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Biomedical subjects

T Matsushita

Publications and source records attributed to T Matsushita.

At least 19 recordsLinked to original sources

Hypoxia-induced nitric oxide protects chondrocytes from damage by hydrogen peroxide.

OBJECTIVE: Because articular cartilage has no vascular supply, chondrocytes are hypoxic under normal physiological conditions. Nitric oxide (NO) plays an important role in chondrocyte damage, such as apoptosis. Although oxygen stress with hydrogen peroxide was found to cause chondrocyte damage, these data were obtained under normoxic (21% O2) conditions. We investigated the effects of hypoxia on hydrogen peroxide-induced chondrocyte damage METHODS: Bovine articular chondrocytes were used in this study. Proteoglycan (PG) synthesis and the induction of apoptosis were analyzed with [(35)S]-sulfate incorporation and annexin V staining, respectively. The induction of NO was examined using a fluorescent probe and RT-PCR. RESULTS: Cells maintained at 5% O2 had the maximum PG synthesis. Under normoxic conditions, hydrogen peroxide inhibited PG synthesis and induced annexin V positive cells in a dose-dependent fashion. However, in those cells cultured under hypoxic (5%) conditions, the hydrogen peroxide-induced annexin V expression was attenuated. Chondrocytes exposed to hypoxia showed induction of NO. When the hypoxia-induced NO was inhibited, the hypoxia-enhanced PG synthesis was abolished and hydrogen peroxide clearly induced cell damage. CONCLUSIONS: Endogenous NO induced by hypoxia protects chondrocytes from apoptosis induced by an oxidative stress.

Animals↗

Serum soluble CTLA-4 levels are increased in diffuse cutaneous systemic sclerosis.

OBJECTIVE: To determine serum levels of soluble cytotoxic T-lymphocyte associated molecule-4 (sCTLA-4) and clinical association in patients with systemic sclerosis (SSc). METHODS: Serum sCTLA-4 levels from 32 patients with diffuse cutaneous SSc (dSSc) and 27 patients with limited cutaneous SSc (lSSc) were examined by enzyme-linked immunosorbent assay (ELISA). For a longitudinal study, 211 sera from 30 SSc patients were analysed (follow-up 2.1-7.0 yr). RESULTS: Serum sCTLA-4 levels were elevated in dSSc patients compared with normal controls (n = 41), lSSc patients and patients with active systemic lupus erythematosus (SLE) (n = 23). By contrast, sCTLA-4 levels in patients with lSSc or SLE were normal. SSc patients with elevated sCTLA-4 levels had a shorter disease duration and more frequent presence of digital pitting scars, contracture of phalanges, diffuse pigmentation, pulmonary fibrosis and decreased percentage vital capacity (%VC) than those with normal sCTLA-4 levels. sCTLA-4 levels correlated positively with the extent of skin fibrosis, serum IgG levels and anti-topoisomerase I antibody levels. In a longitudinal study, sCTLA-4 levels decreased on a parallel with improvement of skin sclerosis in five dSSc patients. Skin sclerosis did not improve in two of six dSSc patients with high sCTLA-4 levels throughout the follow-up, while the remaining four patients showed improvement of skin sclerosis. CONCLUSION: These results suggest that sCTLA-4 correlates with disease severity and activity of SSc and that sCTLA-4 plays a role in immunological abnormalities of SSc, since sCTLA-4 may augment humoral immune responses as well as T-cell responses by interfering with B7-CTLA-4 interactions that induce negative signals in T and B cells.

Antigens, CD↗

Mini-incision posterior approach for total hip arthroplasty.

We compared the short-term outcomes of 50 total hip arthroplasties performed through a mini-incision posterior approach with those of 42 arthroplasties performed through a conventional posterior approach. There were no significant differences in age, gender, and bodymass index between groups. The mean operative time was shorter (99+/-26 versus 123+/-30 min), and the peroperative mean blood loss was smaller with the mini-incision (339+/-210 versus 422+/-177 ml). There was no significant difference between groups in post-operative mean blood loss, mean inclination angle of acetabular components, percentage of hips with good inclination angle, and mean hip score at 6 months after surgery. There was one infection in the conventional group but none in the mini group. There were no dislocations or symptomatic pulmonary embolism in either group. With the mini-incision posterior approach, surgical invasion was reduced, and short-term outcome was as good as with a conventional posterior approach.

Arthroplasty, Replacement, Hip↗

Crystal structure and magnetic interactions in nickel(II) dibridged complexes formed by two azide groups or by both phenolate oxygen-azide, -thiocyanate, -carboxylate, or -cyanate groups.

Tridentate/tetradentate Schiff base ligands L(1) and L(2), derived from the condensation of o-vanillin or pyridine-2-aldehyde with N,N-dimethylethylenediammine, react with nickel acetate or perchlorate salt and azide, cyanate, or thiocyanate to give rise to a series of dinuclear complexes of formulas [Ni(L(1))(micro(1,1)-N(3))Ni(L(1))(N(3))(OH(2))].H(2)O (1), [[Ni(L(1))(micro(1,1)-NCS)Ni(L(1))(NCS)(OH(2))][Ni(L(1))(micro-CH(3)COO)Ni(L(1))( NCS) (OH(2))]] (2) [[2A][2B]], [Ni(L(1))(micro(1,1)-NCO)Ni(L(1))(NCO)(OH(2))].H(2)O (3), and [Ni(L(2)-OMe)(micro(1,1)-N(3))(N(3))](2) (4), where L(1) = Me(2)N(CH(2))(2)NCHC(6)H(3)(O(-))(OCH(3)) and L(2) = Me(2)N(CH(2))(2)NCHC(6)H(3)N. We have characterized these complexes by analytical, spectroscopic, and variable-temperature magnetic susceptibility measurements. The coordination geometry around all of the Ni(II) centers is a distorted octahedron with bridging azide, thiocyanate/acetate, or cyanate in a micro(1,1) mode and micro(2)-phenolate oxygen ion for 1-3, respectively, or with a double-bridging azide for 4. The magnetic properties of the complexes were studied by magnetic susceptibility (chi(M)) versus temperature measurements. The chi(M) nus T plot reveals that compounds 1 and 4 are strongly ferromagnetically coupled, 3 shows a weak ferromagnetic behavior, and 2 is very weakly antiferromagnetically coupled.

Journal Article↗

Adeno-associated virus vector-mediated interleukin-10 gene transfer inhibits atherosclerosis in apolipoprotein E-deficient mice.

Inflammation is a major contributor to atherosclerosis by its effects on arterial wall biology and lipoprotein metabolism. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that may modulate the atherosclerotic disease process. We investigated the effects of adeno-associated virus (AAV) vector-mediated gene transfer of IL-10 on atherogenesis in apolipoprotein E (ApoE)-deficient mice. A murine myoblast cell line, C2C12, transduced with AAV encoding murine IL-10 (AAV2-mIL10) secreted substantial amounts of IL-10 into conditioned medium. The production of monocyte chemoattractant protein-1 (MCP-1) by the murine macrophage cell line, J774, was significantly inhibited by conditioned medium from AAV2-mIL10-transduced C2C12 cells. ApoE-deficient mice were injected with AAV5-mIL10 into their anterior tibial muscle at 8 weeks of age. The expression of MCP-1 in the vascular wall of the ascending aorta and serum MCP-1 concentration were decreased in AAV5-mIL10-transduced mice compared with AAV5-LacZ-transduced mice. Oil red-O staining of the ascending aorta revealed that IL-10 gene transfer resulted in a 31% reduction in plaque surface area. Serum cholesterol concentrations were also significantly reduced in AAV5-mIL10-transduced mice. To understand the cholesterol-lowering mechanism of IL-10, we measured the cellular cholesterol level in HepG2 cells, resulting in its significant decrease by the addition of IL-10 in a dose-dependent manner. Furthermore, IL-10 suppressed HMG-CoA reductase expression in the HepG2 cells. These observations suggest that intramuscular injection of AAV5-mIL10 into ApoE-deficient mice inhibits atherogenesis through anti-inflammatory and cholesterol-lowering effects.

Adenoviridae↗

Autoantibody against matrix metalloproteinase-3 in patients with systemic sclerosis.

Systemic sclerosis (SSc) is characterized by multi-organ fibrosis with an autoimmune background. Although autoantibodies are detected frequently in SSc patients, the role of autoantibody in the development of fibrosis remains unknown. Connective tissue homeostasis is a balance between the synthesis and degradation of the extracellular matrix (ECM); ECM degradation is regulated mainly by matrix metalloproteinases (MMPs). Anti-MMP-1 antibody is suggested to inhibit MMP-1 and be involved in the development of the fibrosis in SSc. However, the accumulation of various ECM components in the tissue of SSc cannot be explained by the anti-MMP-1 antibody alone. In this study, we examined the presence or levels of antibody to MMP-3, a protein which degrades various ECM components relevant to SSc fibrosis. Enzyme-linked immunosorbent assay (ELISA) using human recombinant MMP-3 revealed that IgG anti-MMP-3 autoantibody levels were elevated significantly in the sera from SSc patients, but not in patients with active systemic lupus erythematosus or dermatomyositis. IgG and IgM anti-MMP-3 antibody levels were significantly higher in diffuse cutaneous SSc, a severe form, than those in limited cutaneous SSc. Consistently, IgG anti-MMP-3 antibody levels correlated significantly with fibrosis of the skin, lung and renal blood vessels. The presence of IgG anti-MMP-3 autoantibody in sera from SSc patients was confirmed by immunoblotting analysis. Remarkably, MMP-3 activity was inhibited by IgG anti-MMP-3 antibody. These results suggest that anti-MMP-3 antibody is a serological marker that reflects the severity of SSc and also suggest that it may contribute to the development of fibrosis by inhibiting MMP-3 activity and reducing the ECM turnover.

Autoantibodies↗

Schwannoma in the sublingual space.

In this report, we present CT and MRI findings of a case of a schwannoma that developed in the floor of the oral cavity. A 49-year-old woman visited our hospital with a painless swelling in the oral floor. CT and MRI revealed a well circumscribed oval mass in the sublingual space, which showed cystic degeneration in most of the lesion. In addition, a thickened wall that strongly enhanced after injection of contrast medium and formation of fluid level were observed in the mass. The mass was removed and was histopathologically diagnosed as schwannoma. Only a few cases of schwannoma in the oral floor have been reported. However, when the characteristic findings are observed on CT and MRI, schwannoma should be added to the differential diagnosis.

Contrast Media↗

Characterization of microparticles in raw, treated, and distributed waters by means of elemental and particle size analyses.

The elemental composition and particle size distribution of suspended particles in raw water, treated water, and distributed water were determined to understand the behavior of particles during the water treatment-distribution process. The weight of suspended particles collected on a 0.6-microm filter was 1.1 times (raw water), 1.4 times (treated water), and 1.5 times (distributed water) that collected on a 2.7-microm filter, suggesting that smaller particles may remain after conventional water treatment. Organic suspended particles were removed less efficiently than inorganic suspended particles. After sand filtration, the Al content in the fixed suspended solids (FSS) markedly increased, indicating that either a small percentage of aluminium floc passed through during sand filtration or dissolved aluminum precipitated after sand filtration. The Mn and Fe concentrations increased after chlorination. The percentages of carbon and nitrogen in the volatile suspended solids (VSS) were roughly the same in the raw, treated, and distributed waters. The carbon/nitrogen/phosphate/VSS ratios indicated that the VSS of the suspended particles consisted of organic matter originating from microorganisms. The major constituents of the FSS in the treated and distributed waters were compounds of Fe, Al, Ca, Mg, and Mn, but these compounds accounted for only 16% or less of the FSS in raw water, indicating the existence of Si compounds. In distribution pipes, the total suspended solids concentration, especially the FSS concentration, was higher than that of water just after treatment. The Fe concentration in distributed water increased, probably due to oxidation and rusting of iron pipes.

Aluminum↗

Irreversible and reversible adhesion between virus particles and hydrolyzing-precipitating aluminium: a function of coagulation.

The infectivity of viruses (Qbeta, MS2, T4, and P1) after dosing virus-contaminated water with 4 types of aluminium coagulant was investigated. The concentrations of infectious viruses were determined after dissolving aluminium hydroxide flocs in alkaline solution. The concentration of infectious viruses did not recover to the initial value after a short floc-dissolution time (5 s). Although the infectious virus concentration increased as the floc-dissolution time was extended to 5 h, it did not recover fully. Irreversible adhesion between virus particles and aluminium coagulant is responsible for the insufficient recovery. We interpret this phenomenon as a virucidal activity of the aluminium coagulant. All tested aluminium coagulants (PACl, alum, and reagent grade aluminium chloride and aluminium sulfate) inactivated all types of viruses tested. PACl had the highest virucidal activity. The virucidal activity of aluminium coagulants was lower in river water, presumably owing to the presence of natural organic matter.

Adsorption↗

Production of adrenomedullin from synovial cells in rheumatoid arthritis patients.

It was recently reported that plasma levels of adrenomedullin (AM), identified as a vasorelaxant peptide, are significantly higher in rheumatoid arthritis (RA) patients than in osteoarthritis (OA) patients. The objective of the present study was to elucidate AM production in synovial cells from patients with RA. Adrenomedullin mRNA was detected in cultured synovial cells from RA patients by reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemical analysis demonstrated the presence of AM in synovial cells from RA patients. In addition, we investigated AM levels in knee joint fluids from RA and OA patients. Those from RA patients were elevated approximately threefold over those of OA patients. In this study, we demonstrated for the first time AM expression in synovial cells from RA patients and high levels of AM production in RA joint fluid.

Adrenomedullin↗

Cyclic tensile stretch loaded on bovine chondrocytes causes depolymerization of hyaluronan: involvement of reactive oxygen species.

OBJECTIVE: We have previously demonstrated that reactive oxygen species (ROS) are involved in cartilage degradation. Decreased size of hyaluronan (HA), the major macromolecule in synovial fluid, to which it imparts viscosity, is reported in patients with arthritis. The purpose of this study was to determine the alteration in the molecular weight range of HA as a result of mechanical deformation loaded on the chondrocytes, as well as the involvement of ROS in this action. METHODS: ROS were generated via the oxidation of hypoxanthine by xanthine oxidase. Cyclic tensile stretch was loaded using a vacuum-operated instrument. Levels of HA were measured using a sandwich enzyme-binding assay. Superoxide dismutase (SOD) activity and ROS were measured using water-soluble tetrazolium and a chemiluminescent probe, respectively. RESULTS: ROS depolymerized HA molecules. Cyclic tensile stretch depolymerized HA and induced ROS. SOD inhibited not only ROS induction but also HA depolymerization caused by the mechanical stress. CONCLUSION: ROS play an important role in mechanical stress-induced HA depolymerization.

Animals↗

Epstein-Barr virus-associated T-cell lymphoma: a case of eyelid swelling and intramuscular infiltration mimicking dermatomyositis.

Association with Epstein-Barr virus (EBV) infection has been noted in various types of cutaneous lymphoproliferative disorders. We report a 57-year-old Japanese woman with T-cell lymphoma mimicking dermatomyositis that was associated with chronic active EBV infection. She presented with low-grade fever, bilateral erythematous swellings on the eyelids, and necrotic papules on the face. Serum creatine kinase levels were elevated and a diffuse reticular shadow was detected in both lung fields. The infiltrate of atypical lymphocytes found in skin and muscle, which contained EBV-encoded small nuclear RNA-1 and EBV, was also detected in the CD4+ peripheral blood cells. Treatment with prednisolone resolved her lesions with no relapse for 3 years, after which there was a recurrence in her left lung. Combination chemotherapy was not effective against the lung lesion and she died with multiple organ failure 2 months after the recurrence.

Dermatomyositis↗

Predicting pesticide concentrations in river water with a hydrologically calibrated basin-scale runoff model.

Hydrological diffuse pollution models require calibration before they can be used to make accurate long-term predictions for a range of hydrological and meteorological conditions. As such, the applicability of the models to the dispersion of new pesticides is limited due to the lack of calibration data. In this study, the performance of a GIS-based basin-scale runoff model for predicting the concentrations of paddy-farming pesticides in river water was examined when calibrated using hydrological data alone, without optimization based on empirical pesticide concentration data. The prediction accuracy on a daily or hourly scale was somewhat unsatisfactory due to inevitable compromises concerning rice farming schedules. However, the month-averaged pesticide concentrations were satisfactorily accurate; more than 50% of predicted values were between half and twice the observed values, considering the deficiencies of the input data, particularly for pesticide usage, which may include up to 50% error.

Calibration↗

Intra-articular fracture of the knee with spondyloepiphyseal dysplasia congenita: successful result of open reduction and internal fixation.

In spondyloepiphyseal dysplasia congenita (SEDC), since the cartilage is congenitally abnormal, functional recovery of an intra-articular fracture is uncertain even with surgical treatment. We report a 29-year-old Japanese woman with SEDC whose left knee injury (intercondylar femur fracture and tibial plateau fracture) was surgically reduced and fixed. Although special care was required during the operation for associated atlantoaxial instability and cardiopulmonary suppression due to severe thoracolumbar kyphoscoliosis as well as osteopenia, she had neither restriction of knee motion nor pain at follow-up 2 years and 4 months after surgery. Therefore, although the situation involving fractures in a patient with SEDC is complicated, we believe the main problem to be solved is whether the risk-related kyphoscoliosis and atlantoaxial instability can be managed or not. Fractures themselves can be treated based on the principles used for patients without SEDC.

Adult↗

Development and characterization of an antisense-mediated prepackaging cell line for adeno-associated virus vector production.

One of the limitations of recombinant adeno-associated virus (rAAV) vector systems for gene therapy applications has been the difficulty in producing the vector in sufficient quantity for adequate evaluation. Since the AAV Rep proteins are cytotoxic, it is not easy to establish stable cell lines that express them constitutively. We describe a novel 293-derived prepackaging cell line which constitutively expresses the antisense rep/cap driven by a loxP-flanked CMV promoter. This cell line was converted into a packaging cell line expressing Rep/Cap for rAAV vector production through adenovirus-mediated introduction of a Cre recombinase gene. Without the introduction of the Cre recombinase gene, the cell line was shown to produce neither Rep nor Cap. rAAV vector was produced (1 x 10(9) genome copies/3.5-cm dish) 4 days after the transduction with Cre-expression adenovirus vector together with transfection of AAV vector plasmid. We further showed that the addition of Cap-expression adenovirus vector caused a 10-fold increase in the yield of rAAV vector. This system is also capable of producing rAAV as a transfection-free system by using a small amount of rAAV instead of vector plasmid.

Adenoviridae↗

Syndecan-4 deficiency leads to high mortality of lipopolysaccharide-injected mice.

Syndecan-4 is a transmembrane heparan sulfate proteoglycan belonging to the syndecan family. Following intraperitoneal injection of lipopolysaccharide (LPS), syndecan-4-deficient mice exhibited high mortality compared with wild-type controls. Severe endotoxin shock was observed in the deficient mice: systolic blood pressure and left ventricular fractional shortening were lower in the deficient mice than in the wild-type controls 9 h after LPS injection. Although histological examinations revealed no apparent differences between two groups, the plasma level of interleukin (IL)-1beta was higher in the deficient mice than in the wild-type controls 9 h after LPS injection. Consistent with the regulatory roles of syndecan-4, its expression in monocytes and endothelial cells of microvasculature increased in the wild-type mice after LPS administration. Although IL-1beta was produced to the same extent by macrophages from syndecan-4-deficient and wild-type mice after LPS stimulation, inhibition of its production by transforming growth factor-beta1 was impaired in the syndecan-4-deficient macrophages. These results indicate that syndecan-4 could be involved in prevention of endotoxin shock, at least partly through the inhibitory action of transforming growth factor-beta1 on IL-1beta production.

Animals↗

Adenosine deaminase activity of insect-derived growth factor is essential for its growth factor activity.

Insect-derived growth factor (IDGF) was originally isolated from conditioned medium of NIH-Sape-4 cells derived from flesh fly embryos. Here we demonstrated that IDGF has adenosine deaminase activity. The substrate specificity of IDGF was similar to that of the mammalian cytoplasmic adenosine deaminase. The adenosine deaminase activity of IDGF was shown to be indispensable for its growth factor activity toward NIH-Sape-4 cells. We found that there are specific binding sites for IDGF on the surface of NIH-Sape-4 cells and that it binds to these sites with a K(d) value of 2.4 x 10(-10) m. We propose that the cell surface binding sites for IDGF are specific receptors modified with an adenosine moiety. When IDGF binds to these receptors, it may deaminate the adenosine moiety, and this process may be prerequisite for the signal transduction via this receptor.

Adenosine Deaminase↗

X-ray magnetic circular dichroism imaging with hard X-rays.

X-ray polarization-contrast images resulting from X-ray magnetic circular dichroism (XMCD) in the hard X-ray region have been successfully recorded for the first time. The apparatus used consisted of an X-ray polarizer, double X-ray phase retarders, and a high-spatial-resolution X-ray charge-coupled-device detector. The sample used was a hexagonal-close-packed cobalt polycrystal foil having a thickness of about 4 microns. The X-ray polarization-contrast image resulting from XMCD was observed at a photon energy of 10 eV above the cobalt K-absorption edge (7709 eV). The observed contrast in the image was reversed by inversion of the magnetic field. Furthermore, the contrast was reversed again at a photon energy of 32 eV above the cobalt K-absorption edge.

Circular Dichroism↗