tbuckley/cabot-search huggingface dataset:
Abnormal Respiratory Control in Acquired Dysautonomia
Authors: John H. Eisele, Carroll E. Cross, David C. Rausch, Cornelis J. Kurpershoek, Robert F. Zelis
Journal: New England Journal of Medicine (1971)

Abstract In a patient with acquired dysautonomia respiratory as well as circulatory control mechanisms were abnormal. In response to breathing of 10 per cent oxygen in nitrogen there was no respiratory drive, and at the same time the arterial-blood pressure fell, indicating the absence or failure of peripheral chemoreceptor function. Abnormal blood-pressure responses to tilting and Valsalva maneuvers showed a lack of sympathetic vasoconstriction, whereas the pupillary and cardiac responses to methacholine and atropine indicated parasympathetic nervous-system impairment. The ventilatory response to carbon dioxide was weak — a fact that may or may not mean central chemoreceptor involvement. The normal rapid breathing response at the onset of exercise developed in spite of the lack of sympathetic nervous and peripheral chemoreceptor functions.
P5 Lipid-laden Macrophages In Bronchoalveolar Lavage Fluid Are Not Diagnostic Of Airway Reflux
Authors: Y. Hayman, L. Sadofsky, S. Faruqi, S. Hart, A. Morice
Journal: Thorax (2014)

<h3>Aims</h3> Demonstration of lipid-laden macrophages in respiratory secretions has been suggested to be a marker of reflux and aspiration. However studies looking at the diagnostic value of quantifying macrophage ingested lipids have been inconclusive. We wanted to look evaluate the utility of this technique in diagnosing airway reflux. <h3>Methods</h3> In this prospective study bronchoalveolar lavage samples were collected from patient’s undergoing flexible bronchoscopy for various indications (lung cancer, chronic cough, ILD etc). Cells collected were stained with Oil-Red-O. Lipid-laden macrophage index (LLMI) was used to quantify lipid accumulation. This is calculated by grading the amount of intracellular Oil-Red-O positive particles per 100 alveolar macrophages. A score of 0 (no opacification) to 4 (total opacification) is assigned to each macrophage. The sum of the scores yields the LLMI. Patients were asked to complete the Hull Airways Reflux Questionnaire (HARQ), a validated tool to diagnose airways reflux. One of the investigators, blind to the analysis, independently reviewed the clinical notes to establish a diagnosis of associated airway reflux. The investigator performing cell analysis was blind to the clinical details. The groups with and without a clinical diagnosis of airway reflux were compared. Correlations between the HARQ score and LLMI were sought. <h3>Results</h3> Twenty nine patients (19 females, mean age 64 years) were included in the study. Of these in 11 a clinical diagnosis of associated airway reflux was made. The mean [SD] LLMI in the group with airway reflux (95[105]) was not significantly different from those without airway reflux (90[75]). There was a weak correlation observed between the HARQ score and the LLMI (0.09) which was not statistically significant (p = 0.69). <h3>Conclusions</h3> We fail to demonstrate significant association between LLMI and either a clinical diagnosis of airway reflux or the HARQ score. This could be due to the fact that macrophages scavenge both exogenous and endogenous material. However our study is limited by small numbers and disparate underlying clinical diagnoses. The small correlation of LLMI with HARQ scores merits further evaluation. Whether the proportion of macrophages phagocytising lipids or the degree of lipid ingestion by the macrophages is more important needs further study.
Abstract 5023: Stem cell hypothesis and function of Lgr5 in the development of colon cancer.
Authors: Daniela D. Hirsch, Nick Barker, Nicole McNeil, Yue Hu, Jordi Camps, Katherine McKinnon, Hans Clevers, Thomas Ried, Timo Gaiser
Journal: Cancer Research (2013)

Abstract Similar to normal colonic epithelium, colorectal carcinomas (CRC) comprise subpopulations of cells with stem-like properties. Leucine-rich-repeat-containing G-protein-coupled receptor 5 (Lgr5) is associated with these stem cells in normal colonic epithelium and CRC. Here, we analyzed the functional and molecular consequences of shRNA-mediated silencing of Lgr5 in CRC cell lines SW480 and HT-29. Additionally, we exposed Lgr5-EGFP-IRES-Cre-ERT2 mice to azoxymethane/dextrane sodium sulfate (AOM/DSS) which induces inflammation-driven colon tumors. Tumors were then flow-sorted into Lgr5 high and low epithelial cell fractions and molecularly characterized using gene expression profiling and array comparative genomic hybridization. Silencing of Lgr5 in SW480 cells resulted in a depletion of the spheroid cell fraction, yet did not affect the adherently growing cell population. It also reduced proliferation, migration, and colony formation in vitro as well as tumorigenicity in vivo, consistent with a down-regulation of Notch signaling. Spheroid cells were enriched for several stem cell-associated genes including Lgr5. Lgr5 high cells of AOM/DSS-induced mouse colon tumors displayed higher Wnt signaling compared to both their Lgr5 low tumor cell counterparts as well as Lgr5 high normal colon stem cells. Lgr5 high and low tumor cells were both chromosomally stable. In conclusion, our data suggest Lgr5 as a functionally important marker for stem-like cells in CRC, representing a potential therapeutic target. Citation Format: Daniela D. Hirsch, Nick Barker, Nicole McNeil, Yue Hu, Jordi Camps, Katherine McKinnon, Hans Clevers, Thomas Ried, Timo Gaiser. Stem cell hypothesis and function of Lgr5 in the development of colon cancer. [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 5023. doi:10.1158/1538-7445.AM2013-5023
IM-15 * ANTI-TUMOR EFFICACY OF ADOPTIVE CELLULAR THERAPY IS SIGNIFICANTLY INCREASED BY HEMATOPOIETIC STEM CELLS
Authors: C. Flores, C. Pham, T. Wildes, R. Abraham, J. Drake, D. Mitchell
Journal: Neuro-Oncology (2015)

Immunotherapeutic approaches against solid tumors can be curative with a demonstrably high degree of specificity, and adoptive T cell therapies have proven to be efficacious platform against metastatic disease. Superior clinical outcomes in response to adoptive cellular therapies are correlated with anti-tumor function, intratumoral migration and persistence of adoptively transferred tumor-specific T cells at the tumor site. Adoptive cellular therapy after lymphodepletive conditioning can induce dramatic clinical responses, but this approach has been largely limited to melanoma due to a lack of reliable methods for expanding tumor-specific lymphocytes from the majority of other solid cancers. We have employed tumor RNA-pulsed dendritic cells to reliably expand CD4+ and CD8+ tumor-reactive T lymphocytes for curative adoptive cellular therapy in a highly-invasive, chemotherapy- and radiation-resistant malignant glioma model. We have identified the TCR Vb clone largely responsible for immunologic rejection of intracranial murine glioma. Curative treatment of established intracranial tumors involved a synergistic interaction between myeloablative conditioning, adoptively transferred tumor-specific T cells, and tumor RNA-pulsed dendritic cell (DC) vaccines. Hematopoietic stem cells (HSCs), administered for salvage from myeloablative conditioning, rapidly migrated to areas of intracranial tumor growth and facilitated the recruitment of tumor-specific lymphocytes through HSC-elaborated chemokines and enhanced immunologic rejection of intracranial tumors during adoptive cellular therapy. In addition, we found that HSCs mediate a significant expansion of tumor-specific T cells under both myeloablative and non-myeloablative host conditioning. The expansion of tumor-specific T cells expressing specific TCR Vβ clones in intracranial tumor bearing mice is associated with tumor rejection. Our data indicate novel roles for the use of HSCs in the immunologic treatment of malignant gliomas and possibly other solid tumors.
INCIDENCIA Y CARACTERÍSTICAS EPIDEMIOLÓGICAS DEL ESÓFAGO DE BARRETT EN CATALUÑA.
Authors: A Rodríguez-D'Jesús, J Gordillo, H Uchima, H Córdova, A Ginès, A Cárdenas, M Pellisé, O Sendino, B González, I Elizalde, E Saperas, J Llach, G Fernández-Esparrach
Journal: Endoscopy (2012)

Introducción: La incidencia del esófago de Barrett (EB) es del 0,45% al 2,2% en los pacientes que se realizan una endoscopia digestiva alta y superior al 12% si la indicación es por síntomas de reflujo. En los últimos años se ha descrito un aumento progresivo del diagnóstico de EB. Sin embargo, se desconoce cuál es la incidencia de esta entidad en la población de Cataluña. Objetivos: Determinar la incidencia del EB y sus características epidemiológicas en nuestro medio. Material y método: Se evaluaron de forma prospectiva todos los pacientes mayores de 18 años que acudieron a las Unidades de Endoscopia del Hospital Clínic y Hospital General de Catalunya para la realización de una endoscopia digestiva alta. Se excluyeron pacientes con EB conocido, endoscopia digestiva alta previa, cirugía esófago-gástrica o negativa de participar en el estudio. Se registraron datos demográficos, consumo de alcohol y tabaco, infección por Helicobacter Pylori (HP) y consumo de IBP, entre otros. Los participantes completaron un cuestionario estandarizado para valorar la presencia de síntomas de RGE y su severidad. Resultados: Entre julio 2010 y julio 2012 se incluyeron 200 pacientes (100 en cada centro). El 93% eran de nacionalidad española. La media de edad fue de 50±15 años y 60% fueron mujeres. 46 pacientes (23%) tenían síntomas de RGE y 31 (16%) presentaron algún grado de esofagitis. La infección por HP estaba presente en 29%. En 14 (7%) pacientes hubo sospecha endoscópica de EB, con confirmación histológica en 8 (4%). El género masculino se asoció a un mayor hallazgo de EB (6/80 vs. 2/120, p=0,04). La presencia de síntomas de reflujo no se asoció a un mayor diagnóstico de EB. Tampoco se encontró ninguna asociación con las otras variables clásicamente consideradas de riesgo (edad, IMC, consumo de tabaco y, ausencia de HP. Conclusión: La incidencia de EB en nuestro medio es similar a la descrita en los países occidentales y es más frecuente en varones. La ausencia de síntomas de reflujo, no descarta la posibilidad de EB.
Iliofemoropopliteal Arterial Reconstructions for Arteriosclerosis Obliterans
Authors: Richard Warren, J. Leonel Villavicencio
Journal: New England Journal of Medicine (1959)

IT is more than eleven years since dos Santos1 reported his pioneer attempts at the reconstruction of arterial channels that had been closed by arteriosclerosis obliterans. He used a method of curettement called thrombendarterectomy, which removed the diseased central layers of the arterial segment, consisting of thrombus, degenerated intima and the part of the media, often varying in width at different levels, involved in the pathologic process.Venous autografts and arterial homografts had been known for some time to function in laboratory animals2 3 4 5 6 and in reconstructions of traumatic lesions7 , 8 and of aneurysms9 in man. Isolated examples of late results were . . .
AB0013 The uncoupling TJ cluster is a protective factor against osteoarthritis in Spain and UK
Authors: A. Soto-Hermida, M. Fernandez-Moreno, N. Oreiro, C. Fernandez-Lopez, I. Rego-Perez, F.J. Blanco
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Oxidative stress and reactive oxygen species (ROS) production are key factors in the development of OA. Some reports have shown that those mtDNA haplogroups related with the mild uncoupling of the mitochondrial oxidative phosphorylation system (OXPHOS) are less prone to produce ROS. <h3>Objectives</h3> Taking into account that the mtDNA haplogroup J is a protective factor against OA in Spanish populations, the aim of this work is to compare the frequency distribution of the mtDNA haplogroups in OA patients and healthy controls between United Kingdom (UK) and Spain. <h3>Methods</h3> We used the single base extension (SBE) assay combined with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to obtain the European mtDNA haplogroups in 1471 OA patients and 406 healthy controls from Spain, and 453 OA patients and 280 healthy controls from UK. Some of the differential single nucleotide polymorphisms (SNPs) haplogroup J-related between both populations were also analyzed using the SBE assay. The resulting frequencies were analyzed with SPSS software (v.18) following appropriate statistical analyses. <h3>Results</h3> The mtDNA haplogroup J appeared significantly underrepresented in OA patients from the north of Spain when compared with healthy controls (OR=0.614; 95% CI: 0.426–0.884; p=0.008). Individuals from UK carrying the mtDNA haplogroup T showed a significantly decreased risk of OA (OR=0.581; 95% CI: 0.365–0.926; p=0.021). The mtDNA haplogroup J bordered the statistical significance towards a decreased presence in healthy controls from UK (OR=1.686; 95% CI: 0.929–3.061; p=0.083). The analysis of the differentially expressed haplogroup J-related SNPs in Spain and UK, m.14798t&gt;c, m.15257g&gt;a and m.3394t&gt;c, showed that the SNP m.3394t&gt;c appeared significantly underrepresented in the UK cohort (p=0.029). <h3>Conclusions</h3> The mitochondrial uncoupling mechanism, derived from the mtDNA haplogroups, is a protective factor against OA in Spain and UK populations. This association is probably due to a reduced reactive oxygen species production as a consequence of the climate adaptation of these mtDNA haplogroups. <h3>Disclosure of Interest</h3> None Declared
Complement Activation during Cardiopulmonary Bypass
Authors: Dennis E. Chenoweth, Steven W. Cooper, Tony E. Hugli, Robert W. Stewart, Eugene H. Blackstone, John W. Kirklin
Journal: New England Journal of Medicine (1981)

We observed complement activation in 15 adults undergoing total cardiopulmonary bypass. Plasma levels of C3a were significantly elevated (P < 0.0001) at the beginning of the procedure, and they continued to increase steadily thereafter. At the end of the procedure, C3a levels were more than five times higher than preoperative levels. Plasma levels of C5a (a factor that binds avidly to neutrophils) did not change significantly during cardiopulmonary bypass. Instead, there was significant neutrophilia (P = 0.03) during bypass, and significant transpulmonary neutropenia (P = 0.0002) occurred when cardiopulmonary circulation was reestablished at partial bypass. The neutropenia is consistent with pulmonary-vascular sequestration of C5a-activated granulocytes. We also found that incubation of blood with the nylon-mesh liner of bubble oxygenators, as well as vigorous oxygenation of whole blood, promotes conversion of complement. We conclude that the complement-derived inflammatory mediators C3a and C5a produced during extracorporeal circulation may contribute to the pathogenesis of "post-pump syndromes."
Abstract 2464: Targeting liver cancer stem cells for molecular imaging and therapeutic application
Authors: Lina Wang, Ze Liu, Dan Lu, Si Chen, Na Li, Rong Xiang, Zongjin Li
Journal: Cancer Research (2011)

Abstract Conventional therapies target rapidly proliferating non-tumorigenic cells and spare the relatively quiescent cancer stem cells (CSCs) and the CSCs will remain viable after therapy and re-establish the tumor. Thus developing therapeutic strategies to target CSCs to prevent tumor recurrence will be vital for cancer therapy. To date, it has been shown that CSCs in hepatocellular carcinoma (HCC) can be identified by several cell surface antigens CD133, CD90, CD44, OV6 and the epithelial cell adhesion molecule (EpCAM). Here, we developed a novel strategy which targeted CSCs by anti-CD44 antibody mediated nanoparticles delivery system loaded with a triple fusion gene containing the suicide gene-herpes simplex virus truncated thymidine kinase (TTK), renilla luciferase (RL) and RFP (TF, RL-RFP-TTK). The in situ liver cancer model was established by injection of 1.0×105 HepG2 cells, which carry a reporter system encoding the genes of firefly luciferase (FL) and GFP into the liver of NOD/SCID mice. The mice were subsequently treated with ganciclovir (GCV). Then the growth status of tumor was monitored by the optical bioluminescence imaging of firefly luciferase(FL) and the specific targeting of the nanoparticles was tracked by imaging of renilla luciferase(RL). Our results demonstrated that the anti-CD44 antibody mediated nanoparticles loaded with TTK could specifically target the CSCs of HCC, and thereafter were endocytosed by the plasma membrane to transport the triple fusion (TF, RL-RFP-TTK) into the cells, resulted in the apoptosis of the targeted cells. Taken together, our study demonstrated a novel therapeutic strategy by targeted CSCs, we also developed a useful multimodality imaging techniques to monitor HepG2 cells’ fate in vivo and assessed the targeting efficacy of the nanoparticles. This may open a new application for the treatment of the HCC by targeting CSCs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2464. doi:10.1158/1538-7445.AM2011-2464
Industry Asked To Help Develop Better Diagnostic Techniques
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Industry Asked To Help Develop Better Diagnostic Techniques Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 24, 20 December 1989, Pages 1866–1867, https://doi.org/10.1093/jnci/81.24.1866-a Published: 20 December 1989
Abstract ADV19: A mayo clinic cancer center spore-wide approach to advocacy.
Authors: Mark Rieder
Journal: Cancer Research (2013)

Abstract The Mayo Clinica Inter-SPORE Advocates Group is to help all of the patient advocates at mayo become more educated and qualified. Our mission statement is: Support and improve each disease-specific SPORE advocace group through sharing ideas, information and experiences. The goals of the Mayo Clinic Inter-SPORE Advocates Group are: - promote a collaborative relationship among the disease specific SPORE advocate groups in support of SPORE research, education and activities - explore opportunities for collaboration on activities - support a collaborative relationship across the SPOREs to further the translational research goals of each SPORE - promote communications, education, and awareness among researchers, advcoates and patients - participate in development of research proposals and informed consent for SPORE projects and clinical studies The Mayo Clinic Inter-SPORE Advocates Group meets quarterly to share ideas information and experiences in its pursuit of a collaboratie relationship among the disease-specific SPORE advocate groups. Conference call-in is provided for those who cannot attend in person. The Group will continually assiss its efforts and look for opportunities to add value to the SPORE advocate groups. Citation Format: Mark Rieder. A mayo clinic cancer center spore-wide approach to advocacy. [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 ADV19. doi:10.1158/1538-7445.AM2013-ADV19
Social Medicine: Its Derivations and Objectives
Journal: JAMA (1949)

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Abstract SY40-01: Anti-CD40 as an anticancer agent
Authors: Robert H. Vonderheide
Journal: Cancer Research (2012)

Abstract Pancreatic ductal adenocarcinoma (PDA) is an almost uniformly lethal disease for which novel effective therapies are critically needed. Although immunotherapy offers a distinct and promising therapeutic approach, the ability of pancreas carcinoma to orchestrate immune suppression represents a significant clinical obstacle. Previous studies to model pancreatic tumor immune responses in mice have been limited by the use of implantable tumor models or non-PDA tumors of islet cells. To circumvent these obstacles, we have evaluated immune surveillance in PDA using a genetically engineered mouse (GEM) model of this disease in which endogenous expression of KrasG12D and Trp53R172H is targeted to the pancreas of immune competent mice and for which the salient clinical, histopathologic, and molecular features of the human disease are strikingly recapitulated. In this ‘KPC’ model, progression to PDA is intimately associated with a suppressive immune reaction, particularly in the myeloid compartment, such that adaptive anti-tumor immunity is essentially non-existent. Because CD40 activation can reverse immune suppression and drive potent anti-tumor T cell responses, we tested the combination of an agonist CD40 antibody with gemcitabine chemotherapy in the KPC model. We observed tumor regression in 30% of mice and found further that tumor regression required macrophages but not T cells or gemcitabine. CD40-activated macrophages rapidly infiltrated tumors, became tumoricidal, and facilitated the depletion of tumor stroma. T cells, as expected, were activated following CD40 therapy but never infiltrate the tumor. Based on these preclinical findings, we performed a clinical study to test the hypothesis that CD40 activation in humans can cooperate with chemotherapy for the treatment of chemotherapy-naïve, surgically incurable PDA. Twenty-one patients (90% with metastatic disease) received gemcitabine weekly on days 1, 8, and 15 with the agonist CD40 mAb CP-870,893 (Pfizer) administered on day 3 of each 28 day cycle. Treatment was well-tolerated overall, and the most common side effect was mild-to-moderate cytokine release syndrome managed in the outpatient clinic. Metabolic responses were observed by FDG-PET/CT in both the primary and metastatic lesions in 88% of patients evaluated after 2 cycles of therapy. By RECIST, 5 of 21 patients developed a partial response. Thus, productive cancer immune surveillance does not necessarily depend on T cells; rather, our findings demonstrate a CD40-dependent mechanism for targeting cancer-associated inflammation in the treatment of cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY40-01. doi:1538-7445.AM2012-SY40-01