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121.
The insulin-like growth factor I receptor (IGF-IR) is expressed in many cell types and is critical for normal growth and development.
In the healthy mammary gland, the role of IGF-IR is not fully elucidated. However, IGF-IR, which is primarily expressed in
the mammary epithelial cells, is known to play an obligatory role in cellular transformation, facilitating the progression
to breast cancer. We have utilized the tetracycline regulatory (tet-on) system to generate an in vitro model system to allow
us to further investigate IGF-I/IGF-IR function in mammary epithelial cells. A plasmid construct containing a mutant IGF-I
receptor (IGF-IR-DN) fused to the tetracycline operator (tetOPhCMV-IGF-IR-DN) was stably transfected into MCF-7 human breast cancer cells. The conditional regulation of the IGF-IR-DN gene
expression was studied in four independent clonal lines. The translated IGF-IR-DN protein was detected only in the stably
transfected doxycycline-induced cells, and its expression was up-regulated (three- to sixfold) following induction. IGF-I
stimulated cell proliferation diminished (twofold) in doxycycline-induced cells compared to uninduced cells, demonstrating
that the transgene construct was functional and ruling out any pleiotropic effect that may be attributed to doxycycline. Interestingly,
autophosphorylation of the IGF-IR and phosphorylation of the downstream substrate, insulin receptor substrate-1 (IRS-1), was
not inhibited in doxycycline/IGF-I treated cells, suggesting the possibility that activation of downstream substrates other
than the IRS-1 may be critical for optimal cell proliferation. This novel in vitro model should allow us to more directly
examine the role of IGF-I/IGF-IR signaling and function in mammary epithelial cells. 相似文献
122.
Dimitra Micha Dong‐chuan Guo Yvonne Hilhorst‐Hofstee Fop van Kooten Dian Atmaja Eline Overwater Ferdy K. Cayami Ellen S. Regalado René van Uffelen Hanka Venselaar Sultana M.H. Faradz Gerrit Vriend Marjan M. Weiss Erik A. Sistermans Alessandra Maugeri Dianna M. Milewicz Gerard Pals Fleur S. van Dijk 《Human mutation》2015,36(12):1145-1149
We report three families with arterial aneurysms and dissections in which variants predicted to be pathogenic were identified in SMAD2. Moreover, one variant occurred de novo in a proband with unaffected parents. SMAD2 is a strong candidate gene for arterial aneurysms and dissections given its role in the TGF‐β signaling pathway. Furthermore, although SMAD2 and SMAD3 probably have functionally distinct roles in cell signaling, they are structurally very similar. Our findings indicate that SMAD2 mutations are associated with arterial aneurysms and dissections and are in accordance with the observation that patients with pathogenic variants in genes encoding proteins involved in the TGF‐β signaling pathway exhibit arterial aneurysms and dissections as key features 相似文献
123.
Anna Maria Bosco Natalie Williams Jacqueline Marie Graham Dianne Lorraine Malagas Yvonne Hauck 《Collegian (Royal College of Nursing, Australia)》2018,25(1):73-80
Background
Nurses working in clinical settings are instrumental to translating research into practice. The Delphi approach has been used by clinicians worldwide to set research agendas relevant to their clinical work.Aim
To identify nursing research priorities at the tertiary women's hospital in Western Australia and to develop an agenda for gynaecological nursing research.Methods
A three-round Delphi study was used. Round one incorporated an open-ended questionnaire to generate ideas or issues important to gynaecology nurses. During round two, the 32 topics generated from the first round were prioritised into 12 topics with a final ranking performed in round three.Findings
Fifty-four nurses who work in gynaecology clinical areas at the study hospital were invited to participate with 18 (33.3%) participating in round one, 41 (75.9%) in round two and 40 nurses (74.1%) in the final round. The highest ranked research priorities were: managing trial of void; providing compassionate care to women who experience pregnancy loss – the role of the gynaecological nurse; and understanding a woman's journey of treatment following a diagnosis of gynaecological cancer.Discussion
We explore potential factors from the literature around the identified gynaecology research topics plus challenges around the generation and translation of evidence into clinical practice.Conclusion
Establishing a partnership between researchers and gynaecology nurses has contributed to the development of a nursing research agenda. We anticipate that using the Delphi approach may facilitate future collaboration in implementing this research agenda and translating the findings into clinical practice. 相似文献124.
125.
Yvonne W. S. Jauw Dennis F. Heijtel Josée M. Zijlstra Otto S. Hoekstra Henrica C. W. de Vet Danielle J. Vugts Henk M. Verheul Ronald Boellaard Sonja Zweegman Guus A. M. S. van Dongen C. Willemien Menke-van der Houven van Oordt Adriaan A. Lammertsma Marc C. Huisman 《Molecular imaging and biology》2018,20(6):1025-1034
Purpose
Positron emission tomography (PET) with Zirconium-89 (Zr-89)-labeled antibodies can be used for in vivo quantification of antibody uptake. Knowledge about measurement variability is required to ensure correct interpretation. However, no clinical studies have been reported on measurement variability of Zr-89 immuno-PET. As variability due to low signal-to-noise is part of the total measurement variability, the aim of this study was to assess noise-induced variability of Zr-89 -immuno-PET using count-reduced clinical images.Procedures
Data were acquired from three previously reported clinical studies with [89Zr]antiCD20 (74 MBq, n?=?7), [89Zr]antiEGFR (37 MBq, n?=?7), and [89Zr]antiCD44 (37 MBq, n?=?13), with imaging obtained 1 to 6 days post injection (D0–D6). Volumes of interest (VOIs) were manually delineated for liver, spleen, kidney, lung, brain, and tumor. For blood pool and bone marrow, fixed-size VOIs were used. Original PET list mode data were split and reconstructed, resulting in two count-reduced images at 50 % of the original injected dose (e.g., 37 MBq74inj).Repeatability coefficients (RC) were obtained from Bland-Altman analysis on standardized uptake values (SUV) derived from VOIs applied to these images.Results
The RC for the combined manually delineated organs for [89Zr] antiCD20 (37 MBq74inj) increased from D0 to D6 and was less than 6 % at all time points. Blood pool and bone marrow had higher RC, up to 43 % for 37 MBq74inj at D6. For tumor, the RC was up to 42 % for [89Zr]antiCD20 (37 MBq74inj). For [89Zr]antiCD20, (18 MBq74inj), [89Zr]antiEGFR (18 MBq37inj), and [89Zr]antiCD44 (18 MBq37inj), measurement variability was independent of the investigated antibody.Conclusions
Based on this study, noise-induced variability results in a RC for Zr-89-immuno-PET (37 MBq) around 6 % for manually delineated organs combined, increasing up to 43 % at D6 for blood pool and bone marrow, assuming similar biodistribution of antibodies. The signal-to-noise ratio leads to tumor RC up to 42 %.126.
127.
Morgan K. Boes Rachel E. Bollaert Richard M. Kesler Yvonne C. Learmonth Mazharul Islam Matthew N. Petrucci Robert W. Motl Elizabeth T. Hsiao-Wecksler 《Archives of physical medicine and rehabilitation》2018,99(3):484-490
Objective
To determine whether a powered ankle-foot orthosis (AFO) that provides dorsiflexor and plantar flexor assistance at the ankle can improve walking endurance of persons with multiple sclerosis (MS).Design
Short-term intervention.Setting
University research laboratory.Participants
Participants (N=16) with a neurologist-confirmed diagnosis of MS and daily use of a prescribed custom unilateral passive AFO.Interventions
Three 6-minute walk tests (6MWTs), 1 per footwear condition: shoes (no AFO), prescribed passive AFO, and portable powered AFO (PPAFO). Assistive devices were worn on the impaired limb.Main Outcome Measures
Distance walked and metabolic cost of transport were recorded during each 6MWT and compared between footwear conditions.Results
Each participant completed all three 6MWTs within the experimental design. PPAFO use resulted in a shorter 6MWT distance than did a passive AFO or shoe use. No differences were observed in metabolic cost of transport between footwear conditions.Conclusions
The current embodiment of this PPAFO did not improve endurance walking performance during the 6MWT in a sample of participants with gait impairment due to MS. Further research is required to determine whether expanded training or modified design of this powered orthosis can be effective in improving endurance walking performance in persons with gait impairment due to MS. 相似文献128.
129.
Atul Maheshwari Michael Fischer Pierluigi Gambetti Alicia Parker Aarthi Ram Claudio Soto Luis Concha-Marambio Yvonne Cohen Ermias D. Belay Ryan A. Maddox Simon Mead Clay Goodman Joseph S. Kass Lawrence B. Schonberger Haitham M. Hussein 《Emerging infectious diseases》2015,21(5):750-759
Variant Creutzfeldt-Jakob disease (vCJD) is a rare, fatal prion disease resulting from transmission to humans of the infectious agent of bovine spongiform encephalopathy. We describe the clinical presentation of a recent case of vCJD in the United States and provide an update on diagnostic testing. The location of this patient’s exposure is less clear than those in the 3 previously reported US cases, but strong evidence indicates that exposure to contaminated beef occurred outside the United States more than a decade before illness onset. This case exemplifies the persistent risk for vCJD acquired in unsuspected geographic locations and highlights the need for continued global surveillance and awareness to prevent further dissemination of vCJD. 相似文献
130.
Soliciting views of various communities on health research: a prelude to engagement in specific research projects
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Howard L. Taras MD Michael W. Kalichman PhD Gery Schulteis PhD Jill Dumbauld MPH Yvonne Bell MBA Fe Fidelis Seligman MA Kathy D. West MBA 《Health expectations》2015,18(6):2753-2763
BackgroundMembers of the public are increasingly engaged in health‐service and biomedical research and provide input into the content of research, design and data sharing. As there is variation among different communities on how research is perceived, to engage all sectors of the general public research institutions need to customize their approach.ObjectiveThis paper explores how research institutions and community leaders can partner to determine the best ways to engage different sectors of the public in research.DesignFollowing a literature review, a research institution engaged with four different sectors of the public through their respective representative community‐based organizations (CBOs) by interviews with leaders, community member focus groups and a joint project.SettingSan Diego and Imperial Counties, California, United States of America (USA).ConclusionBefore embarking on more specific research projects, investigators can gain valuable insights about different communities'' attitudes to, and understanding of, health services and biomedical research by interacting directly with members of the community, collaborating with community leaders, and jointly identifying steps of engagement tailored to the community. 相似文献