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M Yoshitatsu

Publications and source records attributed to M Yoshitatsu.

17 recordsLinked to original sources

Changes in coagulation condition, cytokine, adhesion molecule after repair of type A aortic dissection.

OBJECTIVE: Because residual dissection often exists even after the repair of a type A dissection, we evaluated coagulation conditions, cytokine levels, and adhesion molecule levels in mid-term follow up after repair of type A dissections. METHODS: Thrombin-antithrombin III complex (TAT), D-dimer, soluble interleukin-2 receptor (sIL-2R), soluble intercellular adhesion molecule (sICAM)-1, and type III procollagen peptide (PIIIP) were measured in 12 patients (mean age=63 years) following the repair of a type A aortic dissection at 6-82 months after repair (median=33 months). RESULTS: In the chronic phase, TAT and D-dimer were significantly higher in patients following the repair of a type A dissection compared to healthy controls (TAT; 12+/-8 vs. 2.5+/-1.2 ng/ml, P = 0.0001, D-dimer; 779+/-1384 vs. 104+/-46 U/ml, P = 0.0001). Cytokine was significantly higher in the affected patients (sIL-2R; 556+/-205 vs. 398+/-132 U/ml, P = 0.003, sICAM-1; 255+/-131 vs. 211+/-48 ng/ml, P = 0.136). Collagen turnover (PIIIP) showed a significantly higher value in the affected patients (0.80+/-0.32, vs. 0.58+/-0.13 U/ml, P = 0.002). sIL-2R, sICAM-1 and PIIIP showed a negative correlation with the follow-up period (sIL-2R; r = -0.733, P = 0.0067, sICAM-1; r = -0.61, P = 0.035, PIIIP; r = -0.692, P = 0.0126). We found a positive correlation between aortic size and TAT (r = 0.644, P = 0.0238, n = 12) as well as with D-dimer (r = -0.7831, P = 0.0106, n = 12) and TAT showed significantly higher values in the residual dissection group compared to those without residual dissection (16.6+/-7.9 vs. 7.45+/-4.75 ng/ml, P = 0.035). CONCLUSION: Hypercoagulation conditions continued even after repair. Both TAT and D-dimer would be good indices for following up patients having repaired aortic dissections. Furthermore, cytokine, adhesion molecules, and collagen turnover would return to a stable state unless impairment and expansion of the vessel wall occurred.

Adult↗

A surface-bound form of human C1 esterase inhibitor improves xenograft rejection.

BACKGROUND: The purpose of the present study was to investigate the effect of the C1 esterase inhibitor (C1-INH) molecule against human complement attack on a swine endothelial cell (SEC) membrane. Human C1-INH functions as an inhibitor for complement reaction in the first step of the classical pathway in the fluid phase. METHODS: A surface-bound form of human C1-INH (C1-INH-PI) consisting of a full-length coding sequence of C1-INH and a glycosylphosphatidylinositol (GPI) anchor of the decay-accelerating factor (CD55) was constructed, and stable Chinese hamster ovarian tumor (CHO) cell lines and SEC lines expressing C1-INH-PI were then prepared by transfection of the constructed cDNA. The basic function of the transfected molecules on the xenosurface was investigated using CHO transfectants for the sake of convenience. The efficacy of C1-INH-mediated protection of SEC from human complement was then assessed as an in vitro hyperacute rejection model of a swine-to-human discordant xenograft. RESULTS: Flowcytometric profiles of the stable CHO and SEC transfectants with C1-INH-PI showed a medium level of expression of these molecules. The C1-INH levels were significantly reduced as a result of phosphatidylinositol-specific phospholipase C (PI-PLC) treatment, suggesting that the molecules were present as the PI-anchor form. Approximately 51.3 x 10(4) and 13.3 x 10(4) molecules of C1-INH-PI blocked human complement-mediated cell lysis by approximately 75% on the CHO cell and by 60-65% on the SEC cell, respectively. In addition, the complement-inhibiting activity of human C1-INH molecules is not homologously restricted. CONCLUSIONS: The results suggest that the surface-bound form of C1-INH represents a good candidate as a safeguard against hyperacute rejection of xenografts.

Animals↗

Importance of preoperative marking for minithoracotomy and for internal thoracic artery harvesting in minimally invasive direct coronary artery bypass grafting.

Minimally invasive direct coronary artery bypass has the potential to cause an anastomotic failure because of a limited exposure of the operative field and the difficulty of internal thoracic artery harvesting. In the present study, the importance of preoperative marking for an accurate minithoracotomy location and a successful internal thoracic artery harvest was assessed. A paperclip was placed on the left nipple and a chest X-ray was performed in the supine position. By aligning the position of the paperclip to the location of the left anterior descending coronary artery from a coronary arteriogram frontal view, the intercostal space for the minithoracotomy was thus determined. Marking the incisional intercostal space during preoperative left internal thoracic arteriography revealed the number and location of the internal thoracic artery branches at the beginning of the harvest. This preoperative marking technique allowed for a more adequate exposure of the operative field and an easier internal thoracic artery harvest which therefore contributed to an improvement in the operative results.

Aged↗

Porcine MCP gene promoter directs high level expression of human DAF (CD55) in transgenic mice.

Porcine membrane cofactor protein (pMCP), a complement regulatory protein, is widely expressed in various tissues. Particularly, it is highly expressed on vascular endothelium. The objective of this study was to investigate whether the pMCP gene promoter can induce efficient expression of a human complement regulatory protein, decay-accelerating factor (DAF; CD55) in transgenic mice. Two fragments of the 5'-flanking region of pMCP gene (0.9 kb and 5.4 kb) connected with human DAF minigene (0.9/hDAF and 5.4/hDAF) were used to produce transgenic mice. The expression of hDAF in heart, liver, kidney, lung, pancreas, brain and testis of the transgenic mice was examined by immunohistochemical analysis. The vascular endothelia and the nerves in all organs examined were intensely stained. The staining pattern in these tissues was similar in all transgenic mice examined regardless of the length of the promoters. The surface expression levels of hDAF on peripheral red blood cells and splenocytes from a mouse carrying 5.4/hDAF hemizygously was twice the level of expression on corresponding human cells. The red blood cells and splenocytes from the transgenic mice exhibited resistance to lysis by human serum in a manner dependent upon expressed hDAF level. The hearts from the transgenic mice functioned for a significantly longer time than those from normal mice under perfusion with human serum in the Langendorff perfusion system. These results demonstrated that the pMCP gene promoter is a good candidate of the regulatory element in the transgene to produce transgenic animals for xenotransplantation.

Animals↗

Function of human factor H and I on xenosurface.

The cell membrane-bound forms of mini-factor H with 1-4 short consensus repeats (fH-PI) and factor I (fI-PI) were constructed. Swine endothelial cell (SEC) lines and Chinese hamster ovary (CHO) cell expressing fH-PI or fI-PI were established and confirmed by flow cytometry. The cell lysate of the SEC line expressing fH-PI showed strong cofactor activity for the cleavage of C3b, and fI-PI demonstrated the protease activity for C4b and C3b not only in the fluid phase but also on the cell membrane. In addition, fH-PI blocked human complement-mediated cell lysis by approximately 30-40%. An SEC line with a low expression of fI-PI showed a weak inhibition of cell lysis in human serum, whereas a CHO cell transfectant with a high expression of fI-PI showed over a 60% inhibition of cell lysis. The results suggest that fH-PI and fI-PI have potential for use in clinical xenotransplantation.

Animals↗

Prevention of hyperacute rejection by phosphatidylinositol-anchored mini-complement receptor type 1.

Complement receptor type 1 (CR1, CD35) contains both factor I cofactor activity and convertase decay accelerating activity, but is, in general, thought to be an extrinsic regulator of complement activation. In this study, we prepared a phosphatidylinositol (PI)-anchored mini-CR1, which is composed of the short consensus repeat (SCR) 8-11 of CR1 and the PI anchor of DAF, and expressed it stably on a swine endothelial cell (SEC) line. We then examined the intrinsic regulatory activity of the mini-CR1, with respect to complement-mediated cell lysis as an in vitro hyperacute rejection model of a swine to human discordant xenograft. Flowcytometric profiles of the stable SEC lines with mini-CR1 showed a moderate level of expression for this molecule. Mini-CR1 blocked human complement-mediated cell lysis by approximately 50-70% on SEC. From the data of this study and our previous studies, mini-CR1 was more effective than membrane cofactor protein (MCP, CD46), and as effective as decay accelerating factor (DAF, CD55) in this system. The results suggest that PI-anchored mini-CR1 represents a useful molecule for clinical xenotransplantation.

Animals↗

Successful experimental multiorgan transplant from non-heart-beating donors using percutaneous cardiopulmonary support.

Organ procurement from non-heart-beating donors (NHBDs) may expand donor pools. In this study, the method of reanimation of heart, lung, and kidney in NHBDs by percutaneous cardiopulmonary support (PCPS) was evaluated. Thirteen beagles were asphyxiated after being given prostacyclin analogue, verapamil, propranolol, and nafmostat mesilate intravenously. Thirty minutes after cardiac arrest, the body was reperfused by PCPS for 1 hr. PCPS priming fluid contained the four drugs above and KCl. Eight hearts immersed in University of Wisconsin (Madison, WI) solution for 24 hr were transplanted orthotopically using leukocyte depleted blood cardioplegia, five left lungs immersed in modified Collins solution were transplanted orthotopically, and five kidneys immersed in University of Wisconsin solution were transplanted heterotopically. All donor hearts arrested without ventricular fibrillation. All transplanted hearts beat spontaneously, and all animals were weaned from cardiopulmonary bypass without inotropic support. The oxygen and carbon dioxide pressure of pulmonary vein blood in the donor lung were no different from those in the recipient lung. All transplanted kidneys made urine soon after reperfusion. These data suggested that hearts, lungs, and kidneys from NHBDs pretreated with four drugs and reanimated with PCPS can be transplanted successfully and that this method may expand the donor pool.

Adenosine↗