tbuckley/cabot-search huggingface dataset:
SP0013 Biomineralization: the Mechanism of Crystal Formation in Bone and Other Mineralized Tissues. Considerations on the Relevance to Gout
Authors: L. Addadi
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Crystals of minerals and organic materials are deposited physiologically by the large majority of organisms. The deposition of carbonated apatite crystals in bone and teeth is probably the best known and the most relevant biological crystallization process in humans, but is by far not the most significant in biomineralization. Suffice it to mention the guanine and uric acid crystals responsible for the silvery shine in fish scales and scarab cuticle, which are undoubtedly relevant to gout. Physiological crystallization processes, in contrast to pathological crystallizations, have the advantage of being reproducible and highly controlled. They may be potentially followed in vivo during their onset and evolution. In contrast, the hallmark of pathological crystallization phenomena is that they are not controlled and not reproducible, and they are thus extremely difficult to follow in vivo. This lecture will concern the knowledge that has been acquired from the study of biological crystal formation and growth in organisms and its possible relations to pathological crystallizations, in particular in gout. <h3>Leading reference</h3> Steve Weiner and Lia Addadi, Crystallization Pathways in Biomineralization. Annu. Rev. Mater. Res. 41:21-40 (2011). <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6124
Abstract 1518: P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) limit sunitinib brain accumulation which can be enhanced by oral elacridar treatment
Authors: Seng Chuan Tang, Jurjen S. Lagas, Nienke Lankheet, Hilde Rosing, Jos H. Beijnen, Alfred H. Schinkel
Journal: Cancer Research (2010)

Abstract Sunitinib malate is an orally active, multi-targeted receptor tyrosine kinase inhibitor, which has been used as a standard treatment for metastatic renal cell carcinoma. However, the efficacy of sunitinib in patients with brain metastases has not been extensively explored. The purpose of this study was to investigate the individual and combined roles of ABCB1 and ABCG2 in sunitinib brain accumulation. Active transport of sunitinib was assessed in Madin-Darby canine kidney cells and its subclones expressing human ABCB1 and murine ABCG2. Sunitinib was found to be a good substrate of murine ABCG2 and moderate substrate of human ABCB1. In cells transfected with murine ABCG2 and human ABCB1, transport of sunitinib was markedly increased, resulting in 14.4-fold and 2.4-fold higher transport ratios compared to parental cells, respectively. To establish the roles of ABCB1 and ABCG2 in the pharmacokinetics and brain accumulation of sunitinib, sunitinib malate (10 mg/kg) was administered orally to wild-type, Abcb1a/1b−/−, Abcg2−/− and Abcb1a/1b;Abcg2−/− mice. Bioavailability of sunitinib after oral administration was not restricted by ABCB1 and/or ABCG2. Furthermore, sunitinib brain accumulation, 1 hour after sunitinib administration was not affected by single ABCB1 or ABCG2 deficiency. However, the brain penetration of orally administered sunitinib was 9.8-fold increased in Abcb1a/1b;Abcg2−/− mice compared to wild-type mice. In addition, brain-to-plasma ratios were significantly increased in Abcb1a/1b−/− knockout mice (2.6-fold) and Abcb1a/1b;Abcg2−/− mice (18.2-fold), but not altered in single Abcg2−/− knockout mice. To test the hypothesis that the dual ABCB1 and ABCG2 inhibitor elacridar could enhance brain penetration of sunitinib, we orally coadministered elacridar (100 mg/kg) and sunitinib malate (10 mg/kg) to wild-type and Abcb1a/1b;Abcg2−/− mice. Sunitinib brain concentration and brain-to-plasma ratio in wild-type mice were significantly increased by 12-fold and 12.7-fold, respectively, compared to wild-type mice without elacridar treatment, and these values were very similar to those observed for Abcb1a/1b;Abcg2−/− mice. In conclusion, sunitinib is transported in vitro and in vivo by ABCB1 and ABCG2, with ABCB1 being the more important factor in limiting sunitinib distribution into the brain in mice. Our results suggest that coadministration of oral elacridar with sunitinib might improve therapeutic efficacy in cancer patients with brain metastases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1518.
Progress in the Treatment of Subacute Bacterial Endocarditis
Authors: Cutting B. Favour, Charles A. Janeway, John G. Gibson, Samuel A. Levine
Journal: New England Journal of Medicine (1946)

IT IS extremely gratifying for the medical profession to witness progress in therapy, especially when it applies to ailments that were formerly fatal. To the diseases of this kind, such as diabetes, pernicious anemia, Addison's disease and various forms of bacterial meningitis, which in the past almost always resulted in death it may soon be possible to add some types of bacterial endocarditis. Among the common diseases of the heart, none has been so resistant to treatment and so invariably fatal as subacute bacterial endocarditis. Although isolated cures occurred before the introduction of the sulfonamides, there is little evidence that . . .
P03.03 * TARGETING ORTHOTOPIC GLIOMA IN MICE WITH GENETICALLY ENGINEERED SALMONELLA TYPHIMURIUM
Authors: S. Jung, M. Wen, K. Moon, S. Jiang, J. Min
Journal: Neuro-Oncology (2014)

OBJECTIVE: With the growing interests of bacteria as a targeting vector for cancer treatment, diverse genetically engineered Salmonella has been reported to be capable of targeting primary or metastatic tumor regions after intravenous injection into mouse tumor model. The purpose of this study was to investigate the capability of the genetically engineered Salmonella typhimurium to access the glioma xenograft, which was monitored in mouse brain tumor models using optical bioluminescence imaging technique. METHODS: U87-MG malignant glioma cells (U87-MG) stably transfected with firefly luciferase (Fluc) were implanted into BALB/cAnN nude mice by stereotactic injection into the striatum. After tumor formation, attenuated Salmonella typhimurium expressing bacterial luciferase (Lux) was injected into the tail vein. Bioluminescence signals from transfected cells or bacteria were monitored using a cooled charge-coupled device (CCD) camera to identify the tumor location or to trace the bacterial migration. Immunofluorescence staining was also performed in frozen sections of mouse glioma xenograft. RESULTS: The injected S. typhimurium exclusively localized in the glioma xenograft region of U87MG-bearing mouse. Immunofluorescence staining also demonstrated the accumulation of Salmonella typhimurium in the brain tumors. CONCLUSION: The present study demonstrated that Salmonella typhimurium can target glioma xenograft, and may provide a potentially therapeutic probe for glioma.
AB0915 No Association between Etanercept and New or Worsening Atopic Dermatitis in Children with Jia: an Analysis from the BSPAR Etanercept Cohort Study: Table 1.
Authors: T. Begum, R. Davies, L. Kearsley-Fleet, T.R. Southwood, K.L. Hyrich
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Etanercept (ETN) has significantly improved outcomes for children with severe juvenile idiopathic arthritis (JIA), but there are concerns regarding its long-term safety. Recently, 2 case reports have suggested ETN may be associated with a worsening of atopic dermatitis (AD). <h3>Objectives</h3> The purpose of this analysis is to study the risk of new or flare of AD in ETN versus MTX treated children using data from The British Society for Paediatric and Adolescent Rheumatology (BSPAR) ETN Cohort Study. <h3>Methods</h3> The BSPAR ETN cohort study, launched in 2004, is prospectively following children with JIA starting either ETN or MTX. Demographic, disease, treatment and adverse events data are collected at regular intervals. Reports of AD both at the time of and after treatment start were identified. Incidence rates of new/worsening AD were calculated for both groups and the risk compared using Cox proportional hazard models adjusted by deciles of propensity score. <h3>Results</h3> To 30/11/13, 700 ETN and 200 MTX treated children were recruited, with 7% recording a history of AD at treatment start. Over 2214 person-years (pyrs) of exposure there were 24 (ETN) and 6 (MTX) first reports of new/flare AD, giving an on-treatment incidence of 1.5 (95% CI 1.0, 2.2) and 1.0 (95% CI 0.4, 2.1)/100pyrs respectively. The adjusted hazard ratio for risk of new/flare AD in patients receiving ETN compared to MTX was 2.10 (95% CI 0.67, 6.52). <h3>Conclusions</h3> Overall, the use of ETN was not associated with new/worsening AD compared to MTX, although small numbers prevented robust estimates. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3543
POSITIVE EFFECT OF RADIOFREQUENCY CATHETER ABLATION ON MITRAL REGURGITATION SECONDARY TO ATRIAL FIBRILLATION
Authors: Daimon Kuwahara, Nozomi Watanabe, Keiichi Ashikaga, Shun Nishino, Hirohide Matsuura, Tomoko Fukuda, Tatsuya Nakama, Makoto Furugen, Hiroshi Koiwaya, Nehiro Kuriyama, Yoshisato Shibata
Journal: Journal of the American College of Cardiology (2016)
Stat Bite: Geographic Variation in U.S. BreastCancer Death Rates
Authors: S. S. Devesa, D. Grauman
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Stat Bite: Geographic Variation in U.S. BreastCancer Death Rates Get access Susan S. Devesa, Ph.D., Susan S. Devesa, Ph.D. Division of Cancer Epidemiology and Genetics, Nanal Cancer Institute Search for other works by this author on: Oxford Academic PubMed Google Scholar Dan Grauman Dan Grauman Division of Cancer Epidemiology and Genetics, Nanal Cancer Institute Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 24, 20 December 1995, Page 1831, https://doi.org/10.1093/jnci/87.24.1831 Published: 20 December 1995
648 HYPONATREMIA IS A MAJOR FACTOR OF THE IMPAIRED HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH CIRRHOSIS AND ASCITES
Authors: E. Solá, M. Guevara, E. Rodriguez, R. Barreto, M. Pavesi, V. Arroyo, E. Smadja-Lew, H. Watson, P. Ginés
Journal: Journal of Hepatology (2012)
Accumulation of Nuclear p53 and Tumor Progression in Bladder Cancer
Authors: David Esrig, Donald Elmajian, Susan Groshen, John A. Freeman, John P. Stein, Su-Chiu Chen, Peter W. Nichols, Donald G. Skinner, Peter A. Jones, Richard J. Cote
Journal: New England Journal of Medicine (1994)

We have previously demonstrated a strong association between nuclear accumulation of p53 protein, as determined by immunohistochemical analysis, and mutations in the p53 gene. The purpose of this study was to determine the relation between nuclear accumulation of p53 and tumor progression in transitional-cell carcinoma of the bladder.
Unusual Localization of Hydatid Cyst
Authors: Mustafa Yildirim, Erhan Varoglu, Nesrin Gursan, Umran Yildirim, Besir Erdogmus, Sabahattin Dalga
Journal: Clinical Nuclear Medicine (2002)

YILDIRIM, MUSTAFA; VAROGLU, ERHAN; GURSAN, NESRIN; YILDIRIM, UMRAN; ERDOGMUS, BESIR; DALGA, SABAHATTIN Author Information
Detection Of Choledocholithiasis Using Endoscopic Ultrasanography - One Centre's Experience
Authors: DO Donovan, S Sengupta, P MacMathuna, E Clarke
Journal: Endoscopy (2006)

Aims: To evaluate the utility of endoscopic ultrasonography (EUS) in assessing patients with biliary symptoms and to compare the sensitivity of EUS with other modalities in the detection of choledocholithiasis (CDL).
Abstract 3171: Stromal palladin is a poor prognostic marker in renal cell carcinoma
Authors: Vivekanand Gupta, Jeffrey Simons, Daniel Bassi, Tahseen I. Al-Saleem, Robert G. Uzzo, Edna Cukierman
Journal: Cancer Research (2011)

Abstract Renal cell carcinoma (RCC) is a fatal disease in urgent need of novel diagnostic and treatment tools. Metastasis to the secondary site is the main cause of death in RCC. Although renal tumor cells are intercalated within a mesenchymal stromal microenvironment during RCC tumorigenesis, not much is known about this specific stroma. Therefore, questioning the specific importance of RCC's stroma is of noteworthy interest. In this study we questioned whether stromal and tumor components progress at similar rates and whether assessing rates of stromal progression are of clinical importance. Our experimental system uses fibroblasts harvested from patient matched normal kidney, as well as primary and secondary RCC surgical samples. We tested several stromal markers such as actin binding protein palladin, alpha-smooth muscle actin and fibronectin spliced form EDA, all known to be upregulated in tumor associated stroma, and uncovered that their expression levels depend on the production of stromal extracellular matrices (ECMs) using an in vitro 3-D stromal system derived from the harvested fibroblasts. In addition, using a well annotated tumor micro array, we specifically demonstrate that stromal palladin and α-SMA expression levels correlate to each other. Moreover, we observed that stromal palladin expression levels are indicative of poor outcomes in early non-metastatic RCCs. Here we not only introduce an in vitro 3-D stroma system which accurately mimics the in vivo features of human RCC-associated stroma, but we demonstrate a clinical relevance to assessing stromal activation in human pathological RCC samples. Results from this study underscore a distinctive clinical relevance to assessing stromal progression in renal cell carcinomas. 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 3171. doi:10.1158/1538-7445.AM2011-3171
To Teach Them This Art
Authors: Leland S. McKittrick
Journal: New England Journal of Medicine (1962)

KNOWINGLY or unknowingly the young physician accepts responsibilities and obligations not equaled by those entering any other profession; responsibilities for the maintenance of high moral and ethical standards in his relation to his associates, to the public he serves and to the community in which he lives; and obligations to assure a continuing supply of highly motivated, well educated and trained physicians to meet the health needs of the nation.After more than two thousand years the philosophies expressed in the Hippocratic Oath continue to represent the ideals of, as well as the idealism in, medicine. Many now believe that . . .
The impact of adipose stromal cells on migration and invasion of breast cancer cells.
Authors: M Walter, S Liang, S Ghosh, P Hornsby, R Li
Journal: Cancer Research (2009)

Abstract Abstract #1056 Epidemiological studies have identified obesity as a significant risk factor for developing breast cancer among postmenopausal women. Adipose tissue is an important extragonadal source of estrogen. Although circulatory estrogen levels in postmenopausal women decline, tissue-specific estrogen levels remain virtually unchanged and are even found elevated in breast tissue from obese patients and patients with breast cancer. Therefore, excessive estrogen production due to overall adiposity is considered to be a critical contributing factor to obesity-associated breast cancer risk. However, it is not clear whether adipose tissue per se can also affect breast cancer development in a hormone-independent manner. In the current study, we used adipocyte stromal cells (ASCs) isolated from lipoaspirates from cancer-free patients and studied their possible influence on tumor cell behaviors. Using the Boyden-chamber assay, we found that ASCs had a stimulatory effect on the migration of both ER-positive (MCF-7) and ER-negative breast cancer cells (MDA-MB-231), suggesting that ASCs can influence the behaviors of breast cancer cells in an estrogen-independent manner. A similar effect of ASCs on MDA-MB-231 cells was also observed in a wound-healing assay. Furthermore, in a xenograft experiment using co-transplanted MDA-MB-231 and ASCs, we observed a significant role of ASCs in promoting the invasiveness of MDA-MB-231 cells. These data indicate that, in addition to their established role in supplying local estrogen, ASCs may facilitate tumor invasion into surrounding tissue and subsequently metastasis. The possible molecular basis for this effect of ASCs on tumor cell migration and invasion will be discussed. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1056.
Abstract 3906: Twist regulates estrogen receptor expression in breast cancer
Authors: Farhad Vesuna, Ala Lisok, Brian Kimble, John Domek, Yoshinori Kato, Dmitri Artemov, Jeanne Kowalski, Hetty Carraway, Paul van Diest, Venu Raman
Journal: Cancer Research (2010)

Abstract Background: Estrogen receptor alpha (ER) plays a crucial role in breast cancer development and progression due to its role as an effector/mediator of the mitogenic hormone estrogen. However, the role of transcriptional regulation of ER in tumor progression is not completely characterized. While defining the role of the basic helix loop helix transcription factor Twist (TWIST1) in breast cancer development, we identified ER as a downstream target of Twist in breast cells. Methods: A knock-up and knock-down approach in Twist negative and positive cell lines was used in order to characterize the regulation of ER by Twist. We analyzed ER expression by immunoblotting, ER transcriptional activity by promoter assays, DNA binding by chromatin immunoprecipitation, and estrogen independent growth in the presence of stripped serum or the estrogen antagonist tamoxifen (TAM). Additionally, ER promoter methylation was measured by methylation specific quantitative PCR (MS-qPCR). Using orthotopic xenografts in SCID mice, tumor growth was determined in presence of TAM and assayed for vascular permeability and volume by functional magnetic resonance imaging. Finally, the relationship between Twist and ER expression in breast tumors was evaluated by quantitative reverse-transcription PCR (qRTPCR). Results: Twist transcriptionally down-regulated ER expression by direct promoter modulation. Twist over-expression caused estrogen independence and TAM resistance, and induced hypermethylation of the ER promoter. In vivo, Twist expression resulted in estrogen independent growth and resistance to TAM. Twist over-expressing tumor xenografts exhibited high vascular volume and permeability. Moreover, Twist and ER expression were inversely correlated in primary breast cancer patient samples. Conclusion: The regulation of ER by Twist might be an underlying mechanism for ER negativity seen in breast tumors and could have important clinical implications for ER negative breast cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3906.
Physical Fitness Among Swedish Military Conscripts and Long-Term Risk for Type 2 Diabetes Mellitus
Authors: Casey Crump, Jan Sundquist, Marilyn A. Winkleby, Weiva Sieh, Kristina Sundquist
Journal: Annals of Internal Medicine (2016)

Background: Early-life physical fitness has rarely been examined in relation to type 2 diabetes mellitus (DM) in adulthood because of the lengthy follow-up required. Elucidation of modifiable risk factors at young ages may help facilitate earlier and more effective interventions. Objective: To examine aerobic capacity and muscle strength at age 18 years in relation to risk for type 2 DM in adulthood. Design: National cohort study. Setting: Sweden. Participants: 1 534 425 military conscripts from 1969 to 1997 (97% to 98% of all men aged 18 years nationwide) without prior type 2 DM. Measurements: Aerobic capacity and muscle strength (measured in watts and newtons per kilogram of body weight, respectively) were examined in relation to type 2 DM identified from outpatient and inpatient diagnoses from 1987 to 2012 (maximum age, 62 years). Results: 34 008 men were diagnosed with type 2 DM in 39.4 million person-years of follow-up. Low aerobic capacity and muscle strength were independently associated with increased risk for type 2 DM. The absolute difference in cumulative incidence of type 2 DM between the lowest and highest tertiles of both aerobic capacity and strength was 0.22% at 20 years of follow-up (95% CI, 0.20% to 0.25%), 0.76% at 30 years (CI, 0.71% to 0.81%), and 3.97% at 40 years (CI, 3.87% to 4.06%). Overall, the combination of low aerobic capacity and muscle strength was associated with a 3-fold risk for type 2 DM (adjusted hazard ratio, 3.07 [CI, 2.88 to 3.27]; P < 0.001), with a positive additive interaction (P < 0.001). These associations were seen even among men with normal body mass index. Limitation: This cohort did not include women and did not measure physical fitness at older ages. Conclusion: In this large cohort of Swedish male military conscripts, low aerobic capacity and muscle strength at age 18 years were associated with increased long-term risk for type 2 DM, even among those with normal body mass index. Primary Funding Source: National Institutes of Health.
Orbital and Cerebral Arteriovenous Malformations
Authors: Omar Choudhri, Steven Daniel Chang
Journal: New England Journal of Medicine (2011)

An 8-year-old girl had a 3-month history of progressively impaired vision in the right eye, with paresthesias and spastic paresis of the left arm and leg. Examination of the right eye revealed the tortuous blood vessels of a complex intraorbital arteriovenous malformation.
220 MONITORING BLOOD EOSINOPHILS CAN PREDICT RESPONSE TO CORTICOSTEROIDS IN PATIENTS WITH ACUTE CELLULAR REJECTION AFTER LIVER TRANSPLANTATION
Authors: M.L. Rodríguez, G. Germani, E. Thalassinos, N. Rolando, T.V. Luong, A.P. Dhillon, J. O'Beirne, D. Patch, A.K. Burroughs
Journal: Journal of Hepatology (2012)
slan-defined subsets of CD16-positive monocytes: impact of granulomatous inflammation and M-CSF receptor mutation
Authors: Thomas P. Hofer, Adam M. Zawada, Marion Frankenberger, Kerstin Skokann, Anna A. Satzl, Wolfgang Gesierich, Madeleine Schuberth, Johannes Levin, Adrian Danek, Björn Rotter, Gunnar H. Heine, Loems Ziegler-Heitbrock
Journal: Blood (2015)
Rapid Diagnosis of Measles from Urinary Sediments Stained with Fluorescent Antibody
Authors: Rizalina Llanes-Rodas, Chien Liu
Journal: New England Journal of Medicine (1966)

SEVERAL acute systemic viral illnesses have been associated with the presence of multinucleated giant cells or inclusion-bearing cells (or both) detected in nasal discharges1 and specimens of urine in human patients.2 3 4 5 6 7 Such cells have also been observed in the urinary sediments of children vaccinated with poliovirus and measles.3 , 8 Nevertheless, conclusive evidence that these cytologic changes are directly related to viral infections is still lacking. Others have reported the application of the fluorescent-antibody staining technic, to demonstrate viral antigens in clinical specimens whereby specific diagnosis can be made in infections caused by influenza,9 , 10 rabies,11 herpes simplex12 and infections with Coxsackie virus . . .