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Mohamad H Yamani - One of the best experts on this subject based on the ideXlab platform.

  • Does acute Cellular Rejection correlate with cardiac allograft vasculopathy
    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2004
    Co-Authors: Mohamad H Yamani, Robert E. Hobbs, Randall C. Starling, Norman B. Ratliff, Mohammed Yousufuddin, Murat Tuzcu, Daniel J. Cook, Ashraf Abdo, Tim Crowe, Gustavo Rincon
    Abstract:

    Abstract Background Previous studies of the association between acute Cellular Rejection and cardiac allograft vasculopathy (CAV) have yielded conflicting conclusions. We explored a possible association between acute Cellular Rejection and the extent of CAV, and we found a potential confounding variable that may obscure such an association. Methods We investigated 140 patients (mean age, 51 ± 11 years) who underwent serial intravascular ultrasound examinations at baseline and at 1 year after heart transplantation to assess CAV as change in maximal intimal thickness (CMIT). Patients were classified according to the presence or absence of biopsy-proven myocardial fibrosis. We used a standard biopsy-scoring system and a novel biopsy-scoring system, developed in our institution, to assess acute Cellular Rejection. Using univariate analysis, we found that CMIT was not associated with acute Cellular Rejection in the overall patient population ( n = 140). However, we observed a correlation between CMIT and acute Cellular Rejection (standard method, r = 0.30, p = 0.01; novel method, r = 0.51, p n = 57). Step-wise multiple regression showed that the Rejection score derived from our novel method was associated more closely with the CMIT than was that derived from the traditional method. Conclusions This data indicate that the presence of myocardial fibrosis masks an actuarial association between acute Cellular Rejection and the development of de novo allograft vasculopathy. As previously suspected, myocardial fibrosis is a marker for non–immune-mediated graft injury independently associated with an increased incidence of CAV.

  • Acute Cellular Rejection following human heart transplantation is associated with increased expression of vitronectin receptor (integrin αvβ3)
    American Journal of Transplantation, 2002
    Co-Authors: Mohamad H Yamani, Patrick M. Mccarthy, Randall C. Starling, Edward F. Plow, Jiacheng Yang, Carolyna S. Masri, Norman B. Ratliff, Meredith Bond, James B. Young
    Abstract:

    The vitronectin receptor (integrin αvβ3), a cell-surface adhesion receptor, has been shown to play a significant role in endothelial cell migration, apoptosis, atherosclerosis, and T-lymphocyte activation. This study was undertaken to test the hypothesis that cardiac allograft Rejection is associated with increased expression of αvβ3. We also determined whether fibronectin receptor (α5β1) and tissue factor are up-regulated in the presence of acute Cellular Rejection. We evaluated endomyocardial biopsy specimens with histologic evidence of different degrees of acute Cellular Rejection (grade 0, n = 10; grade 1A, n = 10; grade 2, n = 10; grade 3A, n = 10). Biopsies were obtained 2–4 weeks after cardiac transplantation. Immunoperoxidase staining was performed for αvβ3, tissue factor, and α5β1, and protein levels were further determined by Western blot analysis. Specimens with grade 2 and grade 3A Rejection showed positive staining of αvβ3 in lymphocytic aggregates and vascular endothelial cells. By immunoblotting, we identified significantly increased expression of αvβ3 in the presence of acute Rejection, grade 2 (3-fold, p = 0.01) and grade 3A (3.6-fold, p = 0.005) compared to grade 0 and 1A specimens. There was no evidence of increased expression of α5β1 or tissue factor. Acute Cellular Rejection, a process characterized by T-lymphocyte activation and release of inflammatory cytokines, is associated with increased expression of αvβ3.

  • Myocardial ischemic-fibrotic injury after human heart transplantation is associated with increased progression of vasculopathy, decreased Cellular Rejection and poor long-term outcome
    Journal of the American College of Cardiology, 2002
    Co-Authors: Mohamad H Yamani, Randall C. Starling, Norman B. Ratliff, Daniel J. Cook, Ashraf Abdo, Tim Crowe, Showkat A. Haji, E. Murat Tuzcu, Michelle Secic, Patrick M. Mccarthy
    Abstract:

    Abstract Objectives We sought to assess the influence of peritransplant ischemia and fibrosis on the development of allograft vasculopathy, acute Cellular Rejection and long-term outcome. Background Allograft vasculopathy is a common long-term complication of cardiac transplantation. One of the potential risk factors is peritransplant allograft ischemia. Methods One hundred forty heart transplant recipients had baseline and one-year intravascular ultrasound analysis done to assess the progression of allograft vasculopathy. Serial endomyocardial biopsies were evaluated for Cellular Rejection, vascular Rejection, ischemia and fibrosis. Based on histology, patients were classified into one of the following groups: nonischemic (n = 32), ischemia (n = 24), fibrosis (n = 62) or vascular Rejection (n = 22). Three-color flow cytometry crossmatching (FCXM) was used to assess donor-specific human lymphocyte antigens (HLA) sensitization. Long-term outcome of patients in each group was assessed by estimating incidence of graft failure or deaths over a seven-year follow up. Results Patients in the fibrosis group had the lowest incidence of donor-specific HLA sensitization (40%, p = 0.008) and lowest average episodes of Cellular Rejection (1.7 ± 1.4, p = 0.04), but they had increased coronary vasculopathy progression (change in coronary intimal thickness = 0.59 ± 0.28 mm, p Conclusions The development of fibrosis after cardiac transplantation is associated with advanced coronary vasculopathy, although a low incidence of acute Cellular Rejection is noted, suggesting the presence of nonimmune mechanisms in mediating the pathogenesis of allograft vasculopathy.

  • Efficacy of tacrolimus in patients with steroid-resistant cardiac allograft Cellular Rejection.
    Journal of Heart and Lung Transplantation, 2000
    Co-Authors: Mohamad H Yamani, D. Pelegrin, Luba Platt, Mark Majercik, Patrick M. Mccarthy, Robert E. Hobbs, Randall C. Starling, James B. Young
    Abstract:

    Abstract Background Tacrolimus is an immunosuppressive agent that is gaining widespread use in solid organ transplantation. This study was undertaken to evaluate the efficacy of tacrolimus in treating steroid-resistant Cellular myocardial Rejection. Methods We retrospectively analyzed the incidence of Rejection and clinical outcome of 21 heart transplant recipients who were electively converted from cyclosporine to tacrolimus for recurrent episodes of steroid-resistant Cellular Rejection. These were compared to a historic group of 6 hemodynamically stable patients who were treated electively with Orthoclone OKT3 (Muromonab/CD3) for recurrent Rejection. Results Eighty five percent (56/66) of the episodes of Rejection occurred within the first 3 months after heart transplantation. Tacrolimus was started 2.4 ± 2.0 months post-transplant, and the mean follow-up duration on tacrolimus was 11.0 ± 7.0 months. After conversion, a significant decline was noted in both the number of episodes of acute Rejection per patient (3.14 ± 0.85–0.57 ± 0.87, p p p p = 0.5). Conclusions Outpatient conversion to tacrolimus is safe, well tolerated, and an effective therapeutic strategy for the treatment of steroid-resistant Cellular Rejection in heart transplant recipients. It is more cost-effective than OKT3 in the hemodynamically stable patient and outcomes are similar.

Patrick M. Mccarthy - One of the best experts on this subject based on the ideXlab platform.

  • Acute Cellular Rejection following human heart transplantation is associated with increased expression of vitronectin receptor (integrin αvβ3)
    American Journal of Transplantation, 2002
    Co-Authors: Mohamad H Yamani, Patrick M. Mccarthy, Randall C. Starling, Edward F. Plow, Jiacheng Yang, Carolyna S. Masri, Norman B. Ratliff, Meredith Bond, James B. Young
    Abstract:

    The vitronectin receptor (integrin αvβ3), a cell-surface adhesion receptor, has been shown to play a significant role in endothelial cell migration, apoptosis, atherosclerosis, and T-lymphocyte activation. This study was undertaken to test the hypothesis that cardiac allograft Rejection is associated with increased expression of αvβ3. We also determined whether fibronectin receptor (α5β1) and tissue factor are up-regulated in the presence of acute Cellular Rejection. We evaluated endomyocardial biopsy specimens with histologic evidence of different degrees of acute Cellular Rejection (grade 0, n = 10; grade 1A, n = 10; grade 2, n = 10; grade 3A, n = 10). Biopsies were obtained 2–4 weeks after cardiac transplantation. Immunoperoxidase staining was performed for αvβ3, tissue factor, and α5β1, and protein levels were further determined by Western blot analysis. Specimens with grade 2 and grade 3A Rejection showed positive staining of αvβ3 in lymphocytic aggregates and vascular endothelial cells. By immunoblotting, we identified significantly increased expression of αvβ3 in the presence of acute Rejection, grade 2 (3-fold, p = 0.01) and grade 3A (3.6-fold, p = 0.005) compared to grade 0 and 1A specimens. There was no evidence of increased expression of α5β1 or tissue factor. Acute Cellular Rejection, a process characterized by T-lymphocyte activation and release of inflammatory cytokines, is associated with increased expression of αvβ3.

  • Myocardial ischemic-fibrotic injury after human heart transplantation is associated with increased progression of vasculopathy, decreased Cellular Rejection and poor long-term outcome
    Journal of the American College of Cardiology, 2002
    Co-Authors: Mohamad H Yamani, Randall C. Starling, Norman B. Ratliff, Daniel J. Cook, Ashraf Abdo, Tim Crowe, Showkat A. Haji, E. Murat Tuzcu, Michelle Secic, Patrick M. Mccarthy
    Abstract:

    Abstract Objectives We sought to assess the influence of peritransplant ischemia and fibrosis on the development of allograft vasculopathy, acute Cellular Rejection and long-term outcome. Background Allograft vasculopathy is a common long-term complication of cardiac transplantation. One of the potential risk factors is peritransplant allograft ischemia. Methods One hundred forty heart transplant recipients had baseline and one-year intravascular ultrasound analysis done to assess the progression of allograft vasculopathy. Serial endomyocardial biopsies were evaluated for Cellular Rejection, vascular Rejection, ischemia and fibrosis. Based on histology, patients were classified into one of the following groups: nonischemic (n = 32), ischemia (n = 24), fibrosis (n = 62) or vascular Rejection (n = 22). Three-color flow cytometry crossmatching (FCXM) was used to assess donor-specific human lymphocyte antigens (HLA) sensitization. Long-term outcome of patients in each group was assessed by estimating incidence of graft failure or deaths over a seven-year follow up. Results Patients in the fibrosis group had the lowest incidence of donor-specific HLA sensitization (40%, p = 0.008) and lowest average episodes of Cellular Rejection (1.7 ± 1.4, p = 0.04), but they had increased coronary vasculopathy progression (change in coronary intimal thickness = 0.59 ± 0.28 mm, p Conclusions The development of fibrosis after cardiac transplantation is associated with advanced coronary vasculopathy, although a low incidence of acute Cellular Rejection is noted, suggesting the presence of nonimmune mechanisms in mediating the pathogenesis of allograft vasculopathy.

  • Efficacy of tacrolimus in patients with steroid-resistant cardiac allograft Cellular Rejection.
    Journal of Heart and Lung Transplantation, 2000
    Co-Authors: Mohamad H Yamani, D. Pelegrin, Luba Platt, Mark Majercik, Patrick M. Mccarthy, Robert E. Hobbs, Randall C. Starling, James B. Young
    Abstract:

    Abstract Background Tacrolimus is an immunosuppressive agent that is gaining widespread use in solid organ transplantation. This study was undertaken to evaluate the efficacy of tacrolimus in treating steroid-resistant Cellular myocardial Rejection. Methods We retrospectively analyzed the incidence of Rejection and clinical outcome of 21 heart transplant recipients who were electively converted from cyclosporine to tacrolimus for recurrent episodes of steroid-resistant Cellular Rejection. These were compared to a historic group of 6 hemodynamically stable patients who were treated electively with Orthoclone OKT3 (Muromonab/CD3) for recurrent Rejection. Results Eighty five percent (56/66) of the episodes of Rejection occurred within the first 3 months after heart transplantation. Tacrolimus was started 2.4 ± 2.0 months post-transplant, and the mean follow-up duration on tacrolimus was 11.0 ± 7.0 months. After conversion, a significant decline was noted in both the number of episodes of acute Rejection per patient (3.14 ± 0.85–0.57 ± 0.87, p p p p = 0.5). Conclusions Outpatient conversion to tacrolimus is safe, well tolerated, and an effective therapeutic strategy for the treatment of steroid-resistant Cellular Rejection in heart transplant recipients. It is more cost-effective than OKT3 in the hemodynamically stable patient and outcomes are similar.

James B. Young - One of the best experts on this subject based on the ideXlab platform.

  • Acute Cellular Rejection following human heart transplantation is associated with increased expression of vitronectin receptor (integrin αvβ3)
    American Journal of Transplantation, 2002
    Co-Authors: Mohamad H Yamani, Patrick M. Mccarthy, Randall C. Starling, Edward F. Plow, Jiacheng Yang, Carolyna S. Masri, Norman B. Ratliff, Meredith Bond, James B. Young
    Abstract:

    The vitronectin receptor (integrin αvβ3), a cell-surface adhesion receptor, has been shown to play a significant role in endothelial cell migration, apoptosis, atherosclerosis, and T-lymphocyte activation. This study was undertaken to test the hypothesis that cardiac allograft Rejection is associated with increased expression of αvβ3. We also determined whether fibronectin receptor (α5β1) and tissue factor are up-regulated in the presence of acute Cellular Rejection. We evaluated endomyocardial biopsy specimens with histologic evidence of different degrees of acute Cellular Rejection (grade 0, n = 10; grade 1A, n = 10; grade 2, n = 10; grade 3A, n = 10). Biopsies were obtained 2–4 weeks after cardiac transplantation. Immunoperoxidase staining was performed for αvβ3, tissue factor, and α5β1, and protein levels were further determined by Western blot analysis. Specimens with grade 2 and grade 3A Rejection showed positive staining of αvβ3 in lymphocytic aggregates and vascular endothelial cells. By immunoblotting, we identified significantly increased expression of αvβ3 in the presence of acute Rejection, grade 2 (3-fold, p = 0.01) and grade 3A (3.6-fold, p = 0.005) compared to grade 0 and 1A specimens. There was no evidence of increased expression of α5β1 or tissue factor. Acute Cellular Rejection, a process characterized by T-lymphocyte activation and release of inflammatory cytokines, is associated with increased expression of αvβ3.

  • Efficacy of tacrolimus in patients with steroid-resistant cardiac allograft Cellular Rejection.
    Journal of Heart and Lung Transplantation, 2000
    Co-Authors: Mohamad H Yamani, D. Pelegrin, Luba Platt, Mark Majercik, Patrick M. Mccarthy, Robert E. Hobbs, Randall C. Starling, James B. Young
    Abstract:

    Abstract Background Tacrolimus is an immunosuppressive agent that is gaining widespread use in solid organ transplantation. This study was undertaken to evaluate the efficacy of tacrolimus in treating steroid-resistant Cellular myocardial Rejection. Methods We retrospectively analyzed the incidence of Rejection and clinical outcome of 21 heart transplant recipients who were electively converted from cyclosporine to tacrolimus for recurrent episodes of steroid-resistant Cellular Rejection. These were compared to a historic group of 6 hemodynamically stable patients who were treated electively with Orthoclone OKT3 (Muromonab/CD3) for recurrent Rejection. Results Eighty five percent (56/66) of the episodes of Rejection occurred within the first 3 months after heart transplantation. Tacrolimus was started 2.4 ± 2.0 months post-transplant, and the mean follow-up duration on tacrolimus was 11.0 ± 7.0 months. After conversion, a significant decline was noted in both the number of episodes of acute Rejection per patient (3.14 ± 0.85–0.57 ± 0.87, p p p p = 0.5). Conclusions Outpatient conversion to tacrolimus is safe, well tolerated, and an effective therapeutic strategy for the treatment of steroid-resistant Cellular Rejection in heart transplant recipients. It is more cost-effective than OKT3 in the hemodynamically stable patient and outcomes are similar.

Randall C. Starling - One of the best experts on this subject based on the ideXlab platform.

  • Does acute Cellular Rejection correlate with cardiac allograft vasculopathy
    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2004
    Co-Authors: Mohamad H Yamani, Robert E. Hobbs, Randall C. Starling, Norman B. Ratliff, Mohammed Yousufuddin, Murat Tuzcu, Daniel J. Cook, Ashraf Abdo, Tim Crowe, Gustavo Rincon
    Abstract:

    Abstract Background Previous studies of the association between acute Cellular Rejection and cardiac allograft vasculopathy (CAV) have yielded conflicting conclusions. We explored a possible association between acute Cellular Rejection and the extent of CAV, and we found a potential confounding variable that may obscure such an association. Methods We investigated 140 patients (mean age, 51 ± 11 years) who underwent serial intravascular ultrasound examinations at baseline and at 1 year after heart transplantation to assess CAV as change in maximal intimal thickness (CMIT). Patients were classified according to the presence or absence of biopsy-proven myocardial fibrosis. We used a standard biopsy-scoring system and a novel biopsy-scoring system, developed in our institution, to assess acute Cellular Rejection. Using univariate analysis, we found that CMIT was not associated with acute Cellular Rejection in the overall patient population ( n = 140). However, we observed a correlation between CMIT and acute Cellular Rejection (standard method, r = 0.30, p = 0.01; novel method, r = 0.51, p n = 57). Step-wise multiple regression showed that the Rejection score derived from our novel method was associated more closely with the CMIT than was that derived from the traditional method. Conclusions This data indicate that the presence of myocardial fibrosis masks an actuarial association between acute Cellular Rejection and the development of de novo allograft vasculopathy. As previously suspected, myocardial fibrosis is a marker for non–immune-mediated graft injury independently associated with an increased incidence of CAV.

  • Acute Cellular Rejection following human heart transplantation is associated with increased expression of vitronectin receptor (integrin αvβ3)
    American Journal of Transplantation, 2002
    Co-Authors: Mohamad H Yamani, Patrick M. Mccarthy, Randall C. Starling, Edward F. Plow, Jiacheng Yang, Carolyna S. Masri, Norman B. Ratliff, Meredith Bond, James B. Young
    Abstract:

    The vitronectin receptor (integrin αvβ3), a cell-surface adhesion receptor, has been shown to play a significant role in endothelial cell migration, apoptosis, atherosclerosis, and T-lymphocyte activation. This study was undertaken to test the hypothesis that cardiac allograft Rejection is associated with increased expression of αvβ3. We also determined whether fibronectin receptor (α5β1) and tissue factor are up-regulated in the presence of acute Cellular Rejection. We evaluated endomyocardial biopsy specimens with histologic evidence of different degrees of acute Cellular Rejection (grade 0, n = 10; grade 1A, n = 10; grade 2, n = 10; grade 3A, n = 10). Biopsies were obtained 2–4 weeks after cardiac transplantation. Immunoperoxidase staining was performed for αvβ3, tissue factor, and α5β1, and protein levels were further determined by Western blot analysis. Specimens with grade 2 and grade 3A Rejection showed positive staining of αvβ3 in lymphocytic aggregates and vascular endothelial cells. By immunoblotting, we identified significantly increased expression of αvβ3 in the presence of acute Rejection, grade 2 (3-fold, p = 0.01) and grade 3A (3.6-fold, p = 0.005) compared to grade 0 and 1A specimens. There was no evidence of increased expression of α5β1 or tissue factor. Acute Cellular Rejection, a process characterized by T-lymphocyte activation and release of inflammatory cytokines, is associated with increased expression of αvβ3.

  • Myocardial ischemic-fibrotic injury after human heart transplantation is associated with increased progression of vasculopathy, decreased Cellular Rejection and poor long-term outcome
    Journal of the American College of Cardiology, 2002
    Co-Authors: Mohamad H Yamani, Randall C. Starling, Norman B. Ratliff, Daniel J. Cook, Ashraf Abdo, Tim Crowe, Showkat A. Haji, E. Murat Tuzcu, Michelle Secic, Patrick M. Mccarthy
    Abstract:

    Abstract Objectives We sought to assess the influence of peritransplant ischemia and fibrosis on the development of allograft vasculopathy, acute Cellular Rejection and long-term outcome. Background Allograft vasculopathy is a common long-term complication of cardiac transplantation. One of the potential risk factors is peritransplant allograft ischemia. Methods One hundred forty heart transplant recipients had baseline and one-year intravascular ultrasound analysis done to assess the progression of allograft vasculopathy. Serial endomyocardial biopsies were evaluated for Cellular Rejection, vascular Rejection, ischemia and fibrosis. Based on histology, patients were classified into one of the following groups: nonischemic (n = 32), ischemia (n = 24), fibrosis (n = 62) or vascular Rejection (n = 22). Three-color flow cytometry crossmatching (FCXM) was used to assess donor-specific human lymphocyte antigens (HLA) sensitization. Long-term outcome of patients in each group was assessed by estimating incidence of graft failure or deaths over a seven-year follow up. Results Patients in the fibrosis group had the lowest incidence of donor-specific HLA sensitization (40%, p = 0.008) and lowest average episodes of Cellular Rejection (1.7 ± 1.4, p = 0.04), but they had increased coronary vasculopathy progression (change in coronary intimal thickness = 0.59 ± 0.28 mm, p Conclusions The development of fibrosis after cardiac transplantation is associated with advanced coronary vasculopathy, although a low incidence of acute Cellular Rejection is noted, suggesting the presence of nonimmune mechanisms in mediating the pathogenesis of allograft vasculopathy.

  • Efficacy of tacrolimus in patients with steroid-resistant cardiac allograft Cellular Rejection.
    Journal of Heart and Lung Transplantation, 2000
    Co-Authors: Mohamad H Yamani, D. Pelegrin, Luba Platt, Mark Majercik, Patrick M. Mccarthy, Robert E. Hobbs, Randall C. Starling, James B. Young
    Abstract:

    Abstract Background Tacrolimus is an immunosuppressive agent that is gaining widespread use in solid organ transplantation. This study was undertaken to evaluate the efficacy of tacrolimus in treating steroid-resistant Cellular myocardial Rejection. Methods We retrospectively analyzed the incidence of Rejection and clinical outcome of 21 heart transplant recipients who were electively converted from cyclosporine to tacrolimus for recurrent episodes of steroid-resistant Cellular Rejection. These were compared to a historic group of 6 hemodynamically stable patients who were treated electively with Orthoclone OKT3 (Muromonab/CD3) for recurrent Rejection. Results Eighty five percent (56/66) of the episodes of Rejection occurred within the first 3 months after heart transplantation. Tacrolimus was started 2.4 ± 2.0 months post-transplant, and the mean follow-up duration on tacrolimus was 11.0 ± 7.0 months. After conversion, a significant decline was noted in both the number of episodes of acute Rejection per patient (3.14 ± 0.85–0.57 ± 0.87, p p p p = 0.5). Conclusions Outpatient conversion to tacrolimus is safe, well tolerated, and an effective therapeutic strategy for the treatment of steroid-resistant Cellular Rejection in heart transplant recipients. It is more cost-effective than OKT3 in the hemodynamically stable patient and outcomes are similar.

Norman B. Ratliff - One of the best experts on this subject based on the ideXlab platform.

  • Does acute Cellular Rejection correlate with cardiac allograft vasculopathy
    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2004
    Co-Authors: Mohamad H Yamani, Robert E. Hobbs, Randall C. Starling, Norman B. Ratliff, Mohammed Yousufuddin, Murat Tuzcu, Daniel J. Cook, Ashraf Abdo, Tim Crowe, Gustavo Rincon
    Abstract:

    Abstract Background Previous studies of the association between acute Cellular Rejection and cardiac allograft vasculopathy (CAV) have yielded conflicting conclusions. We explored a possible association between acute Cellular Rejection and the extent of CAV, and we found a potential confounding variable that may obscure such an association. Methods We investigated 140 patients (mean age, 51 ± 11 years) who underwent serial intravascular ultrasound examinations at baseline and at 1 year after heart transplantation to assess CAV as change in maximal intimal thickness (CMIT). Patients were classified according to the presence or absence of biopsy-proven myocardial fibrosis. We used a standard biopsy-scoring system and a novel biopsy-scoring system, developed in our institution, to assess acute Cellular Rejection. Using univariate analysis, we found that CMIT was not associated with acute Cellular Rejection in the overall patient population ( n = 140). However, we observed a correlation between CMIT and acute Cellular Rejection (standard method, r = 0.30, p = 0.01; novel method, r = 0.51, p n = 57). Step-wise multiple regression showed that the Rejection score derived from our novel method was associated more closely with the CMIT than was that derived from the traditional method. Conclusions This data indicate that the presence of myocardial fibrosis masks an actuarial association between acute Cellular Rejection and the development of de novo allograft vasculopathy. As previously suspected, myocardial fibrosis is a marker for non–immune-mediated graft injury independently associated with an increased incidence of CAV.

  • Acute Cellular Rejection following human heart transplantation is associated with increased expression of vitronectin receptor (integrin αvβ3)
    American Journal of Transplantation, 2002
    Co-Authors: Mohamad H Yamani, Patrick M. Mccarthy, Randall C. Starling, Edward F. Plow, Jiacheng Yang, Carolyna S. Masri, Norman B. Ratliff, Meredith Bond, James B. Young
    Abstract:

    The vitronectin receptor (integrin αvβ3), a cell-surface adhesion receptor, has been shown to play a significant role in endothelial cell migration, apoptosis, atherosclerosis, and T-lymphocyte activation. This study was undertaken to test the hypothesis that cardiac allograft Rejection is associated with increased expression of αvβ3. We also determined whether fibronectin receptor (α5β1) and tissue factor are up-regulated in the presence of acute Cellular Rejection. We evaluated endomyocardial biopsy specimens with histologic evidence of different degrees of acute Cellular Rejection (grade 0, n = 10; grade 1A, n = 10; grade 2, n = 10; grade 3A, n = 10). Biopsies were obtained 2–4 weeks after cardiac transplantation. Immunoperoxidase staining was performed for αvβ3, tissue factor, and α5β1, and protein levels were further determined by Western blot analysis. Specimens with grade 2 and grade 3A Rejection showed positive staining of αvβ3 in lymphocytic aggregates and vascular endothelial cells. By immunoblotting, we identified significantly increased expression of αvβ3 in the presence of acute Rejection, grade 2 (3-fold, p = 0.01) and grade 3A (3.6-fold, p = 0.005) compared to grade 0 and 1A specimens. There was no evidence of increased expression of α5β1 or tissue factor. Acute Cellular Rejection, a process characterized by T-lymphocyte activation and release of inflammatory cytokines, is associated with increased expression of αvβ3.

  • Myocardial ischemic-fibrotic injury after human heart transplantation is associated with increased progression of vasculopathy, decreased Cellular Rejection and poor long-term outcome
    Journal of the American College of Cardiology, 2002
    Co-Authors: Mohamad H Yamani, Randall C. Starling, Norman B. Ratliff, Daniel J. Cook, Ashraf Abdo, Tim Crowe, Showkat A. Haji, E. Murat Tuzcu, Michelle Secic, Patrick M. Mccarthy
    Abstract:

    Abstract Objectives We sought to assess the influence of peritransplant ischemia and fibrosis on the development of allograft vasculopathy, acute Cellular Rejection and long-term outcome. Background Allograft vasculopathy is a common long-term complication of cardiac transplantation. One of the potential risk factors is peritransplant allograft ischemia. Methods One hundred forty heart transplant recipients had baseline and one-year intravascular ultrasound analysis done to assess the progression of allograft vasculopathy. Serial endomyocardial biopsies were evaluated for Cellular Rejection, vascular Rejection, ischemia and fibrosis. Based on histology, patients were classified into one of the following groups: nonischemic (n = 32), ischemia (n = 24), fibrosis (n = 62) or vascular Rejection (n = 22). Three-color flow cytometry crossmatching (FCXM) was used to assess donor-specific human lymphocyte antigens (HLA) sensitization. Long-term outcome of patients in each group was assessed by estimating incidence of graft failure or deaths over a seven-year follow up. Results Patients in the fibrosis group had the lowest incidence of donor-specific HLA sensitization (40%, p = 0.008) and lowest average episodes of Cellular Rejection (1.7 ± 1.4, p = 0.04), but they had increased coronary vasculopathy progression (change in coronary intimal thickness = 0.59 ± 0.28 mm, p Conclusions The development of fibrosis after cardiac transplantation is associated with advanced coronary vasculopathy, although a low incidence of acute Cellular Rejection is noted, suggesting the presence of nonimmune mechanisms in mediating the pathogenesis of allograft vasculopathy.

  • comparison of myocardial cell injury in acute Cellular Rejection versus acute vascular Rejection in cyclosporine treated heart transplants
    Journal of Heart and Lung Transplantation, 1995
    Co-Authors: Sharon Hook, J F Caple, James T Mcmahon, Jonathan Myles, Norman B. Ratliff
    Abstract:

    Background: Myocyte necrosis has been cited as a key feature in the diagnosis and classification of both moderate and severe acute Cellular Rejection (InternationaI Society for Heart and Lung Transplantation grades 3A to 4). However, our previous work suggests that myocyte necrosis is not a typical feature of Cellular Rejection. Methods: To clarify this point and to elucidate differences between Cellular Rejection and acute vascular Rejection, we compared the light and electron microscopic features of 35 consecutive endomyocardial biopsy specimens from six patients with acute vascular Rejection diagnosed with positive immunofluorescence, 12 consecutive endomyocardial biopsy specimens from three patients with mixed acute vascular Rejection and Cellular Rejection, and 435 endomyocardial biopsy specimens of International Society for Heart and Lung Transplantation grades 2 to 4 Cellular Rejection. Results: Endomyocardial biopsy specimens from eight of nine patients with acute vascular Rejection and mixed acute vascular Rejection/Cellular Rejection exhibited classic myocyte necrosis as the typical form of myocardial cell injury. Myocyte necrosis was characterized by lysis of the sarcolemma, marked swelling of mitochondria, and intramitochondrial flocculent densities. In contrast, the typical form of myocardial cell injury in Cellular Rejection was reversible. Reversible Cellular Rejection was characterized by extensive loss of myosin filaments and Z-lines with subsarcolemmal and intracytoplasmic accumulation of Z-band material. Cell swelling, mitochondrial swelling, intramitochondrial densities, and lysis of sarcolemma were not observed. Conclusions: We conclude that myocyte necrosis is a characteristic feature of acute vascular Rejection, whereas reversible myocardial cell injury is characteristic of Cellular Rejection, including grade 4. Myocyte necrosis is not a feature of Cellular Rejection. The presence of true myocyte necrosis in endomyocardial biopsy specimens from cyclosporine-treated heart transplants implicates some process other than Cellular Rejection. Processes producing myocyte necrosis include acute vascular Rejection, peritransplantation ischemia, and accelerated atherosclerosis