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Yoshiki Sawa

Publications and source records attributed to Yoshiki Sawa.

At least 19 recordsLinked to original sources
PubMed2006

Lung tissue engineering technique with adipose stromal cells improves surgical outcome for pulmonary emphysema.

RATIONALE AND OBJECTIVES: Hepatocyte growth factor (HGF) is a potent regenerative factor generated after a lung injury, and HGF supplementation after surgical reduction has been shown to enhance compensatory growth in remnant lungs and improve pathophysiologic conditions in a rat model of emphysema. Adipose tissue-derived stromal cells (ASCs) produce a large amount of angiogenic factors, including HGF. After lung volume reduction surgery (LVRS), we treated rats by implanting HGF-secreting ASCs with a scaffold onto the remnant lung tissue to determine the usefulness of this technique for treating respiratory dysfunction. METHODS AND MAIN RESULTS: Cells were isolated from rat inguinal adipose tissue and characterized by flow cytometry. ASCs were cultured on a polyglycolic acid felt sheet as a sealant material, and were shown to secrete significantly greater amounts of HGF than other angiogenic factors. Next, ASCs on polyglycolic acid felt sheets were used to cover the cut edge of the remaining lungs after LVRS for emphysema in rats. One week after implantation of the ASCs, both alveolar and vascular regeneration were significantly accelerated as compared with the rats that underwent LVRS alone. Consequently, gas exchange and exercise tolerance were also significantly restored, with these good results persisting for more than 1 mo. CONCLUSIONS: The present findings demonstrate the therapeutic potential of cell therapy using ASCs with a scaffold for selective delivery of HGF to remnant lungs, which resulted in enhancement of compensatory growth, after surgical resection. This approach may provide a new strategy for lung tissue engineering to improve LVRS outcome.

Adipose Tissue↗
PubMed2006

Angiogenic gene cell therapy using suicide gene system regulates the effect of angiogenesis in infarcted rat heart.

BACKGROUND: Although angiogenic gene therapy has been reported to be effective in restoring ischemic heart function, there are several obstacles to its clinical application, such as unreliable efficiency of transfection and uncontrollable expression. We developed human HGF (hHGF)-producing cells that regulated hHGF production using the thymidine kinase gene of Herpes Simplex Virus (TK) and the Ganciclovir (GCV) system. We tested whether these cells induced and regulated angiogenic effects in infarcted myocardium. METHODS: NIH3T3 cells were stably transfected with an hHGF cDNA expression plasmid (NIH/HGF). Next, the NIH/HGF cells were stably transfected with TK (NIH/HGF/TK). The left anterior descending artery was ligated in the heart of severe combined immunodeficiency rats, and four materials were transplanted: 1) NIH/HGF (n=10), 2) NIH/HGF/TK, with orally administered GCV (n=10), 3) NIH3T3 (n=10), and 4) culture medium (n=10). RESULTS: In vitro, the proliferation of NIH/HGF/TK cells was suppressed by GCV. In vivo, significant increases in cardiac performance and angiogenesis were observed in the NIH/HGF and NIH/HGF/TK groups 4 weeks after transplantation. Although tumorous lesions were detected in the NIH/HGF group, their growth was completely controlled in the NIH/HGF/TK group. CONCLUSIONS: Angiogenic gene cell therapy using the TK-GCV suicide gene system induces and regulates angiogenesis under the control of cell growth, suggesting it as a promising system for therapeutic angiogenesis.

Animals↗
PubMed2006

Neuroprotective effects of activated protein C through induction of insulin-like growth factor-1 (IGF-1), IGF-1 receptor, and its downstream signal phosphorylated serine-threonine kinase after spinal cord ischemia in rabbits.

BACKGROUND AND PURPOSE: Activated protein C (APC) has beneficial effects on ischemia reperfusion injury in neuron. However, the possible mechanism of such beneficial effects is not fully understood. The aim of this study was to investigate the effects and possible mechanisms of APC on ischemic spinal cord damage. METHODS: After induction of spinal cord ischemia, APC (group A) or vehicle (group I) was injected intravenously. Severity of ischemic damage was analyzed by counting the number of motor neurons. To investigate the mechanisms by which APC prevents ischemic spinal cord damage, we performed immunoreactivity and Western blotting of insulin-like growth factor 1 (IGF-1), IGF-1 receptor, and phosphorylated serine-threonine kinase (p-Akt). RESULTS: APC eased the functional deficits and increased the number of motor neurons after ischemia. Immunoreactivity of IGF-1 in group A was stronger than in group I at 8 hours after reperfusion but was at the same level at 1 day. Induction of IGF-1 receptor and the downstream factor p-Akt was stronger and more prolonged in group A. CONCLUSIONS: These results indicate that induction of IGF-1, IGF-1 receptor, and p-Akt might partially explain the neuroprotective effects of APC after transient spinal cord ischemia in rabbit.

Animals↗
PubMed2006

Longer preservation of cardiac performance by sheet-shaped myoblast implantation in dilated cardiomyopathic hamsters.

OBJECTIVES: Cell therapy is a promising strategy for ischemic cardiomyopathy. However, the direct injection method has limitations for generalized cell delivery, especially in dilated cardiomyopathy (DCM). We hypothesized that a sheet-shaped myoblast graft would be superior to direct injection for improving cardiac performance in DCM. METHODS: Male 27-week-old BIO TO-2 (DCM) hamsters that showed moderate cardiac remodeling were used as recipients. Myoblasts isolated from BIO F1B hamsters were cultured on dishes coated with poly(N-isopropylacrylamide), a temperature-responsive polymer, and spontaneously detached as a sheet-shaped graft at 20 degrees C without enzymatic treatment. Three different therapies were conducted: (1) sheet-shaped myoblast graft implantation (S group, n=29); (2) myoblast injection (M group, n=28); and (3) sham operation (C group, n=28). In the S group, two sheet-shaped myoblast grafts were implanted on the left ventricle (LV) wall, and in the M group, myoblasts were injected into the right ventricle (RV) and LV walls. RESULTS: After the sheet-shaped myoblast grafts were implanted, echocardiography demonstrated that the dilated LV dimension was significantly reduced, whereas the hearts in other groups showed a progression of LV dilation. The fractional shortening in the M and C groups decreased significantly while that in the S group was maintained at the preoperative level for 3 months after the operation. Histological examination demonstrated that in the S group, the LV wall thickness was increased, with viable myoblasts, and myocardial fibrosis was decreased compared with the other groups. Immunohistochemical staining demonstrated alpha-sarcoglycan and beta-sarcoglycan expression on the basement membrane of the cardiomyocytes in the S group but not in the other groups. The life expectancy was significantly prolonged in the S group. CONCLUSION: Sheet-shaped myoblast graft implantation improved cardiac performance and prolonged life expectancy, associated with a reduction in myocardial fibrosis and re-organization of the cytoskeletal proteins in DCM hamsters. Thus, sheet-shaped autologous myoblast graft implantation may induce restoration of the heart in DCM.

Animals↗
PubMed2006

Effect of a polymorphonuclear elastase inhibitor (sivelestat sodium) on acute lung injury after cardiopulmonary bypass: findings of a double-blind randomized study.

PURPOSE: We evaluated the effect of sivelestat sodium (SiV), a novel synthesized polymorphonuclear (PMN) elastase inhibitor, on acute lung injury (ALI) caused by cardiopulmonary bypass (CPB). METHODS: Fourteen patients who underwent cardiopulmonary surgery using CPB, followed by the development of both systemic inflammatory response syndrome (SIRS) and ALI, were treated with either 0.2 mg/kg per hour SiV (SiV group, n = 7) or saline (control group, n = 7) for 4 days from the time of arrival in the intensive care unit. RESULTS: The SiV group had a significantly lower ratio of serum PMN elastase and interleukin (IL)-8, a significantly lower ratio of the respiratory index, and a significantly higher ratio of PaO(2)/FiO(2) after 24 h of treatment than the control group. CONCLUSION: Sivelestat sodium suppressed the production of PMN elastase and IL-8, resulting in improved respiratory function in patients with ALI caused by CPB.

Acute Disease↗
PubMed2006

Large vessel - sternum adhesion after cardiac surgery; a risk-factor analysis.

PURPOSE: To study the clinical results of resternotomy in patients with dense and direct adhesion between the large vessels and the sternum, and define the morphologic features of the adhesion. METHODS: Between 2000 and 2003, 67 patients with a history of cardiac surgery underwent median resternotomy. We studied each patient's profile and the measurements taken from preoperative computed tomography scans. We then conducted multivariate logistic regression analysis to determine the predictive morphologic features of adhesion between the large vessels and the sternum in these 67 patients. RESULTS: Twenty (29.9%) of the 67 patients had direct adhesion between the large vessels and the sternum. Sternal re-entry was performed without injury to the large vessels in 18 (90%) but the aorta was injured in 2 (10%) patients, resulting in catastrophic hemodynamic disorder and operative death in one. Multivariate logistic regression analysis revealed that an extracardiac conduit and a high occupying rate of the aorta and pulmonary artery in the mediastinal space were significant morphologic factors. CONCLUSION: The morphologic features of large vessels to sternal dense adhesion as possible risk factors for injury to the large vessels are the presence of an extracardiac conduit and a large ascending aorta or pulmonary artery in relation to the mediastinal space.

Adult↗
PubMed2006

Left ventricular assist system through the left ventricle for acute myocardial infarction: report of a case.

A 49-year-old man, who had suffered from acute myocardial infarction due to left main trunk occlusion, developed cardiogenic shock and was successfully treated with an implantation of a left ventricular assist system with left ventricular apical drainage. At present he is awaiting a heart transplant at approximately 485 days since the operation. The timely application of a left ventricular assist system before the development of multiple organ failure is thus considered to be effective for patients demonstrating acute myocardial infarction with cardiogenic shock.

Heart Ventricles↗
PubMed2006

ONO-5046 attenuation of delayed motor neuron death and effect on the induction of brain-derived neurotrophic factor, phosphorylated extracellular signal-regulated kinase, and caspase3 after spinal cord ischemia in rabbits.

OBJECTIVE: The mechanism of spinal cord injury is believed to be related to the vulnerability of spinal motor neuron cells to ischemia. The aim of this study was to investigate whether ONO-5046, a specific inhibitor of neutrophil elastase that can attenuate tissue or organ injury in various pathologic conditions, could protect against ischemic spinal cord damage. METHODS: After induction of spinal ischemia, ONO-5046 or vehicle was injected intravenously. Cell damage was analyzed by counting the number of motor neurons. To investigate the mechanism by which ONO-5046 prevents ischemic spinal cord damage, we observed the immunoreactivity of CPP32 (caspase3), brain-derived neurotrophic factor, and phosphorylated extracellular signal-regulated kinase. RESULTS: ONO-5046 eased the functional deficits and increased the number of motor neurons after ischemia. The induction of caspase3 was significantly reduced by ONO-5046 treatment. Furthermore, the expressions of brain-derived neurotrophic factor and phosphorylated extracellular signal-regulated kinase were prolonged. CONCLUSION: ONO-5046 may protect motor neurons from ischemic injury by reducing caspase3 and prolonging the expressions of brain-derived neurotrophic factor and phosphorylated extracellular signal-regulated kinase. ONO-5046 may be a strong candidate for use as a therapeutic agent in the treatment of ischemic spinal cord injury.

Animals↗
PubMed2006

Grafted skeletal myoblast sheets attenuate myocardial remodeling in pacing-induced canine heart failure model.

OBJECTIVE: To overcome problems related to the intramyocardial injection of cells, including cell loss and a limited graft area, we developed a cell delivery system that uses tissue-engineered myoblast grafts grown as sheets. Here, we assessed the feasibility and efficacy of our method in a canine dilated cardiomyopathy model. METHODS: Skeletal myoblasts were incubated on temperature-responsive culture dishes, and the sheets of cells were detached by decreasing the temperature. Twelve dogs were given continuous ventricular pacing at 230 beats/min for 4 weeks; then the myoblast sheets (n = 5) were grafted onto the left ventricular wall or a sham operation was performed (n = 7). The number of cells was adjusted to 1.5 approximately 2.5 x 10(6) cells per graft, and each dog received approximately 20 grafts. RESULTS: The cell sheets were easily grafted onto a large area of the left ventricular surface, and there were no serious sequelae. Four weeks after graft implantation, echocardiography demonstrated that the left ventricular ejection fraction (graft, 26.0% +/- 5.6%; control, 19.5% +/- 6.8%; P < .05) and fractional shortening (graft, 17.9% +/- 3.6%; control, 7.8% +/- 2.1%; P < .05) were significantly ameliorated with reduced left ventricular dilatation (graft, 7.3 +/- 1.3 cm2; control, 10.2 +/- 0.4 cm2; P < .05) and increased wall thickness (graft, 5.6 +/- 0.7 mm; control, 4.4 +/- 0.6 mm; P < .05). Histologic evidence indicated the grafted myoblasts had survived, accompanied by a significant reduction in fibrosis and apoptosis, and a significant increase in proliferation. CONCLUSIONS: Grafting of skeletal myoblast sheets attenuated cardiac remodeling and improved cardiac performance. This novel method was feasible and effective in a large animal model, suggesting an innovative and promising strategy for treating patients with end-stage dilated cardiomyopathy.

Animals↗
PubMed2006

Long-term outcomes after a variety of video-assisted thoracoscopic lobectomy approaches for clinical stage IA lung cancer: a multi-institutional study.

BACKGROUND: Although video-assisted thoracic surgery (VATS) has been in use for more than a decade, its application to major lung resection for lung cancer is still not widely practiced. The success of a cancer operation is judged by the long-term survival of the treated patients. Therefore, the goal of the present study was to evaluate long-term outcomes associated with various video-assisted lobectomy techniques and conventional surgery in patients with peripheral non-small cell lung cancer less than or equal to 2 cm in diameter (stage IA). METHODS: A multi-institutional, retrospective review was performed in 145 consecutive patients. Patients with clinical stage IA disease, with tumor size less than or equal to 2 cm in diameter, from three institutions underwent a complete VATS (c-VATS, n = 56), an assisted VATS (a-VATS, n = 34), or a conventional open (open, n = 55) approach for pulmonary lobectomy and lymph node dissection. RESULTS: Patients undergoing lobectomy and lymph node dissection with c-VATS had less blood loss, faster recovery, shorter hospitalization, and longer operating times than did patients undergoing the lobectomy with the a-VATS and open approaches. At a mean follow-up of 38.8 months, Kaplan-Meier probabilities of survival at 5 years were as follows: c-VATS, 96.7%; a-VATS, 95.2%; open, 97.2%. There was no significant difference in the rate of recurrence among the 3 different procedures. CONCLUSION: VATS lobectomy, a safe procedure with earlier return to normal activities, can be regarded as an acceptable cancer operation for the patients with peripheral non-small cell lung cancer less than or equal to 2 cm in diameter (clinical stage IA) with the same long-term survivals as open surgery.

Aged↗
PubMed2006

A study of the xenoantigenicity of neonatal porcine islet-like cell clusters (NPCC) and the efficiency of adenovirus-mediated DAF (CD55) expression.

BACKGROUND: The pig pancreas is considered to be the most suitable source of islets for xenotransplantation in patients with type I diabetes. The objective of this study was to assess the antigenicity of neonatal porcine islet-like cell clusters (NPCC), including the Galalpha1-3Galbeta1-4GlcNAc-R (alpha-Gal) and Hanganutziu-Deicher (H-D) antigens, and the pathway involved in human complement activation. The efficiency of expression of human decay-accelerating factor (DAF: CD55) on NPCC by adenoviral transduction was also examined, and the functional capacity of DAF was also estimated. METHODS: The deposition of human natural antibodies, immunoglobulin (Ig)G and IgM, and the expression of alpha-Gal and H-D antigens on NPCC were investigated by FACS analysis. The downregulation in the antigenicity to human natural antibodies, including the alpha-Gal and H-D antigens on NPCC by treatment with tunicamycin, PDMP and neuraminidase were also examined. In addition, complement-mediated islet lysis was examined using factor D-deficient and C1-deficient sera. An adenovirus encoding DAF under the control of the cytomegalovirus promoter, Ad.pCMV-DAF, was then constructed, and used for transducing NPCC. The amelioration of complement-dependent cytotoxicity of the NPCC by the transduced DAF was assessed as an in vitro hyperacute rejection model of a pig to human xenograft. RESULTS: The NPCC clearly expressed the alpha-Gal epitope, and the human natural antibodies, IgG and IgM, and the anti-H-D antibody also reacted with the NPCC. Treatment of NPCC with tunicamycin led to a drastic reduction in the extent of deposition of IgG, indicating the importance of N-linked sugars on the islets, presumably related to alpha-Gal expression on N-linked sugars. Neuraminidase treatment indicated the presence of, not only the H-D antigen, but also other sialic acid antigens which reacted with the human natural antibody, especially IgG. The complement deposition of factor B on NPCC was clear, and the alternative pathway-mediated NPCC killing accounted for approximately 30% of that by the total complement pathway. On the other hand, approximately 90% of the NPCC could be transduced to express DAF by the adenovector, Ad.pCMV-DAF. The expressed DAF showed an approximately 50-62% suppression in complement-dependent NPCC lysis. CONCLUSION: The origin of the antigenicity of NPCC is mainly N-linked sugars including alpha-Gal and sialic acid antigens, and NPCC expressed the transduced molecule in high efficiency by the adenovector.

Adenoviridae↗
PubMed2006

Graft replacement and muscle wrap for infected aneurysm of thoracic aorta.

A 68-year-old man was admitted with high fever and enlargement of the distal aortic arch on chest radiography. Computed tomography showed a huge proximal descending thoracic aortic aneurysm. Graft replacement of the proximal descending thoracic aorta was performed on an emergency basis, and a pectoralis major muscle flap was wrapped around the graft. Salmonella enteritidis was detected in the resected tissue. The patient recovered well, with no signs of infection.

Aged↗
PubMed2006

[Surgical strategy for severe heart failure].

Heart transplantation had been an only effective treatment for severe congestive heart failure secondary to dilated or ischemic cardiomyopathy. Recently, mitral valve repair and left ventricular reconstruction have been introduced to restore their own cardiac function. These operations can be one of treatment options for relatively stable congestive heart failure patients. For those with severer heart failure complicated with cardiogenic shock or end-organ dysfunction, use of mechanical assist device should be included in the treatment strategies. Perioperative problems of implantation of left ventricular assist device include right heart failure, multi-organ failure, infection and anti-coagulation. Implantable LVAS, which provides potent circulatory assist is useful to overcome organ dysfunction and render good QOL during long waiting period for heart transplantation.

Cardiac Surgical Procedures↗
PubMed2006

Paraplegia and paraparesis after descending thoracic aortic aneurysm repair: a risk factor analysis.

BACKGROUND: The risk factors of paraplegia and paraparesis (P/P) after surgical repair of descending thoracic aortic aneurysm (TAA) are controversial. PATIENTS AND METHODS: Seventy five patients underwent surgical repair of descending TAA from 2001 through 2002. The mean age was 64.2+/-5.2 years old (range; 26-81) and 58 patients (77.3%) are male. There were 47 patients (62.7%) with nondissecting aortic aneurysm and 28 patients (37.3%) with chronic dissecting aortic aneurysm. Emergent operation was performed in 13 cases (17.3%). Retrospective analysis based on data of these 75 patients was performed to determine the risk factors of P/P. RESULTS: 30-days hospital mortality was 2.7%. The overall incidence of P/P was 12.0% (9/75) overall (immediate paraplegia; 4 (5.3%), delayed paraplegia; 1 (1.3%), immediate paraparesis; 3 (4.0%), delayed paraparesis; 1 (1.3%)). Logistic regression analysis revealed that predictive factors of the development of P/P were; cases in which the distal part (below Th9) of the descending thoracic aorta was included in the extent of graft replacement (P=0.020; odds ratio (OR), 7.981) and nondissecting aneurysm (P=0.029; OR, 12.109). CONCLUSION: There was an increased risk of P/P after descending TAA repair in cases in which the extent of graft replacement included below the Th9 or in cases with nondissecting aortic aneurysm.

Adult↗
PubMed2006

[Clinical and functional aspects of the World Health Organization histologic classification of thymic epithelial tumors].

The World Health Organization (WHO) histologic classification was presented by the international committee to provide a universal system for clinicians and researchers in 1999 and was further modified in 2004. This classification is mainly based on Müller-Hermelink et al.'s system and six distinct types were defined. Thymomas were classified into type A, AB, B1, B2, and B3 tumors, according to the shape and atypia of epithelial cells and also the abundance of lymphocytes. Another type of tumor is thymic carcinomas, which have apparent atypia of neoplastic cells. Neuroendocrine tumor (carcinoid) of the thymus was categorized as thymic carcinoma because of the resemblance of genetic aberrations. Several studies have shown that the WHO histologic type is correlated with the proportion of invasive tumors and is an independent prognostic factor along with Masaoka stage. Furthermore, association with myasthenia gravis, ability to induce CD4+CD8+T cells and express HLA-DR molecules, and chromosomal imbalances such as loss of heterogeneity were found to be correlated with the WHO histologic type. Thus, the WHO histologic classification system reflects the oncologic, immunologic, and genetic characteristics of thymic epithelial tumors. The clinical application of this classification system is expected.

Carcinoma↗
PubMed2005

Tissue cardiomyoplasty using bioengineered contractile cardiomyocyte sheets to repair damaged myocardium: their integration with recipient myocardium.

BACKGROUND: We hypothesized that tissue-engineered contractile cardiomyocyte sheets without a scaffold would show histological and electrical integration with impaired myocardium, leading to the regeneration of infarcted myocardium. METHODS: Neonatal rat cardiomyocytes were cultured on Poly(N-isopropylacrylamide)-grafted polystyrene dishes and detached as a square cell sheet at 20 degrees C. Two sheets were stacked to make thicker contractile cardiac sheets. In cross-section, the stacked sheets looked like homogeneous heart-like tissue. Two weeks after rats were subjected to left anterior descending (LAD) ligation, two treatments were conducted: 1) cardiomyocyte sheet implantation (T group, n=10), and 2) fibroblast sheet implantation (F group, n=10). The control group underwent no additional treatment (C group, n=10). RESULTS: Echocardiography demonstrated that cardiac performance was significantly ameliorated in the T group 2, 4, and 8 weeks after implantation. The cardiomyocyte sheets became attached to the infarcted myocardium, showed angiogenesis, expressed connexin-43, and appeared as homogeneous tissue in the myocardium Electrophysiological experiments showed a QRS complex with one peak in the treated scar area in the T group, but two peaks, indicative of branch block, in that of the other groups. Furthermore, the threshold for pacing of the recipient heart was lower in the T group than in the other groups. CONCLUSIONS: Cardiomyocyte sheets integrated with the impaired myocardium and improved cardiac performance in a model of ischemic myocardium. Techniques using such tissue-engineered cell sheets are introducing the promising concept of tissue cardiomyoplasty to the field of regenerative medicine.

Animals↗