Biomedical subjects

Satoru Abe

Publications and source records attributed to Satoru Abe.

13 recordsLinked to original sources

PubMed2006

Hydrodynamic-based delivery of an interleukin-22-Ig fusion gene ameliorates experimental autoimmune myocarditis in rats.

IL-22 is one of several cytokines with limited homology to IL-10. However, the biological activities of IL-22 are mostly unknown. The purpose of this study was to evaluate the effect of IL-22 on rat experimental autoimmune myocarditis (EAM) and elucidate an aspect of the biological activities of IL-22. Rats were immunized on day 0; IL-22-Ig-treated rats were injected with pCAGGS-IL-22-Ig and control rats with pCAGGS-Ig using hydrodynamics-based gene delivery on day 1 or day 6. IL-22-Ig gene therapy administered on day 1 or day 6 after immunization was effective in controlling EAM as monitored by the heart weight to body weight ratio, and the myocarditis area in rats was sacrificed on day 17. Examination of the expression of IL-22-related genes in purified cells from EAM hearts suggested that IL-22-Ig acting target cells were noncardiomyocytic (NC) noninflammatory cells such as fibroblasts, smooth muscle cells, and endothelial cells. Therefore, we examined the effect of rIL-22 or serum containing IL-22-Ig on the expression of immune-relevant genes in IL-1-stimulated NC cells cultured from EAM hearts. Results showed that the expression of immunologic molecules (PGE synthase, cyclooxygenase-2, MIP-2, MCP-1, IL-6, and cytokine-induced neutrophil chemoattractant-2) in IL-1-stimulated NC cells was significantly decreased by rIL-22 or serum containing IL-22-Ig. EAM was suppressed by hydrodynamics-based delivery of plasmid DNA encoding IL-22-Ig, and the reason for this effectiveness may be that IL-22 suppressed gene expression of PG synthases, IL-6, and chemokines in activated NC noninflammatory cells.

Animals↗

PubMed2005

Expression of immunological molecules by cardiomyocytes and inflammatory and interstitial cells in rat autoimmune myocarditis.

BACKGROUND: In a heart with myocarditis, there are cardiomyocytes, inflammatory cells, and non-inflammatory interstitial cells. Immunological molecules are thought to influence not only inflammatory cells but also cardiac function and remodeling. Whatever their origin, the cells they target and the intercellular crosstalk they mediate remain unclear. Here, we examined native gene expression of immunological molecules in normal and rat experimental autoimmune myocarditis (EAM) 18 and 90 days after immunization, using real time RT-PCR in cardiomyocytes, CD11b(+) cells, alphabetaT cells and non-cardiomyocytic non-inflammatory (NCNI) cells. METHODS AND RESULTS: Cells were isolated by collagenase perfusion on a Langendorff apparatus and purified by passing through a stainless-steel sieve followed by magnetic bead column separation using appropriate monoclonal antibodies. Most immunological molecules were expressed in inflammatory cells. However, some were expressed in NCNI cells or cardiomyocytes. Interestingly, most of interleukin (IL)-10, monocyte chemoattractant protein (MCP)-1, or tumor necrosis factor (TNF)-alpha receptor were found in NCNI cells and most of fractalkine were found in NCNI cells and cardiomyocytes. Moreover, TNF-alpha significantly upregulated fractalkine and MCP-1 mRNA in cultivated cells from EAM hearts. CONCLUSION: In the rat experimental myocarditis heart, inflammatory cells express many immunological molecules. Some of them are thought to influence NCNI cells or cardiomyocytes directly via receptors on these cell types. It is further suggested that fractalkine, IL-10, and MCP-1 expressed in NCNI cells or cardiomyocytes regulate inflammatory cells.

Animals↗

PubMed2005

The effect of hydrodynamics-based delivery of an IL-13-Ig fusion gene for experimental autoimmune myocarditis in rats and its possible mechanism.

Interleukin (IL)-13 is a pleiotropic cytokine secreted by activated Th2 T lymphocytes. Th1 cytokines are assumed to exacerbate and Th2 cytokines to ameliorate rat experimental autoimmune myocarditis (EAM). Here, we examined the effect of IL-13 on EAM, using a hydrodynamics-based delivery of an IL-13-Ig fusion gene, as well as the possible mechanism of its effect. Rats were immunized on day 0, and IL-13-Ig-treated rats were injected with pCAGGS-IL-13-Ig, and control rats with pCAGGS-Ig, on day 1 or 7. On day 17, the IL-13-Ig gene therapy was effective in controlling EAM as monitored by a decreased heart weight/body weight ratio, by reduced myocarditis and by reduced atrial natriuretic peptide mRNA in the heart, as a heart failure marker. On the basis of IL-13 receptor mRNA expression in separated cells from EAM hearts, we proposed that IL-13-Ig target cells were CD11b(+) cells and non-cardiomyocytic noninflammatory (NCNI) cells, such as fibroblasts, smooth muscle or endothelial cells. IL-13-Ig inhibited expression of the genes for prostaglandin E synthase, cyclooxygenase-2, inducible nitric oxide synthase, IL-1beta and TNF-alpha in cultivated cells from EAM hearts, while it enhanced expression of the IL-1 receptor antagonist gene. We conclude that IL-13-Ig ameliorates EAM and suppose that its effectiveness may be due to the influence on these immunologic molecules in CD11b(+) and NCNI cells.

Animals↗

PubMed2005

Prevention of experimental autoimmune myocarditis by hydrodynamics-based naked plasmid DNA encoding CTLA4-Ig gene delivery.

BACKGROUND: Rat experimental autoimmune myocarditis (EAM) is a T cell-mediated disease that resembled the giant cell myocarditis seen in humans. Soluble CTLA4 improves some autoimmune diseases by blocking costimulatory signals on T cell. We investigated the effect of hydrodynamics-based naked plasmid DNA encoding CTLA4-immunoglobulin (Ig) gene delivery. METHODS AND RESULTS: Lewis rats were immunized with cardiac myosin and treated with hydrodynamic-based transfection, namely a rapid tail vein injection of a large volume of pCAGGS encoding CTLA4-Ig chimera solution on Day 0. The vector-derived CTLA4-Ig mRNA expressions were mainly detected in the liver and plasma CTLA4-Ig protein levels were maintained at about 2 mug/mL during the experiment period. On Day 17, the ratio of heart to body weight, the amount of mRNA of atrial natriuretic peptide, and the inflammatory areas in CTLA4 group were significantly lower than in the control group treated with empty plasmid. Maximum rate of intraventricular pressure rise and decline (dP/dT), minimum dP/dT, left ventricular end-diastolic pressure, and central venous pressure improved significantly after treatment with CTLA4-Ig. On Day 14, expressions of IL-2 in popliteal lymph nodes in the CTLA4-Ig group were significantly lower than in the control group. CONCLUSION: Hydrodynamics-based transfection of plasmid encoding CTLA4-Ig chimera dramatically prevented EAM.

Abatacept↗

PubMed2004

Hierarchical map of protein unfolding and refolding at thermal equilibrium revealed by wide-angle X-ray scattering.

Hierarchical features of the thermal unfolding-refolding structural transition of hen egg white lysozyme (HEWL) have been studied in the temperature range from 13 to 84 degrees C by using high-resolution wide-angle X-ray scattering (WAXS) measurements at a third-generation synchrotron source. We have gathered high-statistic WAXS data of the reversible unfolding-refolding process of HEWL in the q range from approximately 0.05 to approximately 3 A(-1) [q = (4pi/lambda) sin(theta/2), where theta is the scattering angle and lambda the wavelength]. This measured q range corresponds to the spatial distance from approximately 2 to approximately 125 A, which covers all hierarchical structures of a small globular protein such as HEWL, namely, tertiary, domain, and secondary structures. Because of this, we have found that the pH dependence of the thermal structural transition of HEWL is well characterized by the various hierarchical levels and the transition concurrence among them. In this report, we present a new hierarchical map depiction of unfolding-refolding transitions. Using scattering with various ranges of q values, we determine the molar ratio of native-like protein structure defined by the data in each range, thus producing a map of the amount of native-like structure as a function of the hierarchical level or resolution. This map can visualize a detailed feature of the unfolding-refolding transition of a protein depending on various structural hierarchical levels; however, the exact meaning of the map will await sharpening by additional works.

Animals↗

PubMed2004

Plasma concentrations of cytokines and neurohumoral factors in a case of fulminant myocarditis successfully treated with intravenous immunoglobulin and percutaneous cardiopulmonary support.

A 53-year-old Japanese man with fulminant myocarditis was referred. Percutaneous cardiopulmonary support (PCPS) was introduced immediately and intravenous immunoglobulin (IVIG) therapy followed for 2 days. Cardiac function showed signs of recovery on the 4th hospital day and the patient was weaned from PCPS on the 7th hospital day. Creatine kinase-MB peaked at 12 h after admission and was 176 ng/ml. Endomyocardial biopsy showed active myocarditis. A marked increase of the neutralizing antibody titer suggested coxsackievirus B3 infection. Plasma concentrations of cytokines and neurohumoral factors were analyzed. Proinflammatory cytokines, such as interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF-alpha), and anti-inflammatory cytokines, such as IL-1 receptor antagonist, soluble TNF receptor-1 and IL-10, were elevated on admission and all had decreased on the 7th hospital day. Brain natriuretic peptide and noradrenaline were already elevated upon admission (1,940 pg/ml and 4.6 ng/ml, respectively) and decreased thereafter. Although IVIG therapy under PCPS is a common treatment for fulminant myocarditis, the immunological response in vivo remains unclear. This case demonstrated suppression of serum cytokines after IVIG and PCPS treatment. Immunological parameters in those who have been treated with IVIG and PCPS and survived without complications are of great value for evaluation of the therapy. Further analysis with more cases in a multicenter study is necessary.

Cardiology↗

PubMed2004

A novel method to assay proteins in blood plasma after intravenous injection of plasmid DNA.

Gene therapy is expected to lead to new and useful methods to treat diseases. The development of assays to quantitate gene-therapy-derived proteins circulating in blood will be essential to investigate the effects and side effects of the introduced proteins. The purpose of this study is to evaluate whether a protein circulating at trace concentrations in blood can be measured by tagging a peptide corresponding to glucagon residues 19-29 onto its C-terminal end. We constructed plasmids encoding chimeric proteins and transferred them into rats by hydrodynamics-based delivery. When plasmids encoding human IL8-glucagon 19-29 chimeric protein were injected into rats to evaluate the accuracy of this method, there was a high correlation between chimeric proteins measured by an enzyme-linked immunosorbent assay for human IL8 and one by a radioimmunoassay for glucagon. Furthermore, when plasmids coding rat IFN gamma receptor IgG-Fc glucagon 19-29 chimeric protein were injected to evaluate the time course of chimeric proteins in blood plasma, we could calculate the concentrations in blood from 10 microl plasma samples using glucagon 19-29 tag as follows: 2815+/-2318 ng/ml after 4 hours (mean+/-s.D.), 6061+/-2789 ng/ml after 8 hours, 5752+/-2270 ng/ml after 12 hours, 2870+/-1062 ng/ml after one day, 1440+/-334 ng/ml after three days, 1120+/-433 ng/ml after seven days, and 281+/-162 ng/ml after 16 days. Blood sugar levels which might have been increased by glucagon did not increase even at peak chime- ric protein concentrations. These results demonstrate a useful and convenient method to assay gene therapy products circulating in blood using a glucagon 19-29 tagging vector.

Animals↗

PubMed2003

Effects of imidapril and TA-606 on rat dilated cardiomyopathy after myocarditis.

For the management of chronic heart failure, both angiotensin converting enzyme inhibitors (ACEI) and angiotensin II type 1 receptor blockers (ARB) are useful, however, the differences between the two groups of agents are unclear. We compared the effects of long-term treatment with an ACEI (imidapril) and an ARB (TA-606) in rats that had recovered from experimental autoimmune myocarditis (EAM). Forty-two Lewis rats were immunized with porcine cardiac myosin on day 0 and divided into 6 groups, group C (distilled water), group IL (imidapril 0.5 mg/kg/day), group IH (imidapril 2 mg/kg/day), group TL (TA-606 2 mg/kg/day), group TH (TA-606 6 mg/kg/day), and group IT (imidapril 0.5 mg/kg/day + TA-606 2 mg/kg/day). Drugs were administered from day 28. Hemodynamic parameters, heart weight/body weight ratio (HW/BW), and area of fibrosis were measured on days 70-74. Only the high dose of imidapril significantly decreased central venous pressure and significantly increased maximum dP/dt and the absolute value of minimum dP/dt. HW/BW was suppressed in groups IH, TH, and IT. Thus, in treatment of chronic heart failure in rats, a sufficient dose of ACEI was needed to improve hemodynamics and to prevent ventricular hypertrophy. The hemodynamic effects of ARB and combination therapy of both drugs at low doses were not significant.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2003

Diagnostic accuracy of magnetic resonance imaging for detecting posterior ligamentous complex injury associated with thoracic and lumbar fractures.

OBJECT: The posterior ligamentous complex (PLC) in the thoracic and lumbar spine is one of the region's important stabilizers. The precise diagnosis of PLC injury is required to evaluate the instability of the injured spine; however, the accuracy of magnetic resonance (MR) imaging for diagnosing PLC injury has remained unclear. In this study, the authors compared preoperative MR imaging findings with direct intraoperative observation of PLC injury, clarifying the former's diagnostic accuracy regarding detection of PLC injury associated with the thoracic and lumbar fractures. METHODS: Data obtained in 35 patients who sustained thoracic or lumbar injuries were reviewed. There were 17 burst fractures, six flexion-distraction injuries, and 12 fracture dislocations. Each patient underwent MR imaging examination within 3 weeks of injury. Three radiologists independently evaluated sagittal MR images in a blinded fashion. The PLC-related information was retrospectively collected from each operative record. The diagnostic accuracy of MR imaging was analyzed by comparing imaging-documented intraoperative findings. The PLC injuries were detected in 23 patients (65.7%) by direct observation during posterior spinal procedures. The diagnostic accuracy of MR imaging in detecting injury of the supraspinous ligament (SSL) and interspinous ligament (ISL) was 90.5 and 94.3%, respectively. The specificity of T1-weighted MR imaging alone for depicting the SSL was significantly greater than T2-weighted imaging alone (p < 0.05). The overall mean kappa coefficient for MR imaging findings of PLC injury was 0.803, which indicated excellent interobserver reliability; that for ISL (0.915) was significantly greater than that for SSL (0.69) (p < 0.05). CONCLUSIONS: This study clarified a high diagnostic accuracy and interobserver reliability of MR imaging for PLC injury. The precise diagnosis of PLC injury is essential to determine the mechanical instability of the injured thoracic and lumbar spine, especially in differentiating unstable (three-column) burst fractures from the relatively stable (two-column) type. The authors conclude that MR imaging is a powerful diagnostic tool to evaluate PLC injury associated with thoracic and lumbar fractures.

Humans↗

PubMed2003

Angiotensin II type 1 receptor blocker, valsartan, prevented cardiac fibrosis in rat cardiomyopathy after autoimmune myocarditis.

Favorable effects of angiotensin II type 1 receptor blockers on patients with ischemic or idiopathic dilated cardiomyopathy have already been suggested by several human trials but their effects on inflammatory cardiomyopathy remain unknown. We investigated the effects of the angiotensin II type 1 receptor blocker, valsartan, in chronic heart failure after inflammatory cardiomyopathy. Autoimmune myocarditis was induced in Lewis rats by injection with porcine cardiac myosin. In the phase of chronic heart failure, from day 28 until day 70, rats were treated by oral administration of valsartan. Three groups were designated: 1 ml saline, 10 mg/kg valsartan, and 30 mg/kg valsartan. On the 73rd day, hemodynamic parameters, pathological findings and the expression levels of r-ANP mRNA of the ventricle were examined, and were compared with the saline control. The ventricular weight/body weight ratio and area of fibrosis was decreased in the 30 mg/kg valsartan group. The left ventricular end-diastolic pressure and the central venous pressure were decreased in a dose-dependent manner in both valsartan groups, while the first pressure derivatives +dP/dt and -dP/dt did not differ among the three groups. A high dose of valsartan reduced the expression of tissue ANP mRNA compared with the saline group. In conclusion,valsartan suppressed myocardial hypertrophy and fibrosis, and it improved the hemodynamics and cardiac function in an animal model of post-myocarditis dilated cardiomyopathy.

Angiotensin Receptor Antagonists↗

PubMed2003

Analysis of postextrasystolic relaxation response in the human heart.

Postextrasystolic potentiation is the phenomenon in which ventricular contractile force is strengthened by a preceding premature beat. However, the response of diastolic function after an extrasystole is unknown. We studied 58 patients with chronic heart failure (CHF) and two control subjects to evaluate the response of relaxation following extrasystole. At cardiac catheterization, from the derivative of the left ventricular (LV) pressure, the ratio of LV peak negative dP/dt (-dP/dt) of a postextrasystole to a basal beat was calculated and defined as the postextrasystolic relaxation response (PRR). PRR was compared with parameters of left ventriculography: LV end-diastolic volume index (EDVI), LV end-systolic volume index (ESVI), and LV ejection fraction (EF). The PRRs of the two control subjects were 0.80 and 0.84. The mean PRR of the CHF patients was 0.99 +/- 0.15. In all subjects, including patients and controls, correlation analysis between (EDVI, ESVI, and EF) and PRR yielded the following: (a) EDVI vs. PRR: R = 0.273, p = 0.036; (b) ESVI vs. PRR: R = 0.446, p < 0.001; and (c) EF vs. PRR: R = -0.520, p < 0.001. Thus, normal or non-failing human hearts showed a decline of -dP/dt in postextrasystole compared with the basal beats, but failing hearts had potentiated relaxation following an extrasystole.

Adult↗

PubMed2002

Time course of gene expression in rat experimental autoimmune myocarditis.

Genetic responses that characterize experimental autoimmune myocarditis (EAM) have not yet been determined. To investigate gene expression in the myocardium of EAM, absolute copy numbers of 44 mRNA species [calcium-handling proteins, contractile proteins, natriuretic peptides (NPs), cytokines, chemokines, growth factors, renin-angiotensin-aldosterone (RAA) system, endothelins (ETs) and extracellular matrix] in synthesized cDNA from a fixed quantity of total heart RNA were assessed using real-time reverse-transcriptase PCR at days 0, 14, 21 and 28 after immunization. alpha-Cardiac myosin showed a 26.3-fold decrease and beta-cardiac myosin a 3.75-fold increase at day 14. Atrial NP and brain NP increased 47.7- and 6.35-fold at days 21 and 14 respectively. Angiotensin II type 1 receptor, angiotensin-converting enzyme and ET1 increased 22.3-fold at day 21, 6.30-fold at day 21 and 16.8-fold at day 14 respectively. Aldosterone receptor decreased 2.15-fold at day 14, but aldosterone synthetase was detected only at days 14 and 21. Interleukin (IL)-2, IL-10, interferon-gamma and monocyte chemo-attractant protein-1 increased 9.08-fold at day 14, 398-fold at day 21, 43.1-fold at day 14 and 142-fold at day 14 respectively. Collagen type 3, collagen type 1 and fibronectin increased 34.6-, 1.74- and 44.4-fold respectively at day 21. Interestingly, osteopontin showed a 4540-fold increase and it was the highest mRNA of all at day 14. An isoform of cardiac myosin and NP are dramatically changed in EAM. RAA system and ET expressions are changed differently during the EAM time course. Cytokine, chemokine and extracellular matrix greatly increase and, in particular, large numbers of osteopontin mRNA are expressed in early EAM.

Animals↗

PubMedDate not supplied

Two-dimensional diffraction study of ice crystallisation in polymer gels.

Ice crystallisation in crosslinked dextran (Sephadex) gels was studied by the method of two-dimensional X-ray diffraction (XRD) in combination with the simultaneous measurement of differential scanning calorimetry (DSC). With a Sephadex G25 gel where an exotherm due to ice crystallisation is observed in the DSC rewarming trace, it was indicated by the XRD pattern that small ice crystals less than approximately 10 microns in diameter are readily formed during freezing, and that the endothermic trend prior to the exotherm is not due to the glass transition but due to the melting of the small ice crystals. Moreover, the diffraction pattern observed with frozen Sephadex gels depended on the density of crosslink indicating that ice crystals of different size and dimension are formed in the gels.

Crystallization↗