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Biomedical subjects

A Inoue

Publications and source records attributed to A Inoue.

At least 109 records · Page 6Linked to original sources

Perforation of rotator cuff increases interleukin 1beta production in the synovium of glenohumeral joint in rotator cuff diseases.

OBJECTIVE: To study the hypothesis that perforation of the rotator cuff increases the degree of inflammation in the synovium of the glenohumeral joint in rotator cuff diseases. METHODS: Thirty-five synovial specimens in the glenohumeral joint of patients with rotator cuff diseases were examined. They were obtained during surgery and divided into 2 groups on the basis of the presence or absence of rotator cuff perforation, i.e., perforating and nonperforating tears. The expression levels of inflammatory cytokine mRNA of interleukin 1beta (IL-1beta) and 2 forms (secreted type and intracellular type) of IL-1 receptor antagonist (IL-1ra) were measured by reverse transcriptase polymerase chain reaction (RT-PCR). The protein level of IL-1beta was determined by Western blot analysis. IL-1beta producing cells were also identified by in situ RT-PCR and immunohistochemistry. RESULTS: In perforating tears cytokine mRNA in the glenohumeral synovium was more significantly expressed than in nonperforating tears. Also, higher levels of IL-1beta protein were detected in perforating tears. CONCLUSION: Perforation of the rotator cuff increases IL-1beta production in the glenohumeral joint, enhancing inflammatory intensity at the site. These findings suggest the possibility that glenohumeral synovitis in rotator cuff diseases may be a factor for the development of glenohumeral arthropathy.

Adult↗

Pathogenic immunity in Theiler's virus-induced demyelinating disease: a viral model for multiple sclerosis.

Multiple sclerosis involves inflammatory immune responses in the central nervous system (CNS) and is considered as an autoimmune disease potentially associated with viral infection. The majority of experimental models rely heavily on the autoimmune components since similar diseases can be induced following immunization with various myelin antigens. A very attractive alternative model is the Theiler's murine encephalomyelitis virus-induced demyelinating disease. This disease is primarily a CD4+ T cell-mediated, inflammatory demyelinating disease induced following viral infection. Virus-specific inflammatory Th1 cell responses, rather than cytotoxic T lymphocyte response, play a critical role in the pathogenic immune responses. The major pathogenic epitopes have been identified and these are correlated with a Th1 type response to the epitopes following viral infection. In addition, the initial virus-specific immune response is followed by the autoimmune responses to myelin antigens. Assessment of cytokines produced locally in the CNS during the course of disease suggests involvement of inflammatory cytokines in the disease. Furthermore, the manipulation of inflammatory cytokine levels by administration of either recombinant cytokines or antibodies to the cytokines strongly influences the induction and/or progression of disease, supporting the importance of these inflammatory cytokines in this virus-induced demyelinating disease.

CD4-Positive T-Lymphocytes↗

Suppression of experimental autoimmune encephalomyelitis by dermatan sulfate.

The effect of dermatan sulfate (DS) on the treatment of Lewis rats with experimental autoimmune encephalomyelitis (EAE) was examined. DS, a sulfated glycosaminoglycan, has been reported to exhibit anticoagulant and fibrinolytic activities. DS treatment (50 mg/kg/day) facilitates recovery from the clinical manifestations of EAE. In this study, the fibrinolytic activity was higher in DS-treated rats than in saline-treated rats. Although the degree of perivascular mononuclear cell infiltration in the spinal cord was not suppressed in DS-treated rats compared to that in saline-treated rats, perivascular fibrin deposition was markedly suppressed in DS-treated rats. These findings suggest that DS would act as an effective therapeutic agent for EAE by preventing fibrin deposition.

Animals↗

Effect of anti-B7-1 and anti-B7-2 mAb on Theiler's murine encephalomyelitis virus-induced demyelinating disease.

We examined the role of B7-1 and B7-2, costimulatory molecules critical to full activation of T cells, in the development of Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). Treatment with mAbs to B7-1 resulted in significant suppression of the development of this disease both clinically and histologically. In mice treated with these mAbs, the production of TNF-alpha and IFN-gamma in the spleen cells was decreased. The delayed-type hypersensitivity and T cell proliferative response specific for TMEV were decreased by this treatment. In contrast, treatment with Abs to B7-2, resulted in no effect on TMEV-IDD. These data suggest that B7-1 is critically involved in the pathogenesis of TMEV-IDD and that Abs to B7-1 could be a novel therapeutic approach in the clinical treatment of demyelinating diseases such as human multiple sclerosis.

Animals↗

Effects of nicotine on cultured cells suggest that it can influence the formation and resorption of bone.

The acute effects of nicotine [1-methyl-2-(3-pyridyl)pyrrolidine] on the formation and resorption of bone were examined in cultures of clonal rat calvarial osteogenic cells (ROB-C26) and clonal mouse calvarial preosteoblastic cells (MC3T3-E1), as well as in osteoclast-like cells formed during coculture of mouse bone marrow cells and clonal stromal cells from mouse bone marrow, ST2 cells, at concentrations that occur in the saliva of smokeless tobacco users. Nicotine stimulated the rate of deposition of Ca(2+) by ROB-C26 cells, as well as the alkaline phosphatase activity of these cells, in a dose-dependent manner. However, both activities decreased in MC3T3-E1 cells that had been exposed to nicotine. These results indicate that nicotine affected osteoblastic differentiation in osteoblast-like cells. By contrast, nicotine reduced, in a dose-dependent manner, the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs) and the formation of pits on slices of dentine, both of which are typical characteristics of osteoclasts. Our results suggest that nicotine might have critical effects on bone metabolism.

Alkaline Phosphatase↗

Expression and potential role of inducible nitric oxide synthase in the central nervous system of Theiler's murine encephalomyelitis virus-induced demyelinating disease.

Intracerebral inoculation of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in immune-mediated demyelinating disease. We examined the pathogenic roles of nitric oxide (NO) and inducible NO synthase (iNOS) in TMEV-induced demyelinating disease (TMEV-IDD). The presence of iNOS was confirmed in the spinal cords of TMEV-infected mice using immunohistochemical staining with anti-iNOS antibody on day 0 (control) and days 15, 30, 60, and 120. Aminoguanidine (AG), a specific inhibitor of iNOS, was injected intraperitoneally (ip) on 1, 3, 5, 8, 10, and 12 days post-TMEV inoculation as induction phase or 15, 17, 19, 22, 24, and 26 days as effector phase. Control animals in each experiment received phosphate-buffered saline (PBS) ip at similar time intervals. Few iNOS-positive cells were observed in the spinal cords of naive SJL/J mice. In the early phase (day 15) of TMEV-IDD, an increase of iNOS-positive cells was detected in the leptomeninges and perivascular space of the spinal cords. The number of iNOS-positive cells was increased and reached its peak on day 60, when histology of the animals showed peak infiltration with inflammatory cells. The clinical course of TMEV-IDD on each day postintracerebral infection was significantly reduced in mice treated with AG in the effector phase, and there was no significant difference between mice treated with AG in induction phase versus those administered PBS. Thus, NO production via iNOS appears to be a pathogenic factor in the effector phase of TMEV-IDD.

Animals↗

Experimental external fixation combined with percutaneous discectomy in the management of scoliosis.

STUDY DESIGN: An assessment of the value of external fixation with or without percutaneous discectomy for the management of scoliosis in young rabbits with induced progressive thoracic scoliosis. OBJECTIVES: To investigate in an experimental setting the effect of external fixation with or without percutaneous discectomy for the management of scoliosis, as a preliminary study to precede clinical consideration. SUMMARY OF BACKGROUND DATA: External fixation of the spine using percutaneous transpedicular screws has been used clinically for cases of traumatic spinal injury, infectious spine, or chronic low back pain caused by a disc lesion. Percutaneous discectomy for the management of scoliosis has been reported. METHODS: Thirty-two young rabbits underwent partial resection of the right lower ribs. Nine rabbits were not treated after production of scoliosis and were followed as controls. At 4-6 weeks after production of scoliosis, in 23 animals, Kirschner wires were inserted percutaneously into the T9-T10 and L1-L2 disc space, and both ends were attached to an external fixator after correction of the scoliosis. In 8 of those 23 animals, percutaneous discectomy was also performed at the apex of the caudal compensatory curvature. RESULTS: In these 23 animals, the initial correction by fixation on of the caudal vertebrae was accompanied by a derotation in the apex. Five animals treated with external fixation only and four treated with combined percutaneous discectomy survived with external fixation until the age of 17 weeks and were followed to the natural cessation of the curve progression, at which the fixation was removed and a final assessment was made. The mean progression of curvature was 15.8 degrees in the group of five animals with external fixation only, and 33.8 degrees in the controls. In the group of four animals treated with supplementary percutaneous discectomy, however, the treated disc space became rigid, and the mean progression of curvature after removal of the fixation was only 5.3 degrees. CONCLUSIONS: The results of the current study suggest the potential for external fixation to allow for derotation and, when combined with percutaneous discectomy, to offer a feasible method of managing scoliosis in the human adolescent. This study was a preliminary experimental study; further experimental studies are planned to develop this novel technique.

Animals↗

IgG subclass switching is associated with the severity of experimental autoimmune encephalomyelitis induced with myelin oligodendrocyte glycoprotein peptide in NOD mice.

We have recently shown that a single dose of the myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 produces a relapsing-remitting demyelinating disease similar to multiple sclerosis (MS) in Lewis rats. In this study we have assessed the possibility that a subclass of anti-MOG35-55 antibodies influences the clinical outcome of these diseases by examining the classes and isotypes of anti-MOG35-55 antibody produced during the course of MOG35-55-induced demyelinating disease in NOD mice. Following immunization, 7 of the 21 injected mice had only mild diseases, while the 14 others had severe progressive and/or relapsing-remitting diseases. There were no differences in anti-MOG35-55 IgG, IgA, IgM, IgG1, IgG2a, and IgG3 antibody titers between the severe and mild symptoms groups. High levels of IgG2b antibody to MOG35-55 were detected in all mice with severe symptoms. In contrast, none of the mice which contracted a mild disease produced anti-MOG35-55 IgG2b. These results suggest that in NOD mice, the IgG2b antibody response to MOG35-55 is associated with the severity of this MS-like demyelinating disease.

Amino Acid Sequence↗

APS, an adaptor protein containing PH and SH2 domains, is associated with the PDGF receptor and c-Cbl and inhibits PDGF-induced mitogenesis.

Previously we cloned a novel adaptor protein, APS (adaptor molecules containing PH and SH2 domains) which was tyrosine phosphorylated in response to c-kit or B cell receptor stimulation. Here we report that APS was expressed in some human osteosarcoma cell lines, markedly so in SaOS-2 cells, and was tyrosine-phosphorylated in response to several growth factors, including platelet derived growth factor (PDGF), insulin-like growth factor (IGF), and granulocyte-macrophage colony stimulating factor (GM-CSF). Ectopic expression of the wild type APS, but not C-terminal truncated APS, in NIH3T3 fibroblasts suppressed PDGF-induced MAP kinase (Erk2) activation, c-fos and c-myc induction as well as cell proliferation. In vitro binding experiments suggest that APS bound to the beta type PDGF receptor, mainly via phosphotyrosine 1021 (pY1021). Indeed, tyrosine phosphorylation of PLC-gamma, which has been demonstrated to bind to pY1021, but not that of PI3 kinase and associated proteins, was reduced in APS transformants. PDGF induced phosphorylation of the tyrosine residue of APS close to the C-terminal end. In vitro and in vivo binding experiments indicate that the tyrosine phosphorylated C-terminal region of APS bound to c-Cbl, which has been shown to be a negative regulator of tyrosine kinases. Since coexpression of c-Cbl with wild type APS, but not C-terminal truncated APS, synergistically inhibited PDGF-induced c-fos promoter activation, c-Cbl could be a mechanism of inhibitory action of APS on PDGF receptor signaling.

Adaptor Proteins, Signal Transducing↗

The fate of the compressed deformed spinal cord after decompressive surgery: MR imaging and histopathological findings in experimental studies.

The authors conducted a study in which they applied the spinal cord compression-decompression model in rabbits to investigate the morphological changes and histopathological findings in the deformed spinal cord over a long-term period after performing decompressive surgery. Throughout the experimental period, mangnetic resonance (MR) images were obtained frequently; after obtaining a final MR image, the spinal cord was dissected and underwent histological examination. Immediately after decompressive surgery, axial T1-wieighted MR imaging revealed an increase in the cross-sectional area of the spinal cord during the 1st and 2nd weeks. The spinal cord area achieved a peak at an average of 5.9 weeks after decompressive surgery, when it displayed isointensity on T1- and high-intensity on T2-weighted images. The main histological findings were spongy changes in the white matter, which persisted for 4 months postsurgery. There was a significant correlation between the presurgical spinal cord area and the postsurgical decreased number of motor neuron cells. Based on the MR imaging and histopathological studies, although the deformed spinal cord that underwent compression for 3 months was immediately restored morphologically after decompressive surgery, the change in quality in the spinal cord persisted at least 4 months.

Journal Article↗

Changes of plasma hemostatic markers during percutaneous transluminal coronary angioplasty in patients with chronic coronary artery disease.

Changes of hemostatic parameters during percutaneous transluminal coronary angioplasty (PTCA) in 75 patients with chronic coronary artery disease were evaluated. Plasma levels of D-dimer, soluble fibrin monomer, plasmin-alpha2 antiplasmin inhibitor complex, and tissue factor (TF) were significantly increased in all patients with chronic coronary artery disease. The activity of antithrombin and protein C and the levels of protein C antigen were significantly decreased 1 hr after PTCA, but they returned to normal range 1 day after PTCA. There was no significant difference in the level of plasma APC-PCI complex before and 1 hr after PTCA. The plasma levels of D-dimer, soluble fibrin monomer, thrombomodulin, TF and PPIC were significantly decreased 1 hr, and the plasma levels of plasmin-alpha2 antiplasmin inhibitor complex 1 day after PTCA. These findings suggest that the decrease of protein C and antithrombin resulted in activation of the coagulation system. One hour after PTCA, the plasma levels of (total-free) TF pathway inhibitor (TFPI) were significantly decreased, but the plasma levels of total and free-TFPI were significantly increased, suggesting that consumption of (total-free) TFPI occurs during PTCA. Overall, these findings suggest that the hypercoagulable state improves during PTCA and that transient decrease of antithrombin, protein C, (total-free) TFPI or plasmin-alpha2 antiplasmin inhibitor complex may cause restenosis of coronary artery.

Angioplasty, Balloon, Coronary↗

Increased interleukin-1beta production in the synovium of glenohumeral joints with anterior instability.

Macroscopic synovitis of the glenohumeral joint is frequently seen during arthroscopy in patients with anterior instability. Interleukin-1beta is known to be expressed in inflamed tissue, to correlate with the magnitude of inflammation, and to affect articular cartilage in the joint. We hypothesized that chronic synovitis may occur in the glenohumeral joint in patients with anterior instability. The purpose of this study was to examine the expression of interleukin-1beta in the synovium of the glenohumeral joint with anterior instability and to discuss its clinicopathologic significance. Specimens of synovial tissue around the greater tuberosity in the subacromial synovium (as controls) and around the rotator interval in the glenohumeral synovium were obtained from 10 patients who had anterior instability without signs of subacromial impingement. Semiquantitative reverse transcriptase-polymerase chain reaction was used to compare the levels of interleukin-1beta mRNA expression in the glenohumeral joint with those in the subacromial bursa. We also employed immunohistochemistry and in situ reverse transcriptase-polymerase chain reaction to detect the cells producing interleukin-1beta protein and mRNA. The levels of interleukin-1beta mRNA expression were significantly higher in the glenohumeral joint than in the subacromial bursa (p < 0.01). Histology showed nonspecific inflammation in all 10 samples of glenohumeral synovium, whereas no inflammation was seen in seven of 10 samples of subacromial synovium. Immunohistochemistry identified interleukin-1beta protein in the vessels and inflammatory and synovial cells (from lining to sublining layers) in synovium of the glenohumeral joint, whereas immunoreactivity was negative in seven subacromial bursa. The remaining three synovial specimens of subacromial bursa, however, showed positive immunoreactivity that was unremarkable and confined around the vessels. In situ reverse transcriptase-polymerase chain reaction was exclusively performed in the synovial specimens of the glenohumeral joint, which exhibited a positive reaction (in the same kinds of cells as seen with immunohistochemistry) in the lining and sublining layers and to a lesser extent in the stroma. Thus, our data confirmed the increased production of interleukin-1beta in the synovium of the glenohumeral joint in patients with anterior instability, suggesting the presence of chronic inflammation at the site. We conclude that this chronic synovitis may be partly associated with the development of dislocation arthropathy in the long term.

Acromion↗

Bone tumors in the pelvis presenting growth during pregnancy.

Among 56 cases of a giant cell tumor of bone (GCT) and 52 cases of chondrosarcoma (CSA) in our series, four patients were discovered to have a tumor in the pelvic bone that grew in size during pregnancy. These four rare cases are described here. They include three cases of a GCT in the sacrum and one case of a CSA in the innominate bone. The dextran-coated charcoal assay and immunohistochemical techniques demonstrated the independence of these tumors from hormonal regulation despite the growth stimulated during pregnancy. It was concluded that the delay in detection of these tumors in the pelvis was just related to the opportunity afforded for unexpected growth during pregnancy. Surgical management was difficult due to the delay in tumor detection. The initial complaints such as pain, discomfort, or numbness around the pelvis were misinterpreted as symptoms of pregnancy. It should be kept in mind that during pregnancy, any pain or numbness in the pelvic region could be the direct result of a tumor in the pelvic bone.

Adult↗

An improved physical and genetic map of the genome of alkaliphilic Bacillus sp. C-125.

Among alkaliphilic bacteria reported so far, Bacillus sp. C-125 is the strain most thoroughly characterized physiologically, biochemically, and genetically. A physical map of the chromosome of this strain was constructed to facilitate further genome analysis, and the genome size was revised from 3.7 to 4.25Mb. Complete digestion of the chromosomal DNA with two rare cut restriction endonucleases, AscI and Sse8387I, each yielded 20 fragments ranging in size from 20 to 600 kb. Seventeen linking clones were isolated in each instance to join the adjacent AscI or Sse8387I fragments in the chromosomal map. All AscI linking clones isolated were sequenced and analyzed by comparison with the BSORF database to map the genes in the chromosome of strain C-125. Several ORFs showing significant similarities to those of B. subtilis in the AscI linking clones were positioned on the physical map. The oriC region of the C-125 chromosome was identified by southern blot analysis with a DNA probe containing the gyrB region.

Bacillus↗

Sequencing of three lambda clones from the genome of alkaliphilic Bacillus sp. strain C-125.

The nucleotide sequences of three independent fragments (designated no. 3, 4, and 9; each 15-20 kb in size) of the genome of alkaliphilic Bacillus sp. C-125 cloned in a lambda phage vector have been determined. Thirteen putative open reading frames (ORFs) were identified in sequenced fragment no. 3 and 11 ORFs were identified in no. 4. Twenty ORFs were also identified in fragment no. 9. All putative ORFs were analyzed in comparison with the BSORF database and non-redundant protein databases. The functions of 5 ORFs in fragment no. 3 and 3 ORFs in fragment no. 4 were suggested by their significant similarities to known proteins in the database. Among the 20 ORFs in fragment no. 9, the functions of 11 ORFs were similarly suggested. Most of the annotated ORFs in the DNA fragments of the genome of alkaliphilic Bacillus sp. C-125 were conserved in the Bacillus subtilis genome. The organization of ORFs in the genome of strain C-125 was found to differ from the order of genes in the chromosome of B. subtilis, although some gene clusters (ydh, yqi, yer, and yts) were conserved as operon units the same as in B. subtilis.

Bacillus↗

Biodiversity in deep-sea sites located near the south part of Japan.

We obtained 100 isolates of bacteria from deep-sea mud samples collected at various depths (1050-10897m). Various types of bacteria such as alkaliphiles, thermophiles, psychrophiles, and halophiles were recovered on agar plates at a frequency of 0.8 x 10(2) to 2.3 x 10(4)/ g of dry sea mud. No acidophiles were recovered. These extremophilic bacteria were widely distributed, being detected at each deep-sea site, and the frequency of isolation of such extremophiles from the deep-sea mud was not directly influenced by the depth of the sampling sites. Phylogenetic analysis of deep-sea isolates based on 16S rDNA sequences revealed that a wide range of taxa were represented in the deep-sea environments. Growth patterns under high hydrostatic pressure were determined for the deep-sea isolates obtained in this study. No extremophilic strains isolated in this study showed growth at 60MPa, although a few of the other isolates grew slightly at this hydrostatic pressure.

Bacteria↗

SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein.

The E2A-HLF fusion gene transforms human pro-B lymphocytes by interfering with an early step in apoptotic signaling. In a search for E2A-HLF-responsive genes, we identified a zinc finger transcription factor, SLUG, whose product belongs to the Snail family of developmental regulatory proteins. Importantly, SLUG bears close homology to the CES-1 protein of C. elegans, which acts downstream of CES-2 in a neuron-specific cell death pathway. Consistent with the postulated role of CES-1 as an antiapoptotic transcription factor, SLUG was nearly as active as Bcl-2 or Bcl-xL in promoting the survival of IL-3-dependent murine pro-B cells deprived of the cytokine. We conclude that SLUG is an evolutionarily conserved transcriptional repressor whose activation by E2A-HLF promotes the aberrant survival and eventual malignant transformation of mammalian pro-B cells otherwise slated for apoptotic death.

Animals↗

Analysis of strain distribution in the medial collateral ligament using a photoelastic coating method.

The strain distribution over the entire medial collateral ligament (MCL) was measured using a photoelastic coating method. This new approach utilized a polyurethane monomer as a photoelastic coating film. The initial experiments investigating MCL strain measurement showed that this film had a high sensitivity for strain and good adhesion to the ligament. It was confirmed that strain distribution could be obtained qualitatively over the entire ligament using this method. The mechanism of MCL injury was studied by applying this polyurethane coating film to the entire MCL in a femur-MCL-tibia complex. When simple tension was applied to the complex, strain concentrations were centred at the tibial insertion site, and all the specimens ruptured at the MCL tibial insertion site. With application of a valgus bending moment, increased strain was seen in the MCL from the medial femoral condyle to the medial epicondyle. Histological analysis demonstrated midsubstance ligament ruptures in this same region. For both tests, rupture sites and increased strain concentration sites correlated. In addition, an impingement phenomenon of the MCL on the medial femoral condyle can be seen during application of valgus force, and this phenomenon may explain the higher incidence of MCL injuries on the femoral side seen in the clinical setting. This polyurethane coating method allows for direct and visual measurements, and can qualitatively measure the strain behaviour over the entire MCL surface. This new technique represents a significant improvement over previous point-by-point strain measurement methods.

Animals↗