tbuckley/cabot-search huggingface dataset:
Discussing Religious and Spiritual Issues at the End of Life&lt;SUBTITLE&gt;A Practical Guide for Physicians&lt;/SUBTITLE&gt;
Authors: Bernard Lo, Delaney Ruston, Laura W Kates, Robert M Arnold, Cynthia B Cohen, Kathy Faber-Langendoen, Steven Z Pantilat, Christina M Puchalski, Timothy R Quill, Michael W Rabow, Simeon Schreiber, Daniel P Sulmasy, James A Tulsky
Journal: JAMA (2002)

As patients near the end of life, their spiritual and religious concerns may be awakened or intensified. Many physicians, however, feel unskilled and uncomfortable discussing these concerns. This article suggests how physicians might respond when patients or families raise such concerns. First, some patients may explicitly base decisions about life-sustaining interventions on their spiritual or religious beliefs. Physicians need to explore those beliefs to help patients think through their preferences regarding specific interventions. Second, other patients may not bring up spiritual or religious concerns but are troubled by them. Physicians should identify such concerns and listen to them empathetically, without trying to alleviate the patient's spiritual suffering or offering premature reassurance. Third, some patients or families may have religious reasons for insisting on life-sustaining interventions that physicians advise against. The physician should listen and try to understand the patient's viewpoint. Listening respectfully does not require the physician to agree with the patient or misrepresent his or her own views. Patients and families who feel that the physician understands them and cares about them may be more willing to consider the physician's views on prognosis and treatment. By responding to patients' spiritual and religious concerns and needs, physicians may help them find comfort and closure near the end of life.
Novel Cellular Genes Essential for Transformation of Endothelial Cells by Kaposi's Sarcoma–Associated Herpesvirus
Authors: Camilo Raggo, Rebecca Ruhl, Shane McAllister, Henry Koon, Bruce J. Dezube, Klaus Früh, Ashlee V. Moses
Journal: Cancer Research (2005)

Abstract Kaposi's sarcoma–associated herpesvirus (KSHV) is involved in the development of lymphoproliferative diseases and Kaposi's sarcoma. The oncogenicity of this virus is reflected in vitro by its ability to transform B cells and endothelial cells. Infection of dermal microvascular endothelial cells (DMVEC) transforms the cells from a cobblestone-like monolayer to foci-forming spindle cells. This transformation is accompanied by dramatic changes in the cellular transcriptome. Known oncogenes, such as c-Kit, are among the KSHV-induced host genes. We previously showed that c-Kit is an essential cellular component of the KSHV-mediated transformation of DMVEC. Here, we test the hypothesis that the transformation process can be used to discover novel oncogenes. When expression of a panel of KSHV-induced cellular transcripts was inhibited with antisense oligomers, we observed inhibition of DMVEC proliferation and foci formation using antisense molecules to RDC1 and Neuritin. We further showed that transformation of KSHV-infected DMVEC was inhibited by small interfering RNA directed at RDC1 or Neuritin. Ectopic expression of Neuritin in NIH 3T3 cells resulted in changes in cell morphology and anchorage-independent growth, whereas RDC1 ectopic expression significantly increased cell proliferation. In addition, both RDC1- and Neuritin-expressing cells formed tumors in nude mice. RDC1 is an orphan G protein–coupled receptor, whereas Neuritin is a growth-promoting protein known to mediate neurite outgrowth. Neither gene has been previously implicated in tumorigenesis. Our data suggest that KSHV-mediated transformation involves exploitation of the hitherto unrealized oncogenic properties of RDC1 and Neuritin.
The Behavioral Economics of Substance Use Disorders: Reinforcement Pathologies and Their Repair
Authors: Warren K. Bickel, Matthew W. Johnson, Mikhail N. Koffarnus, James MacKillop, James G. Murphy
Journal: Annual Review of Clinical Psychology (2014)

The field of behavioral economics has made important inroads into the understanding of substance use disorders through the concept of reinforcer pathology. Reinforcer pathology refers to the joint effects of (a) the persistently high valuation of a reinforcer, broadly defined to include tangible commodities and experiences, and/or (b) the excessive preference for the immediate acquisition or consumption of a commodity despite long-term negative outcomes. From this perspective, reinforcer pathology results from the recursive interactions of endogenous person-level variables and exogenous environment-level factors. The current review describes the basic principles of behavioral economics that are central to reinforcer pathology, the processes that engender reinforcer pathology, and the approaches and procedures that can repair reinforcement pathologies. The overall goal of this review is to present a new understanding of substance use disorders as viewed by recent advances in behavioral economics.
Mesenteric fat in Crohn's disease: a pathogenetic hallmark or an innocent bystander?
Authors: L. Peyrin-Biroulet, M. Chamaillard, F. Gonzalez, E. Beclin, C. Decourcelle, L. Antunes, J. Gay, C. Neut, J.-F. Colombel, P. Desreumaux
Journal: Gut (2006)

n the first half of the 20th century, white adipose tissue (WAT) was mainly viewed as an isolated tissue protecting the organism from heat loss and a passive energy storage compartment.Similarly to other species such as Drososophila melanogaster, it is now well recognised that mammalian fat tissue is not solely a reservoir for excess nutrients but also an active and dynamic organ involved in the development of metabolic syndromes and the regulation of immunity and inflammation.The older anatomical literature repeatedly mentions a close association between adipose tissue and lymphoid organs in various mammals including humans, suggesting a potential role of WAT in the host immune response.Several recent studies indicate that adipocytes could function as macrophage-like cells 1 as they express receptors related to the innate immune system and secrete major mediators of inflammation, such as tumour necrosis factor alpha (TNFa).Consistent with this hypothesis, 2 the biology of adipocytes is particularly implicated in chronic diseases, such as obesity 3 and atherosclerosis. 4 This review will focus on the normal and pathophysiological functions of mesenteric WAT (mWAT), which may play an important role in the inflammatory and fibrotic processes in Crohn's disease, a frequent and complex form of inflammatory bowel disease (IBD). ENDOCRINE AND IMMUNE FEATURES OF ADIPOCYTES cLong considered as the ''anatomists' Cinderella'', 5 mWAT is now recognised as a multifunctional organ.Notably located around organs such as the gut or the lungs, adipocytes may have evolved strategies to drive immune responses to microbial invaders by expressing different innate immune sensors.In addition its function as a storage organ, WAT plays a major endocrine and immune role by expressing several hormones and various mediators (fig 1).To clarify the nomenclature, we will refer to the hormones and immunomodulatory molecules derived from adipocytes as adipormones and adipocytokines, respectively.
Management of EGFR mutated nonsmall cell lung carcinoma patients
Authors: Bogdan Grigoriu, Thierry Berghmans, Anne-Pascale Meert
Journal: European Respiratory Journal (2015)

Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) are common in the therapeutic armentarium of lung cancer today. Initially tested in an unselected population, they have been of limited usefulness until the identification EGFR gene mutations. Activating mutations generate conformational changes that result in a shift toward an active state of the catalytic domain and are associated with sensitivity to first generation EGFR TKI. Other mutations have been associated with resistance to these drugs, but for rare mutations there is limited data concerning their role in predicting response to EGFR TKI. To date, four molecules have been approved for the treatment of EGFR mutated lung cancer. Gefitinib and/or erlotinib are available in almost all countries. Afatinib has been approved by the US Food and Drug Administration and by the European Medicines Agency, and icotinib has been approved only in China. Other, more active, third generation agents with a higher binding affinity for the receptor, or that are directed against specific mutations, are under development. EGFR TKIs have a favourable impact on progression-free survival when given as first line treatment in mutated patients, but may also have a moderate effect as a salvage therapy and in maintenance in an unselected population.
Red cell age-related changes of hemoglobins AIa+b and AIc in normal and diabetic subjects.
Authors: J F Fitzgibbons, R D Koler, R T Jones
Journal: Journal of Clinical Investigation (1976)

The minor hemoglobin components, hemoglobin AIa+b and hemoglobin AIc, were measured in the 10% youngest and 10% oldest erythrocytes of 15 normal and 14 diabetic subjects. Erythrocyte fractions were obtained by centrifugation in isopyknic concentrations of dextran: 28.5% of 40,000-mol wt dextran yeilded the 10% lightest of young cells, and 30.5% dextran provided the 10% heaviest or old erythrocytes. Both normal and diabetic erythrocytes contain increased amounts of Hb AIa+b and Hb AIc in old as compared to young cells. In normal subjects, young cells contained 1.2+/-0.2%, and old cells contained 1.8+/-0.4% Hb AIa+b. Corresponding values for diabetic cells were 1.7+/-0.6 and 2.6+/-0.9%. Hb AIc increased from 3.1+/-0.8 to 6.0+/-1.1% in normals and from 5.1+/-2.1 to 10.1+/-3.7% in diabetics. The results indicate that both cell age and diabetes are significant determinants of the amounts of Hb AIa+b and Hb AIc.
Role of interleukin-1 in the pathogenesis of experimental shigellosis.
Authors: P J Sansonetti, J Arondel, J M Cavaillon, M Huerre
Journal: Journal of Clinical Investigation (1995)

The effect of human recombinant interleukin-1 receptor antagonist on intestinal inflammation, tissue destruction, and bacterial invasion during experimental shigellosis caused by Shigella flexneri was studied in the rabbit-ligated loop infection model. Intravenous infusion of the inhibitor at a dose of 2 mg/kg per h, was initiated 30 min before intestinal loops were ligated and infected, and continued during the 8-h period of infection. The animals treated with IL-1 receptor antagonist showed a striking decrease in inflammation, destruction, and bacterial invasion of their tissues, both at the level of the villous intestine and Peyer's patches. This is conclusive evidence that interleukin-1 plays a critical role in the pathogenesis of shigellosis. This proinflammatory cytokine is here proposed as a major trigger of the inflammatory reaction which is characteristic of this invasive disease of the intestine, due to the particular interaction existing between S. flexneri and macrophages.
Is Sjogren myelopathy Devic disease?
Authors: N Sofat, P J Venables
Journal: Annals of the Rheumatic Diseases (2007)

Central nervous system (CNS) involvement in Sjogren syndrome was first described as a condition resembling multiple sclerosis,1 though frequent spinal cord involvement has resulted in the term “Sjogren myelopathy” being used in recent studies.2–4 Devic disease, or neuromyelitis optica (NMO) was described by Devic in 1894 as a necrotising inflammatory myelopathy associated with optic neuritis (reviewed in Wingerchuck et al , 1999 and 2006).5 6 Revised criteria for Devic disease6 include the presence of optic neuritis, a myelopathy spanning more than three vertebral segments of the cord and the presence of NMO IgG, a recently characterised autoantibody to the …
CABYR Is a Novel Cancer-Testis Antigen in Lung Cancer
Authors: Chonglin Luo, Xueyuan Xiao, Danhui Liu, Shaosong Chen, Mingying Li, Anjian Xu, Jifu Liu, Shugeng Gao, Shanshan Wu, Dacheng He
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Cancer-testis (CT) antigens are often expressed in a proportion of tumors of various types. Their restricted normal tissue expression and immunogenicity make them potential targets for immunotherapy. CABYR is a calcium-binding tyrosine phosphorylation–regulated fibrous sheath protein initially reported to be testis specific and subsequently shown to be present in brain tumors. This study was to determine whether CABYR is a novel CT antigen in lung cancer. Experimental Design: mRNA expression of CABYR-a/b (combination of CABYR-a and CABYR-b) and CABYR-c was examined in 36 lung cancer specimens, 14 cancer cell lines, and 1 normal cell line by conventional and real-time reverse transcription-PCR. Protein expression of CABYR was analyzed in 50 lung cancer tissues by immunohistochemistry. Antibodies specific to CABYR were analyzed in sera from 174 lung cancer patients and 60 healthy donors by ELISA and Western blot. Results: mRNA expression of CABYR-a/b and CABYR-c was observed, respectively, in 13 and 15 of 36 lung cancer tissues as well as in 3 and 5 of 14 cancer cell lines, whereas neither of them was observed in adjacent noncancerous tissues or the normal cell line. Protein expression of CABYR-a/b and CABYR-c was observed, respectively, in 20 and 19 of 50 lung cancer tissues. IgG antibodies specific to CABYR-a/b and CABYR-c were detected, respectively, in 11% and 9% of sera from lung cancer patients but not from the 60 healthy donors. Conclusion: CABYR is a novel CT antigen in lung cancer and may be a promising target for immunotherapy for lung cancer patients.
Control Motifs for Intracellular Regulatory Networks
Authors: Christopher V. Rao, Adam P. Arkin
Journal: Annual Review of Biomedical Engineering (2001)

▪ Abstract A number of technological innovations are yielding unprecedented data on the networks of biochemical, genetic, and biophysical reactions that underlie cellular behavior and failure. These networks are composed of hundreds to thousands of chemical species and structures, interacting via nonlinear and possibly stochastic physical processes. A central goal of modern biology is to optimally use the data on these networks to understand how their design leads to the observed cellular behaviors and failures. Ultimately, this knowledge should enable cellular engineers to redesign cellular processes to meet industrial needs (such as optimal natural product synthesis), aid in choosing the most effective targets for pharmaceuticals, and tailor treatment for individual genotypes. The size and complexity of these networks and the inevitable lack of complete data, however, makes reaching these goals extremely difficult. If it proves possible to modularize these networks into functional subnetworks, then these smaller networks may be amenable to direct analysis and might serve as regulatory motifs. These motifs, recurring elements of control, may help to deduce the structure and function of partially known networks and form the basis for fulfilling the goals described above. A number of approaches to identifying and analyzing control motifs in intracellular networks are reviewed.
Isolated Nephron Segments from Rabbit Models of Obstructive Nephropathy
Authors: Michael J. Hanley, Karen Davidson
Journal: Journal of Clinical Investigation (1982)

Micropuncture and microcatheterization studies have been used extensively to investigate the pathophysiologic alterations in renal function induced by urinary tract obstruction. The present isolated tubule microperfusion studies were designed to examine the intrinsic alterations in segmental nephron function induced by 24 h of bilateral (BUO) and unilateral (UUO) urinary tract obstruction. Following UUO superficial proximal convoluted tubule reabsorption rate (J(v)) was not different from contralateral control (0.75+/-0.08 vs. 0.73+/-0.11 nl/mm per min, NS). Following UUO J(v) in juxtamedullary proximal convoluted tubules (JMPCT) was reduced 32% (0.69+/-0.06 vs. 0.47+/-0.04 nl/mm per min, P < 0.02). Following UUO J(v) in proximal straight tubules (PST) was reduced 52% (0.25+/-0.02 vs. 0.12+/-0.03, P < 0.01). Thick ascending limb (T-ALH) function was assessed by measurement of ability to lower perfusate chloride ion concentration (DeltaCl). Following UUO DeltaCl was reduced 76% (-39+/-9 vs. -9+/-1 meq/liter, P < 0.001). Cortical collecting tubule (CCT) function was assessed by measurement of antiduiretic hormone (ADH)-dependent osmotic water flow. Following UUO osmotic water flow was reduced 76% (0.90+/-0.08 vs. 0.22+/-0.04 nl/mm per min, P < 0.01) and this ADH resistance could not be overcome by cAMP. Nephron segments were then examined following relief of BUO. There were no differences in intrinsic function following relief of BUO when compared with UUO. We conclude that in UUO and BUO (a) the intrinsic tubular defects are identical, (b) the natriuresis noted is due, in part, to disordered JMPCT, PST, and T-ALH NaCl reabsorption, (c) the impaired concentrating ability is due, in part, to depressed function in T-ALH and ADH resistance of the CCT, and (d) the ADH resistance occurs at a site distal to the intracellular generation of cAMP.
Positive and Negative Regulation of FcεRI-Mediated Signaling by the Adaptor Protein LAB/NTAL
Authors: Minghua Zhu, Yan Liu, Surapong Koonpaew, Olivia Granillo, Weiguo Zhang
Journal: The Journal of Experimental Medicine (2004)

Linker for activation of B cells (LAB, also called NTAL; a product of wbscr5 gene) is a newly identified transmembrane adaptor protein that is expressed in B cells, NK cells, and mast cells. Upon BCR activation, LAB is phosphorylated and interacts with Grb2. LAB is capable of rescuing thymocyte development in LAT-deficient mice. To study the in vivo function of LAB, LAB-deficient mice were generated. Although disruption of the Lab gene did not affect lymphocyte development, it caused mast cells to be hyperresponsive to stimulation via the FcεRI, evidenced by enhanced Erk activation, calcium mobilization, degranulation, and cytokine production. These data suggested that LAB negatively regulates mast cell function. However, mast cells that lacked both linker for activation of T cells (LAT) and LAB proteins had a more severe block in FcεRI-mediated signaling than LAT−/− mast cells, demonstrating that LAB also shares a redundant function with LAT to play a positive role in FcεRI-mediated signaling.
Metabolomic Profiling of Fatty Acid and Amino Acid Metabolism in Youth With Obesity and Type 2 Diabetes
Authors: Stephanie J. Mihalik, Sara F. Michaliszyn, Javier de las Heras, Fida Bacha, SoJung Lee, Donald H. Chace, Victor R. DeJesus, Jerry Vockley, Silva A. Arslanian
Journal: Diabetes Care (2012)

We compared acylcarnitine (AcylCN) species, common amino acid and fat oxidation (FOX) byproducts, and plasma amino acids in normal weight (NW; n = 39), obese (OB; n = 64), and type 2 diabetic (n = 17) adolescents.Fasting plasma was analyzed by tandem mass spectrometry, body composition by dual energy X-ray absorptiometry and computed tomography, and total-body lipolysis and substrate oxidation by [(2)H(5)]glycerol and indirect calorimetry, respectively. In vivo insulin sensitivity (IS) was assessed with a 3-h hyperinsulinemic-euglycemic clamp.Long-chain AcylCNs (C18:2-CN to C14:0-CN) were similar among the three groups. Medium- to short-chain AcylCNs (except C8 and C10) were significantly lower in type 2 diabetes compared with NW, and when compared with OB, C2-, C6-, and C10-CN were lower. Amino acid concentrations were lower in type 2 diabetes compared with NW. Fasting lipolysis and FOX were higher in OB and type 2 diabetes compared with NW, and the negative association of FOX to C10:1 disappeared after controlling for adiposity, Tanner stage, and sex. IS was lower in OB and type 2 diabetes with positive associations between IS and arginine, histidine, and serine after adjusting for adiposity, Tanner stage, and sex.These metabolomics results, together with the increased rates of in vivo FOX, are not supportive of defective fatty acid or amino acid metabolism in obesity and type 2 diabetes in youth. Such observations are consistent with early adaptive metabolic plasticity in youth, which over time-with continued obesity and aging-may become dysfunctional, as observed in adults.
New Issues and Controversies in the Prevention of Ventilator-associated Pneumonia
Authors: Leonardo Lorente, Stijn Blot, Jordi Rello
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

In the past 2 years, American, Canadian, and European scientific societies have published their new evidence-based guidelines for ventilator-associated pneumonia (VAP) prevention. However, these guidelines did not review some potentially useful strategies, such as the use of an endotracheal tube with an ultrathin cuff membrane, an endotracheal tube with a low-volume/low-pressure cuff, a device for continuous monitoring of the endotracheal tube cuff pressure, a device to remove biofilm from the inner site of the endotracheal tube, and saline instillation before tracheal suctioning. Only a few guidelines analyze the time of tracheostomy, and so no firm recommendations can be made regarding its importance. In addition, the guidelines diverge on the use of heat and moisture exchangers or heated humidifiers and on the use of an endotracheal tube coated with antimicrobial agents. The current review focuses on measures of VAP prevention for which there is no clear recommendation, or the use of which is controversial. A review of the literature suggests that the use of an endotracheal tube with an ultrathin and tapered-shape cuff membrane and coated in antimicrobial agents may reduce the risk of VAP. These features offer an attractive way to optimize the VAP prevention capacity of endotracheal tubes with a lumen for subglottic secretion drainage. We believe that early tracheostomy should be considered, based on the length reduction of mechanical ventilation and intensive care unit stay, reduction of mortality, and on patient comfort, although early tracheostomy has not yet been shown to favorably impact the incidence of VAP. We believed that heat and moisture exchangers should be considered based on the benefits in terms of cost savings. More research is necessary to clarify the role of continuous cuff pressure monitoring, removal of biofilm formation in the endotracheal tubes, and routine saline instillation before tracheal suctioning.
Long-term Outcome of Perianal Fistulizing Crohn's Disease Treated With Infliximab
Authors: Guillaume Bouguen, Laurent Siproudhis, Emmanuel Gizard, Timothée Wallenhorst, Vincent Billioud, Jean–François Bretagne, Marc–André Bigard, Laurent Peyrin–Biroulet
Journal: Clinical Gastroenterology and Hepatology (2013)