tbuckley/cabot-search huggingface dataset:
Merlin Is a Potent Inhibitor of Glioma Growth
Authors: Ying-Ka Ingar Lau, Lucas B. Murray, Sean S. Houshmandi, Yin Xu, David H. Gutmann, Qin Yu
Journal: Cancer Research (2008)

Abstract Neurofibromatosis 2 (NF2) is an inherited cancer syndrome in which affected individuals develop nervous system tumors, including schwannomas, meningiomas, and ependymomas. The NF2 protein merlin (or schwannomin) is a member of the Band 4.1 superfamily of proteins, which serve as linkers between transmembrane proteins and the actin cytoskeleton. In addition to mutational inactivation of the NF2 gene in NF2-associated tumors, mutations and loss of merlin expression have also been reported in other types of cancers. In the present study, we show that merlin expression is dramatically reduced in human malignant gliomas and that reexpression of functional merlin dramatically inhibits both subcutaneous and intracranial growth of human glioma cells in mice. We further show that merlin reexpression inhibits glioma cell proliferation and promotes apoptosis in vivo. Using microarray analysis, we identify altered expression of specific molecules that play key roles in cell proliferation, survival, and motility. These merlin-induced changes of gene expression were confirmed by real-time quantitative PCR, Western blotting, and functional assays. These results indicate that reexpression of merlin correlates with activation of mammalian sterile 20-like 1/2–large tumor suppressor 2 signaling pathway and inhibition of canonical and noncanonical Wnt signals. Collectively, our results show that merlin is a potent inhibitor of high-grade human glioma. [Cancer Res 2008;68(14):5733–42]
Doxycycline in lymphangioleiomyomatosis: not all questions are answered
Authors: B. G. Baldi, C. R. Ribeiro Carvalho
Journal: European Respiratory Journal (2014)

To the Editor: 

We read with interest the article by Chang et al. [1], which demonstrated doxycycline to have no effect on pulmonary function tests (PFTs) and is unlikely to have a potential benefit in lymphangioleiomyomatosis (LAM). An increase in metalloproteinases (MMPs) is considered one of the pathways involved in the pathogenesis of cystic lung destruction in LAM. As a result, doxycycline, a MMP inhibitor, may represent a potential therapeutic target [2–6].

One factor that could have determined a lack of effect on PFTs in the present study was that patients with LAM, treated with doxycycline, had moderate impairment in PFTs when compared with those receiving placebo, which had mild impairment. A recent nonrandomised study from our group has already suggested that patients who would most benefit with doxycycline are those with mild functional impairment [ …
A geochemical basis for endomyocardial fibrosis
Authors: M S VALIATHAN, C C KARTHA, J T EAPEN, H S DANG, C M SUNTA
Journal: Cardiovascular Research (1989)

Analysis of hearts of patients dying from endomyocardial fibrosis showed a significantly greater concentration of cerium, a lanthanide present in leafy vegetables and root tubers, than in control hearts. This may be important in the pathogenesis of the disease and provides a geographical basis for the prevalence of the disease in the tropics.
High Plasma Aldosterone Levels on Admission Are Associated With Death in Patients Presenting With Acute ST-Elevation Myocardial Infarction
Authors: Farzin Beygui, Jean-Philippe Collet, Jean-Jacques Benoliel, Nicolas Vignolles, Raphaelle Dumaine, Olivier Barthélémy, Gilles Montalescot
Journal: Circulation (2006)

Aldosterone, the final mediator of the renin-angiotensin-aldosterone pathway, is at its highest plasma levels at presentation for ST-elevation myocardial infarction (STEMI). Whether aldosterone level at presentation for STEMI is associated with adverse outcome remains unknown.Plasma aldosterone levels were measured at presentation in consecutive patients referred for primary percutaneous coronary intervention for STEMI. We assessed the association between aldosterone levels and in-hospital events and mortality during a 6-month follow-up. Of 356 STEMI patients, 23 and 36 died during the hospital stay and 6-month follow-up period, respectively. Nine other patients survived in-hospital cardiac arrest. High aldosterone levels were associated with an almost stepwise increase in rates of in-hospital death (P=0.01), cardiovascular death (P=0.03), heart failure (P=0.005), ventricular fibrillation (P=0.02), and resuscitated cardiac arrest (P=0.01). After adjustment for age, Killip class, and reperfusion status, compared with patients in the first aldosterone quartile group, those in the highest quartile were at higher risk of death (hazard ratio 3.28, 95% CI 1.09 to 9.89, P=0.035) and death or resuscitated cardiac arrest (hazard ratio 3.74, 95% CI 1.40 to 9.98, P=0.008) during the follow-up.Plasma aldosterone levels on admission among patients referred for primary percutaneous coronary intervention for STEMI are associated with early and late adverse clinical outcomes, including mortality. The association between high aldosterone levels and late mortality is independent of age, heart failure, and reperfusion status. Such results underline the pivotal role of aldosterone and justify a randomized trial to assess the early administration of aldosterone antagonists in the setting of STEMI.
Phytoremediation of trichloroethylene with hybrid poplars.
Authors: M Gordon, N Choe, J Duffy, G Ekuan, P Heilman, I Muiznieks, M Ruszaj, B B Shurtleff, S Strand, J Wilmoth, L A Newman
Journal: Environmental Health Perspectives (1998)

Axenic tumor cultures of poplar cells, clone H11-11, were grown in the presence of [14C]-trichloroethylene (TCE) (uniformly labeled). The cells were capable of metabolizing TCE to produce trichloroethanol, di- and trichloroacetic acid. Some of the carbon from TCE was found in insoluble, nonextractable cell residue, and small amounts were mineralized to [14C]CO2. Poplar cuttings grown in soil and exposed to TCE produced the same metabolites. In field trials, trees were planted in soil in test cells and exposed to TCE via underground water injection during the growing season. During the growing season, at least 95% of the TCE was removed from the influent water stream in cells containing trees. Mass balance studies conducted in the laboratory indicated that 70 to 90% of the TCE was transpired; however, greenhouse and field study results showed that less than 5% of the total TCE taken up by the plants is transpired. These results show that significant TCE uptake and degradation occur in poplars. Poplars appear to be useful for in situ remediation of TCE-contaminated sites under proper conditions.
Relative cerebral blood volume is a potential predictive imaging biomarker of bevacizumab efficacy in recurrent glioblastoma
Authors: Philipp Kickingereder, Benedikt Wiestler, Sina Burth, Antje Wick, Martha Nowosielski, Sabine Heiland, Heinz-Peter Schlemmer, Wolfgang Wick, Martin Bendszus, Alexander Radbruch
Journal: Neuro-Oncology (2015)

To analyze the relevance of dynamic susceptibility-weighted contrast-enhanced MRI (DSC-MRI) derived relative cerebral blood volume (rCBV) analysis for predicting response to bevacizumab (BEV) in patients with recurrent glioblastoma (rGB).A total of 127 patients diagnosed with rGB receiving either bevacizumab (71 patients, BEV cohort) or alkylating chemotherapy (56 patients, non-BEV cohort) underwent conventional anatomic MRI and DSC-MRI at baseline and at first follow-up after treatment initiation. The mean rCBV of the contrast-enhancing tumor (cT1) as well as cT1 and fluid-attenuated inversion recovery (FLAIR) volumes at both time points were correlated with progression-free survival (PFS) and overall survival (OS) using Cox proportional hazard models, logistic regression, and the log-rank test.Baseline rCBV was associated with both PFS (hazard ratio [HR] = 1.3; P < .01) and OS (HR = 1.3; P < .01) in the BEV cohort and predicted 6-month PFS in 82% and 12-month OS in 79% of patients, whereas it was not associated with PFS (HR = 1.0; P = .70) or OS (HR = 1.0; P = .47) in the non-BEV cohort. Corresponding median OS and PFS rates in the BEV cohort for patients with rCBV-values less than 3.92 (optimal threshold from receiver operating characteristic [ROC] analysis of 12-month OS data) were 14.2 and 6.0 months, as compared to 6.6 and 2.8 months for patients with rCBV-values greater than 3.92 (P < .01, respectively). cT1 and FLAIR volumes at first follow-up were significant predictors of 6-month PFS and 12-month OS in the BEV cohort but not in the non-BEV cohort. Corresponding volumes at baseline were not significant in any cohort.Pretreatment rCBV is a potential predictive imaging biomarker in BEV-treated rGB but not alkylating chemotherapy-treated rGB, which is superior to volumetric analysis of conventional anatomic MRI and predicts 6-month PFS and 12-month OS in 80% of BEV-treated patients.
Multiple Mechanisms of Telomere Maintenance Exist and Differentially Affect Clinical Outcome in Diffuse Malignant Peritoneal Mesothelioma
Authors: Raffaella Villa, Maria Grazia Daidone, Rosita Motta, Lorenza Venturini, Cinzia De Marco, Alberto Vannelli, Shigeki Kusamura, Dario Baratti, Marcello Deraco, Aurora Costa, Roger R. Reddel, Nadia Zaffaroni
Journal: Clinical Cancer Research (2008)

Abstract Purpose: This study aims to investigate the prevalence of the two known telomere maintenance mechanisms, telomerase activity (TA) and alternative lengthening of telomeres (ALT), and to assess their prognostic relevance in diffuse malignant peritoneal mesothelioma (DMPM). Experimental Design: In 44 DMPM specimens obtained from 38 patients, TA was determined using the telomeric repeat amplification protocol and ALT was detected by assaying ALT-associated promyelocytic leukemia nuclear bodies. The prognostic significance of telomere maintenance mechanisms was analyzed by Cox regression in the overall series and in a subset of 29 patients who underwent a uniform treatment regimen consisting of cytoreductive surgery and hyperthermic i.p. chemotherapy. Results: Telomere maintenance mechanisms were detectable in 86.4% of DMPM: ALT or TA alone was found in 18.2% or 63.6% of lesions, respectively, whereas two cases (4.6%) were ALT+/TA+. TA and ALT proved to be inversely associated (P = 0.002). In the overall series, TA was prognostic for 4-year relapse (TA+ versus TA−, hazard ratio, 3.30; 95% confidence interval, 1.23-8.86; P = 0.018) and cancer-related death (TA+ versus TA−, hazard ratio, 3.56; 95% confidence interval, 1.03-12.51; P = 0.045), whereas ALT failed to significantly affect clinical outcome. These results held true also in the subset of patients submitted to uniform treatment with cytoreductive surgery and hyperthermic i.p. chemotherapy. Conclusions: Our results indicate that both known telomere maintenance mechanisms, TA and ALT, are present in DMPM and differentially affect patient prognosis.
Defective Complement Inhibitory Function Predisposes to Renal Disease
Authors: Anuja Java, John Atkinson, Jane Salmon
Journal: Annual Review of Medicine (2012)

The role of the complement system in mediating human renal disease has long been recognized in immune-complex excess syndromes such as systemic lupus erythematosus and in dense deposit disease in which no immunoglobulin (Ig) is present. Over the past 15 years, mutations in complement regulatory genes have been demonstrated to predispose to thrombotic microangiopathies including atypical hemolytic uremic syndrome, C3 and C1q glomerulopathies, and preeclampsia. Excessive complement activation on an endothelial cell, due to either an autoantibody or a regulatory protein deficiency, sets up a procoagulant state in these diseases as well as in the antiphospholipid syndrome. Knowledge of the genes involved and the functional consequences of alterations in their structure has led to therapy that blocks complement activation.
Dietary Glycemic Index and Glycemic Load, Carbohydrate and Fiber Intake, and Measures of Insulin Sensitivity, Secretion, and Adiposity in the Insulin Resistance Atherosclerosis Study
Authors: Angela D. Liese, Mandy Schulz, Fang Fang, Thomas M.S. Wolever, Ralph B. D’Agostino, Karen C. Sparks, Elizabeth J. Mayer-Davis
Journal: Diabetes Care (2005)

OBJECTIVE—We studied the association of digestible carbohydrates, fiber intake, glycemic index, and glycemic load with insulin sensitivity (SI), fasting insulin, acute insulin response (AIR), disposition index, BMI, and waist circumference. RESEARCH DESIGN AND METHODS—Data on 979 adults with normal (67%) and impaired (33%) glucose tolerance from the Insulin Resistance Atherosclerosis Study (1992–1994) were analyzed. Usual dietary intake was assessed via a 114-item interviewer-administered food frequency questionnaire from which nutrient intakes were estimated. Published glycemic index values were assigned to food items and average dietary glycemic index and glycemic load calculated per subject. SI and AIR were determined by frequently sampled intravenous glucose tolerance test. Disposition index was calculated by multiplying SI with AIR. Multiple linear regression modeling was employed. RESULTS—No association was observed between glycemic index and SI, fasting insulin, AIR, disposition index, BMI, or waist circumference after adjustment for demographic characteristics or family history of diabetes, energy expenditure, and smoking. Associations observed for digestible carbohydrates and glycemic load, respectively, with SI, insulin secretion, and adiposity (adjusted for demographics and main confounders) were entirely explained by energy intake. In contrast, fiber was associated positively with SI and disposition index and inversely with fasting insulin, BMI, and waist circumference but not with AIR. CONCLUSION—Carbohydrates as reflected in glycemic index and glycemic load may not be related to measures of insulin sensitivity, insulin secretion, and adiposity. Fiber intake may not only have beneficial effects on insulin sensitivity and adiposity, but also on pancreatic functionality.
A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma
Authors: Achim Rothe, Stephanie Sasse, Max S. Topp, Dennis A. Eichenauer, Horst Hummel, Katrin S. Reiners, Markus Dietlein, Georg Kuhnert, Joerg Kessler, Carolin Buerkle, Miroslav Ravic, Stefan Knackmuss, Jens-Peter Marschner, Elke Pogge von Strandmann, Peter Borchmann, Andreas Engert
Journal: Blood (2015)
Levels of Egfr T790M in Plasma Dna As a Predictive Biomarker for Response to Azd9291, a Mutant-Selective Egfr Kinase Inhibitor
Authors: K. Thress, J.C. Yang, M. Ahn, D. Kim, S. Kim, Y. Ohe, D. Planchard, R. Brant, H. Carr, S. Dearden, S. Jenkins, M. Cantarini, S. Ghiorghiu, J.C. Barrett, P.A. Janne, G.R. Oxnard
Journal: Annals of Oncology (2014)
Hematology of Infancy and Childhood
Authors: Ruth Andrea Seeler
Journal: JAMA (1993)

The continuing knowledge explosion in pediatric hematology and oncology is proportionately represented in this fourth edition of the ultimate reference work for the field. As with past editions, the authors have assembled a "who's who" of contributors, including rare non-hematologists. This edition is a major rewrite, much more than a few new sentences thrown into existing chapters. An extremely generous amount of space is given to the tabular material and graphics, which enhance the quality of the individual sections. Although many are literature classics, the section writers have produced numerous illustrations specific to the topic. Particularly impressive are the encompassing summary tables and schematics prepared especially for these volumes. A continuing characteristic from earlier volumes is the inclusive bibliography, from the initial classic descriptions through the recent research at the biochemical and genetic level. The complete index and table of contents for both volumes appear in each, as do the
Neuroinflammatory Cytokine Signaling and Alzheimer's Disease
Authors: W Sue T Griffin
Journal: New England Journal of Medicine (2013)

Immune events may influence development and progression of Alzheimer's disease. In a mouse model, mice depleted of p40, a cytokine subunit, showed reduced cerebral amyloidosis. Administration of anti-p40 antibodies reduced levels of soluble β-amyloid and restored some cognitive function.
Acute sporadic non-A, non-B hepatitis in Northeastern Brazil: Etiology and natural history
Authors: Raymundo Paraná, Ludmila Vitvitski, Zilton Andrade, Christian Trepo, Helma Cotrim, Pascale Bertillon, Fernanda Silva, Luciana Silva, Irismar R. de Oliveira, Luis Lyra
Journal: Hepatology (1999)

In a 4-year follow-up study, patients with acute sporadic non-A, non-B (NANB) hepatitis were evaluated to determine the etiology and natural history of the disease. Acute hepatitis C virus (HCV) was detected in 13 of 43 (30%) of patients, anti-hepatitis E virus (HEV) IgG in 5 (12%), and 25 (58%) were considered non-A-E. The HCV RNA was detected in all HCV patients but none of the non-A-E cases. The initial clinical and biochemical presentation of the HCV and non-A-E cases was quite similar, although 2 of the non-A-E patients had severe disease. The 5 patients who were found to be anti-HEV IgG-reactive recovered within 6 months of follow-up. Of the 13 HCV cases, alanine transaminase (ALT) levels returned to normal in 7 (53. 8%), while 6 (46.2%) continued to show abnormal ALT after 6 months of follow-up. However, 9 (69.2%) of them remained HCV-RNA-positive, denoting virological/biochemical dissociation. Long-term follow-up showed a reappearance of HCV RNA in 2 of the 4 patients who were in virological remission performing 84% of chronicity rate. Acute non-A-E hepatitis patients were less likely to evolve toward chronicity, as compared with acute HCV cases (16% vs. 84%; P =.0001). Only 4 (16%) of the non-A-E patients were hepatitis G virus (HGV)-RNA-positive. Concerning risk factors for acquiring parenterally transmitted viruses, tattooing was the only one that could be associated with HCV transmission (P =.002). No risk factors could be identified for putative non-A-E virus transmission. Liver biopsies performed for chronic HCV patients showed a variable degree of inflammation, while the non-A-E patients presented less severe histological disease.
THE RELATIVE BENEFIT OF FULL PRESCRIPTION COVERAGE VERSUS USUAL PRESCRIPTION COVERAGE IN PATIENTS UNDERGOING PCI: AN ANALYSIS FROM THE MI FREEE TRIAL
Authors: Nihar R. Desai, William H. Shrank, Elliott Antman, Jerry Avorn, Robert Glynn, Raisa Levin, Niteesh Choudhry
Journal: Journal of the American College of Cardiology (2012)
The American College of Rheumatology/European League Against Rheumatism Criteria for the classification of rheumatoid arthritis: a game changer
Authors: S. Cohen, P. Emery
Journal: Annals of the Rheumatic Diseases (2010)

Over the last several years the two pre-eminent professional societies representing rheumatology, the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR), have been discussing increasing their collaboration in areas of interest to rheumatologists worldwide. These discussions resulted in a letter of agreement in 2008 on the framework whereby the two organisations would work together to develop disease classification criteria as well as recommendations for conducting of clinical trials. To enhance communication between the two organisations, ACR representatives now sit on the EULAR Standing Committee for Clinical Affairs and the EULAR Standing Committee of Epidemiology, and EULAR representatives now sit on the ACR Criteria Subcommittee and Quality of Care Committee.

The first result of this effort was the joint publication, in Annals of the Rheumatic Diseases and Arthritis Care & Research , of the recommendations on reporting disease activity in clinical trials of patients with rheumatoid arthritis (RA).1 2 This document was important in that it delineated the minimal standards necessary for clinical trials evaluating new therapeutics in RA. Several collaborative projects are under way on RA, and also on gout, scleroderma, myositis and vasculitis. The positive aspects of developing a consensus between the dominant voices in world of rheumatology are self-evident.

The recent initiative to revise the ACR classification criteria for RA3 is the most significant cooperation so far. For the past 2 years rheumatologists on both sides of the Atlantic have been working on this project, and the fruits of their work are …
Younger Genes Are Less Likely to Be Essential than Older Genes, and Duplicates Are Less Likely to Be Essential than Singletons of the Same Age
Authors: W.-H. Chen, K. Trachana, M. J. Lercher, P. Bork
Journal: Molecular Biology and Evolution (2012)

Recently duplicated genes are believed to often overlap in function and expression.A priori, they are thus less likely to be essential.Although this was indeed observed in yeast, mouse singletons and duplicates were reported to be equally often essential.This contradiction can only partly be explained by experimental biases.We herein show that older genes (i.e., genes with earlier phyletic origin) are more likely to be essential, regardless of their duplication status.At a given phyletic gene age, duplicates are always less likely to be essential compared with singletons.The ''paradoxical'' high essentiality among mouse gene duplicates is then caused by different age profiles of singletons and duplicates, with the latter tending to be derived from older genes.Key words: gene essentiality, yeast, mouse, phyletic age
Randomized Phase III Trial of Induction Chemotherapy With Docetaxel, Cisplatin, and Fluorouracil Followed by Surgery Versus Up-Front Surgery in Locally Advanced Resectable Oral Squamous Cell Carcinoma
Authors: Lai-ping Zhong, Chen-ping Zhang, Guo-xin Ren, Wei Guo, William N. William, Jian Sun, Han-guang Zhu, Wen-yong Tu, Jiang Li, Yi-li Cai, Li-zhen Wang, Xin-dong Fan, Zhong-he Wang, Yong-jie Hu, Tong Ji, Wen-jun Yang, Wei-min Ye, Jun Li, Yue He, Yan-an Wang, Li-qun Xu, Bo-song Wang, Merrill S. Kies, J. Jack Lee, Jeffrey N. Myers, Zhi-yuan Zhang
Journal: Journal of Clinical Oncology (2012)

To evaluate induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) followed by surgery and postoperative radiotherapy versus up-front surgery and postoperative radiotherapy in patients with locally advanced resectable oral squamous cell carcinoma (OSCC).