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排序方式: 共有1348条查询结果,搜索用时 93 毫秒
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Alma Ghirelli MD Nirubol Tosakulwong BS Stephen D. Weigand MS Heather M. Clark PhD Farwa Ali MD Hugo Botha MD Joseph R. Duffy PhD Rene L. Utianski PhD Marina Buciuc MD Melissa E. Murray PhD Sydney A. Labuzan MS Anthony J. Spychalla BS Nha Trang Thu Pham BS Christopher G. Schwarz PhD Matthew L. Senjem MS Mary M. Machulda PhD Matthew Baker BS Rosa Rademakers PhD Massimo Filippi MD Clifford R. Jack Jr MD Val J. Lowe MD Joseph E. Parisi MD Dennis W. Dickson MD Keith A. Josephs MD MST MSc Jennifer L. Whitwell PhD 《Annals of neurology》2020,88(5):1009-1022
3.
OBJECTIVE: To assess the feasibility of using archival oral mucosal tissue to examine gene expression at the ribonucleic acid (RNA) level.
MATERIALS AND METHODS: We describe the isolation of RNA from 8 nm sections of formalin-fixed paraffin-embedded oral mucosal tissue. RNA was reverse transcribed and three candidate genes amplified by polymerase chain reaction (PCR). The ribosomal protein S14 gene is a housekeeping gene which has been used as an internal standard in several quantitative PCR protocols. The thymidine kinase (TK) gene is expressed at low levels in most tissues and, with a well-documented genomic organisation, is a useful tool for discrimination between genomic DNA and cDNA. The RIa gene is reported to be overexpressed in many cancer cell lines, in malignant tissue and in vitro transformed cellS. RESULTS: The S14 gene, the TK gene and the RIα gene of the cAMP-dependent protein kinase (PKA) were amplified successfully from formalin-fixed paraffin-embedded tissue sections. The TK primer pair is a useful additional tool in the unambiguous identification of RNA-derived species.
CONCLUSION: RNA suitable for reverse transcribed (RT)-PCR was extracted from archival oral mucosal tissue. This should permit rapid sequence analysis of transcribed tumor suppressor genes and oncogenes in this material. Furthermore, the RT-PCR approach described may allow quantification of gene expression in oral mucosal archival material processed in a standard fashion. 相似文献
MATERIALS AND METHODS: We describe the isolation of RNA from 8 nm sections of formalin-fixed paraffin-embedded oral mucosal tissue. RNA was reverse transcribed and three candidate genes amplified by polymerase chain reaction (PCR). The ribosomal protein S14 gene is a housekeeping gene which has been used as an internal standard in several quantitative PCR protocols. The thymidine kinase (TK) gene is expressed at low levels in most tissues and, with a well-documented genomic organisation, is a useful tool for discrimination between genomic DNA and cDNA. The RIa gene is reported to be overexpressed in many cancer cell lines, in malignant tissue and in vitro transformed cellS. RESULTS: The S14 gene, the TK gene and the RIα gene of the cAMP-dependent protein kinase (PKA) were amplified successfully from formalin-fixed paraffin-embedded tissue sections. The TK primer pair is a useful additional tool in the unambiguous identification of RNA-derived species.
CONCLUSION: RNA suitable for reverse transcribed (RT)-PCR was extracted from archival oral mucosal tissue. This should permit rapid sequence analysis of transcribed tumor suppressor genes and oncogenes in this material. Furthermore, the RT-PCR approach described may allow quantification of gene expression in oral mucosal archival material processed in a standard fashion. 相似文献
4.
Yong-Jie Zhang Karen Jansen-West Ya-Fei Xu Tania F. Gendron Kevin F. Bieniek Wen-Lang Lin Hiroki Sasaguri Thomas Caulfield Jaime Hubbard Lillian Daughrity Jeannie Chew Veronique V. Belzil Mercedes Prudencio Jeannette N. Stankowski Monica Castanedes-Casey Ena Whitelaw Peter E. A. Ash Michael DeTure Rosa Rademakers Kevin B. Boylan Dennis W. Dickson Leonard Petrucelli 《Acta neuropathologica》2014,128(4):505-524
The occurrence of repeat-associated non-ATG (RAN) translation, an atypical form of translation of expanded repeats that results in the synthesis of homopolymeric expansion proteins, is becoming more widely appreciated among microsatellite expansion disorders. Such disorders include amyotrophic lateral sclerosis and frontotemporal dementia caused by a hexanucleotide repeat expansion in the C9ORF72 gene (c9FTD/ALS). We and others have recently shown that this bidirectionally transcribed repeat is RAN translated, and the “c9RAN proteins” thusly produced form neuronal inclusions throughout the central nervous system of c9FTD/ALS patients. Nonetheless, the potential contribution of c9RAN proteins to disease pathogenesis remains poorly understood. In the present study, we demonstrate that poly(GA) c9RAN proteins are neurotoxic and may be implicated in the neurodegenerative processes of c9FTD/ALS. Specifically, we show that expression of poly(GA) proteins in cultured cells and primary neurons leads to the formation of soluble and insoluble high molecular weight species, as well as inclusions composed of filaments similar to those observed in c9FTD/ALS brain tissues. The expression of poly(GA) proteins is accompanied by caspase-3 activation, impaired neurite outgrowth, inhibition of proteasome activity, and evidence of endoplasmic reticulum (ER) stress. Of importance, ER stress inhibitors, salubrinal and TUDCA, provide protection against poly(GA)-induced toxicity. Taken together, our data provide compelling evidence towards establishing RAN translation as a pathogenic mechanism of c9FTD/ALS, and suggest that targeting the ER using small molecules may be a promising therapeutic approach for these devastating diseases. 相似文献
5.
Naomi Kouri Yari Carlomagno Matthew Baker Amanda M. Liesinger Richard J. Caselli Zbigniew K. Wszolek Leonard Petrucelli Bradley F. Boeve Joseph E. Parisi Keith A. Josephs Ryan J. Uitti Owen A. Ross Neill R. Graff-Radford Michael A. DeTure Dennis W. Dickson Rosa Rademakers 《Acta neuropathologica》2014,127(2):271-282
In order to determine the frequency of microtubule-associated protein tau gene (MAPT) mutations and rare variants in CBD, we performed a systematic sequence analysis of MAPT coding and 3′ untranslated region (3′UTR) in a large cohort of autopsy-confirmed CBD patients (N = 109). This identified a novel MAPT mutation in exon 13, p.N410H, in a case that is neuropathologically indistinguishable from sporadic CBD. On immunoblot, the p.N410H mutation carrier had the same insoluble tau profile as seen in CBD. Additionally, tau expression analysis in brain tissue found a significant increase in the 4R/3R tau mRNA ratio (P = 0.04), indicating that p.N410H disrupts tau isoform homeostasis. Biochemically, recombinant tau protein with p.N410H showed a marked increase in tau filament formation compared to wild-type tau (P < 0.001), had a 19.2 % decrease in rate of microtubule assembly (P < 0.05), and a 10.3 % reduction in the extent of total microtubule polymerization (P < 0.01). Sequence analysis of the complete MAPT 3′UTR in autopsy-confirmed CBD cases further identified two rare variants with nominally significant association with CBD. An ATC nucleotide insertion (“MAPTv8”) was found in 4.6 % of CBD patients compared to 1.2 % of controls (P = 0.031, OR = 3.71), and rs186977284 in 4.6 % CBD patients, but only 0.9 % of controls (P = 0.04, OR = 3.58). Rs186977284 was also present in 2.7 % of a large cohort of autopsy-confirmed PSP patients (N = 566) and only 0.9 % of an additional control series (P = 0.034, OR = 3.08), extending the association to PSP. Our findings show that mutations in MAPT can cause CBD and MAPT non-coding variants may increase the risk of complex 4R tauopathies. 相似文献
6.
Experimental assessment of a new research tool for the estimation of two-dimensional myocardial strain 总被引:5,自引:0,他引:5
Langeland S Wouters PF Claus P Leather HA Bijnens B Sutherland GR Rademakers FE D'hooge J 《Ultrasound in medicine & biology》2006,32(10):1509-1513
One-dimensional strain imaging has been shown to be angle dependent. To address this problem, a new methodology, 2D-strain, has become available. The aim of this study was to validate this methodology in an in vivo set-up against sonomicrometry. In five open chest sheep, ultrasound gray-scale images were acquired of the inferolateral wall from two different angles. The longitudinal and radial strain components were simultaneously extracted using the novel 2D-strain methodology. The extracted values were compared with sonomicrometry using Bland-Altman statistics and correlation coefficients. A good agreement was found for the longitudinal strain component, while, for the radial strain estimates, the accuracy was less. 2D-strain is a fast and accurate tool to assess longitudinal strain from apical views. Further improvements are needed for the method to be sufficiently accurate in estimating the deformation perpendicular or close to perpendicular to the ultrasound beam. 相似文献
7.
L Jones J Moir C Brown R Williams JJ French 《Annals of the Royal College of Surgeons of England》2014,96(6):e1-e3
A 61-year-old man presented with jaundice, and subsequently underwent an extended left hepatectomy and pancreaticoduodenectomy for a cholangiocarcinoma invading the head of the pancreas. The patient developed sepsis due to a biliary leak at the hepaticojejunostomy. We describe the original use of a biodegradable stent, deployed via percutaneous transhepatic cholangiography into the Roux limb, resulting in good drainage and resolution of sepsis. The chief benefit of this procedure is the lack of need for subsequent removal as well as purported reduced biofilm accumulation. We believe this to be the first reported case of this type and the literature surrounding the subject is also discussed. 相似文献
8.
Matthias Oelke Kevin L. J. Rademakers Gommert A. van Koeveringe 《World journal of urology》2014,32(5):1177-1183
Purpose
To investigate to what extent detrusor work during voiding is influenced by bladder outlet obstruction (BOO) in adult men with lower urinary tract symptoms (LUTS).Materials and methods
We reviewed data of patients with LUTS suggestive of benign prostatic hyperplasia who received computer-urodynamic investigations as part of their baseline clinical assessment. BOO was defined by the Schäfer classification and detrusor work during voiding was quantified by calculation of the bladder contractility index (BCI) and maximum Watt factor (W max) obtained by pressure-flow analysis.Results
A total of 786 men with medians of 64 years, IPSS 16 and prostate volume of 35 ml, were included in the study. A total of 462 patients (58.8 %) had BOO (Schäfer 2–6). Both detrusor contraction power parameters continuously increased with rising BOO grade. Median BCI increased from 73.3 in Schäfer 0 to 188.0 in Schäfer 6, whereas W max increased from 9.6 to 23.4 W/m2 (p < 0.001). Results of BCI and W max correlated well (p < 0.001). With increasing BOO grade, there was a significant decrease of voiding efficiency (p < 0.001).Conclusions
In adult male LUTS patients, detrusor contraction power parameters—BCI and W max—continuously increase with rising BOO grade. According to our results, it is impossible to determine a single threshold value for detrusor contraction power to diagnose detrusor underactivity in a group of LUTS patients with different BOO grades. The study is limited to men with non-neurogenic LUTS. Future studies should evaluate exact threshold values for BCI and W max in BOO subgroups to adequately define detrusor underactivity and investigate men with other bladder conditions. 相似文献9.
Background
Management of high-grade T1 (formerly T1G3) bladder cancer continues to be controversial. Should patients with T1G3 bladder cancer have an immediate radical cystectomy or should they receive intravesical bacillus Calmette-Guérin preserving bladder? Gemcitabine and cisplatin (GC) adjuvant chemotherapy may help to strike a balance between intravesical and early cystectomy. For purposes of this study, we continue to refer high-grade T1 lesion as “T1G3.”Objective
To evaluate the characteristics and the long-term outcome of GC adjuvant chemotherapy in T1G3 bladder cancer after transurethral resection of bladder tumor (TURBT).Materials and methods
We, retrospectively, reviewed 48 patients who were newly diagnosed with T1G3 bladder cancer between January 2009 and December 2012. A total of 48 patients received 4 cycles of GC adjuvant chemotherapy after TURBT. One month after 4 cycles of GC adjuvant chemotherapy, response was evaluated by re-TURBT. Median follow-up was 59.5 (range: 18–70) months, all patients have been observed for more than 3 years. Salvage cystectomy was recommended for patients with persistent disease and for tumor progression after initial complete response.Result
Complete response was achieved in 44 (91.7%) patients. Of complete responders, 5 patients experienced recurrence and 5 patients showed progression. The progression rate and disease-specific survival rate were 10.4% and 91.7% at 3 years, respectively. More than 80% of survivors preserved their bladder. Kaplan-Meier curves showed that concomitant carcinoma in situ (CIS) was the only factor that had an influence on progression-free survival (P = 0.022) and disease-specific survival (P = 0.017). Concomitant CIS was the prognostic factor for progression rate and disease-specific survival rate at 3 years (P = 0.008 and P = 0.035).Conclusion
GC adjuvant chemotherapy is a safe conservative treatment for T1G3 bladder cancer, but effective is really a phase II study. Patients with T1G3 bladder cancer with concomitant CIS should be treated more aggressively because of the high risk of progression. 相似文献10.