bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the Oncogenic Activity of the Novel TRIM59 Gene in Mouse Cancer Models
Authors: Valiyeva Fatma , Jiang Fei , Elmaadawi Ahmed , Moussa Madeleine , Yee Siu-Pok , Raptis Leda , Izawa Jonathan I. , Yang Burton B. , Greenberg Norman M. , Wang Fen , Xuan Jim W. 
Published: May 2011

Abstract
A novel TRIM family member, TRIM59 gene was characterized to be upregulated in SV40 Tag oncogene–directed transgenic and knockout mouse prostate cancer models as a signaling pathway effector. We identified two phosphorylated forms of TRIM59 (p53 and p55) and characterized them using purified TRIM59 proteins from mouse prostate cancer models at different stages with wild-type mice and NIH3T3 cells as controls. p53/p55-TRIM59 proteins possibly represent Ser/Thr and Tyr phosphorylation modifications, respectively. Quantitative measurements by ELISA showed that the p-Ser/Thr TRIM59 correlated with tumorigenesis, whereas the p-Tyr-TRIM59 protein correlated with advanced cancer of the prostate (CaP). The function of TRIM59 was elucidated using short hairpin RNA (shRNA)-mediated knockdown of the gene in human CaP cells, which caused S-phase cell-cycle arrest and cell growth retardation. A hit-and-run effect of TRIM59 shRNA knockdown was observed 24 hours posttransfection. Differential cDNA microarrray analysis was conducted, which showed that the initial and rapid knockdown occurred early in the Ras signaling pathway. To confirm the proto-oncogenic function of TRIM59 in the Ras signaling pathway, we generated a transgenic mouse model using a prostate tissue–specific gene (PSP94) to direct the upregulation of the TRIM59 gene. Restricted TRIM59 gene upregulation in the prostate revealed the full potential for inducing tumorigenesis, similar to the expression of SV40 Tag, and coincided with the upregulation of genes specific to the Ras signaling pathway and bridging genes for SV40 Tag–mediated oncogenesis. The finding of a possible novel oncogene in animal models will implicate a novel strategy for diagnosis, prognosis, and therapy for cancer. Mol Cancer Ther; 10(7); 1229–40. ©2011 AACR.
Downregulation of Sec23A Protein by miRNA-375 in Prostate Carcinoma
Authors: Szczyrba Jaroslaw , Nolte Elke , Wach Sven , Kremmer Elisabeth , Stöhr Robert , Hartmann Arndt , Wieland Wolf , Wullich Bernd , Grässer Friedrich A. 
Published: May 2011

Abstract
Prostate carcinoma (CaP) is a leading cause of cancer-related death in men. We have previously determined the microRNA (miRNA) profile of primary CaP in comparison with nontumor prostate tissue. miRNAs are small, noncoding RNAs that inhibit protein synthesis on a posttranscriptional level by binding to the 3′-untranslated region (3′-UTR) of their target genes. In primary CaP tissue, we have previously found by miRNA sequencing that miR-375 and miR-200c were upregulated 9.1- and 4.5-fold, respectively. A computational analysis predicted the 3′-UTR of the SEC23A gene as a potential target for both miR-375 and miR-200c. Here, we show that the 3′-UTR of SEC23A mRNA is indeed a target for miR-375 and miR-200c and that both miRNAs downregulate Sec23A protein expression when ectopically expressed in human 293T cells. In primary samples of CaP, we found a direct correlation between reduction of SEC23A mRNA and overexpression of miR-375 but not of miR-200c. The reduced levels of Sec23A protein were inversely correlated to the increased amount of miR-375 in the LNCaP and DU145 CaP cell lines when compared with normal prostate fibroblasts. In primary CaP, we also detected decreased amounts of Sec23A protein when compared with corresponding normal prostate tissue. Ectopically overexpressed Sec23A in LNCaP and DU145 CaP cells significantly reduced the growth properties, indicating that Sec23A might play a role in the induction or growth of prostate carcinoma. Sec23A overexpression reduced cell growth but did not induce apoptosis, whereas inhibition of Sec23A stimulated cell proliferation. Mol Cancer Res; 9(6); 791–800. ©2011 AACR.
Rapamycin Partially Mimics the Anticancer Effects of Calorie Restriction in a Murine Model of Pancreatic Cancer
Authors: Lashinger Laura M. , Malone Lauren M. , Brown Graham W. , Daniels Elizabeth A. , Goldberg Jason A. , Otto Glen , Fischer Susan M. , Hursting Stephen D. 
Published: May 2011

Abstract
Etiologic factors for pancreatic cancer, the 4th deadliest malignant neoplasm in the United States, include obesity and abnormal glucose metabolism. Calorie restriction (CR) and rapamycin each affect energy metabolism and cell survival pathways via inhibition of mammalian target of rapamycin (mTOR) signaling. By using a Panc02 murine pancreatic cancer cell transplant model in 45 male C57BL/6 mice, we tested the hypothesis that rapamycin mimics the effects of CR on pancreatic tumor growth. A chronic regimen of CR, relative to an ad libitum-fed control diet, produced global metabolic effects such as reduced body weight (20.6 ± 1.6 g vs. 29.3 ± 2.3 g; P &lt; 0.0001), improved glucose responsiveness, and decreased circulating levels of insulin-like growth factor (IGF)-1 (126 ± 8 ng/mL vs. 199 ± 11 ng/mL; P = 0.0006) and leptin (1.14 ± 0.2 ng/mL vs. 5.05 ± 1.2 ng/mL; P = 0.01). In contrast, rapamycin treatment (2.5 mg/kg intraperitoneal every other day, initiated in mice following 20 weeks of ad libitum control diet consumption), relative to control diet, produced no significant change in body weight, IGF-1 or leptin levels, but decreased glucose responsiveness. Pancreatic tumor volume was significantly reduced in the CR group (221 ± 107 mm3; P &lt; 0.001) and, to a lesser extent, the rapamycin group (374 ± 206 mm3; P = 0.04) relative to controls (550 ± 147 mm3), and this differential inhibition correlated with expression of the proliferation marker Ki-67. Both CR and rapamycin decreased phosphorylation of mTOR, p70/S6K, and S6 ribosomal protein, but only CR decreased phosphorylation of Akt, GSK-3β, extracellular signal regulated kinase/mitogen-activated protein kinase, and STAT3TYR705. These findings suggest that rapamycin partially mimics the anticancer effects of CR on tumor growth in a murine model of pancreatic cancer. Cancer Prev Res; 4(7); 1041–51. ©2011 AACR.
Genetic Reduction of Insulin-like Growth Factor-1 Mimics the Anticancer Effects of Calorie Restriction on Cyclooxygenase-2–Driven Pancreatic Neoplasia
Authors: Lashinger Laura M. , Malone Lauren M. , McArthur Mark J. , Goldberg Jason A. , Daniels Elizabeth A. , Pavone Amy , Colby Jennifer K. , Smith Nicole C. , Perkins Susan N. , Fischer Susan M. , Hursting Stephen D. 
Published: May 2011

Abstract
Risk of pancreatic cancer, the fourth deadliest cancer in the United States, is increased by obesity. Calorie restriction (CR) prevents obesity, suppresses carcinogenesis in many models, and reduces serum levels of IGF-1. In the present study, we examined the impact of CR on a model of inflammation-associated pancreatitis and pancreatic dysplasia, with a focus on the mechanistic contribution of systemic IGF-1. Administration of a 30% CR diet for 14 weeks decreased serum IGF-1 levels and hindered pancreatic ductal lesion formation and dysplastic severity, relative to a higher calorie control diet, in transgenic mice overexpressing COX-2 [bovine keratin-5 promoter (BK5.COX-2)]. These findings in CR mice correlated with reductions in Ki-67–positive cells, vascular luminal size, VEGF expression, and phosphorylation and total expression of downstream mediators of the IGF-1 pathway. Cell lines derived from BK5.COX-2 ductal lesions (JC101 cells) formed pancreatic tumors in wild-type FVB mice that were significantly reduced in size by a 14-week CR regimen, relative to the control diet. To further understand the impact of circulating levels of IGF-1 on tumor growth in this model, we orthotopically injected JC101 cells into liver-specific IGF-1–deficient (LID) mice. The approximate 65% reduction of serum IGF-1 levels in LID mice resulted in significantly decreased burden of JC101 tumors, despite modestly elevated levels of circulating insulin and leptin. These data show that CR prevents development of dysplasia and growth of pancreatic cancer through alterations in IGF-1, suggesting that modulation of this pathway with dietary and/or pharmacologic interventions is a promising pancreatic cancer prevention strategy. Cancer Prev Res; 4(7); 1030–40. ©2011 AACR.
Changes in the Frequency of Different Categories of Temperature Extremes in India
Authors: Dash S. K. , Mamgain Ashu 
Published: May 2011

AbstractIn the context of climate change and its impact on sectors like agriculture and health, it is important to examine the changes in the characteristics of temperature extremes of different intensities and duration. In this study, an India Meteorological Department gridded temperature dataset is used to examine the changes in the frequency of occurrence of extreme temperatures over India and its seven homogeneous regions during the period 1969–2005. Results indicate a significant decrease in the frequency of occurrence of cold nights in the winter months in India and in its homogeneous regions in the north except in the western Himalaya. Southern regions show a drastic decrease in the frequency of cold nights relative to the period 1969–75. A significant increasing trend in the number of warm days in summer is noticed only in the interior peninsula. In the entire country and on the east coast and west coast, the maximum number of warm days in summer has been noticed only during the last decade, 1996–2005. Further, in the whole country the maximum number of intense warm days and nights in summer has been observed in the last decade. A significant increase in the number of cold days in winter is observed in the north-central and northeast regions. Changes in the frequency of warm and cold exceedances indicate maximum warming in the west coast as compared with all other regions. In sum, such spatial and temporal changes in the characteristics of all categories of temperature extremes broadly suggest warming trends in large parts of India.
Snow Cover and Spring Flood Flow in the Northern Part of Western Siberia (the Poluy, Nadym, Pur, and Taz Rivers)
Authors: Zakharova E. A. , Kouraev A. V. , Biancamaria S. , Kolmakova M. V. , Mognard N. M. , Zemtsov V. A. , Kirpotin S. N. , Decharme B. 
Published: May 2011

AbstractThe paper aims to quantitatively estimate the role of snowmelt in the spring flood flow and the redistribution of river runoff for the northern (Arctic) part of the western Siberian Plain (the rivers Poluy, Nadym, Pur, and Taz). In this region, the presence of wetlands and thermokarst lakes significantly influences the seasonal redistribution of river discharge. First the study region is described, and the snow regime from in situ observations at the Tarko-Sale meteorological station is analyzed. As Special Sensor Microwave Imager (SSM/I) estimates of snow depth for this region are lower than in situ observations, a correction of the SSM/I snow depth estimates is done using snow parameters measured on the snow transect near the meteorological station Tarko-Sale for 1991–96. This reestimated snow depth is then used to assess the volume of water stored every winter on the watersheds for 1989–2006. This snow product is compared with the spring flood streamflow estimated from in situ observations, and the regional relationship between the snow water storage and flood flow is constructed. The proportion of meltwater that does not reach the main rivers and is thus evaporated or stored by the wetlands is estimated to be on average 30% (varying from 0% to 74%). We observe an increasing trend of this value from 20%–30% in the early 1990s to 50%–60% in the mid-2000s. This increase could be attributed to several factors such as increased air temperature (leading to increased evaporation, changes in vegetation cover, and active layer depth) and also to human activity.
Histological and Immunohistochemical Study of Pars Tensa Retraction Pocket
Authors: Shunyu N. Brian , Gupta Siddhartha Datta , Thakar Alok , Sharma Suresh C. 
Published: May 2011

ObjectiveTo study the histological and proliferation characteristics of the pars tensa retraction pocket. To investigate the hypothesis that such retraction pockets may demonstrate breaks in the epithelial basement membrane.Study DesignProspective evaluation. Fifty stage II‐IV surgically resected retraction pockets.SettingTertiary care academic hospital.MethodsParaffin sections stained with hematoxylin and eosin. Basement membrane evaluation by Periodic acid‐Schiff (PAS) and silver‐methenamine (SM). Evaluation of cellular proliferation by immunohistochemistry (MIB‐1 score).ResultsFollowing are findings noted as frequent but not invariable in pars tensa retraction pockets: (1) subepithelial chronic inflammation (86%), (2) proliferation and hyperkeratinization of the outer epithelial layer, (3) epithelial cones with proliferating cells (increased MIB‐1 score) in the basal epithelial layer (39%), (4) loss of the middle double collagen layer (71%), and (5) loss of the inner mucosal layer (33%). Inflammation and cellular proliferation were noted as ubiquitous among all grades. A trend was noted along progressive grades of retraction (II‐IV) for an increasing incidence of basal epithelial cones, middle collagen layer loss, and inner mucosal layer loss. Focal loss of basement membrane was noted in several cases with PAS staining, but further staining with the SM in all such cases indicated the basement membrane to be intact.ConclusionA continuum of progressive histological features akin to cholesteatoma is noted with increasing grades of retraction (II‐IV). Breach of the basement membrane was recently reported as a feature of cholesteatoma but is not a feature of retraction. The near universal presence of inflammation as noted suggests an etiological role.
Physiological Assessment of Active Middle Ear Implant Coupling to the Round Window in Chinchilla lanigera
Authors: Lupo J. Eric , Koka Kanthaiah , Hyde Blake J. , Jenkins Herman A. , Tollin Daniel J. 
Published: May 2011

ObjectiveTo study the effects of various active middle ear implant loading parameters on round window stimulation in an animal model.Study DesignPhysiological measurements of the cochlear microphonic and stapes velocity were made from active middle ear implant–generated sinusoidal stimuli with controlled changes in loading parameters.SettingProspective study at an academic research institution.Subjects and MethodsCochlear microphonic and stapes velocities (HEV) were measured in 6 study subjects (Chinchilla lanigera) in response to active middle ear implant (Otologics MET, Boulder, Colorado) round window stimulation with assessment of effects of varying parameters of loading pressure, interposed connective tissue, and angle of stimulation with respect to the round window membrane.ResultsThe measured performance variabilities in repeated applications of the active middle ear implant to the round window were 2.5 dB and 5.0 dB for HEV and cochlear microphonic thresholds, respectively. Loading pressure applied to the round window (51‐574 dynes) and angle of approach (±30° with respect to coronal plane) did not have a significant effect on cochlear microphonic thresholds or HEV. Significant improvements in cochlear microphonic thresholds and HEV were observed for interposed connective tissue regardless of tissue type.ConclusionVariability in performance due to repeated couplings of the active middle ear implant to the round window is small and reproducible. Interposition of connective tissue significantly improves vibration energy transfer to the cochlea. Neither changes in loading pressure nor angle of stimulation of the round window affected active middle ear implant performance.
Dysphagia and Quality of Life May Improve with Mometasone Treatment in Patients with Eosinophilic Esophagitis
Authors: Bergquist Henrik , Larsson Helén , Johansson Leif , Bove Mogens 
Published: May 2011

ObjectiveThe treatment of adult patients with eosinophilic esophagitis remains challenging. The aim was to assess dysphagia and health‐related quality of life (HRQL) using validated scales and questionnaires before and after treatment with mometasone furoate.Study DesignCase series with planned data collection.SettingUniversity hospital and secondary referral hospital.Subjects and MethodsNewly diagnosed patients with eosinophilic esophagitis were included and given 200 µg of orally administered topical mometasone furoate 4 times daily. Questionnaires incorporating the Watson Dysphagia Scale (WDS), the European Organization for Research and Treatment of Cancer Quality of Life–Oesophageal Module 18 (EORTC QLQ‐OES18), and the Short Form–36 (SF‐36) were completed before the initiation of treatment and after 2 months of treatment.ResultsThirty‐one consecutive patients (23 men; mean age, 45 years; range, 18‐89 years) completed the trial. At inclusion, the mean scores of the WDS, the EORTC QLQ‐OES18 dysphagia scale, the eating scale and choking item, and the global health and social functioning dimensions of the SF‐36 were 21.3, 20.4, 35.0, 38.6, 71.1, and 82.3, respectively. Posttreatment, these scores improved to 8.9 (P <. 0001), 4.6 (P <. 00001), 17.8 (P <. 001), 16.0 (P <. 01), 76.1 (P <. 05), and 91.9 (P =. 0001), respectively. Except for 1 case of oral candidiasis, no significant side effects were reported.ConclusionThe dysphagia and impaired HRQL found in untreated patients with eosinophilic esophagitis improved significantly after 2 months of mometasone furoate treatment. A randomized placebo‐controlled trial is warranted to assess causality. The scales and questionnaires used are sensitive instruments appropriate for symptom surveillance in individuals with eosinophilic esophagitis.
2010 Survey on cell phone use while performing cardiopulmonary bypass
Authors: Smith T , Darling E , Searles B 
Published: May 2011

Cell phone use in the U.S. has increased dramatically over the past decade and text messaging among adults is now mainstream. In professions such as perfusion, where clinical vigilance is essential to patient care, the potential distraction of cell phones may be especially problematic. However, the extent of this as an issue is currently unknown. Therefore, the purpose of this study was to (1) determine the frequency of cell phone use in the perfusion community, and (2) to identify concerns and opinions among perfusionists regarding cell phone use. In October 2010, a link to a 19-question survey ( surveymonkey.com ) was posted on the AmSECT (PerfList) and Perfusion.com (PerfMail) forums. There were 439 respondents. Demographic distribution is as follows; Chief Perfusionist (30.5%), Staff Perfusionist (62.0%), and Other (7.5%), with age ranges of 20-30 years (14.2%), 30-40 years (26.5%), 40-50 years (26.7%), 50-60 years (26.7%), >60 years (5.9%). The use of a cell phone during the performance of cardiopulmonary bypass (CPB) was reported by 55.6% of perfusionists. Sending text messages while performing CPB was acknowledged by 49.2%, with clear generational differences detected when cross-referenced with age groups. For smart phone features, perfusionists report having accessed e-mail (21%), used the internet (15.1%), or have checked/posted on social networking sites (3.1%) while performing CPB. Safety concerns were expressed by 78.3% who believe that cell phones can introduce a potentially significant safety risk to patients. Speaking on a cell phone and text messaging during CPB are regarded as “always an unsafe practice” by 42.3% and 51.7% of respondents, respectively. Personal distraction by cell phone use that negatively affected performance was admitted by 7.3%, whereas witnessing another perfusionist distracted with phone/text while on CPB was acknowledged by 33.7% of respondents. This survey suggests that the majority of perfusionists believe cell phones raise significant safety issues while operating the heart-lung machine. However, the majority also have used a cell phone while performing this activity. There are clear generational differences in opinions on the role and/or appropriateness of cell phones during bypass. There is a need to further study this issue and, perhaps, to establish consensus on the use of various communication modes within the perfusion community.
Occupational exposure to sevoflurane during cardiopulmonary bypass
Authors: Blokker–Veldhuis MJ , Rutten PMMJ , De Hert SG 
Published: May 2011

Volatile anaesthetic agents are widely used for maintenance of anaesthesia in all kinds of surgical procedures. Despite the implementation of measures such as adequate ventilation of the operating room and the use of efficient scavenging systems, concern remains about the risks for occupational exposure, especially in situations associated with an increased risk of anaesthetic gas waste, such as with the use of volatile anaesthetic agents on cardiopulmonary bypass. The present contribution reports the results of a preliminary safety assessment involving measurements of sevoflurane concentrations in the ambient air of a cardiac surgery operating room. In 22 cardiac surgical procedures with cardiopulmonary bypass (11 with open and 11 with closed venous reservoir), measurements of trace concentrations were obtained every 10 min at the following sites: at the outlet of the oxygenator, at the outlet of the cardiotomy reservoir, in the breathing zone of the perfusionist and above the surgical field. The concentrations were measured on-line using a photoacoustic infrared spectrometer. Mean sevoflurane waste concentrations remained consistently below the recommended target value of 4.68 ppm throughout the observation period at the different measurement sites. These results indicate that, with the use of sevoflurane on cardiopulmonary bypass, the recommended levels for occupational exposure are not exceeded, provided adequate operation room ventilation and waste gas scavenging is performed.
The L-kynurenine signalling pathway in trigeminal pain processing: A potential therapeutic target in migraine?
Authors: Guo Song , Vecsei L , Ashina Messoud 
Published: May 2011

Introduction: In recent years the kynurenine family of compounds, metabolites of tryptophan, has become an area of intensive research because of its neuroactive properties. Two metabolites of this family have become of interest in relation to migraine and pain processing. Discussion: Experimental studies have shown that kynurenic acid (KYNA) plays an important role in the transmission of sensory impulses in the trigeminovascular system and that increased levels of KYNA decrease the sensitivity of the cerebral cortex to cortical spreading depression. Furthermore, another metabolite of the kynurenine family, L-kynurenine, exerts vasodilating effects similar to nitric oxide by increasing cyclic guanosine monophosphate. Conclusion: This review summarizes current knowledge of the role of kynurenine signalling in trigeminal and central pain processing, including its therapeutic prospects in migraine treatment.