The prevalence of allergic and autoimmune diseases has been increasing from the last decades of 20th century. Intestinal microflora contributes to antigen exposure in early life and is one of the most abundant sources...The prevalence of allergic and autoimmune diseases has been increasing from the last decades of 20th century. Intestinal microflora contributes to antigen exposure in early life and is one of the most abundant sources of early immune stimulation as well as adaptation. Because allergic and autoimmune responses manifest early in life, there has been obvious interest in the potential benefits of modifying the gastrointestinal flora by using probiotic supplementation. So far, there have been several studies to address the role of probiotics in primary prevention and therapy, with a reported suspicious reduction in the incidence of atopic and autoimmune diseases. Here, our aim is to evaluate the available knowledge of mechanisms of preventative and therapeutic role of probiotics in different allergic and autoimmune disorders. Promising mechanisms of probiotic effects may be categorized as local and systemic effects. Local influences of probiotics potentially include reduction of gut permeability and systemic penetration of antigens, increased local immunoglobulin A production, and alteration of local inflammation or tolerance induction. Some possible systemic effects consist of anti-inflammatory effects mediated by Th17 cells and Toll-like receptors, Th1 skewing of responses to allergens, activation of tolerogenic dendritic cells, in addition to T-regulatory cell production.展开更多
Prior research establishing that bone interacts in coordination with the bone marrow microenvironment(BMME)to regulate hematopoietic homeostasis was largely based on analyses of individual bone-associated cell populat...Prior research establishing that bone interacts in coordination with the bone marrow microenvironment(BMME)to regulate hematopoietic homeostasis was largely based on analyses of individual bone-associated cell populations.Recent advances in intravital imaging has suggested that the expansion of hematopoietic stem cells(HSCs)and acute myeloid leukemia cells is restricted to bone marrow microdomains during a distinct stage of bone remodeling.These findings indicate that dynamic bone remodeling likely imposes additional heterogeneity within the BMME to yield differential clonal responses.A holistic understanding of the role of bone remodeling in regulating the stem cell niche and how these interactions are altered in age-related hematological malignancies will be critical to the development of novel interventions.To advance this understanding,herein,we provide a synopsis of the cellular and molecular constituents that participate in bone turnover and their known connections to the hematopoietic compartment.Specifically,we elaborate on the coupling between bone remodeling and the BMME in homeostasis and age-related hematological malignancies and after treatment with bone-targeting approaches.We then discuss unresolved questions and ambiguities that remain in the field.展开更多
We report the development and spontaneous resolution of annular erythematous skin lesions consistent with sarcoid dermatitis in a child with DiGeorge syndrome (DGS) carrying the 22q11.2 microdeletion. The skin lesion ...We report the development and spontaneous resolution of annular erythematous skin lesions consistent with sarcoid dermatitis in a child with DiGeorge syndrome (DGS) carrying the 22q11.2 microdeletion. The skin lesion developed after she was treated with isoniazid (INH) following exposure to active tuberculosis (TB). After resolution of the skin lesions, this child developed sterile hyperplastic osteomyelitis consistent with SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) osteomyelitis in her right mandible triggered by an odontogenic infection. This child had congenital heart disease, dysmorphic facies, recurrent sinopulmonary infection, gastroesophgeal re- flux disease, scoliosis, reactive periostitis, and developmental delay. She had a low CD4 and CD8 T cell count with a normal 4/8 ratio, but normal cell proliferation and T cell cytokine production in response to mitogens. When she was presented with sterile osteomyelitis of right mandible, she revealed polyclonal hypergammaglobulinemia with elevated erythrocyte sedimentation rate (ESR)/ angiotensin converting enzyme (ACE) levels, but negative CRP. Autoimmune and sarcoidosis workup was negative. Inflammatory parameters gradually normalized following resolution of odontogenic infection and with the use of non- steroidal anti- inflammatory drugs (NSAIDs). The broad clinical spectrum of DGS is further expanded with the development of autoimmune and inflammatory complications later in life. This case suggests that patients with the DGS can present with unusual sterile inflammatory lesions triggered by environmental factors, further broadening the clinical spectrum of this syndrome.展开更多
Background:Exposure to household domestic animals such as cats and dogs in early life may have some role in pathogenesis of asthma.Racial differences exist in the prevalence of asthma.We hypothesized that there may al...Background:Exposure to household domestic animals such as cats and dogs in early life may have some role in pathogenesis of asthma.Racial differences exist in the prevalence of asthma.We hypothesized that there may also be racial differences in pet ownership in families with asthma.Methods:A cross sectional study was conducted from June 2011 to December 2014 on 823 of 850(97%)families of children with asthma for pet ownership.Comparisons among racial groups were done using chi square analysis and one-way analysis of variance.Results:The mean age of the cohort was 6.9±4.4 years.A total of 540(65.62%)patients were Caucasian,195(23.7%)African American,42(5.1%)hispanics,and 26(3.2%)biracial with one Caucasian parent.Pets in the home were reported by 470(58.5%)households.Signifi cantly fewer African American and hispanic families had pets in the home(26.9% and 44.7%)than biracial and Caucasian families(72% and 69.9%,P<0.001).Likewise,significantly more biracial and Caucasian families were noted to have dogs(52% and 54.4%)or cats(25.4%and 40%)or both cats and dogs(28% and 18%)than African Americans families(20.3%,P<0.001;7.1%,P<0.001)and(4.6%,P<0.001),respectively.Conclusion:Among families with asthmatic children,pet ownership is significantly more likely in Caucasian families compared with African-American and Hispanic families,thus there is a racial diversity in pet ownership among families of children with asthma.展开更多
文摘The prevalence of allergic and autoimmune diseases has been increasing from the last decades of 20th century. Intestinal microflora contributes to antigen exposure in early life and is one of the most abundant sources of early immune stimulation as well as adaptation. Because allergic and autoimmune responses manifest early in life, there has been obvious interest in the potential benefits of modifying the gastrointestinal flora by using probiotic supplementation. So far, there have been several studies to address the role of probiotics in primary prevention and therapy, with a reported suspicious reduction in the incidence of atopic and autoimmune diseases. Here, our aim is to evaluate the available knowledge of mechanisms of preventative and therapeutic role of probiotics in different allergic and autoimmune disorders. Promising mechanisms of probiotic effects may be categorized as local and systemic effects. Local influences of probiotics potentially include reduction of gut permeability and systemic penetration of antigens, increased local immunoglobulin A production, and alteration of local inflammation or tolerance induction. Some possible systemic effects consist of anti-inflammatory effects mediated by Th17 cells and Toll-like receptors, Th1 skewing of responses to allergens, activation of tolerogenic dendritic cells, in addition to T-regulatory cell production.
基金supported by awards from the National Institute of Health R21AR069789&R01 AG059775(to LX),R01 AG076786&R01 AG079556The Henry and Marilyn Taub Foundation+4 种基金the Edward P.Evans Foundationthe Mangurian Foundationthe National Aeronautics and Space Administration(to LMC)NIH R21 AR081050,R01 AR056702,P30 AR069655&P50 AR072000(to EMS)University of Rochester Aging Institute and the Dresner MDS foundation(to SY)。
文摘Prior research establishing that bone interacts in coordination with the bone marrow microenvironment(BMME)to regulate hematopoietic homeostasis was largely based on analyses of individual bone-associated cell populations.Recent advances in intravital imaging has suggested that the expansion of hematopoietic stem cells(HSCs)and acute myeloid leukemia cells is restricted to bone marrow microdomains during a distinct stage of bone remodeling.These findings indicate that dynamic bone remodeling likely imposes additional heterogeneity within the BMME to yield differential clonal responses.A holistic understanding of the role of bone remodeling in regulating the stem cell niche and how these interactions are altered in age-related hematological malignancies will be critical to the development of novel interventions.To advance this understanding,herein,we provide a synopsis of the cellular and molecular constituents that participate in bone turnover and their known connections to the hematopoietic compartment.Specifically,we elaborate on the coupling between bone remodeling and the BMME in homeostasis and age-related hematological malignancies and after treatment with bone-targeting approaches.We then discuss unresolved questions and ambiguities that remain in the field.
文摘We report the development and spontaneous resolution of annular erythematous skin lesions consistent with sarcoid dermatitis in a child with DiGeorge syndrome (DGS) carrying the 22q11.2 microdeletion. The skin lesion developed after she was treated with isoniazid (INH) following exposure to active tuberculosis (TB). After resolution of the skin lesions, this child developed sterile hyperplastic osteomyelitis consistent with SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) osteomyelitis in her right mandible triggered by an odontogenic infection. This child had congenital heart disease, dysmorphic facies, recurrent sinopulmonary infection, gastroesophgeal re- flux disease, scoliosis, reactive periostitis, and developmental delay. She had a low CD4 and CD8 T cell count with a normal 4/8 ratio, but normal cell proliferation and T cell cytokine production in response to mitogens. When she was presented with sterile osteomyelitis of right mandible, she revealed polyclonal hypergammaglobulinemia with elevated erythrocyte sedimentation rate (ESR)/ angiotensin converting enzyme (ACE) levels, but negative CRP. Autoimmune and sarcoidosis workup was negative. Inflammatory parameters gradually normalized following resolution of odontogenic infection and with the use of non- steroidal anti- inflammatory drugs (NSAIDs). The broad clinical spectrum of DGS is further expanded with the development of autoimmune and inflammatory complications later in life. This case suggests that patients with the DGS can present with unusual sterile inflammatory lesions triggered by environmental factors, further broadening the clinical spectrum of this syndrome.
文摘Background:Exposure to household domestic animals such as cats and dogs in early life may have some role in pathogenesis of asthma.Racial differences exist in the prevalence of asthma.We hypothesized that there may also be racial differences in pet ownership in families with asthma.Methods:A cross sectional study was conducted from June 2011 to December 2014 on 823 of 850(97%)families of children with asthma for pet ownership.Comparisons among racial groups were done using chi square analysis and one-way analysis of variance.Results:The mean age of the cohort was 6.9±4.4 years.A total of 540(65.62%)patients were Caucasian,195(23.7%)African American,42(5.1%)hispanics,and 26(3.2%)biracial with one Caucasian parent.Pets in the home were reported by 470(58.5%)households.Signifi cantly fewer African American and hispanic families had pets in the home(26.9% and 44.7%)than biracial and Caucasian families(72% and 69.9%,P<0.001).Likewise,significantly more biracial and Caucasian families were noted to have dogs(52% and 54.4%)or cats(25.4%and 40%)or both cats and dogs(28% and 18%)than African Americans families(20.3%,P<0.001;7.1%,P<0.001)and(4.6%,P<0.001),respectively.Conclusion:Among families with asthmatic children,pet ownership is significantly more likely in Caucasian families compared with African-American and Hispanic families,thus there is a racial diversity in pet ownership among families of children with asthma.