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排序方式: 共有2397条查询结果,搜索用时 15 毫秒
71.
Tash BR Bewley MC Russo M Keil JM Griffin KA Sundstrom JM Antonetti DA Tian F Flanagan JM 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(27):10855-10860
Tight junctions (TJs) are dynamic cellular structures that are critical for compartmentalizing environments within tissues and regulating transport of small molecules, ions, and fluids. Phosphorylation-dependent binding of the transmembrane protein occludin to the structural organizing protein ZO-1 contributes to the regulation of barrier properties; however, the details of their interaction are controversial. Using small angle X-ray scattering (SAXS), NMR chemical shift perturbation, cross-saturation, in vitro binding, and site-directed mutagenesis experiments. we define the interface between the ZO-1 PDZ3-SH3-U5-GuK (PSG) and occludin coiled-coil (CC) domains. The interface is comprised of basic residues in PSG and an acidic region in CC. Complex formation is blocked by a peptide (REESEEYM) that corresponds to CC residues 468-475 and includes a previously uncharacterized phosphosite, with the phosphorylated version having a larger effect. Furthermore, mutation of E470 and E472 reduces cell border localization of occludin. Together, these results localize the interaction to an acidic region in CC and a predominantly basic helix V within the ZO-1 GuK domain. This model has important implications for the phosphorylation-dependent regulation of the occludin:ZO-1 complex. 相似文献
72.
73.
D McWhirter M den Dulk M Terlizzo HZ Malik SW Fenwick GJ Poston 《Annals of the Royal College of Surgeons of England》2013,95(8):e136-e138
A 74-year old man underwent a radical cholecystectomy for presumed gallbladder cancer. The histology of the resected specimen in fact revealed the lesion to be metastatic renal cell carcinoma from his resected right nephrectomy performed 14 years previously. 相似文献
74.
Miriam E. Delphin-Rittmon Raquel Andres-Hyman Elizabeth H. Flanagan Larry Davidson 《The Psychiatric quarterly》2013,84(1):53-64
Racial and ethnic disparities are disturbing facets of the American healthcare system that document the reality of unequal treatment. Research consistently shows that patients of color experience poorer quality of care and health outcomes contributing to increased risks and accelerated mortality rates relative to their white counterparts. While initially conceptualized as an approach for increasing the responsiveness of children’s behavioral health care, cultural competence has been adopted as a key strategy for eliminating racial and ethnic health disparities across the healthcare system. However, cultural competence research and practices largely focus on improving provider competencies, while agency and system level approaches for meeting the service needs of diverse populations are given less attention. In this article we offer seven essential strategies for promoting and sustaining organizational and systemic cultural competence. These strategies are to: (1) Provide executive level support and accountability, (2) Foster patient, community and stakeholder participation and partnerships, (3) Conduct organizational cultural competence assessments, (4) Develop incremental and realistic cultural competence action plans, (5) Ensure linguistic competence, (6) Diversify, develop, and retain a culturally competent workforce, and (7) Develop an agency or system strategy for managing staff and patient grievances. For each strategy we offer several recommendations for implementation. 相似文献
75.
L. A. Felgendreger S. J. Fluharty D. K. Yee L. M. Flanagan‐Cato 《Journal of neuroendocrinology》2013,25(2):97-106
The renin–angiotensin–aldosterone system makes a critical contribution to body fluid homeostasis, and abnormalities in this endocrine system have been implicated in certain forms of hypertension. The peptide hormone angiotensin II (AngII) regulates hydromineral homeostasis and blood pressure by acting on both peripheral and brain targets. In the brain, AngII binds to the angiotensin type 1 receptor (AT1R) to stimulate thirst, sodium appetite and both arginine vasopressin (AVP) and oxytocin (OT) secretion. The present study used an experimental model of endogenous AngII to examine the role of p44/42 mitogen‐activated protein kinase (MAPK) as a signalling mechanism to mediate these responses. Animals were given a combined treatment of furosemide and a low dose of captopril (furo/cap), comprising a diuretic and an angiotensin‐converting enzyme inhibitor, respectively, to elevate endogenous AngII levels in the brain. Furo/cap induced p44/42 MAPK activation in key brain areas that express AT1R, and this effect was reduced with either a centrally administered AT1R antagonist (irbesartan) or a p44/42 MAPK inhibitor (U0126). Additionally, furo/cap treatment elicited water and sodium intake, and irbesartan markedly reduced both of these behaviours. Central injection of U0126 markedly attenuated furo/cap‐induced sodium intake but not water intake. Furthermore, p44/42 MAPK signalling was not necessary for either furo/cap‐ or exogenous AngII‐induced AVP or OT release. Taken together, these results indicate that p44/42 MAPK is required for AngII‐induced sodium appetite but not thirst or neurohypophysial secretion. This result may allow for the discovery of more specific downstream targets of p44/42 MAPK to curb sodium appetite, known to exacerbate hypertension, at the same time as leaving thirst and neurohypophysial hormone secretion undisturbed. 相似文献
76.
77.
Tristan Townsend Violeta Razanskaite Susanna Dodd Daniel Storey Stephanie Michail James Morgan Michael Davies Douglas Penman Christopher Watters Mira Swaminathan Joseph Sabine Adam Chapman Philip J Smith Paul K. Flanagan Ian Reilly Keith Bodger Sreedhar Subramanian 《Alimentary pharmacology & therapeutics》2020,52(8):1341-1352
78.
Indu Subramanian MD Soania Mathur MD Annelien Oosterbaan MD PhD Richelle Flanagan RD Adrienne M. Keener MD Elena Moro MD PhD 《Movement disorders》2022,37(3):444-455
Personalized medicine considering sex, gender, and cultural context has become the vanguard of delivery of care. However, women's issues in Parkinson disease (PD), especially from a psychosocial standpoint, have been an overlooked field. The key research areas include women-inclusive drug and device studies and genetic and hormonal considerations. Moreover, women with PD need to be educated and empowered on how to communicate their symptoms and needs, get engaged in research, get organized as a community, and support one another. Women with PD need tools to help track and convey their unique motor and nonmotor symptoms and psychological and social support needs. The management of PD needs to be customized to include the unique stages of women's lives, including menstrual cycles, pregnancy, perimenopause, menopause, and postmenopause. Specific guidelines for the use of hormonal treatments and customized dopamine replacement dosing need to be developed. Women need guidance on culturally sensitive wellness and self-care strategies that are customized for them. Basic core competencies in knowledge for all clinicians treating women with PD need to be established, including how to accurately diagnose, proactively identify, and treat the symptoms of PD in women and to ensure timely referral for specialty care, advanced therapies, and research studies. Caregivers and families need guidance on holistically supporting women with PD. The voices of women living with PD must be amplified to catalyze real change in this neglected field. This paper provides an overview of the current knowledge, gaps, and possible strategies to deal with the unmet needs of women living with PD with a focus on the clinical and psychosocial aspects. © 2022 International Parkinson and Movement Disorder Society 相似文献
79.
Cathepsin‐Mediated Alterations in TGFß‐Related Signaling Underlie Disrupted Cartilage and Bone Maturation Associated With Impaired Lysosomal Targeting
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80.
Radial scars/complex sclerosing lesions and malignancy in a screening programme: incidence and histological features revisited 总被引:1,自引:0,他引:1
Doyle EM Banville N Quinn CM Flanagan F O'Doherty A Hill AD Kerin MJ Fitzpatrick P Kennedy M 《Histopathology》2007,50(5):607-614
AIMS: Radial scars (RS) are benign entities, frequently identified on screening mammography, which may be associated with malignancy. Much debate has been generated with regard to the optimum management of RS. We present our experience of RS in the first 5 years of a screening programme. The aim was to evaluate (i) the incidence of atypia and malignancy and (ii) the value of the preoperative core biopsy. We also further characterize the histological features. METHODS AND RESULTS: One hundred and twenty-five histologically confirmed cases of RS were reviewed (111 had preoperative biopsies). Thirty-one (24.8%) patients had a final malignant diagnosis (11 with invasive malignancy) and 28 (22.4%) showed atypia (including lobular carcinoma in situ). In those with core biopsies and a final malignant diagnosis, 12 cases were categorized as B5 (41.3%), three as B4 (10.3%), 12 as B3 (41.3%) and two as B2 (7%). Common histological features included obliterated ducts and chronic inflammation with, less frequently, neural hyperplasia (16.8%) and perineural invasion (3.2%). CONCLUSIONS: The high incidence of atypia and malignancy identified in our study justifies our policy of removing all mammographically detected RS. We emphasize the utility of preoperative core biopsy evaluation in permitting one-stage surgical therapy in those with B5 diagnoses. 相似文献