glutamate is the neurotransmitter of retino-hypothalamic tract responsible for mediating the circadian actions of light in rodents. N-methyl-d-aspartate receptors, particularly NR2B subunit are reported to be principally involved in photic resetting of the biological clock in vivo and in slice culture. But, the precise cellular mechanisms of the resetting are not elucidated, because no adequate neuronal cell lines derived from the suprachiasmatic nucleus have been established. We established a neuronal cell line, N14.5, derived from the suprachiasmatic nucleus of a transgenic rat harboring the temperature-sensitive simian virus 40 large T-antigen gene. When the cells were cultured at 39 degrees C, the morphological features were turned fibroblastic into neuronal round cell body with neurite extensions. These cells showed immunoreactivities for neuronal markers (betaIII-tubulin, microtubule-associated protein 2 and TAU2) and as well as for vasoactive intestinal peptide which is expressed in the ventrolateral region of the suprachiasmatic nucleus. The cells expressed N-methyl-d-aspartate receptors, particularly NR1 and NR2B subunits as revealed by quantitative PCR. N-methyl-d-aspartate activated phosphorylation of p44/42 mitogen-activated protein kinase and increased expression level of Per1 and Per2 mRNA. These results suggest that the N14.5 is a novel neuronal cell line derived from the ventrolateral region of the suprachiasmatic nucleus, and that N-methyl-d-aspartate receptors expressed in the cells are a functional receptor. The N14.5 cells may be a useful tool to elucidate numerous chronobiological processes, especially resetting mechanism induced by an external light signal.
Animals↗
Ligating properties of a potentially tetradentate Schiff base [(CH3)2NCH2CH2N=CHC6H3(OH)(OMe)] with zinc(II), cadmium(II), cobalt(II), cobalt(III) and manganese(III) ions: synthesis and structural studies.
A series of Zn(II), Cd(II), Co(II), Co(III) and Mn(III) complexes with the Schiff base [(CH3)2NCH2CH2N=CHC6H3(OH)(OMe)], LH, derived from 2-dimethylaminoethylamine and o-vanillin, has been synthesised and structures of all the products have been established by X-ray crystallography. In the cases of zinc and cadmium, dimeric complexes [Zn(LH)2(NCS)] [Zn2(L)(mu(1,1)-CH3COO)(NCS)3] (1), [Cd2(L)2(Cl)2] (2) and [Cd2(L)2(NCS)2] (3), and for cobalt and manganese, monomeric complexes [Co(LH)2(NCS)]2 [Co(NCS)4] (4), [Co(LH)2(NCS)]ClO4 (5), [Co(L)(N3)(o-vanillinate)] x 0.5 MeOH (6) and [Mn(LH)2(MeOH)2](ClO4)3 (7), are formed with various terminal ligands. All the complexes have been characterised by elemental analysis and IR spectra. UV-Vis and NMR spectroscopy, magnetic, and electrochemical studies, were also carried out where feasible. The Schiff base functions as a bi-, tri- or tetra-dentate chelating agent and coordinates via the protonated or deprotonated phenolic oxygen, amine and imine nitrogens, and only in case of 1 with the methoxy oxygen atoms, to the metal ion leading to the formation of mono- or bi-metallic complexes.
Journal Article↗
Hypoxia-induced hyaluronan synthesis by articular chondrocytes: the role of nitric oxide.
OBJECTIVE: Articular cartilage is an avascular tissue in which chondrocytes are exposed to hypoxic conditions. We previously demonstrated that reactive oxygen species (ROS) induced apoptosis of chondrocytes. We also demonstrated that nitric oxide (NO) was induced when chondrocytes were exposed to hypoxia and that NO inhibited the ROS-induced apoptosis. Hyaluronan (HA) is a high molecular weight glycosaminoglycan whose antioxidative effects have been reported. The purpose of the present study was to determine whether HA synthesis was induced in chondrocytes exposed to hypoxia, and, if so, whether the hypoxia-induced HA synthesis is regulated by NO. METHODS: Bovine articular chondrocytes were used in this study. Levels of HA were determined by the sandwich enzyme-binding assay. Expression of HA synthase (HAS) was determined with reverse transcription-polymerase chain reaction. The production of NO was examined using the Griess reaction. We also determined inducible nitric oxide synthase (iNOS) enzyme synthesis using the histochemistry and Western blot analysis. RESULTS: Chondrocytes cultured under hypoxic conditions exhibited enhanced HA synthesis. When the NO inhibitors, L-NMMA and L-NAME, were added, the hypoxia-enhanced HA levels in the culture medium were significantly inhibited. CONCLUSIONS: Endogenous NO synthesis plays an important role in hypoxia-enhanced HA synthesis.
Animals↗
Regulation of local and metastatic host-mediated anti-tumour mechanisms by L-selectin and intercellular adhesion molecule-1.
Malignant melanoma is often accompanied by a host response of inflammatory cell infiltration that is highly regulated by multiple adhesion molecules. To assess the role of adhesion molecules, including L-selectin and intercellular adhesion molecule-1 (ICAM-1), in this process, subcutaneous primary growth and metastasis to the lung of B16 melanoma cells not expressing L-selectin, ICAM-1 or their ligands were examined in mice lacking L-selectin, ICAM-1 or both. Primary subcutaneous growth of B16 melanoma was augmented by loss of L-selectin, ICAM-1 or both, while pulmonary metastasis was enhanced by the loss of L-selectin or combined loss of L-selectin and ICAM-1. In both situations, the combined loss of L-selectin and ICAM-1 exhibited the greatest effect. This enhancement was associated generally with a reduced accumulation of natural killer (NK) cells, CD4+ T cells and CD8+ T cells and also with a diminished release of interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha but not interleukin (IL)-6. Cytotoxicity against melanoma was not defective by the absence of ICAM-1, L-selectin or both, suggesting that the enhancement of tumour growth and metastasis caused by the loss of adhesion molecules results from an impaired migration of effector cells into the tissue rather than from a suppression of the cytotoxic response. The results indicate that L-selectin and ICAM-1 contribute co-operatively to the anti-tumour reaction by regulating lymphocyte infiltration to the tumour.
Animals↗
Fatal thrombosis of antithrombin-deficient mice is rescued differently in the heart and liver by intercrossing with low tissue factor mice.
BACKGROUND: We previously reported that the targeted disruption of murine antithrombin (AT) gene resulted in embryonic lethality before 16.5 gestational days (gd) because of severe cardiac and hepatic thrombosis. OBJECTIVE AND METHODS: To investigate the influences of lowered tissue factor (TF) activity upon hypercoagulation of AT-/- embryos, we crossed AT+/- with low TF (mTF-/- hTF+) mice to yield homozygous AT-deficient mice with the extremely low TF activity, that is expressed from the inserted human TF mini gene. RESULTS: AT-/- embryos either with 50% TF (AT-/- mTF+/- hTF+) or with low (approximately 1% TF, AT-/- mTF-/- hTF+) were not born, although the survival was prolonged until 18.5 gd. In both genotypes, histological examination showed disseminated thrombosis in hepatic sinusoidal space or in the portal veins, suggesting that the thrombogenesis caused loss of hepatic blood flow. As in original AT-/-, AT-/- mTF+/- hTF+ showed subcutaneous (s.c.) bleeding and also suffered from the myocardial degeneration apparently because of coronary thrombus formation. However, AT-/- mTF-/- hTF+ had no skin hemorrhage and the thrombosis and degeneration were completely abolished in the heart. Myocardium of adult low TF mice had exhibited fibrosis secondary to hemorrhage; however, it was significantly decreased in low TF mice with AT+/-. CONCLUSIONS: Our current model suggests that, in the heart, TF plays an important role in the thrombogenesis and it counterbalances AT-dependent anticoagulation. AT may be a potent anticoagulant during mice development and the activation and subsequent regulation of TF-procoagulant activity take place differently between the liver and the heart. These differences appear to point to local regulatory mechanisms in murine hemostasis.
Animals↗
Anti-HCV agent, ribavirin, elevates the activity of clotting factor VII in patients with hemophilia: a possible mechanism of decreased events of bleeding in patients with hemophilia by ribavirin.
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Adult↗
In vitro characterization of missense mutations associated with quantitative protein S deficiency.
OBJECTIVE: To elucidate the molecular consequences of hereditary protein S (PS) deficiency, we investigated the in vitro synthesis of the PS missense mutants in COS-1 cells and their activated protein C (APC) cofactor activities. PATIENTS: Four patients with quantitative PS deficiency suffering from venous thrombosis were examined. RESULTS: We identified three distinct novel missense mutations, R275C, P375Q and D455Y, and two previously reported missense mutations, C80Y and R314H. The P375Q and D455Y mutations were found in one patient and observed to be in linkage on the same allele. The R314H mutant showed the lowest level of expression (32.7%), and the C80Y, P375Q + D455Y, and R275C mutants exhibited a moderate impairment of expression, that is, 43.8%, 49.5%, and 72.3% of the wild type, respectively. Furthermore, pulse-chase experiments demonstrated that all mutants showed impaired secretion and longer half-lives in the cells than the wild type PS. In the APC cofactor assays, the C80Y mutant showed no cofactor activity, and the R275C mutant showed reduced activity, 62.3% of the wild type PS, whereas the R314H and P375Q + D455Y mutants exhibited normal cofactor activity. CONCLUSION: These data indicate that the C80Y and R275C mutations affect the secretion and function of the PS molecule, and that the R314H and P375Q + D455Y mutations are responsible for only secretion defects, causing the phenotype of quantitative PS deficiency observed in the patients.
Adult↗
Serum levels of monocyte chemotactic protein-3/CCL7 are raised in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis.
OBJECTIVE: To determine serum levels of monocyte chemotactic protein-3 (MCP-3) and its clinical associations in patients with systemic sclerosis (SSc). METHODS: Serum MCP-3 levels from 69 patients with SSc were examined by ELISA. RESULTS: Serum MCP-3 levels were raised in patients with SSc (n = 69) compared with healthy controls (n = 28). Patients with diffuse cutaneous SSc (n = 36) had higher levels of serum MCP-3 than those with limited cutaneous SSc (n = 33). Patients with raised MCP-3 levels had pulmonary fibrosis and decreased vital capacity (VC) more often than those with normal MCP-3 levels. MCP-3 levels correlated positively with the extent of skin fibrosis, and inversely with %VC and carbon monoxide transfer factor (Tlco) in patients with SSc. CONCLUSION: MCP-3 levels were increased in patients with SSc, and correlated with the extent of skin sclerosis and the severity of pulmonary fibrosis. These results suggest that MCP-3 may have a role in the development of fibrosis in SSc.
Adolescent↗
A clue for telangiectasis in systemic sclerosis: elevated serum soluble endoglin levels in patients with the limited cutaneous form of the disease.
BACKGROUND: The transforming growth factor-beta (TGF-beta) system plays a critical role both in systemic sclerosis (SSc) and hereditary hemorrhagic telangiectasia (HHT). Endoglin, known as a gene responsible for HHT, is a TGF-beta receptor preferentially expressed on endothelial cells. The role of endoglin in SSc is potentially intriguing since limited cutaneous SSc (lcSSc) and HHT share several symptoms, including telangiectasia. OBJECTIVE: To determine serum levels of soluble endoglin (sEndoglin) and clinical associations in patients with SSc. METHODS: Serum sEndoglin levels were examined by ELISA in 70 patients with SSc, 20 patients with systemic lupus erythematosus and 20 healthy individuals. RESULTS: Serum sEndoglin levels were significantly elevated in patients with lcSSc compared with diffuse cutaneous SSc and systemic lupus erythematosus patients as well as normal controls. Patients with elevated sEndoglin levels had telangiectasia more frequently than those with normal sEndoglin levels. Furthermore, pulmonary artery pressure was positively correlated with sEndoglin levels in patients with lcSSc. CONCLUSION: Abnormal expression/function of endoglin may be linked to lcSSc-specific manifestations.
Adolescent↗
Analysing mass balance of viruses in a coagulation-ceramic microfiltration hybrid system by a combination of the polymerase chain reaction (PCR) method and the plaque forming units (PFU) method.
Virus removal experiments using river water spiked with bacteriophages were conducted by an in-line coagulation-ceramic microfiltration hybrid system to investigate the effects of filtration flux (62.5 and 125 L/(m2 x h)) and type of virus (Qbeta and MS2) on virus removal. In addition, the mass balance of viruses through the hybrid system was analysed by quantifying the infectious and inactive viruses by a combination of the polymerase chain reaction (PCR) method and the plaque forming units (PFU) method. Even when the system was operated at high filtration flux (125 L/(m2 x h)), high virus removal (> 6 log) with short coagulation time (2.4 s) was successfully achieved by dosing polyaluminium chloride (PACI) at more than 1.08 mg-Al/L. Removal performances were different between Qbeta and MS2, although their diameters are almost the same: greater virus removal was achieved for MS2 at PACI dosing of 0.54 mg-Al/L, and for Qbeta at PACI dosing of more than 1.08 mg-Al/L. The combination of the PCR and PFU methods revealed that two phenomena, adsorption to/entrapment in aluminium floc and virucidal activity of PACI, partially account for the high virus removal in the coagulation-MF hybrid system.
Bacteriophages↗
Screening level analysis for monitoring pesticide in river water using a hydrological diffuse pollution model with limited input data.
To predict rice-farming pesticide concentrations in river water with imprecise model inputs for screening-level analysis, a basin-scale runoff model was developed. The Monte Carlo method was applied to create estimates of input data regarding agricultural work schedules and parameters for pesticide decomposition and sorption in solids and water. The prediction accuracy of the model was evaluated when used with non-optimised pesticide parameters; the model was calibrated using hydrological data alone without reference to observed pesticide concentration data. Overall, predictions for the pesticide concentrations were successful within order-of-magnitude accuracy. The pesticide rankings according to the predicted concentration roughly agreed with those observed. The success of screening-level analysis indicates that the model prediction can help in selection of pesticides to be monitored and in determining the monitoring schedule for the river basin.
Agriculture↗
Origin of the metallic properties of heavily boron-doped superconducting diamond.
The physical properties of lightly doped semiconductors are well described by electronic band-structure calculations and impurity energy levels. Such properties form the basis of present-day semiconductor technology. If the doping concentration n exceeds a critical value n(c), the system passes through an insulator-to-metal transition and exhibits metallic behaviour; this is widely accepted to occur as a consequence of the impurity levels merging to form energy bands. However, the electronic structure of semiconductors doped beyond n(c) have not been explored in detail. Therefore, the recent observation of superconductivity emerging near the insulator-to-metal transition in heavily boron-doped diamond has stimulated a discussion on the fundamental origin of the metallic states responsible for the superconductivity. Two approaches have been adopted for describing this metallic state: the introduction of charge carriers into either the impurity bands or the intrinsic diamond bands. Here we show experimentally that the doping-dependent occupied electronic structures are consistent with the diamond bands, indicating that holes in the diamond bands play an essential part in determining the metallic nature of the heavily boron-doped diamond superconductor. This supports the diamond band approach and related predictions, including the possibility of achieving dopant-induced superconductivity in silicon and germanium. It should also provide a foundation for the possible development of diamond-based devices.
Journal Article↗
Semen quality of 324 fertile Japanese men.
BACKGROUND: A number of studies have indicated regional differences in semen quality. To examine the current status in Japan, we undertook a cross-sectional study on the semen quality of fertile Japanese men for comparison with recent European results. METHODS: Semen parameters of 324 fertile men from the Kawasaki/Yokohama area were investigated. The semen parameters were compared with those published for fertile men from four European cities, Copenhagen, Paris, Edinburgh and Turku. RESULTS: When adjusting for confounders such as ejaculation abstinence period and age, the lowest sperm concentrations were detected in men from Kawasaki/Yokohama followed by men from Copenhagen, Paris, Edinburgh and Turku, but only the differences between men from Kawasaki/Yokohama and men from Edinburgh and Turku were significant (P=0.0008 and P<0.0001, respectively). Total sperm count, percentage of motile sperm and percentage of normal sperm observed in Kawasaki/Yokohama were significantly lower than those from all European centres except for motile sperm in men from Paris. CONCLUSIONS: Japanese fertile men had a semen quality at the level of Danish men, who have been reported to have the lowest among investigated men in Europe. The low level of semen quality of the fertile Japanese men may be due to lifestyle or other environmental factors; however, ethnic differences caused by different genetic variation or combinations cannot be ruled out by this study.
Ejaculation↗
A novel oligodendrocyte cell line OLP6 shows the successive stages of oligodendrocyte development: late progenitor, immature and mature stages.
The successive stages of development from oligodendrocyte progenitor to mature oligodendrocyte have been investigated in detail by using stage-specific antibodies. However, no cell lines are available that show stepwise differentiation from oligodendrocyte progenitors to mature oligodendrocytes. Here we show the establishment of an immortalized oligodendrocyte cell line, OLP6, from adult transgenic rats harboring the temperature-sensitive simian virus 40 large T-antigen gene. The OLP6 cells had a fibroblastic morphology and continuously proliferated at 33 degrees C. They displayed growth arrest and multipolar morphology when they were cultured at 39 degrees C. They express the oligodendrocytic markers O4, 2'-3'-cyclic-nucleotide 3'-phosphodiesterase, galactocerebroside and second endothelial differentiation gene receptor-2 at 39 degrees C. The OLP6 cells underwent apoptosis upon serum withdrawal at 39 degrees C. Lysophosphatidic acid inhibited this apoptosis and promoted the expression of myelin basic protein. These results demonstrate that the activation of endothelial differentiation gene receptor-2 exerts anti-apoptosis and myelinogenesis effects on the OLP6 cells. Taken together, the OLP6 cells in the late oligodendrocyte progenitor stage can progress to the immature oligodendrocyte stage by shifting culture temperature. Furthermore, lysophosphatidic acid promoted the maturation of OLP6 cells in the immature oligodendrocyte stage. Such OLP6 cells should provide a potent model system for studying the precise mechanism involved in stepwise differentiation of oligodendrocytes.
Animals↗
Cyclic tensile stretch stimulates the release of reactive oxygen species from osteoblast-like cells.
It is known that the excessive generation of reactive oxygen species (ROS) is a significant factor in tissue injury observed in many disease states. To determine whether extreme levels of mechanical stress applied to osteoblasts enhances ROS synthesis, we loaded cyclic tensile stretch on osteoblast-like HT-3 cells. Cyclic tensile stretch loaded on these cells clearly enhanced ROS synthesis in a time- and magnitude-dependent fashion. Cyclic tensile stretch also enhanced superoxide dismutase (SOD) activity. The disruption of microfilaments with cytochalasin D abolished the stress-induced ROS synthesis. Rotenone, an inhibitor of the mitochondrial electron transport chain, enhanced stress-induced ROS synthesis. These data suggest that actin filament and mitochondria are involved in this action.
Actins↗