tbuckley/cabot-search huggingface dataset:
Abstract P6-07-40: Initial Neutrophil-to-Lymphocyte ratio in primary breast cancer patients: a simple and useful biomarker as prognostic factor
Authors: A Han, H Noh, J Lee
Journal: Cancer Research (2012)

Abstract Background: Increasing neutrophil/lymphocyte ratios (NLR) on preoperative blood tests have been associated with worse survival of patients with colorectal, gastric, hepatocellular, pancreatic and lung cancer. However the utility of NLR to predict mortality in breast cancer patients has not been studied. The aim of our study was to determine whether the NLR is predictive of disease specific mortality in breast cancer and subtype-adjusted prognostic effect in breast cancer patients. Methods: We retrospectively identified all the patients with primary breast cancer diagnosed at Yonsei University Wonju Medical School between January 2000 and June 2011 who underwent primary surgery and completed all phase of their treatment. Breast cancer with infiltrating ductal histology was included and divided into 4 subtypes: Luminal A, Luminal B, Her2-enriched, and basal type. Each immunohistochemical characteristics are as followings: Luminal A: ER and/or PgR positive and negative Her2, Luminal B: ER and/or PgR positive with positive HER2, Her2-enriched: negative ER and PR with positive Her2, and triple negative as basal. Results: Patients with NLR≥2.5 showed significantly lower 5-year, 10-year breast cancer specific survival than patients with NLR&amp;lt;2.5. (5-year survival; 88.6% vs. 96.4%, p = 0.009, 10-year survival; 84.3% vs. 92.2%, p = 0.006). Cox proportional multivariate hazard model for cancer-specific mortality showed that patients with NLR≥2.5 has hazard ratio 4.71 with 95% confidence interval 1.77–12.53. Further analysis was done according to stratified patients' subgroup with intrinsic subtype. In Luminal A subtype, patients with NLR≥2.5 showed higher mortality rate(p = 0.014), while NLR≥2.5 failed to show statistical significance in the other subtype such as Luminal B, Her2 enriched, and triple negative subtype. Conclusion: Increased preoperative NLR is a significant prognostic factor in breast cancer specific survival and relevant in Luminal A subtype. This study shows that NLR could be a useful prognostic factor for breast cancer specific survival. And this study suggests that different factors could contribute as prognostic factor to each subtype, such as NLR was significant prognostic factor in Luminal A, while we couldn't find increased NLR is significant in other subtypes. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-40.
hUNC‐93B1, a novel gene mainly expressed in the heart, is related to left ventricular diastolic function, heart failure morbidity and mortality in elderly men
Authors: Johan Ärnlöv, Johan Sundström, Lars Lind, Bertil Andrén, Maria Andersson, Richard Reneland, Lars Berglund, Vladimir Kashuba, Alexei Protopopov, Eugene Zabarovsky, Hans Lithell
Journal: European Journal of Heart Failure (2005)
ORL1 receptor–mediated internalization of N-type calcium channels
Authors: Christophe Altier, Houman Khosravani, Rhian M Evans, Shahid Hameed, Jean B Peloquin, Brian A Vartian, Lina Chen, Aaron M Beedle, Stephen S G Ferguson, Alexandre Mezghrani, Stefan J Dubel, Emmanuel Bourinet, John E McRory, Gerald W Zamponi
Journal: Nature Neuroscience (2005)
Differentiation-associated switches in protein 4.1 expression. Synthesis of multiple structural isoforms during normal human erythropoiesis.
Authors: J A Chasis, L Coulombel, J Conboy, S McGee, K Andrews, Y W Kan, N Mohandas
Journal: Journal of Clinical Investigation (1993)

Erythroid differentiation is accompanied by dramatic alterations in morphology and membrane mechanical properties resulting, in large part, from reorganization of the membrane skeletal protein network. The 80-kD protein 4.1 is an important organizational component of this membrane skeleton. Recently, it has been recognized that multiple structural isoforms of 4.1 are encoded by a single gene via alternative pre-mRNA splicing, and that an upstream ATG can be spliced in and used for translation of high molecular weight 4.1. We are exploring the hypothesis that differentiation-associated switches in protein 4.1 structure play an important role in membrane reorganization. To study changes in 4.1 gene expression during normal human differentiation, we analyzed 4.1 protein and mRNA structure at various developmental stages. Using immunofluorescence microscopy, we observed high molecular weight 4.1 isoforms in preproerythroblasts producing punctate, predominantly cytoplasmic staining with a perinuclear area of intense fluorescence, while mature red cells expressed very little high molecular weight 4.1. Isoforms containing an alternatively expressed 102-nucleotide exon near the COOH terminus were abundant in both preproerythroblasts and mature cells but produced a punctate distribution of fluorescence over the entire preproerythroblast and intense membrane-associated fluorescence in the erythrocyte. Characterization of RNA by polymerase chain reaction and nuclease protection assays revealed a differentiation-associated switch in pre-mRNA splicing in the spectrin-actin binding domain. Since this domain plays a critical role in regulating membrane material properties, we speculate that this switch may be crucial to reorganization of the skeletal network during erythropoiesis. We conclude that 4.1 isoforms are differentially expressed and differentially localized during erythropoiesis, and that this isoform family is likely to have diverse functions during terminal differentiation.
A hypoallergenic variant of the major birch pollen allergen shows distinct characteristics in antigen processing and <scp>T</scp>‐cell activation
Authors: C. Kitzmüller, M. Wallner, S. Deifl, S. Mutschlechner, C. Walterskirchen, G. J. Zlabinger, F. Ferreira, B. Bohle
Journal: Allergy (2012)

Abstract Background BM 4 is a novel genetically engineered variant of the major birch pollen allergen B et v 1 that lacks the typical B et v 1‐like fold and displays negligible I g E ‐binding but strong T cell–activating capacity. The aim of this study was to elucidate possible differences between BM 4 and B et v 1 in internalization, antigen processing, and presentation. Methods Proliferative responses to BM 4 and B et v 1 of peripheral blood mononuclear cells and B et v 1‐specific T ‐cell clones were compared. Fluorescently labeled BM 4 and B et v 1 were used to study surface binding, endocytosis, and intracellular degradation by monocyte‐derived DC (md DC ). Both proteins were digested by endolysosomal extracts of md DC . BM 4‐ and B et v 1‐pulsed md DC were employed to assess the kinetics of activation of B et v 1‐specific T ‐cell clones and the polarization of naïve T cells. Results BM 4 displayed a significantly stronger T cell–activating capacity than B et v 1. Furthermore, BM 4 showed increased surface binding and internalization as well as faster endolysosomal degradation compared with B et v 1. BM 4‐pulsed md DC induced enhanced proliferative responses at earlier time‐points in B et v 1‐specific T ‐cell clones and promoted less IL ‐5 production in T cells than B et v 1‐pulsed md DC . Conclusion The loss of the B et v 1‐fold changes the protein's interaction with the human immune system at the level of antigen‐presenting cells resulting in altered T ‐cell responses. By combining low I g E ‐binding with strong and modulating T cell–activating capacity, BM 4 represents a highly interesting candidate for specific immunotherapy of birch pollen allergy.
Catecholamine Influences and Sympathetic Neural Modulation of Immune Responsiveness
Authors: K S Madden, V M Sanders, D L Felten
Journal: The Annual Review of Pharmacology and Toxicology (1995)

Primary and secondary lymphoid organs are innervated extensively by noradrenergic sympathetic nerve fibers. Lymphocytes, macrophages, and other cells of the immune system bear functional adrenoreceptors. Norepinephrine fulfills criteria for neurotransmission with cells of the immune system as targets. In vitro, adrenergic agonists can modulate all aspects of an immune response (initiative, proliferative, and effector phases), altering such functions as cytokine production, lymphocyte proliferation, and antibody secretion. In vivo, chemical sympathectomy suppresses cell-mediated (T helper-1) responses, and may enhance antibody (T helper-2) responses. Noradrenergic innervation of spleen and lymph nodes is diminished progressively during aging, a time when cell-mediated immune function also is suppressed. In animal models of autoimmune disease, sympathetic innervation is reduced prior to onset of disease symptoms, and chemical sympathectomy can exacerbate disease severity. These findings illustrate the importance of the sympathetic nervous system in modulating immune function under normal and disease states.
Absence of Need for Amniocentesis in Patients with Elevated Levels of Maternal Serum Alpha-Fetoprotein and Normal Ultrasonographic Examinations
Authors: Allan S. Nadel, Jennifer K. Green, Lewis B. Holmes, Fredric D. Frigoletto, Beryl R. Benacerraf
Journal: New England Journal of Medicine (1990)

Recent improvements in the accuracy of sonographic diagnosis of neural-tube and ventral-wall defects have raised a question about the wisdom of routinely offering amniocentesis to women who have elevated levels of maternal serum alpha-fetoprotein with a structurally normal fetus as determined by ultrasonography.
The Open Heart
Authors: Charles G. Roland
Journal: JAMA (1967)

Most of us, if challenged to do so, would have difficulty selecting from our lives two days worthy of recording in a book. A great surgeon and innovator has an easier decision; many working days contain drama and emotion sufficient to fascinate most readers. Amosoff is such a surgeon and he has chosen well. He has selected from his career as a cardiac surgeon two days, widely separated in time. The days remain undated, and dates would be irrelevant. The two days are unrelated in specific subject matter; the binding element is Amosoff. The First Day takes up only one sixth of the book. This section could stand by itself, a deeply moving narrative of the repeated mental crises, the buffets of emotional trauma, which attack a compassionate physician who has lost a patient and convinced himself that he should not have done so. The Second Day is quite defferent.
Hospital ratings rise, but ambulance ratings fall
Authors: Z. Kmietowicz
Journal: BMJ (2003)

A reinvestigation of the relationship between the Crick-Harper-Raper (CHR) and the GIH clinical units (CU) of secretin has been undertaken in anaesthetized cats with the knowledge that for some time before 1970 the CHR standard used by The Boots Company to assay secretin had lost some specific activity. One clinical unit of GIH secretin (batch no. 17421) is 3-8 times more potent than 1 Crick-Harper-Raper unit of restandardized Boots secretin (batch no. 142) in increasing the flow rate of pancreatic juice, and four times more potent in increasing the amount of bicarbonate.
Leadership, Mental Health, and Organizational Efficacy in Health Care Organizations
Authors: Bengt Arnetz, Vanja Blomkvist
Journal: Psychotherapy and Psychosomatics (2007)

&lt;i&gt;Background:&lt;/i&gt; Only a few studies of psychosocial determinants of employee health and organizational development have been prospective, involving more than one organization and applying standardized assessment tools. This limits the ability of providing evidence-based guidance as how to carry out healthy organizational transformations. &lt;i&gt;Methods:&lt;/i&gt; A total of 6,000 employees responded twice to a validated psychosocial-leadership questionnaire within a 2-year period. The assessment focused on changes over time in the three outcome measures – mental health, efficacy, and leadership, determined to be important indicators of a healthy organization. Changes within and between organization were assessed statistically using regular t tests and general linear modeling. &lt;i&gt;Results:&lt;/i&gt; There were major differences between organizations in psychosocial measures, both at the baseline and over time. At the organizational level, changes between study periods in management performance feedback, participatory management, and work tempo were the most consistent predictors of improvements over time in the three outcome measures. &lt;i&gt;Conclusions:&lt;/i&gt; Performance feedback and participatory management might be two common predictors of healthy workplaces. Some of the psychosocial determinants of healthy organizations suggested in previous research might not be universally valid. It is suggested that future research should to a larger degree make use of multiple departments and organizations in studies of psychosocial determinants of healthy organizations.
The beneficial effect of amrinone on acute drug-induced heart failure in the anaesthetised dog
Authors: A. A ALOUSI, J. M CANTER, D. J FORT
Journal: Cardiovascular Research (1985)

Amrinone, a positive inotropic-vasodilator agent, was administered to anaesthetised dogs in an attempt to reverse heart failure induced by drugs possessing negative inotropic properties. Propranolol, a beta-adrenergic blocker; verapamil, a calcium slow-channel blocker procainamide, a type 1 antiarrhythmic agent; or sodium pentobarbital, a barbituate; administered as a bolus injection and/or infusion, produced a sustained depression in canine cardiac function. Cardiac depression was characterised by a greater than 40% reduction in cardiac contractile force (CF) and maximum left ventricular pressure development (LV dp/dtmax), a 30 to 50% reduction in cardiac output (CO) and concomitant increases in mean central venous or mean right atrial blood pressures (CVP, RAP, respectively). Amrinone, when administered intravenously as a bolus injection (1 or 3 mg X kg-1) plus an infusion (0.03 or 0.1 mg X kg-1 X min-1) reversed the depression in cardiac function by increasing CF, CO and LV dp/dtmax and decreasing preload CVP or RAP in all four drug-induced failure models. Due to the vasodilator properties of amrinone, afterload, total peripheral resistance (TPR), was reduced in verapamil and procainamide failures as well as in propranolol failure, the only model where TPR increases. In another model of heart failure, in which ouabain-induced arrhythmias preceded procainamide toxicity, amrinone was also an effective cardiotonic agent. Ouabain's inotropic effect was studied in propranolol-induced heart failure. Although an increase in LV dp/dtmax and a decrease in CVP were noted, ouabain (40 micrograms X kg-1 iv) increased TPR and had little effect on the depression in CF and CO. Drug-induced models of heart failure were useful pharmacological tools for evaluating the cardiotonic agent's ability to overcome severe cardiac depression. In propranolol-, verapamil-, procainamide-, and pentobarbital-induced cardiac toxicity, amrinone could be of therapeutic value.
KNOTTING OF DUODENAL TUBE DURING BILIARY DRAINAGE
Authors: Russell S. Boles
Journal: JAMA (1924)

Mrs. M. N., aged 48, complained for one year of attacks of pain in the upper right abdomen. The pain was very severe, of a colicky nature, and extended across the upper abdomen and to the back. It usually came on during the night and bore no relation to eating or posture. She felt distended after eating, and usually brought up considerable gas. She had always been constipated, but more so for the past six months, and suffered frequently with indigestion and "bilious spells." Following one severe attack of pain three months before I saw her, she stated that the stools were very light, but jaundice was not perceptible. The physical examination was negative, except for marked tenderness over the gallbladder. June 23, 1923, the gallbladder was drained according to the Meltzer-Lyons method. Within ten minutes after the injection of the magnesium sulphate, bile began to flow, and 6 ounces
Abstract 918: ASP3026, a selective ALK inhibitor, shows anti-tumor activity in a mouse model xenografted with NCI-H2228 intracranially.
Authors: Satoshi Konagai, Hiroshi Fushiki, Hideki Sakagami, Yoko Ueno, Masamichi Mori, Itsuro Shimada, Yutaka Kondoh, Sousuke Miyoshi, Shintaro Nishimura, Sadao Kuromitsu
Journal: Cancer Research (2013)

Abstract EML4-ALK translocation has been validated as a therapeutic target in a subset of non-small cell lung cancer (NSCLC) patients. Crizotinib, an FDA-approved ALK inhibitor, is effective against several types of human cancers with ALK abnormalities including EML4-ALK, RANBP2-ALK and ALK mutations. However, long-term treatment is often limited by the development of resistant tumors and distant metastases. Multiple brain metastases are a critical issue because of their poor prognosis despite the standard radiotherapy. The reason for metastases and development of tumor in the brain could be attributable to the poor penetration of crizotinib into central nervous system, as previously reported. ASP3026 is a selective ALK inhibitor which shows antitumor activities in several crizotinib-refractory models including gate keeper mutants. Here, we established an intracranial xenograft model by implanting NCI-H2228 cells directly in the brain of immunocompromised mice. Xenografted cells develop intracranial tumors which grow in murine brain and eventually become lethal, resembling the clinical tumors that metastasized in the brain. To determine the anti-tumor activity against tumors in the brain, mice were treated with ASP3026 or crizotinib for 2 weeks and held to observe survival duration. Ten, 30 and 100 mg/kg daily oral administration of ASP3026 dose dependently inhibited tumor growth in brain, and tumor regression was achieved in 30 and 100 mg/kg groups confirmed by MR imaging. These results were supported by the observation that Ktrans and IAUC (90s) were significantly decreased in 30 and 100 mg/kg groups using dynamic contrast enhanced MR imaging (DCE-MRI). Furthermore, ASP3026 significantly prolonged the survival of tumor bearing mice compared to vehicle treatment group. On the other hand, 30mg/kg daily oral administration of crizotinib inhibited the tumor growth during the treatment period but did not produce significant survival benefit. Taken together, these results indicate that ASP3026 shows better efficacy than crizotinib and improves overall survival in an intracranial mouse xenograft model, suggesting that ASP3026 may have potential to benefit EML4-ALK positive NSCLC patients with brain metastases. Citation Format: Satoshi Konagai, Hiroshi Fushiki, Hideki Sakagami, Yoko Ueno, Masamichi Mori, Itsuro Shimada, Yutaka Kondoh, Sousuke Miyoshi, Shintaro Nishimura, Sadao Kuromitsu. ASP3026, a selective ALK inhibitor, shows anti-tumor activity in a mouse model xenografted with NCI-H2228 intracranially. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 918. doi:10.1158/1538-7445.AM2013-918
Normalizing the prothrombin time
Authors: Olivier Chazouilléres, Annie Robert
Journal: Hepatology (2000)

To the Editor: I read with great interest and more than a little dismay the article by Myers, Gregor, and Marotta 1 on the cost-effectiveness of hepatitis A vaccination in patients with chronic hepatitis C. While I found the article to be very well written and thorough, I find the premise for the article to be totally unacceptable.Are we to withhold a simple vaccination from our patients, knowing that they run the risk of severe morbidity or death simply because it may not be "cost effective" in a population study?This article calls to mind a story that was recently played out in the courts in the United States.There was once a large automobile manufacturer that produced a vehicle it knew was unsafe.Not only did they know that it was unsafe, they also knew how to fix the problem to render the vehicle safe.However, rather than do the right thing and fix the vehicle (at a cost of $11 per vehicle), they embarked on a course similar to Myers et al.They first calculated the cost of correcting the defect and then compared it with the cost they may incur if the defect was not corrected.They used data from the federal government and that the National Highway Traffic Safety Administration made available to them.They calculated the average damage per person killed by their vehicle.They added medical costs, property damage, insurance administration, legal and court costs, employer losses, victim pain and suffering, and funeral bills as well as "other costs."When they found that this cost would be less than the cost of correcting the defect on the vehicle, they elected to take their chances in court.Their strategy ultimately landed them in court and resulted in one of the largest settlements in the American legal system.The ethics involved in their decision-making process was headline news throughout the nation.The parallels between this story and the conclusions drawn from this article I find to be quite remarkable.I can see myself in the future consoling Mrs. X upon the death of her husband from hepatitis A superimposed on hepatitis C, a disease that could have been prevented by a simple vaccination, by handing her the article and saying, "but as you can see here, clearly it would not have been cost effective for me to have given your husband a simple vaccine."I was surprised that this article did not provoke more editorial comments from the editors of HEPATOLOGY and I certainly hope that the ACIP does not reconsider its stance on vaccinating all patients with hepatitis C with the hepatitis A vaccine.
Disease-Specific Gene Expression Profiling in Multiple Models of Lung Disease
Authors: Christina C. Lewis, Jean Yee Hwa Yang, Xiaozhu Huang, Suman K. Banerjee, Michael R. Blackburn, Peter Baluk, Donald M. McDonald, Timothy S. Blackwell, Vijaya Nagabhushanam, Wendy Peters, David Voehringer, David J. Erle
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Microarray technology is widely employed for studying the molecular mechanisms underlying complex diseases. However, analyses of individual diseases or models of diseases frequently yield extensive lists of differentially expressed genes with uncertain relationships to disease pathogenesis.Objectives: To compare gene expression changes in a heterogeneous set of lung disease models in order to identify common gene expression changes seen in diverse forms of lung pathology, as well as relatively small subsets of genes likely to be involved in specific pathophysiological processes.Methods: We profiled lung gene expression in 12 mouse models of infection, allergy, and lung injury. A linear model was used to estimate transcript expression changes for each model, and hierarchical clustering was used to compare expression patterns between models. Selected expression changes were verified by quantitative polymerase chain reaction.Measurements and Main Results: A total of 24 transcripts, including many involved in inflammation and immune activation, were differentially expressed in a substantial majority (9 or more) of the models. Expression patterns distinguished three groups of models: (1) bacterial infection (n = 5), with changes in 89 transcripts, including many related to nuclear factor-κB signaling, cytokines, chemokines, and their receptors; (2) bleomycin-induced diseases (n = 2), with changes in 53 transcripts, including many related to matrix remodeling and Wnt signaling; and (3) T helper cell type 2 (allergic) inflammation (n = 5), with changes in 26 transcripts, including many encoding epithelial secreted molecules, ion channels, and transporters.Conclusions: This multimodel dataset highlights novel genes likely involved in various pathophysiological processes and will be a valuable resource for the investigation of molecular mechanisms underlying lung disease pathogenesis.