Sameer Mathur - Academia.edu (original) (raw)
Papers by Sameer Mathur
Current allergy and asthma reports, 2011
There is a common perception among physicians and patients that allergic diseases are not relevan... more There is a common perception among physicians and patients that allergic diseases are not relevant in older adults. There is also recognition that innate and adaptive immune functions decline with aging. It is the function of a variety of immune cells in the form of allergic inflammation that is a hallmark of allergic diseases. In fact, there is a fairly consistent observation that measures of allergic sensitization, such as skin prick testing, specific IgE, or total IgE, decline with age. Nonetheless, the association between allergic sensitization and allergic diseases, particularly asthma and allergic rhinitis, remains robust in the older adult population. Consequently, an appropriate evaluation of allergic sensitivities is warranted and indicated in older asthma and rhinitis patients to provide optimal care for the individual and minimize any resultant morbidity and mortality.
Journal of Allergy and Clinical Immunology, 2010
Immunosenescence is defined as changes in the innate and adaptive immune response associated with... more Immunosenescence is defined as changes in the innate and adaptive immune response associated with increased age. The clinical consequences of immunosenescence include increased susceptibility to infection, malignancy, and autoimmunity, decreased response to vaccination and impaired wound healing. However, there are several immune alterations which may facilitate persistence of asthma into late adulthood, or development of asthma after the age of 50-60 years. Asthma in older patients is not uncommon and is a growing population as the average lifespan increases. Specific innate changes which may affect severity of asthma in older patients, or be involved in the development of late onset asthma include impaired in mucociliary clearance, and changes in airway neutrophil, eosinophil and mast cell numbers and function. Additionally, agerelated altered antigen presentation and decreased in specific antibody responses may increases the risk of respiratory infections. Respiratory infections exacerbate asthma in older patients, and possibly play a role in the pathogenesis of late onset asthma. Furthermore, cytokine profiles may be modified with aging; some investigators suggesting a trend towards Th2 cytokine expression. This review examines specific innate and adaptive immune responses affected by aging that may impact the inflammatory response in older adults with asthma.
Journal of Allergy and Clinical Immunology, 2011
Molecular and cellular biology, 1998
Mammalian cells coexpress a family of heat shock factors (HSFs) whose activities are regulated by... more Mammalian cells coexpress a family of heat shock factors (HSFs) whose activities are regulated by diverse stress conditions to coordinate the inducible expression of heat shock genes. Distinct from HSF1, which is expressed ubiquitously and activated by heat shock and other stresses that result in the appearance of nonnative proteins, the stress signal for HSF2 has not been identified. HSF2 activity has been associated with development and differentiation, and the activation properties of HSF2 have been characterized in hemin-treated human K562 erythroleukemia cells. Here, we demonstrate that a stress signal for HSF2 activation occurs when the ubiquitin-proteasome pathway is inhibited. HSF2 DNA-binding activity is induced upon exposure of mammalian cells to the proteasome inhibitors hemin, MG132, and lactacystin, and in the mouse ts85 cell line, which carries a temperature sensitivity mutation in the ubiquitin-activating enzyme (E1) upon shift to the nonpermissive temperature. HSF2 i...
Proceedings of the National Academy of Sciences, 1994
One ofthe basic features of the inducible heat shock response is the activation of heat shock fac... more One ofthe basic features of the inducible heat shock response is the activation of heat shock factor which results in the rapid transcriptional induction of the heat shock genes. Although it is widely considered that the heat shock response is ubiquitous, several reports have indicated that the transcriptional response can vary in both intensity and kinetics and often in a tissue-specific manner. Of interest have been
Molecular and Cellular Biology, 2001
Vertebrate cells express a family of heat shock transcription factors (HSF1 to HSF4) that coordin... more Vertebrate cells express a family of heat shock transcription factors (HSF1 to HSF4) that coordinate the inducible regulation of heat shock genes in response to diverse signals. HSF1 is potent and activated rapidly though transiently by heat shock, whereas HSF2 is a less active transcriptional regulator but can retain its DNA binding properties for extended periods. Consequently, the differential activation of HSF1 and HSF2 by various stresses may be critical for cells to survive repeated and diverse stress challenges and to provide a mechanism for more precise regulation of heat shock gene expression. Here we show, using a novel DNA binding and detection assay, that HSF1 and HSF2 are coactivated to different levels in response to a range of conditions that cause cell stress. Above a low basal activity of both HSFs, heat shock preferentially activates HSF1, whereas the amino acid analogue azetidine or the proteasome inhibitor MG132 coactivates both HSFs to different levels and hemin preferentially induces HSF2. Unexpectedly, we also found that heat shock has dramatic adverse effects on HSF2 that lead to its reversible inactivation coincident with relocalization from the nucleus. The reversible inactivation of HSF2 is specific to heat shock and does not occur with other stressors or in cells expressing high levels of heat shock proteins. These results reveal that HSF2 activity is negatively regulated by heat and suggest a role for heat shock proteins in the positive regulation of HSF2.
Journal of Allergy and Clinical Immunology, 2006
Journal of Allergy and Clinical Immunology, 2011
Asthma in the elderly (AIE) is under diagnosed and under treated and there is a paucity of knowle... more Asthma in the elderly (AIE) is under diagnosed and under treated and there is a paucity of knowledge. The National Institute on Aging convened this workshop to identify what is known, what gaps in knowledge remain and suggest research directions needed to improve the understanding and care of AIE. Asthma presenting at an advanced age often has similar clinical and physiologic consequences as seen with younger individuals but co-morbid illnesses and the psychosocial effects of aging may affect the diagnosis, clinical presentation and care of asthma in this population. At least two phenotypes exist among elderly asthma; those with long-standing asthma have more severe airflow limitation and less complete reversibility than those with lateonset asthma. Many challenges exist in the recognition and treatment of asthma in the elderly. Furthermore, the pathophysiological mechanisms of AIE are likely to be different from those seen in young asthmatics and these differences may influence the clinical course and outcomes of asthma in this population.
Immunity & Ageing, 2010
Page 1. This Provisional PDF corresponds to the article as it appeared upon acceptance. Fully for... more Page 1. This Provisional PDF corresponds to the article as it appeared upon acceptance. Fully formatted PDF and full text (HTML) versions will be made available soon. Characterization of leukotrienes in a pilot study of older asthma subjects ...
Clinical Immunology, 2014
Semaphorin 7A (sema7a) plays a major role in TGF-β1-induced lung fibrosis. Based on the accumulat... more Semaphorin 7A (sema7a) plays a major role in TGF-β1-induced lung fibrosis. Based on the accumulating evidence that eosinophils contribute to fibrosis/remodeling in the airway, we hypothesized that airway eosinophils may be a significant source of sema7a. In vivo, sema7a was expressed on the surface of circulating eosinophils and upregulated on bronchoalveolar lavage eosinophils obtained after segmental bronchoprovocation with allergen. Based on mRNA levels in unfractionated and isolated bronchoalveolar cells, eosinophils are the predominant source of sema7a. In vitro, among the members of the IL-5-family cytokines, sema7a protein on the surface of blood eosinophils was increased more by IL-3 than by GM-CSF or IL-5. Cytokine-induced expression of cell surface sema7a required translation of newly synthesized protein. Finally, a recombinant sema7a induced alpha-smooth muscle actin production in human bronchial fibroblasts. semaphorin 7A is a potentially important modulator of eosinophil profibrotic functions in the airway remodeling of patients with chronic asthma.
CHEST Journal, 2008
Background-Aging results in changes in immune cell function which have been described for T-cells... more Background-Aging results in changes in immune cell function which have been described for T-cells, macrophage, neutrophils, and dendritic cells, but not yet for eosinophils. We sought to define age-related changes in eosinophil function and their potential implications for asthma. Methods. We recruited human subjects with asthma in two age groups, a younger group (20-40 years old) and older group (55-80 years old). Lung function, induced sputum, and peripheral blood were obtained from each subject. Eosinophils isolated from the peripheral blood were examined for in vitro functional activities including degranulation, superoxide anion production, adhesion, and chemotaxis.
B21. NEUTROPHIL STUDIES IN ASTHMA AND COPD, 2011
/ Poster Discussion Session / Monday, May 16/8:15 AM-10:45 AM / Room B21 NEUTROPHIL STUDIES IN AS... more / Poster Discussion Session / Monday, May 16/8:15 AM-10:45 AM / Room B21 NEUTROPHIL STUDIES IN ASTHMA AND COPD ... Lower Airway Rhinovirus Burden And The Risk Of Asthma Exacerbation ... , RL Sorkness , W. Lee , MD Evans , M. Wolff , S. Mathur , G. Crisafi , K. ...
Current allergy and asthma reports, 2011
There is a common perception among physicians and patients that allergic diseases are not relevan... more There is a common perception among physicians and patients that allergic diseases are not relevant in older adults. There is also recognition that innate and adaptive immune functions decline with aging. It is the function of a variety of immune cells in the form of allergic inflammation that is a hallmark of allergic diseases. In fact, there is a fairly consistent observation that measures of allergic sensitization, such as skin prick testing, specific IgE, or total IgE, decline with age. Nonetheless, the association between allergic sensitization and allergic diseases, particularly asthma and allergic rhinitis, remains robust in the older adult population. Consequently, an appropriate evaluation of allergic sensitivities is warranted and indicated in older asthma and rhinitis patients to provide optimal care for the individual and minimize any resultant morbidity and mortality.
Journal of Allergy and Clinical Immunology, 2010
Immunosenescence is defined as changes in the innate and adaptive immune response associated with... more Immunosenescence is defined as changes in the innate and adaptive immune response associated with increased age. The clinical consequences of immunosenescence include increased susceptibility to infection, malignancy, and autoimmunity, decreased response to vaccination and impaired wound healing. However, there are several immune alterations which may facilitate persistence of asthma into late adulthood, or development of asthma after the age of 50-60 years. Asthma in older patients is not uncommon and is a growing population as the average lifespan increases. Specific innate changes which may affect severity of asthma in older patients, or be involved in the development of late onset asthma include impaired in mucociliary clearance, and changes in airway neutrophil, eosinophil and mast cell numbers and function. Additionally, agerelated altered antigen presentation and decreased in specific antibody responses may increases the risk of respiratory infections. Respiratory infections exacerbate asthma in older patients, and possibly play a role in the pathogenesis of late onset asthma. Furthermore, cytokine profiles may be modified with aging; some investigators suggesting a trend towards Th2 cytokine expression. This review examines specific innate and adaptive immune responses affected by aging that may impact the inflammatory response in older adults with asthma.
Journal of Allergy and Clinical Immunology, 2011
Molecular and cellular biology, 1998
Mammalian cells coexpress a family of heat shock factors (HSFs) whose activities are regulated by... more Mammalian cells coexpress a family of heat shock factors (HSFs) whose activities are regulated by diverse stress conditions to coordinate the inducible expression of heat shock genes. Distinct from HSF1, which is expressed ubiquitously and activated by heat shock and other stresses that result in the appearance of nonnative proteins, the stress signal for HSF2 has not been identified. HSF2 activity has been associated with development and differentiation, and the activation properties of HSF2 have been characterized in hemin-treated human K562 erythroleukemia cells. Here, we demonstrate that a stress signal for HSF2 activation occurs when the ubiquitin-proteasome pathway is inhibited. HSF2 DNA-binding activity is induced upon exposure of mammalian cells to the proteasome inhibitors hemin, MG132, and lactacystin, and in the mouse ts85 cell line, which carries a temperature sensitivity mutation in the ubiquitin-activating enzyme (E1) upon shift to the nonpermissive temperature. HSF2 i...
Proceedings of the National Academy of Sciences, 1994
One ofthe basic features of the inducible heat shock response is the activation of heat shock fac... more One ofthe basic features of the inducible heat shock response is the activation of heat shock factor which results in the rapid transcriptional induction of the heat shock genes. Although it is widely considered that the heat shock response is ubiquitous, several reports have indicated that the transcriptional response can vary in both intensity and kinetics and often in a tissue-specific manner. Of interest have been
Molecular and Cellular Biology, 2001
Vertebrate cells express a family of heat shock transcription factors (HSF1 to HSF4) that coordin... more Vertebrate cells express a family of heat shock transcription factors (HSF1 to HSF4) that coordinate the inducible regulation of heat shock genes in response to diverse signals. HSF1 is potent and activated rapidly though transiently by heat shock, whereas HSF2 is a less active transcriptional regulator but can retain its DNA binding properties for extended periods. Consequently, the differential activation of HSF1 and HSF2 by various stresses may be critical for cells to survive repeated and diverse stress challenges and to provide a mechanism for more precise regulation of heat shock gene expression. Here we show, using a novel DNA binding and detection assay, that HSF1 and HSF2 are coactivated to different levels in response to a range of conditions that cause cell stress. Above a low basal activity of both HSFs, heat shock preferentially activates HSF1, whereas the amino acid analogue azetidine or the proteasome inhibitor MG132 coactivates both HSFs to different levels and hemin preferentially induces HSF2. Unexpectedly, we also found that heat shock has dramatic adverse effects on HSF2 that lead to its reversible inactivation coincident with relocalization from the nucleus. The reversible inactivation of HSF2 is specific to heat shock and does not occur with other stressors or in cells expressing high levels of heat shock proteins. These results reveal that HSF2 activity is negatively regulated by heat and suggest a role for heat shock proteins in the positive regulation of HSF2.
Journal of Allergy and Clinical Immunology, 2006
Journal of Allergy and Clinical Immunology, 2011
Asthma in the elderly (AIE) is under diagnosed and under treated and there is a paucity of knowle... more Asthma in the elderly (AIE) is under diagnosed and under treated and there is a paucity of knowledge. The National Institute on Aging convened this workshop to identify what is known, what gaps in knowledge remain and suggest research directions needed to improve the understanding and care of AIE. Asthma presenting at an advanced age often has similar clinical and physiologic consequences as seen with younger individuals but co-morbid illnesses and the psychosocial effects of aging may affect the diagnosis, clinical presentation and care of asthma in this population. At least two phenotypes exist among elderly asthma; those with long-standing asthma have more severe airflow limitation and less complete reversibility than those with lateonset asthma. Many challenges exist in the recognition and treatment of asthma in the elderly. Furthermore, the pathophysiological mechanisms of AIE are likely to be different from those seen in young asthmatics and these differences may influence the clinical course and outcomes of asthma in this population.
Immunity & Ageing, 2010
Page 1. This Provisional PDF corresponds to the article as it appeared upon acceptance. Fully for... more Page 1. This Provisional PDF corresponds to the article as it appeared upon acceptance. Fully formatted PDF and full text (HTML) versions will be made available soon. Characterization of leukotrienes in a pilot study of older asthma subjects ...
Clinical Immunology, 2014
Semaphorin 7A (sema7a) plays a major role in TGF-β1-induced lung fibrosis. Based on the accumulat... more Semaphorin 7A (sema7a) plays a major role in TGF-β1-induced lung fibrosis. Based on the accumulating evidence that eosinophils contribute to fibrosis/remodeling in the airway, we hypothesized that airway eosinophils may be a significant source of sema7a. In vivo, sema7a was expressed on the surface of circulating eosinophils and upregulated on bronchoalveolar lavage eosinophils obtained after segmental bronchoprovocation with allergen. Based on mRNA levels in unfractionated and isolated bronchoalveolar cells, eosinophils are the predominant source of sema7a. In vitro, among the members of the IL-5-family cytokines, sema7a protein on the surface of blood eosinophils was increased more by IL-3 than by GM-CSF or IL-5. Cytokine-induced expression of cell surface sema7a required translation of newly synthesized protein. Finally, a recombinant sema7a induced alpha-smooth muscle actin production in human bronchial fibroblasts. semaphorin 7A is a potentially important modulator of eosinophil profibrotic functions in the airway remodeling of patients with chronic asthma.
CHEST Journal, 2008
Background-Aging results in changes in immune cell function which have been described for T-cells... more Background-Aging results in changes in immune cell function which have been described for T-cells, macrophage, neutrophils, and dendritic cells, but not yet for eosinophils. We sought to define age-related changes in eosinophil function and their potential implications for asthma. Methods. We recruited human subjects with asthma in two age groups, a younger group (20-40 years old) and older group (55-80 years old). Lung function, induced sputum, and peripheral blood were obtained from each subject. Eosinophils isolated from the peripheral blood were examined for in vitro functional activities including degranulation, superoxide anion production, adhesion, and chemotaxis.
B21. NEUTROPHIL STUDIES IN ASTHMA AND COPD, 2011
/ Poster Discussion Session / Monday, May 16/8:15 AM-10:45 AM / Room B21 NEUTROPHIL STUDIES IN AS... more / Poster Discussion Session / Monday, May 16/8:15 AM-10:45 AM / Room B21 NEUTROPHIL STUDIES IN ASTHMA AND COPD ... Lower Airway Rhinovirus Burden And The Risk Of Asthma Exacerbation ... , RL Sorkness , W. Lee , MD Evans , M. Wolff , S. Mathur , G. Crisafi , K. ...