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41.
Identification of cooperative genes for NUP98-HOXA9 in myeloid leukemogenesis using a mouse model 总被引:6,自引:2,他引:6
Iwasaki M Kuwata T Yamazaki Y Jenkins NA Copeland NG Osato M Ito Y Kroon E Sauvageau G Nakamura T 《Blood》2005,105(2):784-793
The chromosomal translocation t(7; 11)(p15;p15), observed in human myeloid leukemia, results in a NUP98 and HOXA9 gene fusion. We generated a transgenic mouse line that specifically expressed the chimeric NUP98-HOXA9 gene in the myeloid lineage. While only 20% of the transgenic mice progressed to leukemia after a latency period, myeloid progenitor cells from nonleukemic transgenic mice still exhibited increased proliferative potential. This suggested that the NUP98-HOXA9 fusion induced a preleukemic phase, and other factors were required for complete leukemogenesis. NUP98-HOXA9 expression promoted the onset of retrovirus-induced BXH2 myeloid leukemia. This phenomenon was used to identify cooperative disease genes as common integration sites (CISs). Meis1, a known HOX cofactor, was identified as a CIS with a higher integration frequency in transgenic than in wild-type BXH2 mice. By the same means we identified further 4 candidate cooperative genes, Dnalc4, Fcgr2b, Fcrl, and Con1. These genes cooperated with NUP98-HOXA9 in transforming NIH 3T3 cells. The system described here is a powerful tool to identify cooperative oncogenes and will assist in the clarification of the multistep process of carcinogenesis. 相似文献
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Christiane Horwood Lyn Haskins Ameena Goga Tanya Doherty Vaughn John Ingunn M.S. Engebretsen Ute Feucht Nigel Rollins Max Kroon David Sanders Thorkild Tylleskar 《Maternal & child nutrition》2020,16(2)
Clinical guidelines are used to translate research findings into evidence‐based clinical practice but are frequently not comprehensively adopted by health workers (HWs). HIV and infant feeding guidelines were revised by the World Health Organization to align feeding advice for HIV‐exposed and unexposed infants, and these were adopted in South Africa in 2017. We describe an innovative, team‐based, mentoring programme developed to update HWs on these guidelines. The intervention was underpinned by strong theoretical frameworks and aimed to improve HWs' attitudes, knowledge, confidence, and skills about breastfeeding in the context of HIV. On‐site workshops and clinical mentoring used interactive participatory methods and a simple low‐tech approach, guided by participants' self‐reported knowledge gaps. Workshops were conducted at 24 participating clinics over three sessions, each lasting 1–2 hr. Evaluation data were collected using a self‐administered questionnaire. Of 303 participating HWs, 249/303 (82.2%) attended all workshops. Achieving high workshop attendance was challenging and “catch‐up” sessions were required to achieve good coverage. Common knowledge gaps identified included antiretroviral therapy adherence monitoring during breastfeeding and management of viral load results (173 participants), management of breast conditions (79), and advice about expressing and storing breastmilk (64). Most participants reported all their knowledge gaps were addressed and anticipated that their practice would change. We describe a feasible, sustainable approach to updating HWs on HIV and infant feeding guidelines and improving skills in breastfeeding counselling in resource‐constrained settings. This approach could be adapted to other topics and, with further evaluation, implemented at scale using existing resources. 相似文献
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Fleur M. van der Valk Jeffrey Kroon Wouter V. Potters Rogier M. Thurlings Roelof J. Bennink Hein J. Verberne Aart J. Nederveen Max Nieuwdorp Willem J.M. Mulder Zahi A. Fayad Jaap D. van Buul Erik S.G. Stroes 《Journal of the American College of Cardiology》2014
Background
Understanding how leukocytes impact atherogenesis contributes critically to our concept of atherosclerosis development and the identification of potential therapeutic targets.Objectives
The study evaluates an in vivo imaging approach to visualize peripheral blood mononuclear cell (PBMC) accumulation in atherosclerotic lesions of cardiovascular (CV) patients using hybrid single-photon emission computed tomography/computed tomography (SPECT/CT).Methods
At baseline, CV patients and healthy controls underwent 18fluorodeoxyglucose positron emission tomography-computed tomography and magnetic resonance imaging to assess arterial wall inflammation and dimensions, respectively. For in vivo trafficking, autologous PBMCs were isolated, labeled with technetium-99m, and visualized 3, 4.5, and 6 h post-infusion with SPECT/CT.Results
Ten CV patients and 5 healthy controls were included. Patients had an increased arterial wall inflammation (target-to-background ratio [TBR] right carotid 2.00 ± 0.26 in patients vs. 1.51 ± 0.12 in controls; p = 0.022) and atherosclerotic burden (normalized wall index 0.52 ± 0.09 in patients vs. 0.33 ± 0.02 in controls; p = 0.026). Elevated PBMC accumulation in the arterial wall was observed in patients; for the right carotid, the arterial-wall-to-blood ratio (ABR) 4.5 h post-infusion was 2.13 ± 0.35 in patients versus 1.49 ± 0.40 in controls (p = 0.038). In patients, the ABR correlated with the TBR of the corresponding vessel (for the right carotid: r = 0.88; p < 0.001).Conclusions
PBMC accumulation is markedly enhanced in patients with advanced atherosclerotic lesions and correlates with disease severity. This study provides a noninvasive imaging tool to validate the development and implementation of interventions targeting leukocytes in atherosclerosis. 相似文献46.
47.
van Rijk MC Tanis PJ Nieweg OE Loo CE Olmos RA Oldenburg HS Rutgers EJ Hoefnagel CA Kroon BB 《Annals of surgical oncology》2007,14(2):627-632
Background Preliminary data have shown encouraging results of a single intratumoral radiopharmaceutical injection that enables both sentinel
node biopsy and probe-guided excision of the primary tumor in patients with nonpalpable breast cancer. The aim of the study
was to evaluate this approach in a large group of patients.
Methods Lymphoscintigraphy was performed in 368 patients with nonpalpable breast cancer after intratumoral injection of 99mTc-nanocolloid (.2 mL, 123 MBq, 3.3 mCi) guided by ultrasound or stereotaxis. The sentinel node was pursued with the aid of
vital blue dye (1.0 mL, intratumoral) and a gamma ray detection probe. In case of breast-conserving surgery, the probe was
used to guide the excision.
Results At least one sentinel node could be identified intraoperatively in 357 patients (97%), of whom 69 had involved nodes (19%).
Age over 60 years was associated with less frequent nonaxillary lymphatic drainage and absence of internal mammary chain dissemination.
Tumor-free margins were obtained in 262 (89%) of the 293 patients who underwent segmental excision. Re-excision of the primary
tumor bed was performed in six patients (2%). During a median follow-up of 22 months, one breast recurrence and one axillary
recurrence were observed.
Conclusions Lymphatic mapping and probe-guided tumor excision of nonpalpable breast cancer by intralesional administration of a single
dose of 99mTc-nanocolloid and blue dye resulted in 97% identification of the sentinel node and in tumor-free margins in 89% of the patients
who underwent breast-conserving surgery. Longer follow-up is needed to substantiate the accuracy and safety of this technique. 相似文献
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49.
Ingegerd Olsson Anna-Karin Abrahamsson Ulla-Beth Kroon 《International urogynecology journal》2010,21(6):679-683
Introduction and hypothesis
The aim was to evaluate the long-term cure rates and the late complications of the tension-free vaginal tape (TVT). 相似文献50.
Ingrid J. M. Scheffers Abraham A. Kroon Peter W. de Leeuw 《Current hypertension reports》2010,12(2):61-66
Electrical activation of the carotid baroreceptor system is an attractive therapy for the treatment of resistant hypertension.
In the past, several attempts were made to directly activate the baroreceptor system in humans, but the method had to be restricted
to a few selected patients. Adverse effects, the need for better electrical devices and better surgical techniques, and the
lack of knowledge about long-term effects has greatly hampered developments in this area for many years. Recently, a new and
promising device was evaluated in a multicenter feasibility trial, which showed a clinically and statistically significant
reduction in office systolic blood pressure (>20 mm Hg). This reduction could be sustained for at least 2 years with an acceptable
safety profile. In the future, this new device may stimulate further application of electrical activation of the carotid baroreflex
in treatment-resistant hypertension. 相似文献