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31.
Dutmer Alisa L. Soer Remko Wolff André P. Reneman Michiel F. Coppes Maarten H. Schiphorst Preuper Henrica R. 《European spine journal》2022,31(4):901-916
European Spine Journal - A scoping review was conducted with the objective to identify and map the available evidence from long-term studies on chronic non-specific low back pain (LBP), to examine... 相似文献
32.
Partial trisomies of chromosome 21 in man. Two new observations due to translocations 19;21 and 4;21
Partial trisomy of the distal portion of the long arm of chromosome no. 21, resulting from a (familial) translocation between the chromosomes no. 19 and 21 in a female twin with Down's syndrome, supports the hypothesis that triplication of 21q22 is the cause of the physical signs of mongolism. Partial trisomy of the remaining segments of chromosome no. 21 due to a (familial) translocation between the chromosomes no. 4 and 21, however, may only cause mental deficiency. 相似文献
33.
34.
Wijtmans M Celanire S Snip E Gillard MR Gelens E Collart PP Venhuis BJ Christophe B Hulscher S van der Goot H Lebon F Timmerman H Bakker RA Lallemand BI Leurs R Talaga PE de Esch IJ 《Journal of medicinal chemistry》2008,51(10):2944-2953
Research on the therapeutic applications of the histamine H3 receptor (H3R) has traditionally focused on antagonists/inverse agonists. In contrast, H3R agonists have received less attention despite their potential use in several disease areas. The lower availability of H3R agonists not only hampers their full therapeutic exploration, it also prevents an unequivocal understanding of the structural requirements for H3R activation. In the light of these important issues, we present our findings on 4-benzyl-1H-imidazole-based H3R agonists. Starting from two high throughput screen hits (10 and 11), the benzyl side chain was altered with lipophilic groups using combinatorial and classical chemical approaches (compounds 12-31). Alkyne- or oxazolino-substituents gave excellent affinities and agonist activities up to the single digit nM range. Our findings further substantiate the growing notion that basic ligand sidechains are not necessary for H 3R activation and reveal the oxazolino group as a hitherto unexplored functional group in H3R research. 相似文献
35.
Chemo(radio)therapy is becoming the new standard for patients with locally advanced pancreatic cancer. In case of tumor regression on imaging, surgical resection can be undertaken, albeit often with the need for extended procedures. Reevaluation of the current routine pathology procedures is required to establish the appropriate histopathological approach of the resulting specimens. This review focusses on margin status, which is universally considered a core data item of the pathology report, of relevance to both the management of the individual patient and the evaluation of the result of surgery in this particular patient group. As explained in this review, due to the cytoreductive effect of neoadjuvant therapy, the conventional definition of a tumor-free margin (“R0”) based on 1 mm clearance is not adequate. Furthermore, the complexity of many of the specimens following extended or multivisceral en bloc surgical resection make margin assessment challenging. These large specimens require extensive sampling, which is not always easily implemented in daily practice. At present, there is marked divergence in pathology practice, and consequently, neither the true R0-rate nor the exact prognostic effect of the margin status have been definitively established for resected locally advanced pancreatic cancer. A concerted effort towards uniform and optimal margin assessment is unfortunately still lacking. 相似文献
36.
37.
Viola M.J. Verhoef Daniëlle A.M. Heideman Folkert J. van Kemenade Lawrence Rozendaal Remko P. Bosgraaf Albertus T. Hesselink Ruud L.M. Bekkers Leon F.A.G. Massuger Renske D.M. Steenbergen Peter J.F. Snijders Johannes Berkhof Chris J.L.M. Meijer 《Gynecologic oncology》2014
Objectives
Methylation marker analysis using bi-marker panel MAL/miR-124-2 is a promising triage test for identifying cervical (pre)cancer in high-risk human papillomavirus (hrHPV) positive women. Bi-marker panel MAL/miR-124-2 can be applied directly on self-sampled cervico-vaginal material and its sensitivity is non-inferior to that of cytology, yet at the cost of more colposcopy referrals. Our objective was to increase specificity of MAL/miR-124-2 methylation analysis by varying the assay thresholds and adding HPV16/18 genotyping.Methods
1019 hrHPV-positive women were selected from a randomized controlled self-sampling trial (PROHTECT-3; 33–63 years, n = 46,001) and nine triage strategies with methylation testing of MAL/miR-124-2 and HPV16/18 genotyping were evaluated. The methylation assay threshold was set at four different predefined levels which correspond with clinical specificities for end-point cervical intra-epithelial grade 3 or worse (CIN3 +) of 50%, 60%, 70%, and 80%.Results
The CIN3 + sensitivity of methylation analysis decreased (73.5 to 44.9%) while specificity increased (47.2 to 83.4%) when increasing the assay threshold. CIN3 + sensitivity and specificity of HPV16/18 genotyping were 68.0% and 65.6%, respectively. Combined methylation analysis at threshold-80 and HPV16/18 genotyping yielded similar CIN3 + sensitivity as that of methylation only at threshold-50 (77.6%) with an increased specificity (54.8%).Conclusions
Combined triage by MAL/miR-124-2 methylation analysis with threshold-80 and HPV16/18 genotyping reaches high CIN3 + sensitivity with increased specificity to identify women with cervical (pre)cancer among HPV self-sample positive women. The combined strategy is attractive as it is fully molecular and identifies women at the highest risk of cervical (pre)cancer because of strongly elevated methylation levels and/or HPV16/18 positivity. 相似文献38.
39.
Remko de Pril Barbara Hobo Paula van Tijn Raymund A.C. Roos Fred W. van Leeuwen David F. Fischer 《Molecular and cellular neurosciences》2010,43(3):281-286
UBB+1, a mutant form of ubiquitin, is both a substrate and an inhibitor of the proteasome which accumulates in the neuropathological hallmarks of Huntington disease (HD). In vitro, expression of UBB+1 and mutant huntingtin synergistically increase aggregate formation and polyglutamine induced cell death. We generated a UBB+1 transgenic mouse line expressing UBB+1 within the neurons of the striatum. In these mice lentiviral driven expression of expanded huntingtin constructs in the striatum results in a significant increase in neuronal inclusion formation. Although UBB+1 transgenic mice show neither a decreased lifespan nor apparent neuronal loss, they appear to be more vulnerable to toxic insults like expanded polyglutamine proteins due to a modest proteasome inhibition. These findings underscore the relevance of an efficient ubiquitin–proteasome system in HD. 相似文献
40.
Remko Soer Patrick Vroomen Roy Stewart Maarten Coppes Patrick Stegeman Pieter Dijkstra Michiel Reneman 《The spine journal》2017,17(4):603-609