tbuckley/cabot-search huggingface dataset:
TRAF6 Upregulates Expression of HIF-1α and Promotes Tumor Angiogenesis
Authors: Heng Sun, Xue-Bing Li, Ya Meng, Li Fan, Min Li, Jing Fang
Journal: Cancer Research (2013)

TNF receptor (TNFR)-associated factor TRAF6 is a key activator of NF-κB, playing a critical role in the regulation of innate immune responses and their connection to adaptive immune responses. TRAF6 interactions determine receptor-induced cell death versus survival. TRAF6 has been implicated in cancer but its contributions have not been investigated deeply. In this study, we show that TRAF6 upregulates expression of hypoxia-inducible factor (HIF)-1α. TRAF6 affects HIF-1α protein levels but has little effect on mRNA level. TRAF6 increases HIF-1α protein independent of oxygen. We found that TRAF6 binds HIF-1α and mediates its K63-linked polyubiquitination. The E3 ligase activity of TRAF6 was required to increase HIF-1α protein levels. Finally, we showed that TRAF6 promoted tumor angiogenesis and growth. Our results reveal how TRAF6 functions to upregulate HIF-1α expression and promote tumor angiogenesis.
Sequence Comparative Analysis Using Networks: Software for Evaluating De Novo Transcript Assembly from Next-Generation Sequencing
Authors: Ian Misner, Cédric Bicep, Philippe Lopez, Sébastien Halary, Eric Bapteste, Christopher E. Lane
Journal: Molecular Biology and Evolution (2013)

DNA sequencing technology is becoming more accessible to a variety of researchers as costs continue to decline. As researchers begin to sequence novel transcriptomes, most of these data sets lack a reference genome and will have to rely on de novo assemblers. Making comparisons across assemblies can be difficult: each program has its strengths and weaknesses, and no tool exists to comparatively evaluate these data sets. We developed software in R, called Sequence Comparative Analysis using Networks (SCAN), to perform statistical comparisons between distinct assemblies. SCAN uses a reference data set to identify the most accurate de novo assembly and the "good" transcripts in the user's data. We tested SCAN on three publicly available transcriptomes, each assembled using three assembly programs. Moreover, we sequenced the transcriptome of the oomycete Achlya hypogyna and compared de novo assemblies from Velvet, ABySS, and the CLC Genomics Workbench assembly algorithms. One thousand one hundred twenty-eight of the CLC transcripts were statistically similar to the reference, compared with 49 of the Velvet transcripts and 937 of the ABySS transcripts. SCAN's strength is providing statistical support for transcript assemblies in a biological context. However, SCAN is designed to compare distinct node sets in networks, therefore it can also easily be extended to perform statistical comparisons on any network graph regardless of what the nodes represent.
Contribution of Endothelin-1 to Myocardial Injury in a Murine Model of Myocarditis
Authors: Koh Ono, Akira Matsumori, Tetsuo Shioi, Yutaka Furukawa, Shigetake Sasayama
Journal: Circulation (1999)

Background —Endothelin (ET) is one of the most important contributing factors in the pathophysiology of cardiovascular diseases. However, little is known about its role in myocarditis. Methods and Results —Four-week-old DBA/2 mice were inoculated with the encephalomyocarditis virus. Expression levels of ET-converting enzyme-1 (ECE-1) and prepro-ET-1 mRNA were significantly increased at 7 and 14 days after virus inoculation. Plasma and myocardial ET-1 levels were significantly higher in infected than noninfected mice between 5 and 14 days after virus inoculation. Immunohistochemical analyses revealed that not only endothelial cells and myocytes but also infiltrating mononuclear cells produced ET-1 protein at 7 days. Oral bosentan, a mixed ET-1 receptor antagonist, was administered after virus inoculation in doses of 0 (control group), 10, or 100 mg · kg −1 · d −1 , and the animals were killed on day 14. Mean heart weight/body weight ratios were 8.3±1.8 versus 11.2±2.4 versus 10.8±2.4 in the bosentan 100 mg · kg −1 · d −1 versus 10 mg · kg −1 · d −1 versus control groups, respectively ( P &lt;0.05). Corresponding histological scores for myocardial necrosis were 2.0±0.2 versus 2.9±0.3 versus 3.0±0.4 ( P &lt;0.05), and cellular infiltration scores were 2.3±0.3 versus 2.9±0.4 versus 3.3±0.4 ( P &lt;0.05). Animals killed on day 5 had significantly smaller necrotic areas after treatment with bosentan 100 mg · kg −1 · d −1 than the group treated with a lower dose or the control group, despite the absence of differences in virus titers. Conclusions —This study suggests that ET-1 plays an important pathophysiological role in viral myocarditis. Treatment with bosentan had a cardioprotective effect without modifying viral replication.
IMPROVEMENT IN QUALITY OF CARE OVER 4 YEARS: NATIONWIDE ASSESSMENT OF QUALITY OF DISCHARGE PRESCRIPTION AFTER ACUTE MYOCARDIAL INFARCTION IN FRANCE
Authors: Francois Schiele, Frederic Capuano, Nicolas Danchin, Christian Ziccarelli, Linda Banaei-Bouchareb, Jean-Francois Thebaut, Armelle Desplanques-Leperre, Catherine Grenier
Journal: Journal of the American College of Cardiology (2014)
Hospital level under-utilization of minimally invasive surgery in the United States: retrospective review
Authors: M. A. Cooper, S. Hutfless, D. L. Segev, A. Ibrahim, H. Lyu, M. A. Makary
Journal: BMJ (2014)

<b>Objective</b> To determine casemix adjusted hospital level utilization of minimally invasive surgery for four common surgical procedures (appendectomy, colectomy, total abdominal hysterectomy, and lung lobectomy) in the United States. <b>Design</b> Retrospective review. <b>Setting</b> United States. <b>Participants</b> Nationwide inpatient sample database, United States 2010. <b>Methods</b> For each procedure, a propensity score model was used to calculate the predicted proportion of minimally invasive operations for each hospital based on patient characteristics. For each procedure, hospitals were categorized into thirds (low, medium, and high) based on their actual to predicted proportion of utilization of minimally invasive surgery. <b>Main outcome measures</b> The primary outcome measures were the actual and predicted proportion of procedures performed with minimally invasive surgery. Secondary outcome measures included surgical complications and hospital characteristics. <b>Results</b> Mean hospital utilization of minimally invasive surgery was 71.0% (423/596) for appendectomy (range 40.9-93.1% (244-555)), 28.4% (154/541) for colectomy (6.7-49.8% (36/541-269/541)), 13.0% (65/499) for hysterectomy (0.0-33.6% (0/499-168/499)), and 32.0% (67/208) for lung lobectomy (3.6-65.7% (7.5/208-137/208)). Utilization of minimally invasive surgery was highly variable for each procedure type. There was noticeable discordance between actual and predicted utilization of the surgery (range of actual to predicted ratio for appendectomy 0-1.49; colectomy 0-3.88; hysterectomy 0-6.68; lung lobectomy 0-2.51). Surgical complications were less common with minimally invasive surgery compared with open surgery, respectively: overall rate for appendectomy 3.94% (1439/36 513) <i>v</i> 7.90% (958/12 123), P&lt;0.001; for colectomy: 13.8% (1689/12 242) <i>v</i> 35.8% (8837/24 687), P&lt;0.001; for hysterectomy: 4.69% (270/5757) <i>v</i> 6.64% (1988/29 940), P&lt;0.001; and for lung lobectomy: 17.1% (367/2145) <i>v</i> 25.4% (971/3824), P&lt;0.05. High utilization of minimally invasive surgery was associated with urban location (appendectomy: odds ratio 4.66, 95% confidence interval 1.17 to 18.5; colectomy: 4.59, 1.04 to 20.3; hysterectomy: 15.0, 2.98 to 75.0), large hospital size (hysterectomy: 8.70, 1.62 to 46.8), teaching hospital (hysterectomy: 5.41, 1.27 to 23.1), Midwest region (appendectomy: 7.85, 1.26 to 49.1), south region (appendectomy: 21.0, 3.79 to 117; colectomy: 10.0, 1.83 to 54.7), and west region (appendectomy: 9.33, 1.48 to 58.8). <b>Conclusion</b> Hospital utilization of minimally invasive surgery for appendectomy, colectomy, total abdominal hysterectomy, and lung lobectomy varies widely in the United States, representing a disparity in the surgical care delivered nationwide.
Regional distribution of the molecular forms of acetylcholinesterase in adult rat heart.
Authors: C Nyquist-Battie, K Trans-Saltzmann
Journal: Circulation Research (1989)

Acetylcholinesterase (AChE), the enzyme that degrades acetylcholine, exists as a multiple molecular forms that differ in their quaternary structure and mode of attachment to the cell surface. The distribution of the individual molecular forms of AChE in various cardiac regions with distinct anatomical characteristics was investigated. The results confirmed those of others by showing that the total pool of cardiac AChE had a nonuniform distribution in heart that paralleled the distribution of choline acetyltransferase. The rank order of this distribution was right atrial appendage greater than interatrial septum greater than left atrial appendage = right ventricle = interventricular septum greater than left ventricle. Velocity sedimentation in sucrose gradients of extracts from selected cardiac areas showed that four molecular forms were present in all areas but that the proportions of these forms differed as a function of area. The right and left ventricular walls, the apical portion of the interventricular septum, and the left atrial appendage contained G1 and G4 (globular) AChE in near-equal proportions, but in the basal portion of interventricular septum, the contribution of G4 AChE was greater than that of G1 AChE. The right atrial appendage and the interatrial septum had the largest amount of activity attributable to G4 AChE and the lowest amount attributable to G1 AChE. In all cardiac regions, A12 (asymmetric) AChE comprised 8-10% of the total AChE pool.(ABSTRACT TRUNCATED AT 250 WORDS)
Mucosal Immunity Against HIV-1 Infection by the Green Tea Catechin, Epigallocatechin Gallate
Authors: C.L. Nance, E. Siwak, M. D'Souza, A. McMullen, S. Sanga, Z. Rajput, A. Victores, W.T. Shearer
Journal: Journal of Allergy and Clinical Immunology (2009)
Assessment of enthesitis in ankylosing spondylitis
Authors: L Heuft-Dorenbosch
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objective:</b> To assess, firstly, the validity of the enthesis index published by Mander (Mander enthesis index (MEI)) and, secondly, to investigate whether it is possible to define a new enthesis index that is less time consuming to perform with at least similar or better properties. <b>Methods:</b> Data from the OASIS cohort, an international, longitudinal, observational study on outcome in ankylosing spondylitis, were used. In this study, measures of disease activity, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the MEI, were assessed regularly in 217 patients. With the MEI, for each measurement period independently, a process of data reduction was performed to identify the entheses most commonly reported as painful by the patients. A more concise enthesis index was constructed with aid of the entheses found in this way. Correlations with measures of disease activity were used to test the validity of several entheses indices. <b>Results:</b> Reduction of the number of entheses from 66 to 13 and omitting grading of the intensity of pain resulted in an index which was named the "Maastricht Ankylosing Spondylitis Enthesitis Score" (MASES). The MASES (range 0–13) has much greater feasibility than the MEI (range 0–90). However, up to 21% of patients with a score &gt;0 on the MEI were not identified by a score on the MASES &gt;0. Only 2.1% of the patients with an original enthesis score &gt;0 had an original score on the MEI &gt;3 (range 0–90) and it can be questioned whether a low score on the MEI index represents clinically important enthesitis. The Spearman correlation coefficient between the MASES score and the MEI was 0.90 and between the MASES and the BASDAI was 0.53 compared with a correlation of 0.59 between the MEI and the BASDAI. <b>Conclusions:</b> MASES seems to be a good alternative to the MEI with much better feasibility.
An electrogenic proton-translocating adenosine triphosphatase from bovine kidney medulla.
Authors: S Gluck, Q Al-Awqati
Journal: Journal of Clinical Investigation (1984)

Urinary acidification in the mammalian collecting tubule is similar to that in the turtle bladder, an epithelium whose H+ secretion is due to a luminal proton-translocating ATPase. We isolated a fraction from bovine renal medulla, which contains ATP-dependent proton transport. H+ transport was found to be electrogenic in that its rate was reduced by a membrane potential. H+ transport activity was inhibited by N-ethyl maleimide and dicyclohexyl carbodiimide, but not by oligomycin or vanadate; its activity did not depend on the presence of potassium, differentiating this ATPase from the mitochondrial F0-F1 ATPase and the gastric H+-K+ ATPase. H+ transport activity had a specific substrate requirement for ATP, distinguishing this pump from the lysosomal H+ ATPase, which uses guanosine or inosine triphosphate as well. The distribution of this H+ pump on linear sucrose density gradient was different from that of markers of lysosomes and basolateral membranes. These results show that the kidney medulla contains an H+ -translocating ATPase different from mitochondrial, gastric, and lysosomal proton pumps, but similar to the turtle bladder ATPase.
Mechanisms of the endothelial toxicity of cyclosporin A. Role of nitric oxide, cGMP, and Ca2+.
Authors: M J Gallego, A L García Villalón, A J López Farre, J L García, M P Garrón, S Casado, L Hernando, C A Caramelo
Journal: Circulation Research (1994)

Cyclosporin A (CyA) is an efficient immunosuppressive agent, which, however, causes functional and structural alterations in endothelial cells. The aim of the present study was to examine the mechanisms of CyA-induced endothelial disfunction. CyA administration (Wistar rats, 25 mg/kg per day for 15 days) induced a significant inhibition of endothelium-dependent relaxation to acetylcholine on isolated femoral arteries. No changes with CyA were detected in the relaxation response to the endothelium-independent agent (sodium nitroprusside) or the endothelium-dependent receptor-independent agent (Ca2+ ionophore). The addition of L-arginine (10(-5) mol/L) shifted to the left the acetylcholine-mediated vasorelaxing response in CyA-treated segments, an effect that was accompanied by a marked increase of cGMP. 45Ca2+ uptake was higher in CyA-treated segments with respect to control segments but became normalized after incubation with L-arginine or sodium nitroprusside. De-endothelialization or incubation with the L-arginine competitive analogue N omega-nitro-L-arginine (NwNLA) increased 45Ca2+ uptake in control segments but not in CyA-treated segments. In conclusion, in isolated rat arteries, chronic CyA therapy affects endothelial function by uncoupling the acetylcholine-mediated relaxation and interfering with an endothelium-mediated pathway that regulates 45Ca2+ uptake by a mechanism reversed by an L-arginine-dependent cGMP generation.
Final Results of a Prospective Clinical Trial With VAMP and Low-Dose Involved-Field Radiation for Children With Low-Risk Hodgkin's Disease
Authors: Sarah S. Donaldson, Michael P. Link, Howard J. Weinstein, Shesh N. Rai, Sam Brain, Amy L. Billett, Craig A. Hurwitz, Matthew Krasin, Larry E. Kun, Karen C. Marcus, Nancy J. Tarbell, Jeffrey A. Young, Melissa M. Hudson
Journal: Journal of Clinical Oncology (2007)

To evaluate outcome and assess complications in children and adolescents with low-risk Hodgkin's disease treated with vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) chemotherapy and low-dose, involved-field radiation therapy (IFRT).One hundred ten children with low-risk Hodgkin's disease were treated with four cycles of VAMP and 15 Gy IFRT for those who achieved a complete response (CR) or 25.5 Gy for those with a partial response after two cycles of VAMP.With median follow-up of 9.6 years (range, 1.7 to 15.0), 5- and 10-year overall survival were 99.1% and 96.1%, respectively, and 5-and 10-year event-free survival (EFS) were 92.7% and 89.4%. Factors contributing to 10-year EFS were: early CR (P = .02), absence of B symptoms (P = .01), lymphocyte predominant histologic subtype (P = .04), and less than three initial sites of disease (P = .02). Organ toxicity has been limited to correctable hypothyroidism in 42% of irradiated patients, and one case of cardiac dysfunction. Seventeen healthy babies have been born to 106 survivors. There have been two malignant tumors: one thyroid cancer within the radiation therapy field and one Ewing's sarcoma outside the radiation therapy field.Risk-adapted, combined-modality therapy using VAMP chemotherapy with radiation is effective and well tolerated. Pediatric patients with low-risk Hodgkin's disease can be cured with therapy without an alkylating agent, bleomycin, etoposide, or high-dose, extended-field radiotherapy. Thus, these children are expected to retain normal fertility, organ function, and be at low risk of a second malignant tumor.
Opportunities and Challenges in the Development of Experimental Drug Combinations for Cancer
Authors: R. W. Humphrey, L. M. Brockway-Lunardi, D. T. Bonk, K. M. Dohoney, J. H. Doroshow, S. J. Meech, M. J. Ratain, S. L. Topalian, D. M. Pardoll
Journal: JNCI Journal of the National Cancer Institute (2011)

It is becoming increasingly evident that cancers are dependent on a number of altered molecular pathways and can develop diverse mechanisms of resistance to therapy with single agents. Therefore, combination regimens may provide the best hope for effective therapies with durable effects. Despite preclinical data to support this notion, there are many challenges to the development of targeted combinations including scientific, economic, legal, and regulatory barriers. A discussion of these challenges and identification of models and best practices are presented with intent of aiding the research community in addressing real and perceived barriers to the development of combination therapies for cancer.
DNA Methylation of Tumor Suppressor Genes in Clinical Remission Predicts the Relapse Risk in Acute Myeloid Leukemia
Authors: Shuchi Agrawal, Matthias Unterberg, Steffen Koschmieder, Udo zur Stadt, Uta Brunnberg, Walter Verbeek, Thomas Büchner, Wolfgang E. Berdel, Hubert Serve, Carsten Müller-Tidow
Journal: Cancer Research (2007)

Epigenetic changes play an important role in leukemia pathogenesis. DNA methylation is among the most common alterations in leukemia. The potential role of DNA methylation as a biomarker in leukemia is unknown. In addition, the lack of molecular markers precludes minimal residual disease (MRD) estimation for most patients with hematologic malignancies. We analyzed the potential of aberrant DNA promoter methylation as a biomarker for MRD in acute leukemias. Quantitative real-time PCR methods with bisulfite-modified DNA were established to quantify MRD based on estrogen receptor alpha (ERalpha) and/or p15(INK4B) methylation. Methylation analyses were done in >370 DNA specimens from 180 acute leukemia patients and controls. Methylation of ERalpha and/or p15(INK4B) occurred frequently and specifically in acute leukemia but not in healthy controls or in nonmalignant hematologic diseases. Aberrant DNA methylation was detectable in >20% of leukemia patients during clinical remission. In pediatric acute lymphoblastic leukemia, methylation levels during clinical remission correlated closely with T-cell receptor/immunoglobulin MRD levels (r = +0.7, P < 0.01) and were associated with subsequent relapse. In acute myelogenous leukemia patients in clinical remission, increased methylation levels were associated with a high relapse risk and significantly reduced relapse-free survival (P = 0.003). Many patients with acute leukemia in clinical remission harbor increased levels of aberrant DNA methylation. Analysis of methylation MRD might be used as a novel biomarker for leukemia patients' relapse risk.
Comparing Standard Versus Prosocial Internet Support Groups for Patients With Breast Cancer: A Randomized Controlled Trial of the Helper Therapy Principle
Authors: Stephen J. Lepore, Joanne S. Buzaglo, Morton A. Lieberman, Mitch Golant, Judith R. Greener, Adam Davey
Journal: Journal of Clinical Oncology (2014)

Purpose Internet support group (ISG) members benefit from receiving social support and, according to the helper therapy principle, by providing support to others. To test the mental health benefits of providing support to others, this trial compared the efficacy of a standard ISG (S-ISG) and an enhanced prosocial ISG (P-ISG). Methods A two-armed randomized controlled trial with 1-month pretest and post-test assessments was conducted with women (N = 184) diagnosed in the past 36 months with nonmetastatic breast cancer who reported elevated anxiety or depression. Women were randomly assigned to either the S-ISG or P-ISG condition. Both conditions included six professionally facilitated live chat sessions (90-minute weekly sessions) and access to an asynchronous discussion board; P-ISG also included structured opportunities to help and encourage others. Results Relative to the S-ISG, participants in the P-ISG condition exhibited more supportive behaviors (emotional, informational, and companionate support), posted more messages that were other-focused and fewer that were self-focused, and expressed less negative emotion (P &lt; .05). Relative to the S-ISG, participants in the P-ISG condition had a higher level of depression and anxiety symptoms after the intervention (P &lt; .05). Conclusion Despite the successful manipulation of supportive behaviors, the P-ISG did not produce better mental health outcomes in distressed survivors of breast cancer relative to an S-ISG. The prosocial manipulation may have inadvertently constrained women from expressing their needs openly, and thus, they may not have had their needs fully met in the group. Helping others may not be beneficial as a treatment for distressed survivors of breast cancer.
Quantitative Dose-Response Relationships of Murine Sarcoma Virus (Moloney) in BALB/c Mice
Authors: George R. Blumenschein, John B. Moloney
Journal: JNCI Journal of the National Cancer Institute (1969)

The quantitative dose-response relationships of a standard lot of Moloney sarcoma virus were investigated in BALB/c mice. Repeated assay of 10−1–10−5 dilutions of the virus material showed a reproducible dose-related development of rhabdomyosarcoma at the site of inoculation in newborn and weanling mice. Time from inoculation to appearance of tumor was a reliable indicator of virus-initiating dose. The induced tumors grew and regressed in a predictable fashion in weanling mice. The data on virus recovery from tumor at points in the growth and regression phases showed a growth curve for the agent with a 3-day latent period, followed by a 5-day log growth phase. As tumor regressed, the virus content decreased. At 21 days after infection, a high percentage of the weanling mice had developed sarcomas and were in a phase of complete tumor regression. The quantity of virus recoverable from tumor induced by a given inoculum was directly related to tumor size. Similarly, virus content of a tumor depended on the dose of the virus inoculum. Spleens from infected animals showed a bimodal spleen-weight per body-weight curve with peaks at 12 and 28 days after inoculation. Sarcoma-inducing virus was recoverable from spleens in both peaks.