tbuckley/cabot-search huggingface dataset:
Cell-specific translational profiling in acute kidney injury
Authors: Jing Liu, A. Michaela Krautzberger, Shannan H. Sui, Oliver M. Hofmann, Ying Chen, Manfred Baetscher, Ivica Grgic, Sanjeev Kumar, Benjamin Humphreys, Winston A. Hide, Andrew P. McMahon
Journal: Journal of Clinical Investigation (2014)

Acute kidney injury (AKI) promotes an abrupt loss of kidney function that results in substantial morbidity and mortality. Considerable effort has gone toward identification of diagnostic biomarkers and analysis of AKI-associated molecular events; however, most studies have adopted organ-wide approaches and have not elucidated the interplay among different cell types involved in AKI pathophysiology. To better characterize AKI-associated molecular and cellular events, we developed a mouse line that enables the identification of translational profiles in specific cell types. This strategy relies on CRE recombinase–dependent activation of an EGFP-tagged L10a ribosomal protein subunit, which allows translating ribosome affinity purification (TRAP) of mRNA populations in CRE-expressing cells. Combining this mouse line with cell type–specific CRE-driver lines, we identified distinct cellular responses in an ischemia reperfusion injury (IRI) model of AKI. Twenty-four hours following IRI, distinct translational signatures were identified in the nephron, kidney interstitial cell populations, vascular endothelium, and macrophages/monocytes. Furthermore, TRAP captured known IRI-associated markers, validating this approach. Biological function annotation, canonical pathway analysis, and in situ analysis of identified response genes provided insight into cell-specific injury signatures. Our study provides a deep, cell-based view of early injury-associated molecular events in AKI and documents a versatile, genetic tool to monitor cell-specific and temporal-specific biological processes in disease modeling.
Extended tumour necrosis factor/HLA-DR haplotypes and asthma in an Australian population sample
Authors: M. F Moffatt, A. James, G. Ryan, A W. Musk, W. O C M Cookson
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Tumour necrosis factor (TNF) is a potent pro-inflammatory cytokine which is prominent in asthmatic airways. TNF shows genetic variations in secretion which are linked to polymorphisms in the TNF gene complex and the surrounding major histocompatibility (MHC) locus. These polymorphisms do not seem to be themselves functionally important. In these circumstances, the identification of disease associated haplotypes (combination of alleles on individual chromosomes) may narrow the search for polymorphisms which alter gene function. <h3>METHODS</h3> TNF-308, LTα<i>Nco</i>I, and HLA-DRB1 polymorphisms were investigated for association with asthma, bronchial responsiveness, and medication use in 1004 subjects in 230 families from a general population sample. <h3>RESULTS</h3> The common LTα <i>Nco</i>I*1/TNF-308*2/HLA-DRB1*03 haplotype, which was present in 11% of unrelated individuals, was weakly associated with asthma (OR = 1.38, p = 0.016, corrected for familial correlation). The rarer LTα<i>Nco</i>I*1/TNF-308*2/HLA-DRB1*02 haplotype, which was found in 0.6% of unrelated subjects, was more strongly associated with asthma (OR = 6.68, p = 0.002). This haplotype also showed association with bronchial hyperresponsiveness (OR = 21.9, p = 0.0000) and the use of inhaled or oral steroids (OR 8.0, p = 0.04). <h3>CONCLUSIONS</h3> The results of this study show only two extended TNF/HLA-DR haplotypes to be associated with asthma. The search for functional alleles responsible for an increased risk of asthma should concentrate on the LTα <i>Nco</i>I*1/TNF-308*2/HLA-DRB1*02 haplotype.
Prognostic Value of International Neuroblastoma Pathology Classification in Localized Resectable Peripheral Neuroblastic Tumors: A Histopathologic Study of Localized Neuroblastoma European Study Group 94.01 Trial and Protocol
Authors: Samuel Navarro, Gabriele Amann, Klaus Beiske, Catherine J. Cullinane, Emanuele S.G. d'Amore, Claudio Gambini, Véronique Mosseri, Bruno De Bernardi, Jean Michon, Michel Peuchmaur
Journal: Journal of Clinical Oncology (2006)

To assess the prognostic value of clinical, biologic, and morphologic data in peripheral neuroblastic tumors, International Neuroblastoma Staging System (INSS) stages 2A and 2B MYCN nonamplified, a multinational protocol entitled Localized Neuroblastoma European Study Group trial 94.01, with a trial of surgery as the only treatment, was initiated in 1995. We present the prognostic value of the revised International Neuroblastoma Pathology Classification (INPC) applied to the patients included in this protocol until its closure in 1999.A total of 120 neuroblastic tumors from trial patients were reviewed by the European International Society of Pediatric Oncology neuroblastoma pathology panel and assigned to a favorable or unfavorable prognostic category according to the INPC guidelines. Overall survival and relapse-free survival (RFS) were estimated by the Kaplan-Meier method and compared by the log-rank test.A total of 115 of 120 patients were assessable and were assigned to the favorable (90 patients; 78.3%) or unfavorable (25 patients; 21.7%) category. The 60-month survival rate was 97.7% in favorable patients compared with 73.8% in unfavorable patients (P = .0002). RFS analysis showed a 60-month relapse rate of 13.4% and 32% in favorable and unfavorable patients (P < .025), respectively. Statistical analysis demonstrated a significant association of unfavorable INPC category and high lactate dehydrogenase level (P < .045).This European study shows for the first time that the INPC prognostic categorization has a significant impact on outcome prediction in INSS stage 2 localized peripheral neuroblastic tumors.
Cardiopulmonary Effects of Aerosolized Prostaglandin E<sub>1</sub> and Nitric Oxide Inhalation in Patients with Acute Respiratory Distress Syndrome
Authors: CHRISTIAN PUTENSEN, CHRISTOPH HÖRMANN, AXEL KLEINSASSER, GABRIELE PUTENSEN-HIMMER
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Ten patients with acute respiratory distress syndrome (ARDS) received in random order nitric oxide (NO) inhalation, aerosolized prostaglandin E1 (PGE1), infusion of PGE1, or no intervention. Inhalation of either aerosolized PGE1 (10 ± 1 ng/kg/min) or NO (7 ± 1 ppm) reduced pulmonary vascular resistance (PVR) from 158 ± 14 to 95 ± 11 dyn · s/cm5/m2 (NO) and 100 ± 12 dyn · s/cm5/m2 (aerosolized PGE1), and improved PaO2 from 78 ± 3 to 96 ± 5 mm Hg (NO) and 95 ± 4 mm Hg (aerosolized PGE1) (p < 0.05), venous admixture (Q˙ va/Q˙ t) from 45 ± 2 to 36 ± 2% (NO), and 36 ± 2% (aerosolized PGE1) (p < 0.05), oxygen delivery (Do 2) from 711 ± 34 to 762 ± 45 ml/min/m2 (NO) and 780 ± 46 ml/min/m2 (aerosolized PGE1) (p < 0.05), and right ventricular ejection fraction (RVEF) from 32 ± 6 to 37 ± 5% (NO), and 36 ± 4% (aerosolized PGE1) (p < 0.05) at a constant cardiac index (CI). Although infusion of PGE1 (12 ± 1 ng/kg/min) caused a similar reduction in PVR as aerosolized PGE1 and NO inhalation, it improved RVEF and increased CI but decreased Q˙ va/Q˙ t and PaO2 . These results suggest that in ARDS patients inhalation of aerosolized PGE1 or NO in low concentrations equally improves PVR and gas exchange by selective vasodilation in ventilated areas.
Effect of Implantable Defibrillators on Arrhythmic Events and Mortality in the Multicenter Unsustained Tachycardia Trial
Authors: Kerry L. Lee, Gail Hafley, John D. Fisher, Michael R. Gold, Eric N. Prystowsky, Mario Talajic, Mark E. Josephson, Douglas L. Packer, Alfred E. Buxton
Journal: Circulation (2002)

Background — The Multicenter Unsustained Tachycardia Trial (MUSTT) was designed to evaluate an antiarrhythmic treatment strategy, including drugs and implantable defibrillators (ICDs), guided by electrophysiological (EP) testing. We performed several statistical analyses to assess the contribution of defibrillators to the observed treatment benefit. Methods and Results — First, the effects of defibrillators were indirectly examined by comparing the randomized treatment arms (EP-guided therapy versus no antiarrhythmic therapy) within subgroups that varied according to ICD usage. Use of ICDs increased during the trial; hence, the randomized treatments were compared according to date of enrollment. There were also site-specific differences in ICD use; hence, the randomized arms were compared within groups of sites defined by level of ICD use. There was a distinct “dose response” in relation to ICD use. Where ICD use was high, EP-guided therapy produced significant reductions in arrhythmic death or cardiac arrest ( P &lt;0.004). Where ICD use was low, there was no benefit of EP-guided therapy. Finally, outcomes of EP-guided therapy patients who received an ICD were directly compared with outcomes of other patients using the Cox proportional hazards model with receipt of an ICD as a time-dependent covariate. Adjusted for other prognostic factors, patients who received an ICD had risk reductions of &gt;70% in arrhythmic death or cardiac arrest and &gt;50% in total mortality ( P &lt;0.001 for both end points). Conclusions — The benefit of EP-guided antiarrhythmic therapy observed in MUSTT was due to improved outcomes among patients who received an ICD but not among patients who received antiarrhythmic drugs.
Children and Adolescents With Velocardiofacial Syndrome: A Volumetric MRI Study
Authors: Stephan Eliez, J. Eric Schmitt, Christopher D. White, Allan L. Reiss
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Velocardiofacial syndrome is a common genetic condition often accompanied by mild cognitive impairment. Children and adolescents with velocardiofacial syndrome also are at greater risk for developing serious neuropsychiatric disorders in adulthood, particularly schizophrenia-like disorders. The purpose of this preliminary study was to 1) elucidate through brain imaging the neurobiological basis of cognitive and neuropsychiatric problems in velocardiofacial syndrome, and 2) consider the association between variations in neuroanatomy in velocardiofacial syndrome subjects and the associated neurobehavioral phenotype. METHOD: Fifteen children and adolescents with velocardiofacial syndrome were matched by age and gender with 15 comparison subjects. High-resolution magnetic resonance imaging scans were analyzed to provide quantitative measures of specified brain tissues and regions. Rater-blind morphometric analyses were conducted to examine tissue volumes of the four lobes and the cerebellum. RESULTS: Total brain volume was approximately 11% smaller in the children with velocardiofacial syndrome. Gray matter volume was reduced to a lesser extent (7.5%) than white matter volume (16.3%). Multivariate analyses of variance indicated a distinct pattern of regional morphological variation among the children with velocardiofacial syndrome. Specifically, frontal lobe tissue tended to be enlarged relative to the overall reduction in brain volume. Normal symmetry of parietal lobe tissue observed in the comparison group was not evident in the velocardiofacial syndrome group. This loss of symmetry was attributable to a significant reduction of gray matter in the left parietal lobe. CONCLUSIONS: Aberrant brain morphology is associated with velocardiofacial syndrome. These changes are potentially related to the language and learning deficits associated with the syndrome and may provide clues about neurodevelopmental pathways associated with schizophrenia.
Normal clinical and ultrasound findings indicate a low risk to sustain jumper’s knee patellar tendinopathy: a longitudinal study on Swedish elite junior volleyball players
Authors: Karl Gisslén, Csaba Gyulai, Peter Nordström, Håkan Alfredson
Journal: British Journal of Sports Medicine (2006)

Background: Jumper’s knee patellar tendinopathy is well known to be a common and difficult injury in volleyball. Knowledge about its aetiology and pathogenesis is sparse. Objective: To prospectively follow clinical status, tendon structure and vascularity in elite junior volleyball players. Methods: 22 volleyball players (44 patellar tendons) beginning their first grade at the Swedish National Centre for high school volleyball were continuously evaluated clinically and by ultrasonography (US) and power Doppler (PD) over the 3 school years. Results: At inclusion, there were 44 tendons being assessed. Jumper’s knee was diagnosed clinically in eight patellar tendons (seven of eight had structural changes and vascularity on US+PD). There were 27 normal (clinical and US+PD) tendons. At 3 years, there were 36 tendons still being assessed. Four individuals (eight tendons) had been excluded. Jumper’s knee had developed in 2 of 25 (2 were excluded) tendons that were normal (clinical and US+PD) at inclusion. Jumper’s knee (clinical and US+PD) was also present in six tendons. Conclusions: Normal clinical tests and ultrasound findings at the start indicated a low risk for these elite junior volleyball players to sustain jumper’s knee during three school years with intensive training and playing.
Multiple-Breath Washout as a Marker of Lung Disease in Preschool Children with Cystic Fibrosis
Authors: Paul Aurora, Andrew Bush, Per Gustafsson, Cara Oliver, Colin Wallis, John Price, John Stroobant, Siobhan Carr, Janet Stocks
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Sensitive measures of lung function applicable to young subjects are needed to detect early cystic fibrosis (CF) lung disease. Forty children with CF aged 2 to 5 years and 37 age-matched healthy control subjects performed multiple-breath inert gas washout, plethysmography, and spirometry. Thirty children in each group successfully completed all measures, with success on first visit being between 68 and 86% for all three measures. Children with CF had significantly higher lung clearance index (mean [95% CI] difference for CF control 2.7 [1.9, 3.6], p < 0.001) and specific airway resistance (1.65 z-scores [0.96, 2.33], p < 0.001), and significantly lower forced expired volume in 0.5 seconds (−0.49 z-scores [−0.95, −0.03], p < 0.05). Abnormal lung function results were identified in 22 (73%) of 30 children with CF by multiple-breath washout, compared with 14 (47%) of 30 by plethysmography, and 4 (13%) of 30 by spirometry. Children with CF who were infected with Pseudomonas aeruginosa had significantly higher lung clearance index, but no significant difference in other lung function measures, when compared with noninfected children. Most preschool children can perform multiple-breath washout, plethysmography, and spirometry at first attempt. Multiple-breath washout detects abnormal lung function in children with CF more readily than plethysmography or spirometry.
Reduced phosphocholine and hyperpolarized lactate provide magnetic resonance biomarkers of PI3K/Akt/mTOR inhibition in glioblastoma
Authors: H. S. Venkatesh, M. M. Chaumeil, C. S. Ward, D. A. Haas-Kogan, C. D. James, S. M. Ronen
Journal: Neuro-Oncology (2011)

The phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway is activated in more than88% of glioblastomas (GBM). New drugs targeting this pathway are currently in clinical trials. However, noninvasive assessment of treatment response remains challenging. By using magnetic resonance spectroscopy (MRS), PI3K/Akt/mTOR pathway inhibition was monitored in 3 GBM cell lines (GS-2, GBM8, and GBM6; each with a distinct pathway activating mutation) through the measurement of 2 mechanistically linked MR biomarkers: phosphocholine (PC) and hyperpolarized lactate.(31)P MRS studies showed that treatment with the PI3K inhibitor LY294002 induced significant decreases in PC to 34 %± 9% of control in GS-2 cells, 48% ± 5% in GBM8, and 45% ± 4% in GBM6. The mTOR inhibitor everolimus also induced a significant decrease in PC to 62% ± 14%, 57% ± 1%, and 58% ± 1% in GS-2, GBM8, and GBM6 cells, respectively. Using hyperpolarized (13)C MRS, we demonstrated that hyperpolarized lactate levels were significantly decreased following PI3K/Akt/mTOR pathway inhibition in all 3 cell lines to 51% ± 10%, 62% ± 3%, and 58% ± 2% of control with LY294002 and 72% ± 3%, 61% ± 2%, and 66% ± 3% of control with everolimus in GS-2, GBM8, and GBM6 cells, respectively. These effects were mediated by decreases in the activity and expression of choline kinase α and lactate dehydrogenase, which respectively control PC and lactate production downstream of HIF-1. Treatment with the DNA damaging agent temozolomide did not have an effect on either biomarker in any cell line. This study highlights the potential of PC and hyperpolarized lactate as noninvasive MR biomarkers of response to targeted inhibitors in GBM.
Increased Number of MicroRNA Target Sites in Genes Encoded in CNV Regions. Evidence for an Evolutionary Genomic Interaction
Authors: K. Felekkis, K. Voskarides, H. Dweep, C. Sticht, N. Gretz, C. Deltas
Journal: Molecular Biology and Evolution (2011)

MicroRNAs (miRNAs) and copy number variations (CNVs) are two newly discovered genetic elements that have revolutionized the field of molecular biology and genetics. By performing in silico whole genome analysis, we demonstrate that both the number of miRNAs that target genes found in CNV regions as well as the number of miRNA-binding sites are significantly higher than those of genes found in non-CNV regions. This suggests that miRNAs may have acted as equilibrators of gene expression during evolution in an attempt to regulate aberrant gene expression and to increase the tolerance to genome plasticity.
A MDR1 (ABCB1) gene single nucleotide polymorphism predicts outcome of temozolomide treatment in glioblastoma patients
Authors: M. Schaich, L. Kestel, M. Pfirrmann, K. Robel, T. Illmer, M. Kramer, C. Dill, G. Ehninger, G. Schackert, D. Krex
Journal: Annals of Oncology (2008)
Social brain dysfunctions in patients with Parkinson’s disease: a review of theory of mind studies
Authors: Rwei-Ling Yu, Ruey-Meei Wu
Journal: Translational Neurodegeneration (2013)

Human social interaction is essential in daily life and crucial for a promising life, especially in people who suffer from disease. Theory of Mind (ToM) is fundamental in social interaction and is described as the ability to impute the mental states of others in social situations. Studies have proposed that a complex neuroanatomical network that includes the frontal cortex mediates ToM. The primary neuropathology of Parkinson's disease (PD) involves the frontal-striatal system; therefore, patients with PD are expected to exhibit deficits in ToM. In this review, we summarize the current research with a particular focus on the patterns of impaired ToM, potential mediators of ToM, and the impact of ToM deficits on clinical disability in PD. Further studies to investigate the progression of ToM and its relationship with dementia in subjects in PD are needed.
Interleukin-4 and low-affinity receptor for IgE on B cells in peripheral blood of patients with atopic bronchial asthma
Authors: Choon Sik Park, Dong Jib Ra, Sang Moo Lee, Seong Whan Jeong, Sootaek Uh, Hyeon Tae Kim, Yong Hoon Kim
Journal: Journal of Allergy and Clinical Immunology (1996)
Phase III Study of Apatinib in Advanced Gastric Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: J. Li, S. Qin, J. Xu, J. Xiong, C. Wu, Y. Bai, W. Liu, J. Tong, Y. Liu, R. Xu, Z. Wang, Q. Wang, X. Ouyang, Y. Yang, Y. Ba, J. Liang, X. Lin, D. Luo, R. Zheng, K. Wu, G. Sun, L. Wang, L. Zheng, H. Guo, J. Wu, N. Xu, J. Yang, H. Zhang, Y. Cheng, N. Wang, L. Chen, Z. Fan, H. Yu
Journal: Annals of Oncology (2014)
Suppression of Colon Cancer Metastasis by Aes through Inhibition of Notch Signaling
Authors: Masahiro Sonoshita, Masahiro Aoki, Haruhiko Fuwa, Koji Aoki, Hisahiro Hosogi, Yoshiharu Sakai, Hiroki Hashida, Arimichi Takabayashi, Makoto Sasaki, Sylvie Robine, Kazuyuki Itoh, Kiyoko Yoshioka, Fumihiko Kakizaki, Takanori Kitamura, Masanobu Oshima, Makoto Mark Taketo
Journal: Cancer Cell (2011)
Gemcitabine plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer previously treated with anthracyclines and taxanes: final results of the phase III Spanish Breast Cancer Research Group (GEICAM) trial
Authors: Miguel Martín, Amparo Ruiz, Monserrat Muñoz, Ana Balil, Jesús García-Mata, Lourdes Calvo, Eva Carrasco, Esther Mahillo, Antonio Casado, José Ángel García-Saenz, M José Escudero, Vicente Guillem, Carlos Jara, Nuria Ribelles, Fernando Salas, Celia Soto, Flavia Morales-Vasquez, César A Rodríguez, Encarna Adrover, José Ramón Mel
Journal: The Lancet Oncology (2007)
DJ-1 regulates mast cell activation and IgE-mediated allergic responses
Authors: Do Kyun Kim, Hyuk Soon Kim, A-Ram Kim, Ji Hyung Kim, Bokyung Kim, Geunwoong Noh, Hyung Sik Kim, Michael A. Beaven, Young Mi Kim, Wahn Soo Choi
Journal: Journal of Allergy and Clinical Immunology (2012)
C-Raf Is Required for the Initiation of Lung Cancer by K-RasG12D
Authors: Florian A. Karreth, Kristopher K. Frese, Gina M. DeNicola, Manuela Baccarini, David A. Tuveson
Journal: Cancer Discovery (2011)

The Ras/Raf/MEK/ERK (extracellular signal-regulated kinase) pathway is primarily responsible for mitogenesis in metazoans, and mutational activation of this pathway is common in cancer. A variety of selective chemical inhibitors directed against the mitogen-activated protein kinase pathway are now available for clinical investigation and thus the determination of the importance of each of the kinases in oncogenesis is paramount. We investigated the role of two Raf kinases, B-Raf and C-Raf, in Ras oncogenesis, and found that although B-Raf and C-Raf have overlapping functions in primary mesenchymal cells, C-Raf but not B-Raf is required for the proliferative effects of K-Ras(G12D) in primary epithelial cells. Furthermore, in a lung cancer mouse model, C-Raf is essential for tumor initiation by oncogenic K-Ras(G12D), whereas B-Raf is dispensable for this process. Our findings reveal that K-Ras(G12D) elicits its oncogenic effects primarily through C-Raf and suggest that selective C-Raf inhibition could be explored as a therapeutic strategy for K-Ras-dependent cancers.
Seven-Year Changes in Body Fat and Visceral Adipose Tissue in Women. Association with indexes of plasma glucose-insulin homeostasis
Authors: Simone Lemieux, Denis Prud'homme, André Nadeau, Angelo Tremblay, Claude Bouchard, Jean Pierre Després
Journal: Diabetes Care (1996)

OBJECTIVE To study the associations between changes in body fatness, visceral adipose tissue (AT), and indexes of plasma glucose-insulin homeostasis over a 7-year follow-up period. RESEARCH DESIGN AND METHODS A sample of 30 nondiabetic women aged 35.2 ± 5.6 (SD) years at baseline was studied. RESULTS Changes in visceral AT and in subcutaneous AT (measured by computed tomography) as well as changes in body fat mass (obtained by hydrostatic weighting) were significantly related to changes in fasting plasma insulin levels and in plasma insulin area measured after a 75-g oral glucose load (0.47 ≤ r ≤ 0.62; P &amp;lt; 0.01). Changes in visceral AT but not in body fat mass or in subcutaneous AT area were significantly associated with changes in plasma glucose area (r = 0.37; P &amp;lt; 0.05). When two subgroups of women with similar mean increases in body fat mass but with either small or large increases in visceral AT were compared, the subgroup with the largest gain in visceral AT showed the greatest deterioration in indexes of plasma glucose-insulin homeostasis. On the other hand, when two subgroups with similar mean increases in visceral AT but with different changes in body fat mass were compared, both subgroups showed similar changes in plasma glucose and insulin concentrations. CONCLUSIONS Results of this 7-year follow-up study in women suggest that changes in indexes of plasma glucose-insulin homeostasis are significantly associated with changes in visceral AT, even after control for changes in body fat mass.