The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Allan R Brasier - One of the best experts on this subject based on the ideXlab platform.
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myh11 mutations result in a distinct Vascular Pathology driven by insulin like growth factor 1 and angiotensin ii
Human Molecular Genetics, 2007Co-Authors: Hariyadarshi Pannu, Van Tranfadulu, Christina L Papke, Steve Scherer, Wesley G Vick, Anthony L Estrera, Allan R Brasier, Caroline Presley, Hazim J. Safi, Ali J MarianAbstract:Non-syndromic thoracic aortic aneurysms and dissections (TAADs) are inherited in an autosomal dominant manner in 20% of cases. Familial TAAD is genetically heterogeneous and four loci have been mapped for this disease to date, including a locus at 16p for TAAD associated with patent ductus arteriosus (PDA). The defective gene at the 16p locus has recently been identified as the smooth muscle cell (SMC)-specific myosin heavy chain gene (MYH11). On sequencing MYH11 in 93 families with TAAD alone and three families with TAAD/PDA, we identified novel mutations in two families with TAAD/PDA, but none in families with TAAD alone. Histopathological analysis of aortic sections from two individuals with MYH11 mutations revealed SMC disarray and focal hyperplasia of SMCs in the aortic media. SMC hyperplasia leading to significant lumen narrowing in some of the vessels of the adventitia was also observed. Insulin-like growth factor-1 (IGF-1) was upregulated in mutant aortas as well as explanted SMCs, but no increase in transforming growth factor-b expression or downstream targets was observed. Enhanced expression of angiotensin-converting enzyme and markers of Angiotensin II (Ang II) Vascular inflammation (macrophage inflammatory protein-1a and b) were also found. These data suggest that MYH11 mutations are likely to be specific to the phenotype of TAAD/PDA and result in a distinct aortic and occlusive Vascular Pathology potentially driven by IGF-1 and Ang II.
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myh11 mutations result in a distinct Vascular Pathology driven by insulin like growth factor 1 and angiotensin ii
Human Molecular Genetics, 2007Co-Authors: Hariyadarshi Pannu, Van Tranfadulu, Christina L Papke, Steve Scherer, Anthony L Estrera, Caroline Presley, Hazim J. Safi, Yaozhong Liu, Dongchuan Guo, Allan R BrasierAbstract:Non-syndromic thoracic aortic aneurysms and dissections (TAADs) are inherited in an autosomal dominant manner in approximately 20% of cases. Familial TAAD is genetically heterogeneous and four loci have been mapped for this disease to date, including a locus at 16p for TAAD associated with patent ductus arteriosus (PDA). The defective gene at the 16p locus has recently been identified as the smooth muscle cell (SMC)-specific myosin heavy chain gene (MYH11). On sequencing MYH11 in 93 families with TAAD alone and three families with TAAD/PDA, we identified novel mutations in two families with TAAD/PDA, but none in families with TAAD alone. Histopathological analysis of aortic sections from two individuals with MYH11 mutations revealed SMC disarray and focal hyperplasia of SMCs in the aortic media. SMC hyperplasia leading to significant lumen narrowing in some of the vessels of the adventitia was also observed. Insulin-like growth factor-1 (IGF-1) was upregulated in mutant aortas as well as explanted SMCs, but no increase in transforming growth factor-beta expression or downstream targets was observed. Enhanced expression of angiotensin-converting enzyme and markers of Angiotensin II (Ang II) Vascular inflammation (macrophage inflammatory protein-1alpha and beta) were also found. These data suggest that MYH11 mutations are likely to be specific to the phenotype of TAAD/PDA and result in a distinct aortic and occlusive Vascular Pathology potentially driven by IGF-1 and Ang II.
Hariyadarshi Pannu - One of the best experts on this subject based on the ideXlab platform.
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myh11 mutations result in a distinct Vascular Pathology driven by insulin like growth factor 1 and angiotensin ii
Human Molecular Genetics, 2007Co-Authors: Hariyadarshi Pannu, Van Tranfadulu, Christina L Papke, Steve Scherer, Wesley G Vick, Anthony L Estrera, Allan R Brasier, Caroline Presley, Hazim J. Safi, Ali J MarianAbstract:Non-syndromic thoracic aortic aneurysms and dissections (TAADs) are inherited in an autosomal dominant manner in 20% of cases. Familial TAAD is genetically heterogeneous and four loci have been mapped for this disease to date, including a locus at 16p for TAAD associated with patent ductus arteriosus (PDA). The defective gene at the 16p locus has recently been identified as the smooth muscle cell (SMC)-specific myosin heavy chain gene (MYH11). On sequencing MYH11 in 93 families with TAAD alone and three families with TAAD/PDA, we identified novel mutations in two families with TAAD/PDA, but none in families with TAAD alone. Histopathological analysis of aortic sections from two individuals with MYH11 mutations revealed SMC disarray and focal hyperplasia of SMCs in the aortic media. SMC hyperplasia leading to significant lumen narrowing in some of the vessels of the adventitia was also observed. Insulin-like growth factor-1 (IGF-1) was upregulated in mutant aortas as well as explanted SMCs, but no increase in transforming growth factor-b expression or downstream targets was observed. Enhanced expression of angiotensin-converting enzyme and markers of Angiotensin II (Ang II) Vascular inflammation (macrophage inflammatory protein-1a and b) were also found. These data suggest that MYH11 mutations are likely to be specific to the phenotype of TAAD/PDA and result in a distinct aortic and occlusive Vascular Pathology potentially driven by IGF-1 and Ang II.
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myh11 mutations result in a distinct Vascular Pathology driven by insulin like growth factor 1 and angiotensin ii
Human Molecular Genetics, 2007Co-Authors: Hariyadarshi Pannu, Van Tranfadulu, Christina L Papke, Steve Scherer, Anthony L Estrera, Caroline Presley, Hazim J. Safi, Yaozhong Liu, Dongchuan Guo, Allan R BrasierAbstract:Non-syndromic thoracic aortic aneurysms and dissections (TAADs) are inherited in an autosomal dominant manner in approximately 20% of cases. Familial TAAD is genetically heterogeneous and four loci have been mapped for this disease to date, including a locus at 16p for TAAD associated with patent ductus arteriosus (PDA). The defective gene at the 16p locus has recently been identified as the smooth muscle cell (SMC)-specific myosin heavy chain gene (MYH11). On sequencing MYH11 in 93 families with TAAD alone and three families with TAAD/PDA, we identified novel mutations in two families with TAAD/PDA, but none in families with TAAD alone. Histopathological analysis of aortic sections from two individuals with MYH11 mutations revealed SMC disarray and focal hyperplasia of SMCs in the aortic media. SMC hyperplasia leading to significant lumen narrowing in some of the vessels of the adventitia was also observed. Insulin-like growth factor-1 (IGF-1) was upregulated in mutant aortas as well as explanted SMCs, but no increase in transforming growth factor-beta expression or downstream targets was observed. Enhanced expression of angiotensin-converting enzyme and markers of Angiotensin II (Ang II) Vascular inflammation (macrophage inflammatory protein-1alpha and beta) were also found. These data suggest that MYH11 mutations are likely to be specific to the phenotype of TAAD/PDA and result in a distinct aortic and occlusive Vascular Pathology potentially driven by IGF-1 and Ang II.
Carol A Derby - One of the best experts on this subject based on the ideXlab platform.
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association between Vascular Pathology and rate of cognitive decline independent of alzheimer s disease Pathology
Journal of the American Geriatrics Society, 2017Co-Authors: Ali Ezzati, Cuiling Wang, Richard B Lipton, Dorothea Altschul, Mindy J Katz, Dennis W Dickson, Carol A DerbyAbstract:Objectives To examine the association between Vascular Pathology and rate of cognitive decline in older adults independent of Alzheimer's disease (AD) Pathology. Design Prospective cohort study. Setting Community sample. Participants Individuals from the Einstein Aging Study autopsy series (N = 62). Measurements The Blessed Information-Memory-Concentration (BIMC) test was used to assess global cognitive status. AD Pathology was quantified according to Braak stage (<3 vs ≥ 3). Vascular Pathology was quantified using a previously reported macroVascular lesion (MVL) score. The association between Vascular Pathology and antemortem rates of cognitive decline adjusted for level of AD Pathology was assessed using linear mixed-effects models. Results Mean age was 81.8 at enrollment and 89.0 at death. Participants with more than two MVLs had faster cognitive decline than those with no MVLs (difference in annual rate of change in BIMC 0.74 points/yr, P = .03). Braak stage was also associated with cognitive decline (difference 0.57 points/yr, P = .03). The difference in rate of cognitive decline between those with more than two MVLs and those free of Vascular lesions persisted after adjustment for AD Pathology (difference in rate of change in BIMC 0.68 points/yr, P = .04). The effect of Vascular Pathology on cognitive decline was not significantly different according to AD Pathology. Conclusion Vascular brain Pathology is associated with rate of cognitive decline after adjusting for level of AD Pathology.
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Vascular Pathology is associated with rate of cognitive decline independent of ad Pathology einstein aging study p6 222
Neurology, 2016Co-Authors: Ali Ezzati, Cuiling Wang, Richard B Lipton, Dorothea Altschul, Mindy J Katz, Dennis W Dickson, Carol A DerbyAbstract:Objective: To examine the separate and joint influence of Vascular Pathology and Alzheimer’s disease (AD) Pathology on the rate of cognitive decline in older adults. Background: Presence of Vascular Pathology exacerbates the clinical presentation of AD and increases risk of clinically evident cognitive impairment. Methods: The Einstein Aging Study (EAS) autopsy series comprises 223 well characterized individuals, including 62 eligible for this study. Eligible participants were free of dementia at study baseline, and had a clinical evaluation within 5 years of death. The Blessed-information memory-concentration test (BIMC) was used to assess global cognitive status. AD Pathology was quantified based on Braak stage (<3 vs. ≥ 3). The Vascular Lesion Score (VLS) quantified Vascular Pathology. The association of Vascular Pathology with antemortem rates of cognitive decline adjusted for level of AD Pathology was assessed using linear mixed effects models with years prior to death as the time scale. Results: The mean age at enrollment was 81.8 and the mean age at death was 89.0 years. Compared to persons free of Vascular lesions, those with moderate/severe Vascular Pathology showed faster cognitive decline (difference in annual rate of change in BIMC=0.74; p=0.03). Braak stage was also associated with greater cognitive decline (p=0.03). The association of VLS with cognitive decline persisted after adjustment for AD Pathology (Difference in rate of change in BIMC=0.68, p=0.04). There was an interaction between Vascular and AD Pathology; Vascular Pathology had a greater effect on cognitive decline in persons who had higher Braak stages. (p for interaction = 0.03). Conclusions: Vascular brain Pathology is associated with the rate of cognitive decline after adjusting for level of AD Pathology. The effect of Vascular Pathology on cognitive decline is greater among individuals with higher burden of AD Pathology. Disclosure: Dr. Ezzati has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Lipton has received personal compensation for activities with Allergan, American Headache Society, Autonomic Technologies, Boston Scientific, Bristol Myers Squibb, Cognimed, Colucid, Eli-Lilly, eNeura Therapeutics, Merck, Novartis, Pfizer, Teva, and V Dr. Altschul has nothing to disclose. Dr. Katz has received research support from Bristol Myers Squibb. Dr. Dickson has nothing to disclose. Dr. Derby has nothing to disclose.
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contribution of Vascular Pathology to the clinical expression of dementia
Neurobiology of Aging, 2010Co-Authors: Dorothea Strozyk, Cuiling Wang, Richard B Lipton, Mindy J Katz, Dennis W Dickson, Carol A Derby, S C Lee, Joe VergheseAbstract:Vascular lesions in the brain are common with advancing age; however, the independent and cumulative contributions of postmortem Vascular lesions to antemortem cognitive status are not well established. We examined association of six Vascular lesions (large infarcts, lacunar infarcts, leukoencephalopathy, microinfarcts, cribriform changes, and cerebral amyloid angiopathy) with antemortem diagnoses of dementia, Alzheimer's disease (AD), and Vascular dementia (VaD) in 190 older adults from an autopsy series. We also developed a summary score based on three macroscopic Vascular lesions: large infarcts (0, 1, and >or=2), lacunar infarcts (0, 1, and >or=2), and leukoencephalopathy (none, mild, and moderate-to-severe). Sixty-eight percent of cases had Vascular lesions. Only leukoencephalopathy was associated with dementia (odds ratio (OR) 3.5, 95% CI 1.0-12.4), and only large infarcts were associated with VaD (OR 4.3, 95% CI 1.2-15.4). The Vascular score was associated with dementia (OR 1.6, 95% CI 1.2-2.3), AD (OR 1.5, 95% CI 1.0-2.1) and VaD (OR 2.0, 95% CI 1.4-3.0). Leukoencephalopathy, large infarcts, and higher Vascular burden is associated with the clinical expression of dementia and subtypes.
Ali J Marian - One of the best experts on this subject based on the ideXlab platform.
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myh11 mutations result in a distinct Vascular Pathology driven by insulin like growth factor 1 and angiotensin ii
Human Molecular Genetics, 2007Co-Authors: Hariyadarshi Pannu, Van Tranfadulu, Christina L Papke, Steve Scherer, Wesley G Vick, Anthony L Estrera, Allan R Brasier, Caroline Presley, Hazim J. Safi, Ali J MarianAbstract:Non-syndromic thoracic aortic aneurysms and dissections (TAADs) are inherited in an autosomal dominant manner in 20% of cases. Familial TAAD is genetically heterogeneous and four loci have been mapped for this disease to date, including a locus at 16p for TAAD associated with patent ductus arteriosus (PDA). The defective gene at the 16p locus has recently been identified as the smooth muscle cell (SMC)-specific myosin heavy chain gene (MYH11). On sequencing MYH11 in 93 families with TAAD alone and three families with TAAD/PDA, we identified novel mutations in two families with TAAD/PDA, but none in families with TAAD alone. Histopathological analysis of aortic sections from two individuals with MYH11 mutations revealed SMC disarray and focal hyperplasia of SMCs in the aortic media. SMC hyperplasia leading to significant lumen narrowing in some of the vessels of the adventitia was also observed. Insulin-like growth factor-1 (IGF-1) was upregulated in mutant aortas as well as explanted SMCs, but no increase in transforming growth factor-b expression or downstream targets was observed. Enhanced expression of angiotensin-converting enzyme and markers of Angiotensin II (Ang II) Vascular inflammation (macrophage inflammatory protein-1a and b) were also found. These data suggest that MYH11 mutations are likely to be specific to the phenotype of TAAD/PDA and result in a distinct aortic and occlusive Vascular Pathology potentially driven by IGF-1 and Ang II.
Dennis W Dickson - One of the best experts on this subject based on the ideXlab platform.
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association between Vascular Pathology and rate of cognitive decline independent of alzheimer s disease Pathology
Journal of the American Geriatrics Society, 2017Co-Authors: Ali Ezzati, Cuiling Wang, Richard B Lipton, Dorothea Altschul, Mindy J Katz, Dennis W Dickson, Carol A DerbyAbstract:Objectives To examine the association between Vascular Pathology and rate of cognitive decline in older adults independent of Alzheimer's disease (AD) Pathology. Design Prospective cohort study. Setting Community sample. Participants Individuals from the Einstein Aging Study autopsy series (N = 62). Measurements The Blessed Information-Memory-Concentration (BIMC) test was used to assess global cognitive status. AD Pathology was quantified according to Braak stage (<3 vs ≥ 3). Vascular Pathology was quantified using a previously reported macroVascular lesion (MVL) score. The association between Vascular Pathology and antemortem rates of cognitive decline adjusted for level of AD Pathology was assessed using linear mixed-effects models. Results Mean age was 81.8 at enrollment and 89.0 at death. Participants with more than two MVLs had faster cognitive decline than those with no MVLs (difference in annual rate of change in BIMC 0.74 points/yr, P = .03). Braak stage was also associated with cognitive decline (difference 0.57 points/yr, P = .03). The difference in rate of cognitive decline between those with more than two MVLs and those free of Vascular lesions persisted after adjustment for AD Pathology (difference in rate of change in BIMC 0.68 points/yr, P = .04). The effect of Vascular Pathology on cognitive decline was not significantly different according to AD Pathology. Conclusion Vascular brain Pathology is associated with rate of cognitive decline after adjusting for level of AD Pathology.
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Vascular Pathology is associated with rate of cognitive decline independent of ad Pathology einstein aging study p6 222
Neurology, 2016Co-Authors: Ali Ezzati, Cuiling Wang, Richard B Lipton, Dorothea Altschul, Mindy J Katz, Dennis W Dickson, Carol A DerbyAbstract:Objective: To examine the separate and joint influence of Vascular Pathology and Alzheimer’s disease (AD) Pathology on the rate of cognitive decline in older adults. Background: Presence of Vascular Pathology exacerbates the clinical presentation of AD and increases risk of clinically evident cognitive impairment. Methods: The Einstein Aging Study (EAS) autopsy series comprises 223 well characterized individuals, including 62 eligible for this study. Eligible participants were free of dementia at study baseline, and had a clinical evaluation within 5 years of death. The Blessed-information memory-concentration test (BIMC) was used to assess global cognitive status. AD Pathology was quantified based on Braak stage (<3 vs. ≥ 3). The Vascular Lesion Score (VLS) quantified Vascular Pathology. The association of Vascular Pathology with antemortem rates of cognitive decline adjusted for level of AD Pathology was assessed using linear mixed effects models with years prior to death as the time scale. Results: The mean age at enrollment was 81.8 and the mean age at death was 89.0 years. Compared to persons free of Vascular lesions, those with moderate/severe Vascular Pathology showed faster cognitive decline (difference in annual rate of change in BIMC=0.74; p=0.03). Braak stage was also associated with greater cognitive decline (p=0.03). The association of VLS with cognitive decline persisted after adjustment for AD Pathology (Difference in rate of change in BIMC=0.68, p=0.04). There was an interaction between Vascular and AD Pathology; Vascular Pathology had a greater effect on cognitive decline in persons who had higher Braak stages. (p for interaction = 0.03). Conclusions: Vascular brain Pathology is associated with the rate of cognitive decline after adjusting for level of AD Pathology. The effect of Vascular Pathology on cognitive decline is greater among individuals with higher burden of AD Pathology. Disclosure: Dr. Ezzati has nothing to disclose. Dr. Wang has nothing to disclose. Dr. Lipton has received personal compensation for activities with Allergan, American Headache Society, Autonomic Technologies, Boston Scientific, Bristol Myers Squibb, Cognimed, Colucid, Eli-Lilly, eNeura Therapeutics, Merck, Novartis, Pfizer, Teva, and V Dr. Altschul has nothing to disclose. Dr. Katz has received research support from Bristol Myers Squibb. Dr. Dickson has nothing to disclose. Dr. Derby has nothing to disclose.
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contribution of Vascular Pathology to the clinical expression of dementia
Neurobiology of Aging, 2010Co-Authors: Dorothea Strozyk, Cuiling Wang, Richard B Lipton, Mindy J Katz, Dennis W Dickson, Carol A Derby, S C Lee, Joe VergheseAbstract:Vascular lesions in the brain are common with advancing age; however, the independent and cumulative contributions of postmortem Vascular lesions to antemortem cognitive status are not well established. We examined association of six Vascular lesions (large infarcts, lacunar infarcts, leukoencephalopathy, microinfarcts, cribriform changes, and cerebral amyloid angiopathy) with antemortem diagnoses of dementia, Alzheimer's disease (AD), and Vascular dementia (VaD) in 190 older adults from an autopsy series. We also developed a summary score based on three macroscopic Vascular lesions: large infarcts (0, 1, and >or=2), lacunar infarcts (0, 1, and >or=2), and leukoencephalopathy (none, mild, and moderate-to-severe). Sixty-eight percent of cases had Vascular lesions. Only leukoencephalopathy was associated with dementia (odds ratio (OR) 3.5, 95% CI 1.0-12.4), and only large infarcts were associated with VaD (OR 4.3, 95% CI 1.2-15.4). The Vascular score was associated with dementia (OR 1.6, 95% CI 1.2-2.3), AD (OR 1.5, 95% CI 1.0-2.1) and VaD (OR 2.0, 95% CI 1.4-3.0). Leukoencephalopathy, large infarcts, and higher Vascular burden is associated with the clinical expression of dementia and subtypes.
