Biomedical subjects

Yukihiro Tomita

Publications and source records attributed to Yukihiro Tomita.

At least 19 recordsLinked to original sources

PubMed2007

Efficacy and limitations of natural killer cell depletion in cyclophosphamide-induced tolerance.

PURPOSE: We previously developed a cyclophosphamide (CP)-induced tolerance protocol, consisting of an intravenous injection of 1 x 10(8) donor spleen cells (SC) given on day 0 and an intraperitoneal injection of 200 mg/kg CP given on day 2. In the present study, we modified this protocol with natural killer cell (NK) depletion in recipient mice, and evaluated the efficacy of tolerance induction. METHODS: We used B10.D2 (H-2d; IE+) and B10 (H-2b; IE-) mice as both donors and recipients. The recipient mice were treated with donor SC, CP, and donor bone marrow cells (BMCs) with or without NK depletion. RESULTS: A higher level of mixed chimerism was achieved in the NK-depleted recipients. Survival of both the skin and heart donor grafts was significantly prolonged in the NK-depleted recipients. Donor reactive Vbeta11+ T cells were found at the same level as in untreated control mice. Pretreatment with recipient NK cell depletion was effective in inducing higher levels of donor mixed chimerism; however, permanent engraftment of donor bone marrow was not achieved. CONCLUSION: Survival of donor grafts was remarkably prolonged in the NK cell-depleted group, but transplantation tolerance could not be induced. Our results suggest that NK cell depletion in CP-induced tolerance conditioning has some effect on the induction of donor-specific tolerance.

Animals↗

PubMed2006

Regulatory roles of NKT cells in the induction and maintenance of cyclophosphamide-induced tolerance.

We have previously reported the sequential mechanisms of cyclophosphamide (CP)-induced tolerance. Permanent acceptance of donor skin graft is readily induced in the MHC-matched and minor Ag-mismatched recipients after treatment with donor spleen cells and CP. In the present study, we have elucidated the roles of NKT cells in CP-induced skin allograft tolerance. BALB/c AnNCrj (H-2(d), Lyt-1.2, and Mls-1(b)) wild-type (WT) mice or Valpha14 NKT knockout (KO) (BALB/c) mice were used as recipients, and DBA/2 NCrj (H-2(d), Lyt-1.1, and Mls-1(a)) mice were used as donors. Recipient mice were primed with 1 x 10(8) donor SC i.v. on day 0, followed by 200 mg/kg CP i.p. on day 2. Donor mixed chimerism and permanent acceptance of donor skin allografts were observed in the WT recipients. However, donor skin allografts were rejected in NKT KO recipient mice. In addition, the donor reactive Vbeta6(+) T cells were observed in the thymus of a NKT KO recipient. Reconstruction of NKT cells from WT mice restored the acceptance of donor skin allografts. In addition, donor grafts were partially accepted in the thymectomized NKT KO recipient mice. Furthermore, the tolerogen-specific suppressor cell was observed in thymectomized NKT KO recipient mice, suggesting the generation of regulatory T cells in the absence of NTK cells. Our results suggest that NKT cells are essential for CP-induced tolerance and may have a role in the establishment of mixed chimerism, resulting in clonal deletion of donor-reactive T cells in the recipient thymus.

Animals↗

PubMed2006

Critical roles of memory T cells and antidonor immunoglobulin in rejection of allogeneic bone marrow cells in sensitized recipient mice.

BACKGROUND: Allosensitization is a major risk factor for graft failure in clinical bone marrow transplantation, even with an human leukocyte antigen (HLA)-matched combination under radiation-based conditioning regimens. The critical components of immunological memory in donor bone marrow graft rejection in allosensitized hosts remain unclear at present. METHODS: C57BL/6-recipient mice, which had been intraperitoneally injected with splenocytes from donor C3H mice on day -35 (sensitized recipients), had been lethally irradiated with 10-Gy whole-body irradiation and were intravenously injected with T-cell-depleted bone marrow cells (TCD-BMC) from C3H mice or third-party SJL mice. RESULTS: Lethally irradiated recipient mice, which had been sensitized by donor splenocytes 5 weeks before the transplantation of TCD-BMC, completely rejected the donor-BMC in a donor-specific manner, whereas none of the nonsensitized recipient mice, all of which showed full allogeneic chimerism, rejected the donor TCD-BMC. Antibody-mediated T cell and/or Natural Killer (NK) cell depletion did not improve the ability of the sensitized recipients to overcome the rejection even when a megadose of TCD-BMC was administered to the sensitized recipients. Furthermore, BMC rejection occurred in sensitized B cell-deficient mice. In adoptive transfer experiments, naive mice, which received a transfer of purified T cells from sensitized mice, rejected the donor BMC, but not those from nonsensitized mice. Moreover, naive mice, which received a transfer of serum containing antidonor immunoglobulin, rejected the donor BMC. CONCLUSIONS: These findings suggest that alloreactive memory T cells and antidonor immunoglobulin independently function to reject donor BMC in sensitized recipients.

Adoptive Transfer↗

PubMed2006

The logistic EuroSCORE predicts the hospital mortality of the thoracic aortic surgery in consecutive 327 Japanese patients better than the additive EuroSCORE.

OBJECTIVE: Risk stratification in thoracic aortic surgery is a topic of major interest. Recent studies have shown the European System for Cardiac Operative Risk Evaluation (EuroSCORE) to be an extremely useful and reliable risk stratification score and also a good indicator of quality of care in cardiac surgery. The purpose of this study was to evaluate the significance of the additive and logistic EuroSCOREs in patients undergoing surgery on the thoracic aorta in Japan. METHODS: We calculated the predicted mortality according to the additive and logistic EuroSCORE algorithms in 327 consecutive patients who underwent surgery of the thoracic aorta during a 30-year period (between 1976 and 2005). We compared the score validity between the two algorithms and also evaluated the score validity for the patients who underwent thoracic aortic surgery. The score validity was assessed by calculating the area under the receiver operating characteristic (ROC) curve. RESULTS: The overall in-hospital mortality was 13%. The area under the ROC curve was satisfactorily high for the additive (0.68, 0.73, 0.73) as well as the logistic EuroSCORE (0.69, 0.74, 0.75) in the patients who underwent thoracic aortic surgery during 30-, 20-, and 10-year periods, respectively. The actual mortality was 7% (Group 1; an additive EuroSCORE of 3-6), 16% (Group 2; 7-11), and 37% (Group 3; >12). The mortality expected by the additive and logistic EuroSCORE in the three different risk groups were (5%, 9%, 19%) and (5%, 14%, 43%), respectively. Namely, the mortality expected by the logistic EuroSCORE perfectly matched with the actual mortality in any of the three risk groups. In contrast, the mortality expected by the additive EuroSCORE tended to dissociate when the number of risks increased. Significant difference was observed between the observed mortality and the mortality expected by the additive EuroSCORE algorithm in the high-risk group (p=0.0473). CONCLUSIONS: Although both the additive and the logistic EuroSCORE reliably predicted the overall operative mortality for thoracic aortic surgery in 327 Japanese patients, the logistic EuroSCORE better matched with the actual mortality in the operative risk especially in the high-risk group.

Aged↗

PubMed2006

Surgical experience of cardiac tumors: early and late results.

PURPOSE: Cardiac tumors include benign and malignant neoplasms that arise within the cardiac chambers or myocardium. This study summarizes our surgical experiences with cardiac tumors. METHODS: Between 1975 and 2003, 51 patients with cardiac tumors were surgically treated. RESULTS: Myxomas. Forty-seven cardiac myxomas were excised in 46 patients with an average age of 51.7 +/- 18 years. The preoperative symptoms included congestive heart failure (37%) and embolism (30%). The incidence of preoperative embolization was significantly higher in the gelatinous and lobated myxomas than in the solid and smooth form (P = 0.017). The early mortality rate was 2.2%. Although the late mortality rate was 9.7%, no patients died from cardiological causes (mean follow-up, 11.2 years). Only 1 patient required surgery for recurrence. Benign nonmyxomatous tumors. Three patients with a mean age of 26.3 +/- 19.0 years showed benign nonmyxomatous tumors. There were no perioperative or late deaths. Malignant tumors. Two patients were diagnosed to have malignant tumors and although there was no perioperative death, both died postoperatively within 6 months. CONCLUSIONS: Cardiac myxomas and nonmyxomatous benign cardiac tumors show excellent results after a surgical excision, with a low morbidity and mortality. A surgical resection should thus be considered as a treatment option for patients with malignant tumors.

Adult↗

PubMed2006

Successful mitral valve repair for active infective endocarditis accompanied by anorexia nervosa.

Infective endocarditis of the mitral area accompanied by anorexia nervosa is extremely rare. A 34-year-old Japanese woman presented with high fever and a heart murmur that had developed over the previous 2-month period. Echocardiography revealed mitral regurgitation and vegetation attached to the anterior mitral leaflet, which had markedly prolapsed to the left atrium. We removed the vegetation with a small part of the anterior mitral leaflet and successfully repaired the mitral valve. The patient showed good recovery, and the mitral regurgitation and left ventricular chamber size had satisfactorily decreased at 2 months after the operation.

Adult↗

PubMed2006

Sequential analysis of anti-alpha Gal natural antibody-producing B cells in GalT knockout mice in cyclophosphamide-induced tolerance.

Previously, we have shown that cyclophosphamide (CP)-induced tolerance, marked by permanent acceptance of donor skin graft and establishment of donor mixed chimerism, was readily induced with treatment with donor spleen cells (SC), CP, busulfan (BU) and donor bone marrow cells (BMC). Here, we investigated the mechanism of anti-donor natural antibody (nAb) producing B-cell tolerance in our CP-induced tolerance systems in alpha1,3-galactosyltransferase-deficient knockout mice (GalT KO; GalT-/-, H-2(b/d)). After induction of tolerance using donor AKR SC and BMC, survival of donor heart and skin grafts and production of anti-Galalpha1-3Galbeta1-4GlcNAc (anti-alphaGal) Ab in recipient GalT KO mice were analyzed. In addition, the production of anti-alphaGal Ab and the presence of Gal-BSA binding B cells in GalT KO mice were analyzed by flow cytometry (FCM) after treatments with rabbit red blood cells (RRBC) and CP. Permanent acceptance of donor skin and heart grafts and abrogation of anti-alphaGal Ab were achieved in GalT KO mice treated with donor SC + CP/BU + BMC. However, in the GalT KO mice treated with donor SC and CP, donor skin grafts were acutely rejected, even though anti-alphaGal Ab was undetectable. Similarly, anti-alphaGal Ab was undetectable in GalT KO mice treated with RRBC and CP. Our data strongly indicated the following mechanisms: the clonal destruction in the early stage and the clonal anergy or ignorance in the late stage after conventional conditioning with RRBC and CP. In conclusion, our drug-induced tolerance protocols are effective to induce tolerance in recipients that produce anti-donor nAb.

Animals↗

PubMed2006

Constrictive pericarditis with atrial septal defect.

We report on a case of constrictive pericarditis (CP) with atrial septal defect (ASD) in a 50-year-old man. The combination of CP with ASD is rare and occasionally difficult to diagnose. Transthoracic echocardiography demonstrated ASD, but the finding of a thickened pericardium was poor. Diagnosis was confirmed by cardiac catheterization. Pericardiectomy and direct closure of ASD was performed during cardioplegic arrest under the support of cardiopulmonary bypass. The postoperative course was uneventful with marked improvement in symptoms.

Cardiac Catheterization↗

PubMed2005

Requirement of a higher degree of chimerism for skin allograft tolerance in cyclophosphamide-induced tolerance.

By using a cyclophosphamide (CP)-induced tolerance system, we previously raised the possibility that the degree of chimerism might determine the induction of heart and skin allograft tolerance. When C3H (H-2k; Thy1.2, Mls-1b) mice were intravenously primed with 1 x 10(8) spleen cells (SCs) from H-2 matched AKR (H-2k; Thy1.1, Mls-1a) mice and then treated intraperitoneally with 200 mg/kg CP, the survival of AKR skin grafts was permanently prolonged in a tolerogen-specific fashion. After this treatment, a minimal degree of mixed chimerism and the clonal destruction of Mls-1a-reactive CD4+Vbeta6+ T cells in the periphery were observed. When AKR SCs and 100 mg/kg CP were used for conditioning, the survival of the AKR skin grafts was mildly prolonged. The clonal destruction of CD4+Vbeta6+ T cells in the periphery was induced and a minimal degree of mixed chimerism was detectable. The degree of mixed chimerism induced with AKR SCs and 200 mg/kg CP was significantly higher than that with AKR SCs and 100 mg/kg CP during the observation. On the other hand, neither skin allograft prolongation nor permanent mixed chimerism could be induced when C3H mice were treated with AKR SCs and 50 mg/kg CP. In order to increase the degree of mixed chimerism, we injected 1 x 10(8) tolerant AKR SCs on day 3 into the recipient C3H mice that had been treated with AKR SCs on day 0 and with 100 mg/kg CP on day 2. The reason that we used tolerant SCs was that untreated AKR SCs caused graft-versus-host disease in most of the recipients. Tolerant AKR SCs were harvested from AKR mice that had been treated with C3H SCs and 200 mg/kg CP 2 weeks earlier, and did not contain regulatory cells. By adoptive transfer, the degree of chimerism was stably and significantly increased in all recipients, and AKR skin graft tolerance was induced in half of the recipients. T-cell-depleted bone marrow cells (BMCs) from untreated AKR mice induced skin allograft tolerance in 83% of recipients. Thus, the present study strongly confirmed the hypothesis that a higher degree of chimerism is required for the induction of skin allograft tolerance in CP-induced tolerance.

Adoptive Transfer↗

PubMed2005

Absent mRNA accumulation of Th1 or Th2 cytokines in heart allografts with chimerism-based drug-induced tolerance.

PURPOSE: We recently described using cyclophosphamide (CP) plus busulfan (BU) to create drug-induced skin and heart allograft tolerance capable of regularly overcoming fully H-2 mismatched barriers in mice. The present study investigates the intragraft mRNA expressions of Th1 and Th2 cytokines. METHODS: This method consists of the intravenous (i.v.) injection of 1 x 10(8) allogeneic spleen cells on day 0, the intraperitoneal injection of 200 mg/kg CP and 30 mg/kg BU on day 2, and the i.v. injection of 1 x 10(7) T cell-depleted allogeneic bone marrow cells from the same strain of mice on day 3. Heart grafting (HG) was performed on day 28. Chimerism in the peripheral blood was monitored by flow cytometric (FCM) analysis. The frequency of certain V(beta) families was determined by FCM to assess deletion of donor-reactive T cells. Th1 (interleukin [IL]-2, interferon [IFN]-gamma) and Th2 (IL-4, IL-10) cytokine expression in the heart grafts was analyzed with reverse transcription-polymerase chain reaction. RESULTS: In a fully MHC mismatched combination of B10.D2 (H-2d, IE+) --> B10 (H-2b, IE-), B10.D2 heart grafts were accepted permanently in a donor-specific manner, mixed chimerism was observed, and IE-reactive V(beta)11+ T cells were specifically reduced in the periphery from the recipient B10 mice. In the donor B10.D2 heart grafts, there was no accumulation of Th1 (IL-2, IFN-gamma) or Th2 (IL-4, IL-10) cytokines. CONCLUSIONS: These results show that the drug-induced tolerance we established can regularly induce long-lasting heart allograft tolerance without intragraft mRNA accumulation of Th1 or Th2.

Animals↗

PubMed2005

Surgical application for a prolapse of the anterior mitral leaflet by replacing artificial chordae with polytetrafluoroethylene grafts.

PURPOSE: There are an increasing number of reports concerning mitral valve repair by a reconstruction of the chordae tendinae using expanded polytetrafluoro-ethylene (PTFE) sutures. However, little information is available about extended application or results of this technique for an extended prolapse of the anterior mitral leaflets. METHODS: Between July 1991 and August 2003, 28 patients with moderate to severe mitral regurgitation as a result of a prolapse of anterior leaflets (age range, 15-73 years) underwent mitral valve repair by reconstruction of the artificial chordae with 4-CV expanded polytetrafluoroethylene sutures without a leaflet resection. Either Kay's suture technique or ring annuloplasty was also performed to correct annular dilatation in all patients. RESULTS: No operative death or late mortality was observed. The prolapsed segment, which was successfully repaired, was within 33% of the anterior mitral leaflet (AML) in 6 patients, from 33% to 50% in 5, from 50% to 99% in 11, and 100% in 6 patients. Before discharge, immediate postoperative echocardiography showed less than moderate mitral regurgitation in 28 of 28 patients. The follow-up, consisting of a clinical examination and serial echocardiograms, was complete in all cases and the mean follow-up period was 80.6 months (range, 12-146). There were two failures that required a reoperation because of a worsening mitral regurgitation and hemolytic anemia (elongation of anchored side of papillary muscle). The other two patients required mitral valve replacement due to a progressive regression of the left ventricular function, although the regurgitation worsened from a mild level to a moderate one. When the reoperated patients were excluded from the following data, the degree of mitral regurgitation, estimated by echocardiography performed at recent follow-up period, was none in 10 patients, trivial in 13 patients, and mild in 1 patient. In addition, the systolic and diastolic dimensions of the left ventricle decreased significantly (P < 0.01). CONCLUSIONS: The replacement of artificial chordae was not complicated and it seemed to help to preserve a good relationship among leaflet tissues, chordae, and papillary muscles. We therefore suggest that the extensive use of PTFE artificial chordae appears to be a promising procedure for the repair of all kinds of mitral lesions causing mitral regurgitation.

Adolescent↗

PubMed2005

Ossifying cardiac myxoma with neovascularity.

We report a 64-year-old man with ossifying cardiac myxoma which radiographically demonstrated visible calcification. A lateral chest radiograph showed abnormal calcification in the cardiac shadow. Two-dimensional and transesophageal echocardiography revealed a heterogeneous mass with a hyperechoic lesion in the left artium. A coronary angiogram showed a neovascular formation extending from the coronary arteries to the tumor. The resected tumor was composed of round or spindle shaped cells with myxoid stroma, accompanied by extensive calcification and ossification containing fatty and hematopoietic marrow tissue. Although a left atrial calcified myxoma is less common than a right sided myxoma, and such radiographically detectable calcified tumors are rare, the presence of radiographic visualized calcification in the cardiac shadow should be ruled out for left as well as right atrial myxomas.

Cardiac Surgical Procedures↗

PubMed2005

Compression of trachea and left main bronchus by arch aneurysm.

We report on the case of a 70-year-old woman who presented dyspnea. Contrast-enhanced computed tomography of the chest revealed the compression of the lower part of the trachea and left main bronchus by an aneurysm of the ascending aorta and aortic arch. Although we performed a replacement of the ascending aorta and aortic arch, we were unable to relieve the stenosis of the trachea and bronchus. By the suspension of the posterior wall of the native aneurysm, we were able to successfully relieve the compression and alleviate the respiratory insufficiency.

Aged↗

PubMed2005

A 10-year experience with the Carbomedics cardiac prosthesis.

BACKGROUND: There are few reports on the long-term results of Carbomedics prosthetic heart valves. METHODS: Five hundred five patients who underwent valve replacement with this prosthesis in the aortic or mitral position were chosen for this study. Patients' mean age was 57 years. There were 173 aortic (AVR), 253 mitral (MVR), and 79 double (DVR) valve implants. The mean follow-up was 5.1 years, and cumulative follow-up was 2,590 patient-years with an overall follow-up rate of 99.2%. RESULTS: The early mortality rate for the total population was 2.8% (AVR 1.2%, MVR 3.6%, DVR 3.8%). Actuarial freedom from thromboembolism at 10 years was 81.8% +/- 5.1%, 85.7% +/- 3.2%, and 88.8% +/- 6.8% for AVR, MVR, and DVR, respectively. At 10 years, 92.7% of AVR, 85.4% of MVR, and 94.7% of DVR patients were free of valve-related death. Overall survival rate at 10 years was 77.6% +/- 4.6%, 71.8% +/- 4.2%, and 81.3% +/- 5.8% for AVR, MVR, and DVR, respectively. The linearized rate of thromboembolism was 1.45%/patient-year, 1.78%/patient-year, 0.67%/patient-year; of major bleeding events, 0.52%/patient-year, 0.85%/patient-year, 0.45%/patient-year; of valve thrombosis, 0%/patient-year, 0.25%/patient-year, 0%/patient-year; of prosthetic valve endocarditis, 0.1%/patient-year, 0.25%/patient-year, 0.22%/patient-year; and of all reoperations, 0.31%/patient-year, 0.93%/patient-year, 1.1%/patient-year for AVR, MVR, and DVR, respectively. CONCLUSIONS: The Carbomedics prosthetic heart valves showed comparable or even better results than those of other mechanical valves with respect to morbidity and mortality. These results may justify the use of Carbomedics valves as one of the mechanical heart valves.

Adult↗

PubMed2005

The regulatory functions of Ly-49A, Ly-49D and Ly-49G2 on NK cells in the recognition and rejection of the alloantigen in vivo.

Ly-49A is an inhibitory receptor that binds H-2Dd and H-2Dk. The downregulation of Ly-49A is thought to mediate NK self tolerance in vivo. In this study, we analyzed the regulation of Ly-49A, D and G2 on NK cells in an in vivo rejection model. After injection with 1 x 10(8) B10.D2 spleen cells (SC) into B 10 mice, we found Ly-49A downregulated within 3 h on NK cells of B10 mice, whereas expressions of Ly-49D and G2 were augmented. To investigate effects of different expression patterns of Ly-49 receptors on NK cells, Ly-49A, D or G2-depleted B10 mice were inoculated with B10.D2 SC. NK cells from SC of Ly-49A-depleted and B10.D2 SC-injected B10 mice showed enhanced cytotoxicity to Dd-positive targets in vitro. Furthermore, reduced numbers of B10.D2 SC were observed in Ly-49A or G2-depleted B10 mice, whereas increased numbers of B10.D2 SC were observed in Ly-49D-depleted B10 mice after inoculation with B10.D2 SC in vivo. These findings indicated that the downregulation of Ly-49A and the augmentation of Ly-49D expression may mediate NK cells to recognize and kill Dd antigen efficiently. In conclusion, each Ly-49 isoform may play independent roles in the regulation of activation or inhibition on NK cells.

Animals↗

PubMed2004

IL-12 gene therapy is an effective therapeutic strategy for hepatocellular carcinoma in immunosuppressed mice.

Immunosuppressive therapy for organ transplantation is essential for controlling rejection. When liver transplantation is performed as a therapy for hepatocellular carcinoma (HCC), recurrent HCC is one of the most fatal complications. In this study, we show that intratumoral murine IL-12 (mIL-12) gene therapy has the potential to be an effective treatment for malignancies under immunosuppression. C3H mice (H-2(k)), injected with FK506 (3 mg/kg) i.p., were s.c. implanted with 2.5 x 10(6) MH134 cells (H-2(k)) and we treated the established HCC with electroporation-mediated gene therapy using mIL-12 plasmid DNA. Intratumoral gene transfer of mIL-12 elevated intratumoral mIL-12, IFN-gamma, and IFN-gamma-inducible protein-10, significantly reduced the number of microvessels and inhibited the growth of HCC, compared with HCC-transferred control pCAGGS plasmid. The inhibition of tumor growth in immunosuppressed mice was comparable with that of mIL-12 gene therapy in immunocompetent mice. Intratumoral mIL-12 gene therapy enhanced lymphocytic infiltration into the tumor and elicited the MH134-specific CTL response even under FK506. The dose of FK506 was sufficient to prevent the rejection of distant allogenic skin grafts (BALB/c mice, H-2(d)) and tumors, B7-p815 (H-2(d)) used as transplants, during mIL-12 gene therapy against MH134. Ab-mediated depletion studies suggested that the inhibition of tumor growth, neovascularization, and spontaneous lung metastasis by mIL-12 was dependent almost entirely on NK cells and partially on T cells. These results suggest that intratumoral mIL-12 gene therapy is a potent effective strategy not only to treat recurrences of HCC in liver transplantation, but also to treat solid malignant tumors in immunosuppressed patients with transplanted organ.

Angiogenesis Inhibitors↗

PubMed2004

The critical role of Fas-Fas ligand interaction in donor-specific transfusion-induced tolerance to H-Y antigen.

BACKGROUND: Donor-specific transfusion (DST) has been clinically used to enhance the survival of transplanted organs, and it has been shown in mice to induce tolerance to male (H-Y) antigen (Ag). Although the biologic mechanisms that initiate and maintain DST-induced tolerance involve clonal deletion, induction of anergy, and generation of regulatory cells, the molecules essential to tolerance induction are still unclear. In this study, we investigated the role of Fas-FasL interaction in DST-induced tolerance to H-Y Ag. METHODS: C57BL/6 (B6) or B6-Fas(lpr) (lpr) female mice were intravenously injected with B6, lpr, or B6-FasL(gld) (gld) male spleen cells (SC). B6 male skin grafts, mixed lymphocyte reaction (MLR) assay, and cytotoxicity assay (CTL) were performed 7 days after DST. In some experiments, purified B-cells were used as transfused cells. RESULTS: B6 female mice treated with B6 male SC permanently accepted B6 male skins, whereas untreated B6 or lpr female mice rejected B6 male skins. On the other hand, B6 female mice treated with gld male SC acceleratingly rejected male skin, as did lpr female mice treated with B6 or gld male SC. The recipient mice in the experimental groups, in which DST resulted in the accelerated rejection of the skin grafts, had strong allo-responses to H-Y Ag in MLR and CTL. Further, B6 female mice treated with gld male B-cells acceleratingly rejected male skins, whereas B6 female mice treated with B6 or lpr male B-cells from mice accepted male skins. CONCLUSIONS: These findings suggest that the interaction between FasL upon infused SC, especially upon B-cells and Fas in a recipient, is essential in DST-induced tolerance to H-Y Ag.

Animals↗

PubMed2004

Mechanical cardiac support system for patients with postcardiotomy cardiogenic shock: analysis of risk factors for survival.

OBJECTIVE: Mechanical cardiac support system (MCSS) has been used for adult patients in postcardiotomy cardiogenic shock and has been shown to provide excellent oxygenation and hemodynamic support. However, MCSS has a number of disadvantages that include high incidence rate of complications (e.g. stroke, bleeding) and limited duration of sufficient support. The objective of this study is to identify perioperative and postoperative factors for survival in patients having MCSS. METHODS: From January 1991 to April 2001, MCSS has been applied to 22 adult patients in postcardiotomy cardiogenic shock. These patients' charts were retrospectively reviewed. RESULTS: Of 22 patients, 9 patients (41%) were successfully weaned, and 6 (27%) were hospital survivors. The duration of assist ranged from 21 to 211 hours (median 66 hours). In 7 (78%) out of 9 patients who could be weaned from MCSS, MCSS were required for less than 3 days. Major complications were reexploration for bleeding (18%), leg ischemia (45%), renal dysfunction (77%), liver dysfunction (59%), infection (31.8%), hypoxia due to lung dysfunction (36%) and cerebral dysfunction (41%). pH, base excess, HCO3-, urine output, transfused platelets at first 24 hours of MCSS and preoperative body surface area were significant predictors for survival. CONCLUSION: The indices of insufficient hemodynamic support such as progression of acidosis or poor urine output are significant predictors for early death. Early conversion from MCSS to long-term assist device, such as left ventricular assist device, should be considered when these factors are associated with poor cardiac recovery.

Acidosis↗