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R Shirakura

Publications and source records attributed to R Shirakura.

At least 109 records · Page 6Linked to original sources
PubMed1994

Effects of transfected complement regulatory proteins, MCP, DAF, and MCP/DAE hybrid, on complement-mediated swine endothelial cell lysis.

We established several swine endothelial cell (SEC) lines, expressing human MCP (CD46), DAF (CD55), and MCP/DAF hybrid by transfection of cDNA, and assessed the function of these transfectant molecules on complement-mediated cell lysis as an in vitro hyperacute rejection model of swine to human discordant xenograft. Discordant organ xenografts are hyperacutely rejected by complement activation. Amelioration of complement-mediated lysis by these transfectant molecules was tested in each SEC line by lactate dehydrogenase assay. Naive swine endothelial cells were markedly damaged by human complement mainly via the classical pathway, activating only minimally the alternative pathway of human complement. Both MCP and DAF protected SEC from human complement attack in parallel with the expression density, with DAF being more effective than MCP. The MCP/DAF hybrid was more effective than MCP alone, and as effective as DAF in this system. The results suggest that the transfection of DAF or the MCP/DAF hybrid cDNA into organs to be transplanted could protect against hyperacute rejection.

Animals↗
PubMed1994

Analysis of rejection mechanism in the rat to mouse cardiac xenotransplantation. Role and characteristics of anti-endothelial cell antibodies.

Recent reports have demonstrated that humoral factors, especially antibodies elicited by xenoantigens, play an important role in the rejection of concordant cardiac xenografts. These induced antibodies, however, have not been well characterized. Therefore, we investigated the rejection mechanism, especially the role of humoral immunological responses in the concordant rat to mouse cardiac xenograft model. Lewis rat hearts transplanted into C3H/HeN mice were rejected in 5-6 days. The essential role of humoral factors in the rejection was demonstrated by histological analysis of the rejected hearts showing interstitial hemorrhage, scant cellular infiltration, and the dense deposition of mouse IgG, IgM, and C3 on the graft endothelial cells. In addition, mice that received hyperimmune serum (serum at the 10th day after transplantation) rejected rat hearts hyperacutely. Flow cytometrical analysis using cultured donor rat coronary endothelial cells demonstrated the xenoreactive antibodies of all subclasses, but especially strong reactivity of IgM and IgG2a in the serum at rejection. These xenoreactive antibodies were produced against not only MHC, but also non-MHC antigens on graft endothelial cells. In vivo depletion of L3T4+ T cells led to the suppression of xenoreactive antibody production and the prolongation of graft survival, indicating that antibody production in this model needs L3T4+ T cell help.

Animals↗
PubMed1994

The rejection mechanism of rat pancreaticoduodenal allografts with a class I MHC disparity.

The present study has demonstrated for the first time that PVG.R1 (RT1.AaBcDcCc) pancreatic grafts are rejected by so-called "low"-responder PVG (RT1.AcBcDcCc) recipients with an isolated class I MHC disparity (mean survival time; MST: 21.4 +/- 1.8 days, n = 5), whereas PVG.R1 heart grafts are able to survive indefinitely (MST: > 100 days, n = 5). Splenic CD4+ T cells but not CD8+ T cells from the PVG recipients of PVG.R1 pancreatic grafts show a remarkable proliferative response against donor class I RT1.Aa alloantigens, while only a minimal proliferation is observed in the PVG recipients of PVG.R1 heart grafts or naive PVG rats. Naive PVG rats display an extremely low frequency of IL-2-producing helper T cell precursors (fThp) of 1/40,609 +/- 15,441 against class I RT1.Aa alloantigen. The PVG recipients of PVG.R1 heart grafts have a slightly greater fThp of 1/17,326 +/- 6822. On the other hand, the PVG recipients that rejected PVG.R1 pancreatic grafts show a significantly increased fThp of 1/5030 +/- 3396 compared with those of PVG.R1 heart grafts (P < 0.05) or naive PVG rats (P < 0.01). The frequency of cytotoxic T cell precursors (fTcp) increases slightly in the PVG recipients of PVG.R1 pancreatic grafts (1/1848 +/- 330) compared with those of PVG.R1 heart grafts (1/2215 +/- 2131) or naive PVG rats (1/2476 +/- 585). The size of cytotoxic T cell clones alone does not adequately account for a proliferation sufficient to complete the rejection of pancreatic grafts. The PVG recipients of PVG.R1 pancreatic grafts, but not heart grafts, demonstrate a strong cytotoxic alloantibody response to donor class I RT1.Aa alloantigens. In the study of alloantibodies, IgM is detected mainly in the early phase and IgG in the late phase during the course of pancreatic rejection. It is determined that in blocking studies by FACS analysis these antibodies target class I MHC antigens. These results suggest that cytotoxic T cells do not appear to be responsible for the rejection of PVG.R1 pancreatic grafts in PVG recipients. Rather, the rejection is mediated by CD4+ T cells and complement-fixing antibodies directed at class I MHC antigens.

Animals↗
PubMed1994

Changes in left ventricular performance after global ischemia: assessing LV pressure-volume relationship.

To determine the effect of ischemia and reperfusion on left ventricular systolic function, we studied the ischemia-induced rightward shift of the ventricular pressure-volume relationship. Eight mongrel dogs were intubated, and their hearts were exposed through a thoracotomy. A conductance catheter and micromanometer were used to obtain instantaneous left ventricular pressure-volume data. The dogs were subjected to 20 minutes of normothermic global myocardial ischemia, followed by 80 minutes of reperfusion under total cardiopulmonary bypass. Data were acquired during transient (10- to 12-second) periods of acute volume loading before ischemia and at 20-minute intervals during reperfusion as bypass was continued. The relationship between stroke work and end-diastolic volume (ie, preload recruitable stroke work [PRSW]) and the end-systolic pressure-volume relationship were highly linear throughout the study (mean r = 0.954 to 0.983 for PRSW; mean r = 0.954 to 0.984 for end-systolic pressure-volume relationship). Ischemia produced changes in the PRSW: (1) the slope decreased significantly at 20 minutes and 40 minutes of reperfusion then returned to preischemic levels at 60 minutes and 80 minutes, and (2) the x-intercept increased significantly up to 60 minutes. The preload recruitable work area (the area under the linear regression line of PRSW) reflected changes in both slope and x-intercept of PRSW and was significantly decreased throughout the 80 minutes of reperfusion despite gradual recovery. The slope and the x-intercept of the end-systolic pressure-volume relationship did not change after ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Study of efficacies of leukocyte-depleted terminal blood cardioplegia in 24-hour preserved hearts.

To evaluate the effect of leukocyte-depleted terminal blood cardioplegia on prolonged preservation, 41 canine hearts were stored in modified Collins' solution and transplanted heterotopically. Hearts were transplanted soon after harvesting in group 1 and after 24-hour preservation in groups 2, 3, and 4. Blood cardioplegia was applied just before aortic unclamping in groups 3 and 4; group 3 received simple blood cardioplegia and group 4 received leukocyte-depleted cardioplegia. The percentage of the preload recruitable stroke work and diastolic compliance after transplantation compared with the preharvesting value in group 4 did not differ from those in group 1, but the percentage of the preload recruitable stroke work in groups 2 and 3 was significantly lower than that in groups 1 and 4. The percentage of diastolic compliance in groups 2 and 3 was significantly higher than that in groups 1 and 4. Coronary blood flow 40 minutes after aortic unclamping in group 4 did not differ from that in group 1, but was significantly higher than the blood flows in groups 2 and 3. Significant production of malondialdehyde was detected during terminal blood cardioplegia and 10 minutes after aortic unclamping in groups 2 and 3, but never in groups 1 and 4. After leukocyte-depleted terminal cardioplegia, the myocardial adenosine triphosphate content increased to the preharvesting value in group 4. Our results suggest that leukocyte-depleted terminal blood cardioplegia may be effective in replenishing the energy-depleted myocardium and reducing reperfusion injury, resulting in adequate cardiac function.

Adenosine Triphosphate↗
PubMed1994

Role of CD4+ T cells in the rat to mouse cardiac xenotransplantation.

T cell subsets involved in rejection of xenografts were analyzed using a rat to mouse cardiac xenotransplant model. Proliferating response and interleulin-2 (IL-2) production in recipients' spleen cells were almost completely abrogated by elimination of L3T4+ T cells, but not by elimination of Lyt2.1+ T cells. Cytotoxic T lymphocyte (CTL) activities were mediated by both L3T4+ and Lyt2.1+ T cells with the help of IL-2-producing L3T4+ T cells. Administration of anti-L3T4 monoclonal antibody (mAb) into recipient mice resulted in a significant prolongation of graft survival (mean graft survival was 29.2 days). Moreover, anti-L3T4 mAb treatment plus thymectomy led to indefinite graft survival. Anti-rat endothelial cell (EC) antibody production in the grafted mice was remarkably suppressed by anti-L3T4 mAb treatment. In contrast, Lyt2.1 mAb treatment did not prolong the graft survival and did not suppress anti-EC antibody production. These results indicated the absolute requirement of L3T4+ T cells in the rejection of rat to mouse cardiac xenografts.

Animals↗
PubMed1994

Neointima formation after vascular stent implantation. Spatial and chronological distribution of smooth muscle cell proliferation and phenotypic modulation.

Intravascular stents have proved useful as angioplasty devices, but intimal hyperplasia after stent implantation remains an unsolved problem. In the present study, we analyzed the spatial and chronological distribution of proliferation and phenotypes of smooth muscle cells (SMCs) in rabbit aortas during the process of neointima formation after stent implantation (Gianturco's Z type) by immunohistochemistry for proliferating cell nuclear antigen (PCNA) and myosin heavy chain isoforms (SM1, SM2, and SMemb). Stent implantation induced regional injury in the arterial wall. Medial SMCs then began to proliferate adjacent to the injured SMCs, maximally on day 4 (PCNA index in the media: 3.9 +/- 3.4% [mean +/- SD]), and were modulated to the embryonic phenotype (SMemb-positive and SM2-negative). They migrated into the intima and proliferated most frequently on day 7 (PCNA index in the intima: 20.3 +/- 5.5%) and subsequently led to fibrocellular neointima formation at 2 weeks and later. At 1 month after implantation and later, SMC proliferation was rare, and the phenotype of intimal SMCs was gradually returning to the adult type (SMemb-negative and SM2-positive). Thus, this stent implantation model demonstrates that the regional effect on arterial wall by stenting leads to neointima formation through transient and regional proliferation and migration of SMCs and their phenotypic modulations.

Animals↗
PubMed1994

[Nearly total aortic replacement for DeBakey type-I aortic dissection in a patient with Marfan's syndrome].

A successful nearly total aortic replacement for DeBakey type-I aortic dissection in a patient with Marfan's syndrome is reported. A 36-year-old woman developed a DeBakey type-I aortic dissection in October 1987. We replaced the ascending aorta and resuspended the aortic valve urgently, when she had not been diagnosed with Marfan's syndrome. In August 1989, we replaced the distal portion of the descending aorta and the infra-renal abdominal aorta because of dilatation in the diameter of these regions. In September 1990, she had sudden severe chest pain. Computed tomography and Doppler ultrasonography revealed that a new aortic dissection developed in the aortic arch and the descending aorta (three-channeled dissection) and that the new false lumen compressed the true and the old false lumens obstructing the blood flow to the abdominal aorta. She was immediately placed an axilo-femoral bypass, and in January 1991 she underwent the arch and descending aorta replacement using permanent bypass to the supra-aortic branches and partial extracorporeal circulation (first reported by Larmi et al). Postoperative course was satisfactory, and she has been well at 3 years after the operation. Because progressive dilatation of an untreated dissecting aorta is common in patients with Marfan's syndrome, aggressive replacement of the diseased aorta is indicated in these patients.

Adult↗
PubMed1994

[Aortic valve replacement in a kidney transplant recipient].

A 62-year-old man with chronic renal failure, who had been treated with hemodialysis, received a kidney transplant from his son in December 1989. He kept good renal function without any episode of graft rejection under the immunosuppressive therapy with Cyclosporine A (CyA), Predonine (PRD), and Mizoribine. In 1990 he started to have exertional dyspnea, and was diagnosed to have aortic valve regurgitation. He underwent aortic valve replacement in September, 1991. He was treated with continuous infusion of CyA and bolus injection of methylprednisolone from the start of the operation, and returned under the preoperative immunosuppressive therapy after oral intake became possible. On the third post-operative day, the level of serum creatinine elevated. Although we couldn't detect significant changes in subpopulations of peripheral blood lymphocytes, steroid pulse therapy was performed as the possibility of acute rejection was underiable. Serum creatinine returned to normal level in a few days and the postoperative course after that was uneventful. He was discharged on the 30th post-operative day.

Aortic Valve↗