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Search Results: 1 - 10 of 174541 matches for " Natalie De Geest "
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The Atonal Proneural Transcription Factor Links Differentiation and Tumor Formation in Drosophila
Wouter Bossuyt,Natalie De Geest,Stein Aerts,Iris Leenaerts,Peter Marynen,Bassem A. Hassan
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1000040
Abstract: The acquisition of terminal cell fate and onset of differentiation are instructed by cell type–specific master control genes. Loss of differentiation is frequently observed during cancer progression, but the underlying causes and mechanisms remain poorly understood. We tested the hypothesis that master regulators of differentiation may be key regulators of tumor formation. Using loss- and gain-of-function analyses in Drosophila, we describe a critical anti-oncogenic function for the atonal transcription factor in the fly retina, where atonal instructs tissue differentiation. In the tumor context, atonal acts by regulating cell proliferation and death via the JNK stress response pathway. Combined with evidence that atonal's mammalian homolog, ATOH1, is a tumor suppressor gene, our data support a critical, evolutionarily conserved, function for ato in oncogenesis.
The Atonal Proneural Transcription Factor Links Differentiation and Tumor Formation in Drosophila
Wouter Bossuyt,Natalie De Geest,Stein Aerts,Iris Leenaerts,Peter Marynen,Bassem A Hassan
PLOS Biology , 2009, DOI: 10.1371/journal.pbio.1000040
Abstract: The acquisition of terminal cell fate and onset of differentiation are instructed by cell type–specific master control genes. Loss of differentiation is frequently observed during cancer progression, but the underlying causes and mechanisms remain poorly understood. We tested the hypothesis that master regulators of differentiation may be key regulators of tumor formation. Using loss- and gain-of-function analyses in Drosophila, we describe a critical anti-oncogenic function for the atonal transcription factor in the fly retina, where atonal instructs tissue differentiation. In the tumor context, atonal acts by regulating cell proliferation and death via the JNK stress response pathway. Combined with evidence that atonal's mammalian homolog, ATOH1, is a tumor suppressor gene, our data support a critical, evolutionarily conserved, function for ato in oncogenesis.
K. Absillis, Vechten tegen de bierkaai. Over het uitgevershuis van Angèle Manteau (1932-1970)
D. De Geest
BMGN : Low Countries Historical Review , 2011,
Abstract:
Atonal homolog 1 Is a Tumor Suppressor Gene
Wouter Bossuyt,Avedis Kazanjian,Natalie De Geest,Sofie Van Kelst,Gert De Hertogh,Karel Geboes,Greg P. Boivin,Judith Luciani,Francois Fuks,Marinee Chuah,Thierry VandenDriessche,Peter Marynen,Jan Cools,Noah F. Shroyer,Bassem A. Hassan
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1000039
Abstract: Colon cancer accounts for more than 10% of all cancer deaths annually. Our genetic evidence from Drosophila and previous in vitro studies of mammalian Atonal homolog 1 (Atoh1, also called Math1 or Hath1) suggest an anti-oncogenic function for the Atonal group of proneural basic helix-loop-helix transcription factors. We asked whether mouse Atoh1 and human ATOH1 act as tumor suppressor genes in vivo. Genetic knockouts in mouse and molecular analyses in the mouse and in human cancer cell lines support a tumor suppressor function for ATOH1. ATOH1 antagonizes tumor formation and growth by regulating proliferation and apoptosis, likely via activation of the Jun N-terminal kinase signaling pathway. Furthermore, colorectal cancer and Merkel cell carcinoma patients show genetic and epigenetic ATOH1 loss-of-function mutations. Our data indicate that ATOH1 may be an early target for oncogenic mutations in tissues where it instructs cellular differentiation.
Atonal homolog 1 Is a Tumor Suppressor Gene
Wouter Bossuyt equal contributor,Avedis Kazanjian equal contributor,Natalie De Geest,Sofie Van Kelst,Gert De Hertogh,Karel Geboes,Greg P Boivin,Judith Luciani,Francois Fuks,Marinee Chuah,Thierry VandenDriessche,Peter Marynen,Jan Cools,Noah F Shroyer ,Bassem A Hassan
PLOS Biology , 2009, DOI: 10.1371/journal.pbio.1000039
Abstract: Colon cancer accounts for more than 10% of all cancer deaths annually. Our genetic evidence from Drosophila and previous in vitro studies of mammalian Atonal homolog 1 (Atoh1, also called Math1 or Hath1) suggest an anti-oncogenic function for the Atonal group of proneural basic helix-loop-helix transcription factors. We asked whether mouse Atoh1 and human ATOH1 act as tumor suppressor genes in vivo. Genetic knockouts in mouse and molecular analyses in the mouse and in human cancer cell lines support a tumor suppressor function for ATOH1. ATOH1 antagonizes tumor formation and growth by regulating proliferation and apoptosis, likely via activation of the Jun N-terminal kinase signaling pathway. Furthermore, colorectal cancer and Merkel cell carcinoma patients show genetic and epigenetic ATOH1 loss-of-function mutations. Our data indicate that ATOH1 may be an early target for oncogenic mutations in tissues where it instructs cellular differentiation.
Early effect of a single intravenous injection of ethanol on hepatic sinusoidal endothelial fenestrae in rabbits
Frank Jacobs, Eddie Wisse, Bart De Geest
Comparative Hepatology , 2009, DOI: 10.1186/1476-5926-8-4
Abstract: After intravenous administration of a single dose of 0.75 g/kg, ethanol concentration peaked at 1.1 ± 0.10 g/l at ten minutes after injection. Compared to control rabbits (103 ± 1.1 nm; n = 8), the average diameter of fenestrae in ethanol-injected rabbits determined at 10 minutes after injection was significantly (p < 0.01) smaller (96 ± 2.2 nm; n = 5). Detailed analysis of distribution histograms of the diameters of fenestrae showed that the effect of ethanol was highly homogeneous.A decrease of the diameter of fenestrae 10 minutes after ethanol administration is likely the earliest morphological alteration induced by ethanol in the liver and underscores the potential role of liver sinusoidal endothelial cells in alcoholic liver injury.It has been postulated that ethanol primarily targets hepatic sinusoidal and perisinusoidal cells [1]. In experimental models and in human studies, plasma hyaluronic acid levels are elevated in alcoholic liver injury, which may reflect a diminished hepatic clearance by liver sinusoidal endothelial cells [2-4]. Chronic ethanol exposure leads to defenestration in liver sinusoidal endothelial cells which is paralleled by the deposition of a basal lamina [5]. Subsequently, capillarization of hepatic sinusoids further impairs microcirculatory exchange of nutrients and the clearance of waste products, enhances tissue fibrosis, and will affect the hepatic parenchyma and its metabolism. Whereas this sequence of events has been corroborated by several studies, it is not well established to which extent a single administration of ethanol affects liver sinusoidal endothelial cells. Previous studies have shown that ethanol slightly (6%) increases the diameter of fenestrae in liver sinusoidal endothelial cells in vitro [6,7]. In contrast, scanning electron microscopy studies in vivo showed significant decreases of the diameter of sinusoidal endothelial fenestrae [8], suggesting that the transport of plasma substances from sinusoids to parenchymal
Testing the feasibility and effects of a self-management support intervention for patients with cancer and their family caregivers to reduce pain and related symptoms (ANtiPain): Study protocol of a pilot study  [PDF]
Antje Koller, Monika Hasemann, Karin Jaroslawski, Sabina De Geest, Gerhild Becker
Open Journal of Nursing (OJN) , 2014, DOI: 10.4236/ojn.2014.42012
Abstract:

Despite effective treatment options, more than 40% of cancer patients receive inadequate pain management. Our previous pilot study resulted in substantial adaptations of a cancer pain self-management intervention, the German PRO-Self? Plus Pain Control Program originally developed in the United States. This program will be implemented into clinical practice at the Medical Center-University of Freiburg. The purpose of this multiple methods pilot study is to test the implementation regarding feasibility and effects in clinical practice. In a randomized, wait-list controlled pilot study, adult oncology in-patients of a palliative care consultation service with pain >3/10 will be recruited. The intervention will be performed by a specialized advanced practice nurse with an in-hospital visit and, after discharge, via phone calls and visits. The follow-up will be personalized according to a clinical algorithm that factors in pain intensity, satisfaction with pain management, and patient adherence. The intervention includes structured and tailored components and is based on three key strategies: information, skill building and nurse coaching. The specific aims of this study are threefold: 1) to test the feasibility of the study and intervention procedures; 2) to establish effect sizes of main outcome variables (e.g. decrease pain intensity, reduce the number of patients with pain as main symptom) for subsequent power calculation; 3) to explore participants’ experiences with pain self-management support and their view of burden and benefit from study participation in a qualitative substudy. During the study period, which includes three data collection time points (T0 before, T1 one week and T2 six weeks after discharge), data will be collected via field notes of study nurses and questionnaires of patients. The results of this pilot study will build the basis for a larger comparative effectiveness study in which long term outcomes of a cancer pain self-management intervention in clinical practice will be evaluated.

The Liver as a Target Organ for Gene Therapy: State of the Art, Challenges, and Future Perspectives
Frank Jacobs,Stephanie C. Gordts,Ilayaraja Muthuramu,Bart De Geest
Pharmaceuticals , 2012, DOI: 10.3390/ph5121372
Abstract: The liver is a target for gene therapy of inborn errors of metabolism, of hemophilia, and of acquired diseases such as liver cancer and hepatitis. The ideal gene transfer strategy should deliver the transgene DNA to parenchymal liver cells with accuracy and precision in the absence of side effects. Liver sinusoids are highly specialized capillaries with a particular endothelial lining: the endothelium contains open fenestrae, whereas a basal lamina is lacking. Fenestrae provide a direct access of gene transfer vectors to the space of Disse, in which numerous microvilli from parenchymal liver cells protrude. The small diameter of fenestrae in humans constitutes an anatomical barrier for most gene transfer vectors with the exception of adeno-associated viral (AAV) vectors. Recent studies have demonstrated the superiority of novel AAV serotypes for hepatocyte-directed gene transfer applications based on enhanced transduction, reduced prevalence of neutralizing antibodies, and diminished capsid immune responses. In a landmark clinical trial, hemophilia B was successfully treated with an AAV8 human factor IX expressing vector. Notwithstanding significant progress, clinical experience with these technologies remains very limited and many unanswered questions warrant further study. Therefore, the field should continue to progress as it has over the past decade, cautiously and diligently.
Falls and consequent injuries in hospitalized patients: effects of an interdisciplinary falls prevention program
René Schwendimann, Hugo Bühler, Sabina De Geest, Koen Milisen
BMC Health Services Research , 2006, DOI: 10.1186/1472-6963-6-69
Abstract: This study used a serial survey design to examine in-patient fall rates and consequent injuries before and after the implementation of an interdisciplinary falls prevention program (IFP) in a 300-bed urban public hospital. The population under study included adult patients, hospitalized in the departments of internal medicine, geriatrics, and surgery. Administrative patient data and fall incident report data from 1999 to 2003 were examined and summarized using frequencies, proportions, means and standard deviations and were analyzed accordingly.A total of 34,972 hospitalized patients (mean age: 67.3, SD ± 19.3 years; female 53.6%, mean length of stay: 11.9 ± 13.2 days, mean nursing care time per day: 3.5 ± 1.4 hours) were observed during the study period. Overall, a total of 3,842 falls affected 2,512 (7.2%) of the hospitalized patients. From these falls, 2,552 (66.4%) were without injuries, while 1,142 (29.7%) falls resulted in minor injuries, and 148 (3.9%) falls resulted in major injuries. The overall fall rate in the hospitals' patient population was 8.9 falls per 1,000 patient days. The fall rates fluctuated slightly from 9.1 falls in 1999 to 8.6 falls in 2003. After the implementation of the IFP, in 2001 a slight decrease to 7.8 falls per 1,000 patient days was observed (p = 0.086). The annual proportion of minor and major injuries did not decrease after the implementation of the IFP. From 1999 to 2003, patient characteristics changed in terms of slight increases (female gender, age, consumed nursing care time) or decreases (length of hospital stay), as well as the prevalence of fall risk factors increased up to 46.8% in those patients who fell.Following the implementation of an interdisciplinary falls prevention program, neither the frequencies of falls nor consequent injuries decreased substantially. Future studies need to incorporate strategies to maximize and evaluate ongoing adherence to interventions in hospital falls prevention programs.Patient falls in
Are patient falls in the hospital associated with lunar cycles? A retrospective observational study
René Schwendimann, Franco Joos, Sabina De Geest, Koen Milisen
BMC Nursing , 2005, DOI: 10.1186/1472-6955-4-5
Abstract: 3,842 fall incident reports of adult in-patients who fell while hospitalized in a 300-bed urban public hospital in Zurich, Switzerland were included. Adjusted fall rates per 1'000 patient days were compared with days of the week, months, and 62 complete lunar cycles from 1999 to 2003.The fall rate per 1000 patient days fluctuated slightly over the entire observation time, ranging from 8.4 falls to 9.7 falls per month (P = 0.757), and from 8.3 falls on Mondays to 9.3 falls on Saturdays (P = 0.587). The fall rate per 1000 patient days within the lunar days ranged from 7.2 falls on lunar day 17 to 10.6 falls on lunar day 20 (P = 0.575).The inpatient fall rates in this hospital were neither associated with days of the week, months, or seasons nor with lunar cycles such as full moon or new moon. Preventive strategies should be focused on patients' modifiable fall risk factors and the provision of organizational conditions which support a safe hospital environment.Falls occur frequently in hospitalized patients. Patient fall rates in hospital settings vary from 2.2 to 9.1 falls per 1000 patient days depending on patient populations and disease groups [1-7]. The etiology of falls in hospitalized patients is multifactorial consisting of both intrinsic and extrinsic risk factors [8-10]. Studies on hospital falls that focus on occurrences over time are limited to the frequencies of falls during the hours of the day [1,5-7,11,12], and to specific time spans e.g. number of falls within the first week of hospitalization [2,4,7,13].Reasons for the fluctuation in fall-rates over time have been debated, but never scientifically researched. There exist anecdotes from health care professionals in our clinical practice that express the idea that the number of patient falls increasing during times of full moon. One survey indicated that specifically mental health professionals including psychologists, nurses and others held the personal belief that lunar phases affect patient's behavio
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