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1.
Ann Taber Youngrok Park Alana Lelo Frederik Prip Jerry Xiao Deborah L. Berry Krysta Chaldekas Jørgen Bjerggaard Jensen George Philips Jung-Sik Kim Brent T. Harris Lars Dyrskjøt Todd Waldman 《Urologic oncology》2021,39(7):438.e1-438.e9
ObjectiveImprovements to bladder cancer risk stratification guidelines are needed to better tailor post-operative surveillance and adjuvant therapy to individual patients. We previously identified STAG2 as a commonly mutated tumor suppressor gene in bladder cancer and an independent predictor of progression in NMIBC. Here we test the value of combining STAG2 immunostaining with other risk stratification biomarkers in NMIBC, and as an individual biomarker in MIBC.Materials and MethodsSTAG2 immunohistochemistry was performed on a progressor-enriched cohort of tumors from 297 patients with NMIBC, and on tumors from 406 patients with MIBC from Aarhus University Hospital in Denmark. Survival analysis was performed using Kaplan-Meier survival analysis, the log rank test, and Cox proportional hazards models.ResultsSTAG2-negative low-grade NMIBC tumors were 2.5 times less likely to progress to muscle invasion than STAG2-positive low-grade NMIBC tumors (Log-rank test, P = 0.008). In a composite group of patients with AUA intermediate and high-risk NMIBC tumors, STAG2-negative tumors were less likely to progress (Log-rank test, P = 0.02). In contrast to NMIBC, we show that STAG2 is not useful as a prognostic biomarker in MIBC.ConclusionsSTAG2 immunostaining can be used to subdivide low-grade NMIBC tumors into two groups with substantially different risks of disease progression. Furthermore, STAG2 immunostaining may be useful to enhance NMIBC risk stratification guidelines, though larger cohorts are needed to solidify this conclusion in individual risk groups. STAG2 is not useful as a biomarker in MIBC. Further study of the use of STAG2 immunostaining as a biomarker for predicting the clinical behavior in NMIBC is warranted. 相似文献
2.
Hampanda Karen Pelowich Krysta Chi Benjamin H. Darbes Lynae A. Turan Janet M. Mutale Wilbroad Abuogi Lisa 《AIDS and behavior》2022,26(2):443-456
AIDS and Behavior - There is increasing focus in HIV prevention and treatment on couples-based approaches. No systematic review has synthesized prospective behavioral couples-based HIV trials... 相似文献
3.
Arjan PM de Brouwer Sander B Nabuurs Ingrid EC Verhaart Astrid R Oudakker Roel Hordijk Helger G Yntema Jannet M Hordijk-Hos Krysta Voesenek Bert BA de Vries Ton van Essen Wei Chen Hao Hu Jamel Chelly Johan T den Dunnen Vera M Kalscheuer Annemieke M Aartsma-Rus Ben CJ Hamel Hans van Bokhoven Tjitske Kleefstra 《European journal of human genetics : EJHG》2014,22(4):480-485
We have identified a deletion of 3 base pairs in the dystrophin gene (DMD), c.9711_9713del, in a family with nonspecific X-linked intellectual disability (ID) by sequencing of the exons of 86 known X-linked ID genes. This in-frame deletion results in the deletion of a single-amino-acid residue, Leu3238, in the brain-specific isoform Dp71 of dystrophin. Linkage analysis supported causality as the mutation was present in the 7.6 cM linkage interval on Xp22.11–Xp21.1 with a maximum positive LOD score of 2.41 (MRX85 locus). Molecular modeling predicts that the p.(Leu3238del) deletion results in the destabilization of the C-terminal domain of dystrophin and hence reduces the ability to interact with β-dystroglycan. Correspondingly, Dp71 protein levels in lymphoblastoid cells from the index patient are 6.7-fold lower than those in control cell lines (P=0.08). Subsequent determination of the creatine kinase levels in blood of the index patient showed a mild but significant elevation in serum creatine kinase, which is in line with impaired dystrophin function. In conclusion, we have identified the first DMD mutation in Dp71 that results in ID without muscular dystrophy. 相似文献
4.
M de Wit W Kegge JB Evers MH Vergeer-van Eijk P Gankema LA Voesenek R Pierik 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(36):14705-14710
Plants in dense vegetation compete for resources, including light, and optimize their growth based on neighbor detection cues. The best studied of such behaviors is the shade-avoidance syndrome that positions leaves in optimally lit zones of a vegetation. Although proximate vegetation is known to be sensed through a reduced ratio between red and far-red light, we show here through computational modeling and manipulative experiments that leaves of the rosette species Arabidopsis thaliana first need to move upward to generate sufficient light reflection potential for subsequent occurrence and perception of a reduced red to far-red ratio. This early hyponastic leaf growth response is not induced by known neighbor detection cues under both climate chamber and natural sunlight conditions, and we identify a unique way for plants to detect future competitors through touching of leaf tips. This signal occurs before light signals and appears to be the earliest means of above-ground plant-plant signaling in horizontally growing rosette plants. 相似文献
5.
Grzegorz Franik Krzysztof Krysta Paweł Madej Beata Gimlewicz-Pięta Barbara Oślizło 《Gynecological endocrinology》2016,32(12):1014-1017
Sleep disturbances in women with Polycystic Ovary Syndrome (PCOS) have been reported in recent years. The majority of published studies are related to Obstructive Sleep Apnea (OSA) while not many researches have analyzed any other causes of sleep disturbances. A group of ninety five women with Polycystic Ovary Syndrome were enrolled into the study. Sleep disturbances were assessed using validated questionnaires. On the grounds of Athens Insomnia Scale (AIS) evaluation a clinically significant insomnia was ascertained in 12.6% of women with PCOS, while according to Insomnia Severity Index (ISI) in 10.5%. Clinically significant insomnia according to both AIS and ISI, occurred significantly more often in women with PCOS than in women without PCOS based on the chi-square test. The Mann–Whitney U test revealed statistically significant difference between women with and without PCOS based on total values of ISI. An excessive daytime sleepiness occurred at 7.4% of women with PCOS. Statistically significant dependance between: clinically significant insomnia in both AIS and ISI and excessive daytime sleepiness indicated by Epworth Sleepiness Scale (ESS) was observed. Sleep disorders are common in women with PCOS. Screening assessment of sleep disturbances should be a part of medical diagnostics in women with PCOS. 相似文献
6.
Cerebellar parallel fibers are among the thinnest known vertebrate axons and represent an extreme anatomical adaptation. Until now a systematic examination of their properties across species has not been carried out. We used transmission electron microscopy and light microscopy to compare parallel fibers in mammals of different brain sizes. From mouse to macaque, the average unmyelinated parallel fiber diameter was 0.2-0.3 microm, consistent with the idea that they are evolutionarily selected for compactness. Average unmyelinated parallel fiber diameter scaled up slightly with brain size, and across species the estimated total conduction time is 5-10 ms. However, these conduction times can vary by milliseconds, and unmyelinated PFs consume large amounts of energy per action potential. These functional disadvantages are overcome in myelinated parallel fibers, which we found in the deep regions nearest the Purkinje cell layer in marmoset, cat and macaque. These axons were 0.4-1.1 microm wide, have expected conduction times of 0.5-1.0 ms, and may convey fast feedforward inhibition via basket cells to Purkinje cells. 相似文献
7.
Cancer cells acquire disruptions in normal signal transduction pathways and homeostatic mechanisms that would trigger apoptosis in normal cells. These abnormalities include genomic instability, oncogene activation, and growth factor independent proliferation. Therefore, cancer cells likely require a block in apoptosis in order to survive. Overexpression of the antiapoptotic protein BCL-2 provides a block in apoptosis that is frequently observed in cancer cells. We have developed methods for the detection and analysis of BCL-2 dependence and here apply them to acute lymphoblastic leukemia (ALL). BH3 profiling, a mitochondrial assay that classifies blocks in the intrinsic apoptotic pathway, indicated a dependence on BCL-2 of both ALL cell lines and primary samples. This dependence predicted that BCL-2 would be complexed with select pro-death BH3 family proteins, a prediction confirmed by the isolation of BCL-2 complexes with BIM. Furthermore, the BH3 profiling and protein analysis predicted that ALL cell lines and primary cells would be sensitive to ABT-737 as a single agent. Finally, BH3 profiling and protein studies accurately predicted a relative degree of sensitivity to BCL-2 antagonism in cell lines. The ALL cells studied exhibit BCL-2 dependence, supporting clinical trials of BCL-2 antagonists in ALL as single agents or combination therapies. 相似文献
8.
Administration of the synthetic cannabinoid receptor agonist WIN 55,212-2 has been shown to increase indices of noradrenergic activity. Neuroanatomical, neurochemical and behavioral studies have provided evidence supporting a marked impact of cannabinoids on the rat coeruleo-cortical pathway. As activity of this pathway is implicated in setting specific attentional modes, the present study assessed the influence of acute and repeated systemic administration of WIN 55,212-2 on novelty investigation in adolescent and adult male rats by using the hole board behavioral paradigm. Animals were individually acclimated to the hole board for 10-min sessions over 3 days, and novel objects were introduced on the fourth day. Novelty-seeking behavior was measured by comparison of the average number of return visits to a hole containing a novel object versus the average number of return visits to an empty hole. While attenuation of novelty preference was observed in adult rats acutely treated with WIN 55,212-2, both acutely treated adolescent groups retained their preference for novelty. All groups treated with repeated administration of either drug or vehicle demonstrated novelty preference, and no differences were found in the measure of novelty investigation between the groups. Furthermore, this study reproduced findings showing significant differences in locomotor activity that did not coincide with differences in novelty-seeking behavior. These data thus suggest a complex effect of CB1 receptor modulation on novelty preference in the male rat that is modulated by age and treatment. 相似文献
9.
Bell GI Broughton HC Levac KD Allan DA Xenocostas A Hess DA 《Stem cells and development》2012,21(1):97-109
Transplanted murine bone marrow (BM) progenitor cells recruit to the injured pancreas and induce endogenous beta cell proliferation to improve islet function. To enrich for analogous human progenitor cell types that stimulate islet regeneration, we purified human BM based on high-aldehyde dehydrogenase activity (ALDH(hi)), an enzymatic function conserved in hematopoietic, endothelial, and mesenchymal progenitor lineages. We investigated the contributions of ALDH(hi) mixed progenitor cells or culture-expanded, ALDH-purified multipotent stromal cell (MSC) subsets to activate endogenous programs for islet regeneration after transplantation into streptozotocin-treated NOD/SCID mice. Intravenous injection of uncultured BM ALDH(hi) cells improved systemic hyperglycemia and augmented insulin secretion by increasing islet size and vascularization, without increasing total islet number. Augmented proliferation within regenerated endogenous islets and associated vascular endothelium indicated the induction of islet-specific proliferative and pro-angiogenic programs. Although cultured MSC from independent human BM samples showed variable capacity to improve islet function, and prolonged expansion diminished hyperglycemic recovery, transplantation of ALDH-purified regenerative MSC reduced hyperglycemia and augmented total beta cell mass by stimulating the formation of small beta cell clusters associated with the ductal epithelium, without evidence of increased islet vascularization or Ngn3(+) endocrine precursor activation. Thus, endogenous islet recovery after progenitor cell transplantation can occur via distinct regenerative mechanisms modulated by subtypes of progenitor cells administered. Further, understanding of how these islet regenerative and pro-angiogenic programs are activated by specific progenitor subsets may provide new approaches for combination cellular therapies to combat diabetes. 相似文献
10.
Gary Remington Ofer Agid George Foussias Larissa Ferguson Krysta McDonald Valerie Powell 《Psychopharmacology》2013,225(3):505-518