Institution
University of Vermont
Education•Burlington, Vermont, United States•
About: University of Vermont is a education organization based out in Burlington, Vermont, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 17592 authors who have published 38251 publications receiving 1609874 citations. The organization is also known as: UVM & University of Vermont and State Agricultural College.
Topics: Population, Poison control, Breast cancer, Myosin, Anxiety
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TL;DR: It is shown that pyridinyl imidazole compounds (specific inhibitors of p38 MAP kinase) block the production of interferon‐γ (IFNγ) by Th1 cells without affecting IL‐4 production by Th2 cells, and that inhibition of p 38 MAP kinases represents a possible site of therapeutic intervention in diseases where a predominant Th1 immune response leads to a pathological outcome.
Abstract: Signal transduction via MAP kinase pathways plays a key role in a variety of cellular responses, including growth factor-induced proliferation, differentiation and cell death. In mammalian cells, p38 MAP kinase can be activated by multiple stimuli, such as pro-inflammatory cytokines and environmental stress. Although p38 MAP kinase is implicated in the control of inflammatory responses, the molecular mechanisms remain unclear. Upon activation, CD4+ T cells differentiate into Th2 cells, which potentiate the humoral immune response or pro-inflammatory Th1 cells. Here, we show that pyridinyl imidazole compounds (specific inhibitors of p38 MAP kinase) block the production of interferon-gamma (IFNgamma) by Th1 cells without affecting IL-4 production by Th2 cells. These drugs also inhibit transcription driven by the IFNgamma promoter. In transgenic mice, inhibition of the p38 MAP kinase pathway by the expression of dominant-negative p38 MAP kinase results in selective impairment of Th1 responses. In contrast, activation of the p38 MAP kinase pathway by the expression of constitutivelyactivated MAP kinase kinase 6 in transgenic mice caused increased production of IFNgamma during the differentiation and activation of Th1 cells. Together, these data demonstrate that the p38 MAP kinase is relevant for Th1 cells, not Th2 cells, and that inhibition of p38 MAP kinase represents a possible site of therapeutic intervention in diseases where a predominant Th1 immune response leads to a pathological outcome. Moreover, our study provides an additional mechanism by which the p38 MAP kinase pathway controls inflammatory responses.
421 citations
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TL;DR: It is discussed that p38 MAPK can also mediate cell survival in specific situations, such as in response to DNA damage, which is important to recognize when considering the potential use of pharmacological inhibitors of p38MAPK in therapeutic treatments for disease.
Abstract: The p38 MAPK kinase pathway is activated in response to a wide range of cellular stress stimuli and cytokines. Our understanding of the important functions of p38 MAPK in the process of differentiation and cell death has grown considerably in the recent years and is now relatively established. Here we discuss the role of p38 MAPK in the mediation of cell cycle checkpoints and cell survival, processes that have received less attention. We describe how p38 MAPK regulates both the G2/M as well as a G1/S cell cycle checkpoint in response to cellular stress such as DNA damage. While p38 MAPK has classically been associated with the induction of apoptosis, we discuss that p38 MAPK can also mediate cell survival in specific situations, such as in response to DNA damage. It is important to recognize these less appreciated functions of p38 MAPK when considering the potential use of pharmacological inhibitors of p38 MAPK in therapeutic treatments for disease.
421 citations
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University of Chicago1, Mayo Clinic2, University of Texas Health Science Center at Houston3, University of Texas Medical Branch4, Cardiff and Vale University Health Board5, Icahn School of Medicine at Mount Sinai6, University of Vermont7, Harvard University8, University of British Columbia9, University of Pittsburgh10, University of Pennsylvania11, Cedars-Sinai Medical Center12, Duke University13, Veterans Health Administration14, Memorial Sloan Kettering Cancer Center15, University of Virginia16
TL;DR: These guidelines are meant to be a practical diagnostic reference for the pathologist, however, some new pathologic predictors of prognosis and response to therapy are also included.
Abstract: Context.— Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose. Objective.— To provide updated, practical guidelines for the pathologic diagnosis of MM. Data Sources.— Pathologists involved in the International Mesothelioma Interest Group and others with an interest and expertise in the field contributed to this update. Reference material included up-to-date, peer-reviewed publications and textbooks. Conclusions.— There was discussion and consensus opinion regarding guidelines for (1) distinguishing benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) recognition of the key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiating epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6) diagnosis of s...
421 citations
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TL;DR: It is demonstrated that human iPSC generated with the use of a humanized version of a single lentiviral “stem cell cassette” vector have the ability to robustly differentiate into definitive endoderm in vitro, the developmental precursor tissue of lung epithelia.
Abstract: The development of methods to achieve efficient reprogramming of human cells while avoiding the permanent presence of reprogramming transgenes represents a critical step toward the use of induced pluripotent stem cells (iPSC) for clinical purposes, such as disease modeling or reconstituting therapies. Although several methods exist for generating iPSC free of reprogramming transgenes from mouse cells or neonatal normal human tissues, a sufficiently efficient reprogramming system is still needed to achieve the widespread derivation of disease-specific iPSC from humans with inherited or degenerative diseases. Here, we report the use of a humanized version of a single lentiviral "stem cell cassette" vector to accomplish efficient reprogramming of normal or diseased skin fibroblasts obtained from humans of virtually any age. Simultaneous transfer of either three or four reprogramming factors into human target cells using this single vector allows derivation of human iPSC containing a single excisable viral integration that on removal generates human iPSC free of integrated transgenes. As a proof of principle, here we apply this strategy to generate >100 lung disease-specific iPSC lines from individuals with a variety of diseases affecting the epithelial, endothelial, or interstitial compartments of the lung, including cystic fibrosis, α-1 antitrypsin deficiency-related emphysema, scleroderma, and sickle-cell disease. Moreover, we demonstrate that human iPSC generated with this approach have the ability to robustly differentiate into definitive endoderm in vitro, the developmental precursor tissue of lung epithelia.
420 citations
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TL;DR: Empirically based assessment provides a robust methodology for assessing and comparing problems reported forChildren from diverse cultures and offers a cost-effective way to identify problems for which children from diverse cultural backgrounds may need help.
Abstract: Objective To compare parent-reported problems for children in 12 cultures. Method Child Behavior Checklists were analyzed for 13,697 children and adolescents, aged 6 through 17 years, from general population samples in Australia, Belgium, China, Germany, Greece, Israel, Jamaica, the Netherlands, Puerto Rico, Sweden, Thailand, and the United States. Results Comparisons of 12 cultures across ages 6 through 11 and 9 cultures across ages 6 through 17 yielded medium effect sizes for cross-cultural variations in Total Problem, Externalizing, and Internalizing scores. Puerto Rican scores were the highest, while Swedish scores were the lowest. With great cross-cultural consistency, Total and Externalizing scores declined with age, while Internalizing scores increased; boys obtained higher Total and Externalizing scores but lower Internalizing scores than girls. Cross-cultural correlations were high among the mean item scores. Conclusions Empirically based assessment provides a robust methodology for assessing and comparing problems reported for children from diverse cultures. Age and gender variations are cross-culturally consistent. Although clinical cutoff points should not necessarily be uniform across all cultures, empirically based assessment offers a cost-effective way to identify problems for which children from diverse cultural backgrounds may need help.
419 citations
Authors
Showing all 17727 results
Name | H-index | Papers | Citations |
---|---|---|---|
Albert Hofman | 267 | 2530 | 321405 |
Ralph B. D'Agostino | 226 | 1287 | 229636 |
George Davey Smith | 224 | 2540 | 248373 |
Stephen V. Faraone | 188 | 1427 | 140298 |
Valentin Fuster | 179 | 1462 | 185164 |
Dennis J. Selkoe | 177 | 607 | 145825 |
Anders Björklund | 165 | 769 | 84268 |
Alfred L. Goldberg | 156 | 474 | 88296 |
Christopher P. Cannon | 151 | 1118 | 108906 |
Debbie A Lawlor | 147 | 1114 | 101123 |
Roger J. Davis | 147 | 498 | 103478 |
Andrew S. Levey | 144 | 600 | 156845 |
Jonathan G. Seidman | 137 | 563 | 89782 |
Yu Huang | 136 | 1492 | 89209 |
Christine E. Seidman | 134 | 519 | 67895 |