tbuckley/cabot-search huggingface dataset:
Nitric Oxide Sensitizes Tumor Cells to Dendritic Cell–Mediated Apoptosis, Uptake, and Cross-Presentation
Authors: Jian Huang, Tomohide Tatsumi, Eva Pizzoferrato, Nikola Vujanovic, Walter J. Storkus
Journal: Cancer Research (2005)

Abstract Dendritic cells are professional antigen-presenting cells associated with efficient antigen processing and presentation to T cells. However, recent evidence also suggests that dendritic cells may mediate direct tumoricidal functions. In this study, we investigated the mechanism by which murine dendritic cells mediate the apoptotic death of murine lymphoma cell lines, and whether dendritic cell effector function could be enhanced by preconditioning tumor cells with the protein phosphatase inhibitor nitric oxide (NO) by altering the balance of proapoptotic/antiapoptotic proteins in the treated cells. We observed that NO donor compound sensitized lymphomas to dendritic cell–mediated cytotoxicity in vitro. Both immature and spontaneously matured bone marrow–derived dendritic cells (SM-DC) were capable of inducing tumor cell apoptosis, with SM-DCs serving as comparatively better killers. Fas ligand (FasL)-Fas engagement proved important in this activity because elevated expression of membrane-bound FasL was detected on SM-DCs, and dendritic cells derived from FasL-deficient mice were less capable of killing NO-sensitized tumor cells than wild-type dendritic cells. As FasL-deficient dendritic cells were still capable of mediating a residual degree of tumor killing, this suggests that FasL-independent mechanisms of apoptosis are also involved in dendritic cell–mediated tumor killing. Because NO-treated tumor cells displayed a preferential loss of survivin protein expression via a proteasome-dependent pathway, enhanced tumor sensitivity to dendritic cell–mediated killing may be associated with the accelerated turnover of this critical antiapoptotic gene product. Importantly, NO-treated tumor cells were also engulfed more readily than control tumor cells and this resulted in enhanced cross-presentation of tumor-associated antigens to specific T cells in vitro.
Close relation of endothelial function in the human coronary and peripheral circulations
Authors: Todd J. Anderson, Akimi Uehata, Marie D. Gerhard, Ian T. Meredith, Sarah Knab, Danielle Delagrange, Eric H. Lieberman, Peter Ganz, Mark A. Creager, Alan C. Yeung, Andrew P. Selwyn
Journal: Journal of the American College of Cardiology (1995)
Endoscopic submucosal tunnel dissection for large esophageal neoplastic lesions
Authors: E. Linghu, X. Feng, X. Wang, J. Meng, H. Du, H. Wang
Journal: Endoscopy (2012)

Endoscopic submucosal dissection (ESD) has been widely used for resection of esophageal neoplastic lesions, but there are still technical challenges in treating large ones. Based on the development of tunneling technique, we report the first series in which the new technique of endoscopic submucosal tunnel dissection (ESTD) was used to remove large lesions in the esophagus. ESTD was attempted in five consecutive patients with esophageal lesions for which resection was indicated. In the operation, once the margin of the lesions had been marked, a submucosal tunnel was created by submucosal dissection from the oral incision to the anal incision. Bilateral resection was then performed to remove the lesion completely. The average length of the five lesions was 5.7 cm, and their extent as a proportion of the whole circumference of the lumen ranged from one third to four fifths. Operative time ranged from 50 minutes to 120 minutes (mean, 77 minutes). En bloc resection with negative lateral and basal margins was achieved in all lesions without complications.
The artistic design stance and the interpretation of Paleolithic art
Authors: Johan De Smedt, Helen De Cruz
Journal: Behavioral and Brain Sciences (2013)

Abstract The artistic design stance is an important part of art appreciation, but it remains unclear how it can be applied to artworks for which art historical context is no longer available, such as Ice Age art. We propose that some of the designer's intentions can be gathered noninferentially through direct experience with prehistoric artworks.
Effect of Glipizide Treatment on Response to an Infused Glucose Load in Patients With NIDDM
Authors: Wayne H H Sheu, Chii-Yuan Jeng, Martin M T Fuh, Y D Ida Chen, Gerald M Reaven
Journal: Diabetes Care (1995)

OBJECTIVE This study was initiated to compare the effect of sulfonylurea treatment on the response to an infused glucose load of patients with non-insulin-dependent diabetes mellitus (NIDDM) at a basal insulin concentration and in response to physiological hyperinsulinemia. RESEARCH DESIGN AND METHODS We used the insulin suppression test, in which subjects were infused for 180 min with somatostatin, exogenous insulin, and glucose. Since similar steady-state plasma insulin (SSPI) concentrations are reached in all subjects, the resultant steady-state plasma glucose (SSPG) concentration permits comparison of the ability of a given individual to maintain glucose homeostasis in response to the infused glucose load. RESULTS We studied 15 nonobese patients at two different SSPI concentrations, before and after glipizide treatment, at basal (68 ± 4 pmol/l) and high (470 ± 31 pmol/l) levels. Values for SSPG concentrations were lower after treatment at both the basal (15.3 ± 0.5 vs. 18.5 ± 0.6 mmol/l; P &amp;lt; 0.001) and the high (10.6 ± 0.7 vs. 14.2 ± 0.7 mmol/l; P &amp;lt; 0.001) SSPI concentrations. To compare the responses of each patient before and after treatment, we calculated the fractional glucose metabolic rate, i.e., (glucose infusion rate — urinary glucose loss) ÷ by SSPG. To provide an alternative method of comparing the effect of sulfonylurea treatment, we divided the incremental increase in fractional metabolic glucose rate between the studies done at the low and high SSPI by the incremental increase in SSPI between the two studies (insulin sensitivity index [S1]). CONCLUSIONS The results of these calculations indicated that glipizide treatment was associated with a significant increase in fractional glucose metabolic rate at a basal insulin concentration (29 ± 3 to 42 ± 2 ml · m−2 · min−1, P &amp;lt; 0.001), and in response to the incremental change in SSPI (14 ± 4 to 23 ± 3 ml · m−2 · min−1, P &amp;lt; 0.02). Finally, S1 also increased in association with sulfonylurea (0.24 ± 0.06 to 0.43 ± 0.07 ml · m−2 · min−1/μU · ml−1, P &amp;lt; 0.001).
Profiling of the Tox21 Chemical Collection for Mitochondrial Function to Identify Compounds that Acutely Decrease Mitochondrial Membrane Potential
Authors: Matias S. Attene-Ramos, Ruili Huang, Sam Michael, Kristine L. Witt, Ann Richard, Raymond R. Tice, Anton Simeonov, Christopher P. Austin, Menghang Xia
Journal: Environmental Health Perspectives (2014)

Mitochondrial dysfunction has been implicated in the pathogenesis of a variety of disorders including cancer, diabetes, and neurodegenerative and cardiovascular diseases. Understanding whether different environmental chemicals and druglike molecules impact mitochondrial function represents an initial step in predicting exposure-related toxicity and defining a possible role for such compounds in the onset of various diseases.We sought to identify individual chemicals and general structural features associated with changes in mitochondrial membrane potential (MMP).We used a multiplexed [two end points in one screen; MMP and adenosine triphosphate (ATP) content] quantitative high throughput screening (qHTS) approach combined with informatics tools to screen the Tox21 library of 10,000 compounds (~ 8,300 unique chemicals) at 15 concentrations each in triplicate to identify chemicals and structural features that are associated with changes in MMP in HepG2 cells.Approximately 11% of the compounds (913 unique compounds) decreased MMP after 1 hr of treatment without affecting cell viability (ATP content). In addition, 309 compounds decreased MMP over a concentration range that also produced measurable cytotoxicity [half maximal inhibitory concentration (IC50) in MMP assay/IC50 in viability assay ≤ 3; p < 0.05]. More than 11% of the structural clusters that constitute the Tox21 library (76 of 651 clusters) were significantly enriched for compounds that decreased the MMP.Our multiplexed qHTS approach allowed us to generate a robust and reliable data set to evaluate the ability of thousands of drugs and environmental compounds to decrease MMP. The use of structure-based clustering analysis allowed us to identify molecular features that are likely responsible for the observed activity.
Upper gastrointestinal EMR service: long-term feasibility, safety, efficacy and cost effectiveness from a large UK centre
Authors: P. J. Basford, R. J. Mead, M. D. Duku, G. R. Longcroft-Wheaton, S. Somers, S. Toh, S. Mercer, D. Poller, D. Cowlishaw, P. Bhandari
Journal: Gut (2011)

<h3>Introduction</h3> Endoscopic resection (ER) is an accepted treatment of early upper gastrointestinal neoplasia in Europe, but surgery remains the gold standard in the UK due to lack of data. We started an upper gastrointestinal ER service in 2005 and are reporting our 6 year outcome data. We serve six different regional cancer centres. <h3>Methods</h3> We analysed our database of all upper gastrointestinal (UGI) endoscopic resection procedures performed at our centre for the period 2005–2010. All procedures were carried out by a single skilled endoscopist. Demographic data, histology, procedure success, long-term outcome and complications were assessed. <h3>Results</h3> We have performed 160 UGI ER procedures (108 oesophageal (O), 29 gastric (G), 33 duodenal/ampullary (D)) in 127 patients (O=75, G=25, D=27). Mean age was 65.9 years (range 25–94). A mean of 1.32 UGI ER procedures were performed per patient (range 1–5). All neoplastic cases were diagnosed as high grade dysplasia or intramucosal cancer prior to EMR. Overall complication rate was 5.0%. Specific complications were four procedural bleeds and two delayed bleeds (all controlled endoscopically) one full thickness perforation clipped endoscopically and one episode of pancreatitis. There were no cases of procedure related mortality. 25 patients (19.7%) were upstaged, having been found to have sm1 invasion or deeper on histological examination of the initial ER specimen. This group were considered for radical treatment if fit, or conservative management if unfit or through patient choice. 16 patients (O=11, G=4, D=1) proceeded to radical surgery, of which 2 patients died of postoperative complications and 2 patients died of local recurrence; the other 12 remain well. 2 patients received chemo/radiotherapy; 1 died of advanced oesophageal cancer, the other remains well. Of the remaining 102 patients complete local remission was achieved in 79.4% of cases following a single ER procedure, and in 97.1% overall. After a mean 2.57 years follow-up; 4% of all patients are known to have recurrence or metachronous disease and are awaiting further ER. Development of our service has potentially led to a cost saving of £91 270 per year, plus 170 bed days saved per year through reduced requirement for radical surgery. <h3>Conclusion</h3> Our data demonstrates the long-term feasibility, efficacy and safety of an innovative ER service. It provides valuable information about the number and type of patients requiring this service helping inform future planning and commissioning. Our data demonstrates significant cost savings for the NHS.
Comparative studies provide evidence for neural reuse
Authors: Paul S. Katz
Journal: Behavioral and Brain Sciences (2010)

Abstract Comparative studies demonstrate that homologous neural structures differ in function and that neural mechanisms underlying behavior evolved independently. A neural structure does not serve a particular function so much as it executes an algorithm on its inputs though its dynamics. Neural dynamics are altered by a neuromodulation, and species-differences in neuromodulation can account for behavioral differences.
Preserve Your Love for Science: Life of William A. Hammond, American Neurologist
Authors: Frank R. Freemon
Journal: JAMA (1992)

"Preserve your love of science," William Hammond advised medical students. This was the maxim that sustained him as his career oscillated from the heights of success to the depths of despair. During the 1850s, Hammond served as a US Army physician beyond the frontier. He used his free time at lonely Western army posts to perform original scientific research, using himself as his sole experimental subject. By measuring chemicals such as urea in his urine, he tried to show metabolic changes produced by prolonged heavy physical exercise and, most interestingly, by prolonged mental exertion. He resigned from the army to begin an academic career with the University of Maryland, but the Civil War began. He returned as a very junior officer, but was soon promoted, over the heads of many other medical officers, to become Surgeon General of the Union Army. His vigorous leadership helped maintain the health of the
Rice burning and asthma hospitalizations, Butte County, California, 1983-1992.
Authors: J Jacobs, R Kreutzer, D Smith
Journal: Environmental Health Perspectives (1997)

We investigated the association between rice burning and daily asthma hospitalizations in Butte County, California, from 1983 to 1992. Eighty-two percent of planted rice was burned, with a mean of 555 acres burned on days when burning was permitted. For 60% of the days during this period, no rice burning occurred. Peak burning occurred in fall and spring but was not correlated with criteria pollutants. Asthma admissions averaged 0.65/day and peaked in March. In the basic Poisson model with daily asthma hospitalizations as the outcome of interest, burn acreage showed a small but statistically significant elevation of risk for hospitalization per acre of rice burned [relative risk (RR) = 1.0001; 95% confidence interval (CI), 1. 00004-1.0002], after adjusting for maximum daily temperature, seasonal factors, and yearly population. In this model, burn acreage showed a dose-response effect as acreage burned increased. Days with the greatest acreage burned (>499 acres) had the largest risk of hospitalization (RR = 1.23; CI, 1.09-1.39), and days with moderate burning (between 100 and 499 acres) had a slightly lower risk of admission (RR = 1.2; CI, 1.05-1.37). Elevations of air pollutants were not associated with days of increased rice burning; however, rice burn acreage was shown to have a small but statistically significant effect on asthma morbidity in Butte County. This evidence suggests that further limitations on the daily amount of rice straw permitted to be burned should be considered to reduce pulmonary morbidity related to asthma.
Lipoprotein Lipase Gene Polymorphisms and the Risk of Target Vessel Revascularization After Percutaneous Coronary Intervention
Authors: Pascalle S. Monraats, Jamal S. Rana, Melchior C. Nierman, Nuno M.M. Pires, Aeilko H. Zwinderman, John J.P. Kastelein, Jan Albert Kuivenhoven, Moniek P.M. de Maat, Saskia Z.H. Rittersma, Abbey Schepers, Pieter A.F. Doevendans, Robbert J. de Winter, René A. Tio, Rune R. Frants, Paul H.A. Quax, Arnoud van Der Laarse, Ernst E. van Der Wall, J. Wouter Jukema
Journal: Journal of the American College of Cardiology (2005)
Abstract B3: HSP27 is required for invasion and metastasis triggered by hepatocyte growth factor
Authors: Simona Pavan, Daniele Musiani, Erica Torchiaro, Giorgia Migliardi, Jessica Erriquez, Martina Olivero, Maria Flavia Di Renzo
Journal: Clinical Cancer Research (2013)

Abstract The Hepatocyte Growth Factor (HGF) also known as Scatter Factor, activates cancer cell invasion and metastasis. We show that in ovarian cancer cells HGF induced the phosphorylation of the small heat shock protein of 27KDa (HSP27) by activating the p38MAPK. HSP27 is increased in many cancers at advanced stage including ovarian cancer and associated with cancer resistance to therapy and poor patients' survival. The phosphorylation of HSP27 regulates both its chaperone activity and its control of cytoskeletal stability. We show that HSP27 was necessary for the motility in vitro and the remodeling of actin filaments induced by HGF. In vivo, HSP27 silencing impaired the ability of the highly metastatic, HGF-secreting ovarian cancer cells to give rise to spontaneous metastases. This was due to defective motility across the vessel wall and reduced growth. Indeed, HSP27 silencing impaired both the ability of ovarian cancer cells to form experimental haematogenous metastases and to grow as subcutaneous xenografts. Moreover, HSP27 suppression resulted in the sensitization of xenografts to low doses of the chemotherapeutic Paclitaxel, likely because HSP27 protected microtubules from bundling caused by the drug. Altogether, these data show that the HSP27 is required for the pro-invasive and pro-metastatic activity of HGF and suggest that HSP27 might be not only a marker of progression of ovarian cancer, but also a suitable target for therapy. Grant sponsors: This work has been supported by grants to M.F.D.: 2012 IG grant and 2010 Special Program Molecular Clinical Oncology 5xMille of the Italian Association of Cancer Research (AIRC), Project n° 9970, and Grant of the CARIPLO Foundation. Citation Format: Simona Pavan, Daniele Musiani, Erica Torchiaro, Giorgia Migliardi, Jessica Erriquez, Martina Olivero, Maria Flavia Di Renzo. HSP27 is required for invasion and metastasis triggered by hepatocyte growth factor. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B3.
Azathioprine for pemphigus and pemphigoid—a 4 year follow-up
Authors: J.L. BURTON, M.W. GREAVES
Journal: British Journal of Dermatology (1974)

Journal Article Azathioprine for pemphigus and pemphigoid—a 4 year follow‐up Get access J.L. BURTON, J.L. BURTON Wellcome Laboratories for Research in Skin Disease, University Department of Dermatology, Newcastle‐upon‐Tyne Search for other works by this author on: Oxford Academic Google Scholar M.W. GREAVES M.W. GREAVES Wellcome Laboratories for Research in Skin Disease, University Department of Dermatology, Newcastle‐upon‐Tyne Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 91, Issue 1, 1 July 1974, Pages 103–109, https://doi.org/10.1111/j.1365-2133.1974.tb06725.x Published: 01 July 1974 Article history Accepted: 01 October 1973 Published: 01 July 1974
Tumor Suppressor 101F6 and Ascorbate Synergistically and Selectively Inhibit Non–Small Cell Lung Cancer Growth by Caspase-Independent Apoptosis and Autophagy
Authors: Shoichiro Ohtani, Arifumi Iwamaru, Wuguo Deng, Kentaro Ueda, Guanglin Wu, Gitanjali Jayachandran, Seiji Kondo, Edward N. Atkinson, John D. Minna, Jack A. Roth, Lin Ji
Journal: Cancer Research (2007)

Abstract 101F6 is a candidate tumor suppressor gene harbored on chromosome 3p21.3, a region with frequent and early allele loss and genetic alterations in many human cancers. We previously showed that enforced expression of wild-type 101F6 by adenoviral vector–mediated gene transfer significantly inhibited tumor cell growth in 3p21.3-deficient non–small cell lung cancer (NSCLC) cells in vitro and in vivo. The molecular mechanism of 101F6-mediated tumor suppression is largely unknown. A computer-aided structural and functional model predicts the 101F6 protein to be a member of the cytochrome b561 protein family that is involved in the regeneration of the antioxidant ascorbate. 101F6 protein is expressed in normal lung bronchial epithelial cells and fibroblasts but is lost in most lung cancers. Treatment with 101F6 nanoparticle–mediated gene transfer in combination with a subpharmacologic dose (200–500 μmol/L) of ascorbate synergistically and selectively inhibited lung cancer cell growth in vitro. Systemic injection of 101F6 nanoparticles plus the i.p. injection of ascorbate synergistically inhibited both tumor formation and growth in human NSCLC H322 orthotopic lung cancer mouse models (P &amp;lt; 0.001). Furthermore, exogenous expression of 101F6 enhanced intracellular uptake of ascorbate, leading to an accumulation of cytotoxic H2O2 and a synergistic killing of tumor cells through caspase-independent apoptotic and autophagic pathways. The antitumor synergism showed by the combination treatment with systemic administration of 101F6 nanoparticles and ascorbate on lung cancer offers an attractive therapeutic strategy for future clinical trials in cancer prevention and treatment. [Cancer Res 2007;67(13):6293–303]
Case of Metastatic Abscesses of the Liver
Authors: G. H. Philipson
Journal: BMJ (1867)

Several important events occur at the maternal–fetal interface, including generation of maternal–fetal tolerance, remodeling of the uterine smooth muscle and its spiral arteries and glands, and placental construction. Fetal-derived extravillous trophoblasts come in direct contact with maternal decidual leukocytes. Macrophages represent ∼20% of the leukocytes at this interface. In this study, two distinct subsets of CD14<sup>+</sup> decidual macrophages (dMɸs) are found to be present in first-trimester decidual tissue, CD11c<sup>HI</sup> and CD11c<sup>LO</sup>. Gene expression analysis by RNA microarray revealed that 379 probes were differentially expressed between these two populations. Analysis of the two subsets revealed several clusters of coregulated genes that suggest distinct functions for these subsets in tissue remodeling, growth, and development. CD11c<sup>HI</sup> dMɸs express genes associated with lipid metabolism and inflammation, whereas CD11c<sup>LO</sup> dMɸs express genes associated with extracellular matrix formation, muscle regulation, and tissue growth. The CD11c<sup>HI</sup> dMɸs also differ from CD11c<sup>LO</sup> dMɸs in their ability to process protein Ag and are likely to be the major APCs in the decidua. Moreover, these populations each secrete both proinflammatory and anti-inflammatory cytokines that may contribute to the balance that establishes fetal–maternal tolerance. Thus, they do not fit the conventional M1/M2 categorization.
Assessing hospital technology in The Netherlands.
Authors: E Borst-Eilers
Journal: BMJ (1993)

Outpatient hysteroscopies and endometrial biopsies are probably not performed more widely in Britain because of the lack of managerial support in providing the facilities to establish clinics specifically for these procedures.Finding the time to perform biopsy and hysteroscopy in a busy gynaecological clinic, with 15 or 20 new referrals, is difficult.Considerable financial savings may result, however, from treating women in outpatient clinics.The continuing widespread use of an operation that is diagnostically inaccurate and therapeutically useless is hard to justify.