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[PMID]:27773452
[Au] Autor:Xu Z; Sharma M; Gelman A; Hachem R; Mohanakumar T
[Ad] Endereço:Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA; Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
[Ti] Título:Significant role for microRNA-21 affecting toll-like receptor pathway in primary graft dysfunction after human lung transplantation.
[So] Source:J Heart Lung Transplant;36(3):331-339, 2017 Mar.
[Is] ISSN:1557-3117
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: MicroRNAs (miRNAs) were recently identified as modulators of immune responses after human lung transplantation (LTx). This study was undertaken to assess the contribution of miRNAs to the pathogenesis of primary graft dysfunction (PGD) after LTx. METHODS: Of the 39 recipients, 14 (35.9%) developed Grade 3 PGD (i.e., severe PGD) within the first 72 hours of LTx. The remaining 25 recipients (64.1%) had Grade 2 or less PGD, and served as the control group. miRNAs were isolated from cells purified by bronchoalveolar lavage (BAL). Bioinformatic prediction and validation by luciferase reporter assays were performed to identify targets regulated by miR-21. Transfection of human monocytic cell line (THP-1) was conducted to determine miR-21's cellular function. RESULTS: Pilot miRNA profiling of donor BAL samples before implantation in PGD (n = 6) revealed significant upregulation in 44 miRNAs and downregulation in 80 miRNAs compared with control (n = 6). Validation using a separate cohort demonstrated significant underexpression of miR-21 in patients with severe PGD. Furthermore, underexpression of miR-21 levels was negatively correlated with clinical PGD grades (Grade 2 PGD vs Grade 0 PGD: p = 0.042; Grade 3 PGD vs Grade 0 PGD: p = 0.004). Molecular analysis demonstrated that miR-21 targeted key components in the toll-like receptor (TLR) signaling pathway, including TLR4, IRAK3 and CXCL10. Further, incubation of THP-1 cells with cell-free BAL from severe PGD resulted in transactivation of inflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α). In contrast, increased expression of miR-21 resulted in marked suppression of IL-1-ß and TNF-α production. CONCLUSIONS: Underexpression of miR-21 may lead to the development of severe PGD by activating key components of the TLR pathway.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica
Transplante de Pulmão/efeitos adversos
MicroRNAs/genética
Disfunção Primária do Enxerto/genética
Receptores Toll-Like/genética
[Mh] Termos MeSH secundário: Adulto
Western Blotting
Líquido da Lavagem Broncoalveolar
Estudos de Coortes
Feminino
Seres Humanos
Transplante de Pulmão/métodos
Masculino
Meia-Idade
Disfunção Primária do Enxerto/fisiopatologia
Prognóstico
Reação em Cadeia da Polimerase em Tempo Real/métodos
Estudos Retrospectivos
Papel (Figurativo)
Sensibilidade e Especificidade
Transdução de Sinais/genética
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MIRN21 microRNA, human); 0 (MicroRNAs); 0 (Toll-Like Receptors)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


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[PMID]:27773450
[Au] Autor:Kovarik JJ; Kopecky C; Antlanger M; Domenig O; Kaltenecker CC; Werzowa J; Hecking M; Mahr S; Grömmer M; Wallner C; Aumayr K; Kain R; Zuckermann A; Poglitsch M; Säemann MD
[Ad] Endereço:Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
[Ti] Título:Effects of angiotensin-converting-enzyme inhibitor therapy on the regulation of the plasma and cardiac tissue renin-angiotensin system in heart transplant patients.
[So] Source:J Heart Lung Transplant;36(3):355-365, 2017 Mar.
[Is] ISSN:1557-3117
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors (ACEis) are beneficial in patients with heart failure, yet their role after heart transplantation (HTx) remains ambiguous. Particularly, the effects of ACEis on plasma and cardiac metabolites of the "classical" and "alternative" renin-angiotensin system (RAS) in HTx patients are unknown. METHODS: This cross-sectional study used a novel mass spectrometry-based approach to analyze plasma and tissue RAS regulation in homogenates of heart biopsy specimens from 10 stable HTx patients without RAS blockade and in 15 patients with ACEi therapy. Angiotensin (Ang) levels in plasma and Ang formation rates in biopsy tissue homogenates were measured. RESULTS: Plasma Ang II formation is exclusively ACE dependent, whereas cardiac Ang II formation is primarily chymase dependent in HTx patients. ACEi therapy substantially increased plasma Ang-(1-7), the key effector of the alternative RAS, leaving plasma Ang II largely intact. Importantly, neprilysin and prolyl-carboxypeptidase but not angiotensin converting enzyme 2 are essential for cardiac tissue Ang-(1-7) formation. CONCLUSION: ACE is the key enzyme for the generation of plasma Ang II, whereas chymase is responsible for cardiac tissue production of Ang II. Furthermore, our findings reveal that neprilysin and prolyl-carboxypeptidase are the essential cardiac enzymes for the alternative RAS after HTx. These novel insights into the versatile regulation of the RAS in HTx patients might affect future therapeutic avenues, such as chymase and neprilysin inhibition, beyond classical Ang II blockade.
[Mh] Termos MeSH primário: Inibidores da Enzima Conversora de Angiotensina/administração & dosagem
Rejeição de Enxerto/prevenção & controle
Insuficiência Cardíaca/sangue
Transplante de Coração/métodos
Sistema Renina-Angiotensina/efeitos dos fármacos
[Mh] Termos MeSH secundário: Idoso
Áustria
Biópsia por Agulha
Estudos Transversais
Ecocardiografia
Feminino
Seguimentos
Sobrevivência de Enxerto
Insuficiência Cardíaca/diagnóstico por imagem
Insuficiência Cardíaca/cirurgia
Transplante de Coração/efeitos adversos
Seres Humanos
Imuno-Histoquímica
Masculino
Meia-Idade
Valores de Referência
Medição de Risco
Papel (Figurativo)
Resultado do Tratamento
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Angiotensin-Converting Enzyme Inhibitors)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


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[PMID]:28453061
[Au] Autor:Hoyos-Hernández PA; Duarte-Alarcón C
[Ad] Endereço:Pontificia Universidad Javeriana, Cali, Colombia, paulahoyos@javerianacali.edu.co.
[Ti] Título:[Roles and challenges of female heads of household with HIV/AIDS].
[Ti] Título:Roles y desafíos de mujeres jefas de hogar con VIH/Sida..
[So] Source:Rev Salud Publica (Bogota);18(4):554-567, 2016 Aug.
[Is] ISSN:0124-0064
[Cp] País de publicação:Colombia
[La] Idioma:spa
[Ab] Resumo:Objective To characterize the roles and challenges that female heads of households with HIV in Valle del Cauca, Colombia assume. Method A qualitative exploratory method, based on Grounded Theory was conducted. Data were collected through in depth interviews to 13 women with HIV, heads of household with ages between 19 and 46,who live in the cities of Cali and Buenaventura. Results The main roles assumed by women are taking care of their children and their homes, expressing affection, providing support during different life events and administrative procedures related to health care services access. The challenges expressed by these women include aspects related to parenting, being a self-care role model, accompanying and leading the diagnosis and adherence to the treatment children with HIV, revealing the diagnosis, providing the best living conditions, and providing access to goods and services. Conclusions The results of the study highlight the challenges that women living with a chronic illness, that is still loaded with stigma and discrimination, have to face. The social, economic, cultural and health aspects related to the inequities and inequalities in health, to gender and access to health services, to decent work and to education are made clear in this work.
[Mh] Termos MeSH primário: Características da Família
Relações Familiares
Infecções por HIV/psicologia
Papel (Figurativo)
[Mh] Termos MeSH secundário: Síndrome de Imunodeficiência Adquirida/psicologia
Adulto
Colômbia
Feminino
Seres Humanos
Meia-Idade
Aceitação pelo Paciente de Cuidados de Saúde
Autocuidado
Estigma Social
Fatores Socioeconômicos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:29280399
[Au] Autor:Subramaniam M; Chong SA; Satghare P; Browning CJ; Thomas S
[Ad] Endereço:1 Research Division, Institute of Mental Health , Singapore, Singapore.
[Ti] Título:Gambling and family: A two-way relationship.
[So] Source:J Behav Addict;6(4):689-698, 2017 Dec 01.
[Is] ISSN:2063-5303
[Cp] País de publicação:Hungary
[La] Idioma:eng
[Ab] Resumo:Background and aims Families play an important role in the evolution of gambling and are also adversely affected by the disordered gambling of any one of their members. The aims of this study were to explore both the role families play in gambling initiation, maintenance, and help-seeking, and the harm caused to families by the gambling behavior using a qualitative approach. Methods Regular older adult gamblers were included in the study. In-depth interviews were conducted with 25 older adults to gain an understanding of gambling from their perspective. Older adult gamblers described their lived experience of gambling ranging from initiation to harm and attempts to cut down or limit gambling. Data were analyzed using thematic network analysis. Results The mean age of the 25 participants was 66.2 years. The majority were male (n = 18), of Chinese ethnicity (n = 16), had secondary education (n = 9), were married (n = 20), and currently employed (n = 15). Four organizing themes related to the role of families in initiation and maintenance of gambling, harm caused to family members, and their role in help-seeking were identified. Discussion and conclusions The study emphasizes the role of Asian families in both initiation and maintenance of gambling. Hence, families must be involved in prevention and outreach programs. Family members must be educated, so that they can encourage help-seeking to ensure early treatment and recovery. There is a need for interventional studies for reducing stress and improving coping among family members.
[Mh] Termos MeSH primário: Atitude
Relações Familiares
Jogo de Azar
Comportamento de Busca de Ajuda
Papel (Figurativo)
[Mh] Termos MeSH secundário: Idoso
Família
Feminino
Seres Humanos
Masculino
Pesquisa Qualitativa
Singapura
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180130
[Lr] Data última revisão:
180130
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171228
[St] Status:MEDLINE
[do] DOI:10.1556/2006.6.2017.082


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[PMID]:29048954
[Au] Autor:McCauley EJ
[Ad] Endereço:Erin J. McCauley is with Policy Analysis and Management, College of Human Ecology, Cornell University, Ithaca NY.
[Ti] Título:The Cumulative Probability of Arrest by Age 28 Years in the United States by Disability Status, Race/Ethnicity, and Gender.
[So] Source:Am J Public Health;107(12):1977-1981, 2017 Dec.
[Is] ISSN:1541-0048
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: To estimate the cumulative probability (c) of arrest by age 28 years in the United States by disability status, race/ethnicity, and gender. METHODS: I estimated cumulative probabilities through birth cohort life tables with data from the National Longitudinal Survey of Youth, 1997. RESULTS: Estimates demonstrated that those with disabilities have a higher cumulative probability of arrest (c = 42.65) than those without (c = 29.68). The risk was disproportionately spread across races/ethnicities, with Blacks with disabilities experiencing the highest cumulative probability of arrest (c = 55.17) and Whites without disabilities experiencing the lowest (c = 27.55). Racial/ethnic differences existed by gender as well. There was a similar distribution of disability types across race/ethnicity, suggesting that the racial/ethnic differences in arrest may stem from racial/ethnic inequalities as opposed to differential distribution of disability types. CONCLUSIONS: The experience of arrest for those with disabilities was higher than expected. Police officers should understand how disabilities may affect compliance and other behaviors, and likewise how implicit bias and structural racism may affect reactions and actions of officers and the systems they work within in ways that create inequities.
[Mh] Termos MeSH primário: Grupos de Populações Continentais/estatística & dados numéricos
Crime/estatística & dados numéricos
Pessoas com Deficiência/estatística & dados numéricos
Grupos Étnicos/estatística & dados numéricos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Criança
Feminino
Seres Humanos
Masculino
Polícia/psicologia
Probabilidade
Política Pública
Papel (Figurativo)
Fatores Sexuais
Estados Unidos/epidemiologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171020
[St] Status:MEDLINE
[do] DOI:10.2105/AJPH.2017.304095


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[PMID]:28971825
[Au] Autor:Abdel-Wahab M; Lahoupe B; Polo A; Zubizarreta E; Adnan RR; Johnston P; Juric A; Haffar FE; Andre M; Meghzifene A
[Ad] Endereço:Division of Human Health, International Atomic Energy Agency, Vienna, Austria. Electronic address: wahabmay@hotmail.com.
[Ti] Título:Assessment of cancer control capacity and readiness: the role of the International Atomic Energy Agency.
[So] Source:Lancet Oncol;18(10):e587-e594, 2017 Oct.
[Is] ISSN:1474-5488
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:During the past six decades, the International Atomic Energy Agency (IAEA) has helped to address the growing cancer burden, by delivering substantial cancer-related assistance to low-income and middle-income member states. IAEA assistance has primarily been facilitated through sustainable radiotherapy and nuclear medicine programmes to establish safe and effective diagnostic imaging, nuclear medicine, and radiotherapy capacity to safely treat patients with cancer. Planning of a National Cancer Control Programme starts with a needs assessment of all aspects of cancer control in the country to ensure evidence-based strategies are adapted to the country's specific needs. The IAEA offers its member states a tool, known as an integrated mission of Programme of Action for Cancer Therapy Review, to assess the status of national capacities for implementation and delivery of cancer control plans and activities and the readiness to develop and implement a long-term radiation medicine infrastructure and plan to improve capacity.
[Mh] Termos MeSH primário: Agências Internacionais/organização & administração
Neoplasias/diagnóstico por imagem
Neoplasias/radioterapia
Energia Nuclear
Radioterapia (Especialidade)/organização & administração
[Mh] Termos MeSH secundário: Países em Desenvolvimento
Feminino
Planejamento em Saúde/organização & administração
Seres Humanos
Masculino
Determinação de Necessidades de Cuidados de Saúde
Medicina Nuclear
Peru
Medição de Risco
Papel (Figurativo)
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE


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[PMID]:28911146
[Au] Autor:van Gucht ALM; Meima ME; Moran C; Agostini M; Tylki-Szymanska A; Krajewska MW; Chrzanowska K; Efthymiadou A; Chrysis D; Demir K; Visser WE; Visser TJ; Chatterjee K; van Dijk TB; Peeters RP
[Ad] Endereço:Department of Internal Medicine, Erasmus University Medical Center, 3000 Rotterdam, The Netherlands.
[Ti] Título:Anemia in Patients With Resistance to Thyroid Hormone α: A Role for Thyroid Hormone Receptor α in Human Erythropoiesis.
[So] Source:J Clin Endocrinol Metab;102(9):3517-3525, 2017 Sep 01.
[Is] ISSN:1945-7197
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Context: Patients with resistance to thyroid hormone (TH) α (RTHα) are characterized by growth retardation, macrocephaly, constipation, and abnormal thyroid function tests. In addition, almost all RTHα patients have mild anemia, the pathogenesis of which is unknown. Animal studies suggest an important role for TH and TH receptor (TR)α in erythropoiesis. Objective: To investigate whether a defect in TRα affects the maturation of red blood cells in RTHα patients. Design, Setting, and Patients: Cultures of primary human erythroid progenitor cells (HEPs), from peripheral blood of RTHα patients (n = 11) harboring different inactivating mutations in TRα (P398R, F397fs406X, C392X, R384H, A382fs388X, A263V, A263S), were compared with healthy controls (n = 11). During differentiation, erythroid cells become smaller, accumulate hemoglobin, and express different cell surface markers. We assessed cell number and cell size, and used cell staining and fluorescence-activated cell sorter analysis to monitor maturation at different time points. Results: After ∼14 days of ex vivo expansion, both control and patient-derived progenitors differentiated spontaneously. However, RTHα-derived cells differentiated more slowly. During spontaneous differentiation, RTHα-derived HEPs were larger, more positive for c-Kit (a proliferation marker), and less positive for glycophorin A (a differentiation marker). The degree of abnormal spontaneous maturation of RTHα-derived progenitors did not correlate with severity of underlying TRα defect. Both control and RTHα-derived progenitors responded similarly when differentiation was induced. T3 exposure accelerated differentiation of both control- and RTHα patient-derived HEPs. Conclusions: Inactivating mutations in human TRα affect the balance between proliferation and differentiation of progenitor cells during erythropoiesis, which may contribute to the mild anemia seen in most RTHα patients.
[Mh] Termos MeSH primário: Anemia/genética
Eritropoese/genética
Regulação da Expressão Gênica
Receptores alfa dos Hormônios Tireóideos/genética
Síndrome da Resistência aos Hormônios Tireóideos/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Anemia/epidemiologia
Anemia/fisiopatologia
Estudos de Casos e Controles
Células Cultivadas
Criança
Pré-Escolar
Eritrócitos/metabolismo
Feminino
Seres Humanos
Incidência
Masculino
Meia-Idade
Mutação
Prognóstico
Valores de Referência
Papel (Figurativo)
Células-Tronco/citologia
Células-Tronco/fisiologia
Síndrome da Resistência aos Hormônios Tireóideos/epidemiologia
Síndrome da Resistência aos Hormônios Tireóideos/fisiopatologia
Adulto Jovem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Thyroid Hormone Receptors alpha)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2017-00840


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[PMID]:28664920
[Au] Autor:Gasser E; Moutos CP; Downes M; Evans RM
[Ad] Endereço:Gene Expression Laboratory, Salk Institute for Biological Studies.
[Ti] Título:FGF1 - a new weapon to control type 2 diabetes mellitus.
[So] Source:Nat Rev Endocrinol;13(10):599-609, 2017 Oct.
[Is] ISSN:1759-5037
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A hypercaloric diet combined with a sedentary lifestyle is a major risk factor for the development of insulin resistance, type 2 diabetes mellitus (T2DM) and associated comorbidities. Standard treatment for T2DM begins with lifestyle modification, and includes oral medications and insulin therapy to compensate for progressive ß-cell failure. However, current pharmaceutical options for T2DM are limited in that they do not maintain stable, durable glucose control without the need for treatment intensification. Furthermore, each medication is associated with adverse effects, which range from hypoglycaemia to weight gain or bone loss. Unexpectedly, fibroblast growth factor 1 (FGF1) and its low mitogenic variants have emerged as potentially safe candidates for restoring euglycaemia, without causing overt adverse effects. In particular, a single peripheral injection of FGF1 can lower glucose to normal levels within hours, without the risk of hypoglycaemia. Similarly, a single intracerebroventricular injection of FGF1 can induce long-lasting remission of the diabetic phenotype. This Review discusses potential mechanisms by which centrally administered FGF1 improves central glucose-sensing and peripheral glucose uptake in a sustained manner. Specifically, we explore the potential crosstalk between FGF1 and glucose-sensing neuronal circuits, hypothalamic neural stem cells and synaptic plasticity. Finally, we highlight therapeutic considerations of FGF1 and compare its metabolic actions with FGF15 (rodents), FGF19 (humans) and FGF21.
[Mh] Termos MeSH primário: Glicemia/efeitos dos fármacos
Diabetes Mellitus Tipo 2/tratamento farmacológico
Diabetes Mellitus Tipo 2/metabolismo
Fator 1 de Crescimento de Fibroblastos/administração & dosagem
Resistência à Insulina
Insulina/metabolismo
[Mh] Termos MeSH secundário: Animais
Glicemia/metabolismo
Diabetes Mellitus Tipo 2/diagnóstico
Modelos Animais de Doenças
Feminino
Fator 1 de Crescimento de Fibroblastos/metabolismo
Seguimentos
Seres Humanos
Masculino
Camundongos Endogâmicos C57BL
Distribuição Aleatória
Papel (Figurativo)
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Blood Glucose); 0 (Insulin); 104781-85-3 (Fibroblast Growth Factor 1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170701
[St] Status:MEDLINE
[do] DOI:10.1038/nrendo.2017.78


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[PMID]:28647348
[Au] Autor:Yuan H; Zhou S; Liu Z; Cong W; Fei X; Zeng W; Zhu H; Xu R; Wang Y; Zheng J; Pan M
[Ad] Endereço:Department of Dermatology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
[Ti] Título:Pivotal Role of Lesional and Perilesional T/B Lymphocytes in Pemphigus Pathogenesis.
[So] Source:J Invest Dermatol;137(11):2362-2370, 2017 Nov.
[Is] ISSN:1523-1747
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pemphigus is a skin and mucosal membrane-targeting autoimmune bullous disease. Previous studies have shown that circulating anti-desmoglein1/3 antibodies are pathogenic and mediate blister formation. However, the role of infiltrating immune cells in lesional skin has not been fully investigated. In this study we showed that there existed a large number of B and T lymphocytes and plasma cells in the skin lesions by immunohistochemistry and immunofluorescence staining. In addition, a significantly increased number of Dsg1- and Dsg3-specific B cells could be identified by flow cytometric analysis or enzyme-linked immunospot technique (i.e., ELISPOT) assay. Furthermore, anti-Dsg1 and Dsg3 antibodies could be detected from the supernatant of in vitro cultures with isolated lymphocytes from lesional skin. We found that most T lymphocytes infiltrating pemphigus vulgaris lesions were CD4 T helper cells expressing IL-21 and IL-17a but not typical T follicular helper cells expressing CXCR5. Additionally, our microarray assay showed that the level of chemokine CCL19 was significantly elevated, suggesting active T-/B-lymphocyte trafficking and aggregation in the pemphigus vulgaris lesions. Collectively, our results suggest a critical role of locally infiltrating lymphocytes in pemphigus pathogenesis.
[Mh] Termos MeSH primário: Linfócitos B/imunologia
Desmogleína 1/metabolismo
Pênfigo/imunologia
Pênfigo/patologia
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Linfócitos B/metabolismo
Biópsia por Agulha
Western Blotting
Estudos de Casos e Controles
Movimento Celular/imunologia
Desmogleína 1/imunologia
Ensaio de Imunoadsorção Enzimática/métodos
ELISPOT
Feminino
Seres Humanos
Imuno-Histoquímica
Interleucina-17/metabolismo
Interleucinas/metabolismo
Masculino
Valores de Referência
Papel (Figurativo)
Linfócitos T/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Desmoglein 1); 0 (Interleukin-17); 0 (Interleukins); 0 (interleukin-21)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170626
[St] Status:MEDLINE


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[PMID]:28637297
[Au] Autor:Delaney MA; Wan YW; Kim GE; Creighton CJ; Taylor MG; Masand R; Park A; Valdes C; Gibbons W; Liu Z; Anderson ML
[Ad] Endereço:Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, Texas 77030.
[Ti] Título:A Role for Progesterone-Regulated sFRP4 Expression in Uterine Leiomyomas.
[So] Source:J Clin Endocrinol Metab;102(9):3316-3326, 2017 Sep 01.
[Is] ISSN:1945-7197
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Context: Despite progesterone's key role in uterine smooth muscle tumorigenesis, the mechanisms by which it promotes the growth of uterine leiomyomas remain poorly understood. Objective: The aim of this study was to identify gene products mediating the effects of progesterone in uterine leiomyomas. Design: Gene expression profiling was used to identify putative progesterone-regulated genes differentially expressed in uterine leiomyomas, which were then studied in vitro. Methods: Gene expression was comprehensively profiled with the Illumina WG BeadChip (version 2.6) and analyzed with a bioinformatic algorithm that integrates known protein-protein interactions. Genomic binding sites for progesterone receptor (PR) were interrogated by chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR). Small interfering RNA was used to study gene function in primary cell lines. Results: Our analyses identified secreted Frizzled-related protein 4 (sFRP4) as a key gene product functionally linked to PR activation whose expression was 2.6 times higher in leiomyomas than myometrium (n = 26, P < 0.01) and 2.5 times higher during the proliferative phase of the menstrual cycle (n = 26, P < 0.01). Direct binding between PR and sFRP4 promoter was observed by ChIP-qPCR. Robust overexpression of sFRP4 was also observed in primary cultures derived from leiomyoma. Progesterone preferentially inhibited sFRP4 expression and secretion in leiomyoma cultures in a dose-dependent manner sensitized by estradiol. Knockdown of sFRP4 inhibited proliferation and apoptosis in primary cultures of both myometrium and leiomyoma. Conclusions: Overexpression of sFRP4 is a robust, progesterone-regulated feature of leiomyomas that increases smooth muscle proliferation. More work is needed to elucidate how progesterone's ability to modulate sFRP4 expression contributes to uterine smooth muscle tumorigenesis.
[Mh] Termos MeSH primário: Regulação Neoplásica da Expressão Gênica
Leiomioma/genética
Progesterona/metabolismo
Proteínas Proto-Oncogênicas/genética
Neoplasias Uterinas/genética
[Mh] Termos MeSH secundário: Biópsia por Agulha
Western Blotting
Proliferação Celular/genética
Progressão da Doença
Feminino
Perfilação da Expressão Gênica
Seres Humanos
Imuno-Histoquímica
Leiomioma/patologia
Miócitos de Músculo Liso/fisiologia
Regiões Promotoras Genéticas/genética
RNA Mensageiro/metabolismo
Reação em Cadeia da Polimerase em Tempo Real/métodos
Papel (Figurativo)
Neoplasias Uterinas/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Proto-Oncogene Proteins); 0 (RNA, Messenger); 0 (SFRP4 protein, human); 4G7DS2Q64Y (Progesterone)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170623
[St] Status:MEDLINE
[do] DOI:10.1210/jc.2016-4014



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