tbuckley/cabot-search huggingface dataset:
X-Linked Lymphoproliferative Disease: A Progressive Immunodeficiency
Authors: Massimo Morra, Duncan Howie, Maria Simarro Grande, Joan Sayos, Ninghai Wang, Chengbin Wu, Pablo Engel, Cox Terhorst
Journal: Annual Review of Immunology (2001)

Our understanding of the X-linked lymphoproliferative syndrome (XLP) has advanced significantly in the last two years. The gene that is altered in the condition (SAP/SH2D1A) has been cloned and its protein crystal structure solved. At least two sets of target molecules for this small SH2 domain-containing protein have been identified: A family of hematopoietic cell surface receptors, i.e. the SLAM family, and a second molecule, which is a phosphorylated adapter. A SAP-like protein, EAT-2, has also been found to interact with this family of surface receptors. Several lines of evidence, including structural studies and analyses of missense mutations in XLP patients, support the notion that SAP/SH2D1A is a natural inhibitor of SH2-domain-dependent interactions with members of the SLAM family. However, details of its role in signaling mechanisms are yet to be unravelled. Further analyses of the SAP/SH2D1A gene in XLP patients have made it clear that the development of dys-gammaglobulinemia and B cell lymphoma can occur without evidence of prior EBV infection. Moreover, preliminary results of virus infections of a mouse in which the SAP/SH2D1A gene has been disrupted suggest that EBV infection is not per se critical for the development of XLP phenotypes. It appears therefore that the SAP/SH2D1A gene controls signaling via the SLAM family of surface receptors and thus may play a fundamental role in T cell and APC interactions during viral infections.
ANAESTHESIA FOR NOSE, THROAT, AND ABDOMINAL SURGERY BY THE NITROUS OXIDE-OXYGEN-C.E. COMBINATION
Authors: H. E. G. Boyle
Journal: BMJ (1921)

NITROUS OXIDE-OXYGEN-C.E.ANAESTHESIA 1MDIA sg9 of the chanaes occurring in disease.There are no doubt other factors, such as emotional excitement, nervous dis- turbances, changes of temperature, etc., which affect the percentage of sugar in the blood, but these are probably of comparatively minor importance under normal conditions, and a discussion of their mode of action would not lhave a material bearing on the subject we are considering, or affect the general principles of the scheme we have outliied.In conclusion, we wish to express our thanks to Pro- fessor Starling for permission to carry out the animal experiments described in his department at University Colleae.
Abstract P5-05-13: Obesity confers chemotherapy resistance in triple negative breast cancer cells
Authors: Victoria R Lehrmann, Laura W Bowers, Andrew J Brenner, Linda A deGraffenried
Journal: Cancer Research (2015)

Abstract Introduction: Obesity is associated with a more aggressive breast cancer and a worse outcome following chemotherapy treatment. Triple negative breast cancer is a highly aggressive subtype of breast cancer characterized by the absence of estrogen, progesterone, and human epidermal growth factor-2 (HER2) receptors. This subtype has also been correlated with a worse prognosis. This study aims to investigate the impact of obesity on triple negative breast cancer cells’ response to chemotherapy treatment and elucidate potential therapeutic options to improve response. Methods: Sera was collected from breast cancer patients at the Cancer Therapy and Research Center at The University of Texas Health Science Center at San Antonio (UTHSCSA) and pooled according to body mass index (BMI) category (Control:18.5 to 24.9 kg/m2; Obese:≥30 kg/m2). MDA-MB-231 cells, a triple negative breast cancer cell line, were grown in serum-free media supplemented with 2% obese or control patient sera to create an in vitro model of obesity. The effects of docetaxel, a chemotherapeutic agent, on cell viability in the presence of obese versus control sera were examined by MTT. Modulation of B-cell lymphoma 2 (Bcl-2), cyclooxygenase-2 (COX-2), and mammalian target of rapamycin (mTOR) were evaluated as possible mechanisms for obesity-induced chemotherapy resistance. Results: The obese sera significantly reduced sensitivity of the MDA-MB-231 cells to docetaxel. In fact, there was no variance in the viability level of cells grown in obese patient sera for 96 hours with and without docetaxel treatment. The mechanism for resistance does not appear to involve Bcl-2 or COX-2, previously implicated in docetaxel resistance. Intriguingly, suppression of mTOR did provide significant benefit, in agreement with our previous in vivo studies investigating obesity and aromatase inhibitor (AI) response. The role of the mTOR pathway in modulating therapeutic response is still being investigated. Conclusion: Exposure to obesity-associated circulating factors confers chemotherapy resistance in triple negative breast cancer cells. Further research will be conducted to determine the mechanism by which obesity promotes chemotherapy resistance and whether modulation of the mTOR pathway will provide significant benefit. Citation Format: Victoria R Lehrmann, Laura W Bowers, Andrew J Brenner, Linda A deGraffenried. Obesity confers chemotherapy resistance in triple negative breast cancer cells [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-05-13.
877 OXIDIZED LOW DENSITY LIPOPROTEIN (OXLDL) IS A PAN-GENOTYPE INHIBITOR OF HCV ENTRY THAT ACTS IN A SR-BI DEPENDENT MANNER
Authors: S. Westhaus, S. Ciesek, D. Bankwitz, C. Agne, M. Luchtefeld, B. Schieffer, M.P. Manns, T. Pietschmann, T. von Hahn
Journal: Journal of Hepatology (2012)
Media have key role in shaping use of health services
Authors: R. Grilli
Journal: BMJ (1999)

EDITOR—Information in the mass media is commonly thought to negatively shape the demand for health services, raising false hopes and generating emotional reactions and irrational behaviours. Oversight and misinterpretation of research information are indeed common ingredients of messages from the lay media, often leading to conflicts and tensions between health services and consumers and to public expectations that are bound to remain largely unmet.

Nevertheless, empirical research shows that the mass media may also positively affect the use of health services, …
Comitogenic effect of catecholamines on rat cardiac fibroblasts in culture
Authors: M Leicht
Journal: Cardiovascular Research (2000)

Objective: We studied the ability of norepinephrine and of other catecholamines to affect the proliferation of cardiac fibroblasts isolated from adult rat hearts. Furthermore, we investigated the possible adrenergic receptor involved in this process. Methods: Norepinephrine (NE), phenylephrine (PE), isoproterenol (ISO), forskolin (FO), epidermal growth factor (EGF), platelet-derived growth factor AA (PDGF-AA) and specific inhibitors of the α1-, α2-, β1- and β2-adrenoceptors and of the protein kinase A (PKA) were applied to cardiac fibroblasts in culture. Cell number was measured by use of a Coulter Counter. Activation of the cAMP response element binding protein (CREB) was measured by Western blotting and subsequent use of a phospho-specific antibody. Activation of the p42- and the p44-mitogen activated protein kinase (p42/p44MAPK) was assessed by detection of phosphorylation shifts and by incorporation of 32P-labelled phosphate into myelin basic protein. Results: Fibroblasts isolated from hearts of adult rats were grown in 10% serum-containing media which induced an increase in cell number by 94%. After 48 h, treatment with 10 μM NE caused an even greater increase in cell number by 222%, i.e. another 128% (comitogenic effect). In contrast, NE alone had no effect on the growth of serum-deprived cells. EGF and PDGF-AA did not replace serum as the basic mitogen. After addition of NE to proliferating cells under serum conditions, there was a rapid, time-dependent significant activation of the p42/p44MAPK and of CREB for up to 60 and 120 min, respectively. In both cases, the maximum of activation was reached after 5 min. Application of FO (0.1–20 μM) caused a strong activation of CREB, while no increase in the phosphorylation of the p42/p44MAPK was detected. Treatment with 20 μM FO led to an identical increase in cell number as application of NE. Specific blockade of PKA with RpcAMPS prevented the activation of CREB and also the comitogenic effect of FO as well as of NE. The α- and β-adrenergic receptor blocker carvedilol (10 μM) normalized all NE-induced effects. Prazosin and yohimbine, inhibitors of α1- and α2-adrenoceptor activation, respectively, did not influence the NE-evoked increase in cell number. In contrast, the non-selective β-adrenoceptor blocker propranolol (1 μM) completely suppressed the comitogenic effect of NE. A similar effect was obtained with the specific β2-adrenoceptor blocker ICI 118,551 (5 μM), while the β1-adrenoceptor blocker metoprolol did not influence the increase in cell number. Conclusions: NE elicits a comitogenic effect on cultured rat cardiac fibroblasts which is prevented by β2-adrenergic blockade. The activation of CREB contributes to the increase in proliferation. The p42/p44MAPK which was also found to be activated by NE might as well be involved in the regulation of the comitogenic effect.
Aortic impedance and hydraulic power in the chick embryo from stages 18 to 29.
Authors: K G Zahka, N Hu, K P Brin, F C Yin, E B Clark
Journal: Circulation Research (1989)

Little is known about the hemodynamic properties of the rapidly expanding arterial bed during embryonic development. Using a servo-null pressure system and 20-MHz pulsed Doppler velocity meter, we recorded simultaneous dorsal aortic pressure and velocity waveforms. The waveforms were digitized at 3-msec intervals and subjected to Fourier analysis. We calculated hydraulic energy and the impedance spectrum to 10 Hz. From stages 18 to 29, heart rate (148 +/- 3 to 193 +/- 9 beats/min), systolic pressure (1.14 +/- 0.12 to 3.04 +/- 0.10 mm Hg), and mean dorsal aortic blood flow (21 +/- 2 to 214 +/- 19 mm3/min) increased. Peripheral vascular resistance (Z0: 30.4 +/- 4.8 to 6.4 +/- 0.7 dyne x sec/mm5), and the impedance moduli (Z1: 6.5 +/- 1.0 to 1.7 +/- 0.2 dyne x sec/mm5; Z2: 6.1 +/- 1.2 to 1.7 +/- 0.1 dyne x sec/mm5; Z3: 7.3 +/- 1.1 to 1.7 +/- 0.2 dyne x sec/mm5) decreased. Total hydraulic power increased from 48 +/- 7 to 2,606 +/- 96 nW, while the proportion of oscillatory energy increased from 29 +/- 2% to 65 +/- 4%. With development hydraulic load decreases, total external work increases and the dorsal aorta and embryonic vascular bed becomes more compliant. A greater proportion of total energy is expanded in pulsatile blood flow, suggesting that ventricular-arterial coupling is less efficient later in development.
Genetic Classification of Lung Adenocarcinoma Based on Array-Based Comparative Genomic Hybridization Analysis: Its Association with Clinicopathologic Features
Authors: Tatsuhiro Shibata, Satomi Uryu, Akiko Kokubu, Fumie Hosoda, Misao Ohki, Tokuki Sakiyama, Yoshihiro Matsuno, Ryosuke Tsuchiya, Yae Kanai, Tadashi Kondo, Issei Imoto, Johji Inazawa, Setsuo Hirohashi
Journal: Clinical Cancer Research (2005)

Abstract The array-based comparative genomic hybridization using microarrayed bacterial artificial chromosome clones allows high-resolution analysis of genome-wide copy number changes in tumors. To analyze the genetic alterations of primary lung adenocarcinoma in a high-throughput way, we used laser-capture microdissection of cancer cells and array comparative genomic hybridization focusing on 800 chromosomal loci containing cancer-related genes. We identified a large number of chromosomal numerical alterations, including frequent amplifications on 7p12, 11q13, 12q14-15, and 17q21, and two homozygous deletions on 9p21 and one on 8p23. Unsupervised hierarchical clustering analysis of multiple alterations revealed three subgroups of lung adenocarcinoma that were characterized by the accumulation of distinct genetic alterations and associated with smoking history and gender. The mutation status of the epidermal growth factor receptor (EGFR) gene was significantly associated with specific genetic alterations and supervised clustering analysis based on EGFR gene mutations elucidated a subgroup including all EGFR gene mutated tumors, which showed significantly shorter disease-free survival. Our results suggest that there exist multiple molecular carcinogenesis pathways in lung adenocarcinoma that may associate with smoking habits and gender, and that genetic cancer profiling will reveal previously uncharacterized genetic heterogeneity of cancer and be beneficial in estimating patient prognosis and discovering novel cancer-related genes including therapeutic targets.
Regulation of Muscle Protein Degradation
Authors: Seoung Woo Lee, Guoli Dai, Zhaoyong Hu, Xiaonan Wang, Jie Du, William E. Mitch
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Muscle proteolysis from catabolic conditions, including chronic kidney disease, requires coordinated activation of both the apoptotic and ATP-ubiquitin-proteasome systems (Ub-P’some), including upregulation of components of the Ub-P’some system. Activation of the apoptotic system is required because caspase-3 initially cleaves myofibrils, yielding substrates for the Ub-P’some system plus a characteristic 14-kD actin fragment. The authors studied insulin deficiency, a model of accelerated muscle atrophy, to understand how regulation of the apoptotic and the Ub-P’some systems could be coordinated. As expected, phosphatidylinositol 3 kinase activity (PI3K) was suppressed in muscle; in addition to decreased insulin, the mechanism includes IRS-1 phosphorylation at serine-307. Caspase-3 activity was also increased, and the authors linked it to a low PI3K-induced activation of the apoptotic system that includes a conformational change in Bax and release of cytochrome C. Coordinated atrogin-1/MAFbx expression is required as a critical factor for Ub-P’some system–dependent muscle proteolysis in diabetes and other catabolic states. The mechanism that regulates atrogin-1/MAFbx expression is unknown. Atrogin-1/MAFbx expression increased when the authors suppressed PI3K activity in muscle cells. The forkhead transcriptional factor, a downstream substrate of PI3K, stimulated atrogin-1/MAFbx promoter transcriptional activity markedly. The authors found in diabetic muscle that mRNA of the forkhead transcriptional factor, its nuclear translocation, and binding to the atrogin-1/MAFbx promoter were increased. When PI3K activity is low, both apoptotic and Ub-P’some pathways are activated coordinately to cause muscle proteolysis. This mechanism could increase muscle atrophy in conditions with impaired insulin responsiveness.
Clinical Impact and Reliability of Pleural Fluid Mesothelin in Undiagnosed Pleural Effusions
Authors: Helen E. Davies, Ross S. Sadler, Silvia Bielsa, Nicholas A. Maskell, Najib M. Rahman, Robert J. O. Davies, Berne L. Ferry, Y. C. Gary Lee
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: Serum mesothelin is a new biomarker for the diagnosis of mesothelioma. Patients with mesothelioma commonly present with pleural effusions. To define the clinical utility of mesothelin quantification in pleural fluid, we assessed its additional value over pleural fluid cytology and its short-term reproducibility and reliability after pleural inflammatory processes, including pleurodesis.Objectives: To assess the diagnostic role of pleural fluid mesothelin and the effect of common clinical factors that may influence measurement accuracy.Methods: Mesothelin was quantified in 424 pleural fluid and 64 serum samples by ELISA. Fluid was collected prospectively from 167 patients who presented with pleural effusions for investigation. Serial pleural fluid samples were obtained from patients (n = 33) requiring repeated drainage. Mesothelin levels were also measured in patients (n = 32) prepleurodesis and postpleurodesis.Measurements and Main Results: Pleural fluid mesothelin concentrations were significantly higher in patients with mesothelioma (n = 24) relative to those with metastatic carcinomas (n = 67) and benign effusions (n = 75): median (interquartile range, 25th−75th percentile) = 40.3 (18.3–68.1) versus 6.1 (1.5–13.2) versus 3.7 (0.0–12.4) nM, respectively, P < 0.0001. Mesothelin measurement was superior to cytological examination in the diagnosis and exclusion of mesothelioma (sensitivity, 71 vs. 35%; specificity, 89 vs. 100%; negative predictive value, 95 vs. 82%, respectively). In patients with "suspicious" cytology, pleural fluid mesothelin was 100% specific for mesothelioma, and in cytology-negative effusions (n = 105) offered a negative predictive value of 94%. Intraindividual reproducibility of pleural fluid mesothelin was excellent: mean (±SD) variation, −0.15 (±8.41) nM in samples collected within 7 days from patients with mesothelioma. Measurements remained reliable after pleurodesis and were not affected by the presence of bacteria.Conclusions: Pleural fluid mesothelin provides additional diagnostic value relative to cytological examination. Mesothelin measurements are reproducible and not affected by inflammatory pleural processes.
Working Memory Deficit as a Core Neuropsychological Dysfunction in Schizophrenia
Authors: Henry Silver, Pablo Feldman, Warren Bilker, Ruben C. Gur
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: This study tested the hypothesis that impaired working memory is a core deficit underlying multiple neuropsychological deficits in schizophrenia patients. METHOD: The subjects were 27 men with stable chronic schizophrenia treated with atypical antipsychotics and 38 normal participants. They were assessed with a battery of neuropsychological tests. Verbal working memory was measured with the WAIS digit span tests, and the Dot Test was used to test spatial working memory. RESULTS: In the patients, verbal working memory showed significant correlations with visual retention, visual orientation, simple motor function, visuomotor coordination, and executive function but not with memory for objects, memory for faces, recognition of facial emotions, or attention. Spatial working memory showed significant correlations with visual retention, visual orientation, memory for objects, memory for faces, and simple motor function but not attention, executive function, or visuomotor coordination. In the comparison group, no correlations between working memory and other neuropsychological functions were found. CONCLUSIONS: These findings support the hypothesis that working memory is a core deficit in schizophrenia. The authors postulate that the lower capacity for verbal and spatial "on-line storage" is rate limiting in the performance of other cognitive functions. Executive functions rely critically on the phonetic loop, complex visual functions such as object and face memory rely on the spatial on-line storage system (visuospatial scratch pad), while other functions such as visual orientation depend critically on both capacities.
Cases of chikungunya virus infection in travellers returning to Spain from Haiti or Dominican Republic, April-June 2014
Authors: A Requena-Méndez, C García, E Aldasoro, J A Vicente, M J Martínez, J A Pérez-Molina, A Calvo-Cano, L Franco, I Parrón, A Molina, M Ruiz, J Álvarez, M P Sánchez-Seco, J Gascón
Journal: Eurosurveillance (2014)

Ten cases of chikungunya were diagnosed in Spanish travellers returning from Haiti (n=2), the Dominican Republic (n=7) or from both countries (n=1) between April and June 2014. These cases remind clinicians to consider chikungunya in European travellers presenting with febrile illness and arthralgia, who are returning from the Caribbean region and Central America, particularly from Haiti and the Dominican Republic. The presence of Aedes albopictus together with viraemic patients could potentially lead to autochthonous transmission of chikungunya virus in southern Europe.
A physical map for the Amborella trichopoda genome sheds light on the evolution of angiosperm genome structure
Authors: Andrea Zuccolo, John E Bowers, James C Estill, Zhiyong Xiong, Meizhong Luo, Aswathy Sebastian, José Goicoechea, Kristi Collura, Yeisoo Yu, Yuannian Jiao, Jill Duarte, Haibao Tang, Saravanaraj Ayyampalayam, Steve Rounsley, Dave Kudrna, Andrew H Paterson, J Pires, Andre Chanderbali, Douglas E Soltis, Srikar Chamala, Brad Barbazuk, Pamela S Soltis, Victor A Albert, Hong Ma, Dina Mandoli, Jody Banks, John E Carlson, Jeffrey Tomkins, Claude W dePamphilis, Rod A Wing, Jim Leebens-Mack
Journal: Genome biology (2011)

Recent phylogenetic analyses have identified Amborella trichopoda, an understory tree species endemic to the forests of New Caledonia, as sister to a clade including all other known flowering plant species. The Amborella genome is a unique reference for understanding the evolution of angiosperm genomes because it can serve as an outgroup to root comparative analyses. A physical map, BAC end sequences and sample shotgun sequences provide a first view of the 870 Mbp Amborella genome. Analysis of Amborella BAC ends sequenced from each contig suggests that the density of long terminal repeat retrotransposons is negatively correlated with that of protein coding genes. Syntenic, presumably ancestral, gene blocks were identified in comparisons of the Amborella BAC contigs and the sequenced Arabidopsis thaliana, Populus trichocarpa, Vitis vinifera and Oryza sativa genomes. Parsimony mapping of the loss of synteny corroborates previous analyses suggesting that the rate of structural change has been more rapid on lineages leading to Arabidopsis and Oryza compared with lineages leading to Populus and Vitis. The gamma paleohexiploidy event identified in the Arabidopsis, Populus and Vitis genomes is shown to have occurred after the divergence of all other known angiosperms from the lineage leading to Amborella. When placed in the context of a physical map, BAC end sequences representing just 5.4% of the Amborella genome have facilitated reconstruction of gene blocks that existed in the last common ancestor of all flowering plants. The Amborella genome is an invaluable reference for inferences concerning the ancestral angiosperm and subsequent genome evolution.