tbuckley/cabot-search huggingface dataset:
Abstract LB-118: 17AAG, through hydrophobic binding, targets mitochondrial VDAC and inhibits cell invasion
Authors: Qian Xie, Robert Wondergem, Yuehai Shen, Greg Cavey, Jiyuan Ke, Ryan Thompson, Robert Bradley, Yong Xu, Jennifer Holtrop, Hanan Omar, David Wenkert, Eric Xu, George F. Vande Woude
Journal: Cancer Research (2010)

Abstract 17-allylamino-17-demethoxygeldanamycin (17AAG) is a member of the geldanamycin (GA) benzoquinone ansamycin family of anticancer drugs that is in clinical trials against several types of cancer. GA compounds bind to the ATP pocket of HSP90, and block its chaperone function resulting in the degradation of a wide variety of substrate oncoproteins, thereby providing a powerful “multi-target therapy”. GA compounds, however, are highly hydrophobic, requiring complicated drug vehicle formulation. In attempting to understand the influence of the hydrophobicity of GA drugs in vitro, we discovered that the hydrophobic molecules, GA or 17AAG, can bind directly to the highly hydrophobic voltage-dependent anion channel (VDAC) or to purified mitochondria where VDAC resides. Moreover, 17AAG binds to purified mitochondria prepared from all tissues and cells tested and compete with HSP90. Consistent with benzoquinone-ubiquinones functioning as classical Ca2+ mitochondrial regulators we associated the benzoquinone ring which all members of the GA family of drugs have as the responsible GA binding moiety with mitochondria. We show that both the ubiquinone, UbO, and GA drugs increase intracellular Ca2+, most likely through intracellular mitochondrial stores and both drugs diminish the plasma cationic current. By contrast, radicicol, with only an ansamycin ring, binds tightly to HSP90, but lacking the benzoquinone ring, has no measurable effect on cationic current or intercellular Ca2+ concentration. Thus, we propose that benzoquinone mitochondria binding through hydrophobic VDAC represents an alternative mode of action of GA drugs that can either alter HSP90 activity or be responsible for toxicity. Both activities must be considered when novel GA derivatives are developed as therapeutics. 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 LB-118.
435 ANTI-HDV-IgM AS A MARKER OF DISEASE ACTIVITY IN HEPATITIS DELTA
Authors: A. Wranke, C. Yurdaydin, B. Heidrich, F.A. Caruntu, M.G. Curescu, K. Yalcin, S. Gürel, S. Zeuzem, A. Erhardt, S. Lüth, G.V. Papatheodoridis, B. Bremer, J. Stift, J. Grabowski, J. Kirschner, K. Port, M. Cornberg, C. Falk, H.P. Dienes, S. Hardtke, M.P. Manns, H. Wedemeyer
Journal: Journal of Hepatology (2013)
VALIDACIÓN DEL UN MODELO DE FORMACIÓN EXPERIMENTAL EN ENDOSCOPIA TERAPÉUTICA BÁSICA
Authors: M Fernández Bermejo, JM Mateos Rodríguez, S Fernández Díez, C Santander Vaquero, E Morcillo Martín, FM Sánchez-Margallo, F Soria Gálvez
Journal: Endoscopy (2013)

Introducción: Las sociedades médicas están involucradas en la capacitación y adiestramiento teórico-práctico en endoscopia diagnóstico-terapéutica, así como el número de procedimientos requeridos para considerarse autónomo. La formación en endoscopia dentro de un programa experimental permite adquirir habilidades suficientes para realizar las técnicas de endoscopia terapéutica. Es requisito realizar una previa validación del programa para determinar si es realmente efectivo para la formación. Objetivo: validar un modelo de formación experimental en Endoscopia Terapéutica mediante la utilización de modelo exvivo y modelo animal. Material y Método: Actividad formativa de 16 horas de duración. Se realiza secuencialmente instrucción teórica, prácticas en modelo exvivo y posteriormente en modelo animal porcino de las diferentes técnicas: dilatación, esclerosis-hemostasia, extracción de cuerpos extraños, polipectomía, mucosectomía, liberación prótesis esofágicas y gastrostomía. La evolución en la adquisición de las destrezas (técnicas y no técnicas) se evalúan mediante una tabla controlando 16 parámetros, en el modelo exvivo, así como al inicio y al final del entrenamiento en modelo porcino. Resultados: Han participado 26 alumnos en dos ediciones. El grado de fiabilidad de la tabla empleada para valorar las destrezas de los alumnos es alto (Coeficiente alfa de Cronbanch = 0,84). No encontramos diferencias estadísticamente significativas entre el simulador exvivo y la primera práctica en modelo animal. Existen diferencias significativas en los 16 parámetros estudiados entre la primera práctica en modelo animal y la última realizada en este modelo de formación. El 83% de los alumnos confirman que han avanzado mucho. El 100% considera que se encontrarían capacitados para llevar a cabo las técnicas. El 100% recomendaría esta actividad. Conclusiones: La metodología descrita y validada permite la formación en endoscopia terapéutica con adquisición de las habilidades necesarias, con posibilidad de repetición de técnicas, en un ambiente sin stress y bajo tutela continuada, que probablemente reducirá la curva de aprendizaje en estas técnicas endoscópicas.
P2-03-02: An IGF1R Antibody Does Not Inhibit Growth of Tamoxifen Resistant MCF-7 Cells.
Authors: DH Fagan, D Yee
Journal: Cancer Research (2011)

Abstract The role of the insulin-like growth factor (IGF) system in breast cancer has been well defined, and inhibitors of this pathway are currently in clinical trials. The majority of anti-IGF1R clinical trials are in estrogen receptor-positive patients who have progressed on prior endocrine therapy with some early reports showing no benefit for addition of IGF1R inhibitors to endocrine therapy. The effect in endocrine-resistant models, mimicking the clinical trial scenario, has not been adequately investigated. To examine the effectiveness of IGF1R inhibitors in vitro, tamoxifen-resistant (TamR) cells were generated by culturing MCF-7L cells in the presence of 4-hydroxy-tamoxifen for more than 1 year. TamR cells had diminished levels of IGF1R with unchanged levels of insulin receptor (IR), and enhanced phosphorylation of Akt. Further, TamR cells failed to further respond to IGF-I-induced Akt activation while retaining responsiveness to both insulin and IGF-II. Additionally, IGF-I failed to enhance the proliferation and anchorage-independent growth of TamR cells; however, both insulin and IGF-II stimulated proliferation and anchorage-independent growth. An IGF1R antibody (dalotuzumab) was able to inhibit IGF-I-mediated Akt phosphorylation, proliferation, and anchorage-independent growth in parental MCF-7L cells and had minimal effect on insulin and IGF-II stimulation. In TamR cells, dalotuzumab failed to inhibit proliferation or anchorage-independent growth in response to either insulin or IGF-II. An IGF1R tyrosine kinase inhibitor, (AEW 541) with equal potency for the IGF1R and IR, inhibited IGF-I-, IGF-II-, and insulin-stimulated Akt phosphorylation, proliferation, and anchorage-independent growth in MCF-7L parental cells. Interestingly, AEW 541 also inhibited insulin- and IGF-II-stimulated Akt phosphorylation, proliferation, and anchorage-independent growth in MCF-7L TamR cells. We conclude that cells selected for tamoxifen resistance in vitro have downregulated IGF1R making antibodies directed against this receptor ineffective. Preliminary studies in vivo, suggest that initial co-treatment with tamoxifen plus dalotuzumab was more effective than either drug alone. In contrast, acquired tamoxifen resistance might require dual inhibition of IGF1R and PI3K targets to completely suppress IGF system signaling as currently under study in the clinic. Alternatively, IGF1R tyrosine kinase inhibitors may be effective by inhibiting both IGF1R and IR signaling in cells selected for tamoxifen resistance. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-03-02.
P1279 HIGH BURDEN OF HCV AND HCV/HIV COINFECTION AMONG INJECTION DRUG USERS IN INDIA: NEED FOR INTEGRATION OF HIV AND HCV SERVICES
Authors: S.S. Solomon, S.H. Mehta, A.K. Srikrishnan, G.M. Lucas, A. McFall, O. Laeyendecker, M.S. Kumar, S.H. Iqbal, S. Solomon, T.C. Quinn
Journal: Journal of Hepatology (2014)
AB0530 Thrombosis Risk Factors in Patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus With/Without Antiphospholipid Syndrome
Authors: M.A. Satybaldyeva
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA), Systemic Lupus Erythematosus (SLE), Antiphospholipid syndrome (APS) are associated with increased mortality and co-morbidity compared with the general population. These patients (pts) may have an increased risk of developing venous thrombotic events (VTEs), based on the high prevalence of many known VTE risk factors (RF). Prevention of thrombosis should be taken commensurated with the risk of VTEs based on the composite risk profile (disease-related and concomitant RF). <h3>Objectives</h3> To analyze thrombosis RF (concomitant and disease-related RF) in pts suffered from rheumatic diseases with thrombosis in past history. <h3>Methods</h3> There were 45 pts (F:36 M:9), 44,8±13,4 years old: 5/45 (11%) pts with SLE, 12/45 (27%) with APS, 14/45 (31%) with SLE+APS and 15/45 (33%) with RA. All the pts had venous thrombosis in past history. We analyzed thrombosis RF (concomitant and disease-related risk factors) among the pts. High levels of antibodies to cardiolipin (aCL), beta 2-glycoprotein-1 (aB2GP1) were related to APS-related RF. Disease-related RF for RA and SLE were the disease activity, hypodynamia due to disease, glucocorticoid (GC) therapy, fractures due to GC and replacement arthroplasty as a main surgical operation. In 29/45 (64%) pts investigation of 4 markers of thrombophilia was performed as additional RF. <h3>Results</h3> All the pts had different RF. 7/45 (16%) pts had surgical treatment before thrombosis. 11/34 (24%) pts with SLE and RA had the flare of disease (5/15 RA pts and 6/19 SLE pts). 10/45 (16%) pts had hypodynamia before thrombosis (in 2/10 cases because of nonspecific surgical treatment, 1/10 - replacement arthroplasty due to RA, 6/10 - the flare of disease). From 26 pts with APS 21 (81%) had high levels of aCl and 18 (69%) - high levels of aB2GP1. 8/45 (18%) pts had such RF as smoking, 10/45 (22%) – obesity (body mass index &gt;30), 4/45 (9%) - long-lasting flights, 4/56 (9%) - traumas and 1/45 (2%) had fracture and further immobilization before thrombosis (fracture was not related to the therapy of rheumatic diseases). 22/45 (49%) pts received GC therapy (4 SLE, 8 SLE+APS and 10 RA). 7/36 (16%) women developed acute thrombosis during pregnancy and labor, 3/36 (8%) women received oral contraceptives. 25/29 (86%) pts had inherited thrombophilia. Frequency of RF did not differ between pts. <h3>Conclusions</h3> Patients with RD have a higher risk of thromboembolic events. The most frequent RFs of thrombosis were GC therapy, surgical treatment, hypodynamia, antiphospholipid antibodies and inherited thrombophilia. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5388
Case 4-2003
Authors: Lindsey R. Baden, Danielle D. Elliott
Journal: New England Journal of Medicine (2003)

Presentation of CaseA 42-year-old woman was admitted to the hospital because of a productive cough, chills, and fever.The patient had been well until seven months earlier, when an intermittent, generally nonproductive cough developed and did not resolve, despite courses of several antibiotics. A chest radiograph was said to be unremarkable. A few months before admission, another chest radiograph was believed to show a hiatal hernia, but a barium-swallow examination failed to reveal the hernia. Several days before admission, the patient began to cough up green, foul-smelling sputum and had a temperature as high as 38.5°C, without chills or . . .
BMA Annual Representative Meeting, Belfast, 26 June to 29 June: Doctors blame untested policies for financial crisis in the NHS
Authors: Zosia Kmietowicz
Journal: BMJ (2006)

Doctors at the BMA's annual meeting of representatives in Belfast have blamed the government for the financial crisis in the NHS, saying that it has taken a record amount of money away from the care of patients and “squandered” it on unproved reforms.​reforms.



Figure 1

James Johnson, the BMA's chairman, addresses the annual representative meeting in Belfast last week



“This financial crisis has nothing to do with diversionary talk of increases in doctors' pay or profligate spending by NHS trusts. It's a result of [the] government's own making—with relentless ideological reforms that have misappropriated billions away from patient care,” said a Middlesex GP and a member of the General Practitioners Committee of the BMA, Chaand Nagpaul.

“[It is] lamentable that this once in a lifetime investment opportunity is being squandered in front of our eyes, leaving the NHS with cuts in services and staff and unable to afford cancer treatments available in other countries,” he added.

Dr Nagpaul was speaking at an open debate on values and funding in the NHS. He said that an estimated £1.5bn (€2.2bn; $2.7bn) had been spent on “perpetual reorganisation” within the NHS, £1bn had been paid to private management consultants, such as those called in to help debt ridden NHS trusts, and £14bn had been overspent on the NHS information technology programme.

“The government cannot act with impunity. It must be held to account for its ideological, nonevidence based policies being the single greatest cause in bringing the NHS into financial standstill,” Dr Nagpaul said.

Jacky Davis, a consultant radiologist at the Whittington Hospital NHS Trust in north London, told the conference that last year the government had spent £33bn on centrally funded initiatives “that do not impact on patient care,” such as the Modernisation Agency and NHS University.

Meanwhile, other representatives attacked the private finance initiative for new hospitals and the introduction of practice based commissioning.
Abstract 979: Understanding the relationship between race and nicotine dependence
Authors: Shondelle M. Wilson, Roland J. Thorpe, Jean G. Ford, Thomas A. LaVeist
Journal: Cancer Research (2010)

Abstract Background: Mounting evidence continues to demonstrate that nicotine dependence is a growing public health issue among current smokers. While duration of smoking, number of cigarettes smoked per day (CPD) and cessation attempts are common indicators of nicotine dependence, African Americans tend to smoke less cigarettes per day (CPD; 10 or less), initiate smoking at a later age and experience greater failed quit attempts, compared to whites, yet develop nicotine dependence. However, no previous study has examined the possibility that race differences in the social context which African Americans and non-Hispanic whites live may contribute to disparities and the persistence of nicotine dependence. Social class and immediate personal interactions occurs in various social contexts, including the living space, workplace, institutions or other physical environments. This project examines the contributions of demographic, behavioral and environmental factors as social contextual factors that contribute to smoking behavior and the persistence of nicotine dependence. Objective: We examined race disparities in nicotine dependence among 761 African American and white current smokers living in similar social and environmental risk exposures and compared these estimates to 1461 black and white current smokers in a national sample of adults aged 20 and over. Methods: Data was assessed from Exploring Health Disparities in Integrated Communities-Southwest Baltimore (EHDIC-SWB; 2003) and National Health and Nutritional Examination Survey (NHANES; 2001-2004) to determine if race disparities in nicotine dependence would be attenuated in EHDIC-SWB. Time to first cigarette was used to assess nicotine dependence. Logistic regression was used to assess the association between race and nicotine dependence, controlling for known confounders. Results: In multivariate analysis, race differences in nicotine dependence were greater among African-Americans in a representative sample of US adults. African Americans in a national sample have a lower odds of nicotine dependence (OR = 0.8; 95% CI 0.46, 0.93) compared to whites. However, no race difference were detected among participants in the EHDIC-SWB study (0.87; 95% CI 0.62, 1.22). Conclusions: Examination of social and environmental factors may reveal important insights into the nature of inequalities between black and white adults in health outcomes such as nicotine dependence. Our results highlight the importance of examining social contextual factors and suggest that the promotion of targeted interventions may reduce the prevalence of nicotine dependence among current smokers. 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 979.
Inclusion of urine analysis not justified
Authors: J. Chard, M. Richardson, S. Murphy
Journal: BMJ (2013)

De and colleagues’ study goes some way towards validating the National Institute for Health and Care Excellence “traffic light” system on feverish illness in children,1 2 the implementation of which has been questioned.3

The study showed that the “traffic light” system had a sensitivity of 85.8% and a specificity of 28.5% in detecting urinary tract infection, pneumonia, or bacteraemia in young children in amber or red categories. Limitations of the study aside, we believe these results show that the system is a valuable screening tool for assessing the risk of serious illness in young children with fever.

De and colleagues suggest that because …
Abstract LB-53: Cancer clinical trials: real answers, real options, real miracles, right here in west Michigan
Authors: Patrick Gavin
Journal: Cancer Research (2012)

Abstract “Cancer survivors sharing clinical trial experiences to increase awareness and knowledge in the search for prevention and cure.” Our goal is to increase the awareness of cancer clinical trials available in West Michigan. The Patient Advisory Board for Clinical Research was formed to capture the passion that clinical trial participants possess in searching for a cure for a disease that has personally affected them. Fear often accompanies a cancer diagnosis. The vision is to replace fear with the knowledge that is brought through clinical trials. The Patient Advisory Board for Clinical Research's objective is to make cancer clinical trials information available and increase general public awareness of this treatment option. 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 LB-53. doi:1538-7445.AM2012-LB-53
Lymphocyte Inclusions in Newborns of Mothers with Systemic Lupus Erythematosus
Authors: John H. Klippel, Philip M. Grimley, John L. Decker
Journal: New England Journal of Medicine (1974)

CYTOPLASMIC tubuloreticular structures have been observed within vascular endothelium and circulating lymphocytes of patients with a variety of connective-tissue disorders.1 2 3 The factors responsible for the occurrence and cellular distribution of these inclusions are not known. There has been speculation regarding a viral association based on the morphologic resemblance to viral nucleocapsids,3 the development of similar structures during experimental viral infections,4 and their induction in human cell lines harboring Epstein–Barr virus.5 We have observed lymphocyte tubuloreticular structures in newborns from two patients with systemic lupus erythematosus.Mononuclear cell samples were prepared from circulating maternal and fetal umbilical-cord blood by Hypaque-Ficoll gradient . . .
FRI0536 Mortality rates among us medicaid recipients with systemic lupus erythematosus, 2000-2006
Authors: J. A. Gómez-Puerta, C. H. Feldman, J. Liu, G. S. Alarcón, M. A. Fischer, K. H. Costenbader
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The U.S. Centers for Disease Control (CDC) reported significant differences by age and race in mortality rates (MRs) among SLE patients, 1979-1998 (1). MRs were highest among African Americans and patients &gt; 45 years old (1), but MRs among U.S. SLE patients with have not been reported more recently. Medicaid is the U.S. federal-state jointly run program for providing medical insurance to low income individuals. <h3>Objectives</h3> To examine MRs among SLE patients enrolled in Medicaid in the U.S. from 2000 to 2006 <h3>Methods</h3> From the Medicaid Analytic eXtract (MAX) data, containing all billing claims from 2000-2006, we identified patients aged 3-65 with prevalent SLE (≥ 3 SLE ICD-9 codes [710.0], &gt;30 days apart), as well as those with lupus nephritis (defined with ≥ 2 additional ICD-9 codes for nephritis, renal insufficiency or renal failure). Demographic data included age, sex, race, ethnicity, and region of residence. MRs were calculated using annual deaths among individuals with SLE in each sociodemographic group in each year (deaths ± SD per 100,000 Medicaid patients with SLE). T-tests were used to compare differences among groups <h3>Results</h3> We identified 43,351 patients with prevalent SLE. 40,417 (93%) were female, 39,283 (91%) were adults (≥ 18 at last follow-up) and 22% of SLE patients had lupus nephritis. Racial and ethnic breakdown was: African American (38%), White (37%), Hispanic (14%), Asian (4%), Native American (2%) and other (5%). 38% of patients lived in the South, 22% in the West, 21% in the Northeast and 19% in the Midwest. During the study period, the overall mean annual MR was 1,185 ± 387 deaths per 100,000. Annual MRs were higher among males than females (1,420 ± 416 vs. 951 ± 153 per 100,000; p=0.02), among those aged 45-64 compared to those aged 15-44 (1,462 ± 248 vs. 730 ± 146 per 100,000, p&lt;0.0001) and higher among African Americans, Whites and Native Americans (compared to Hispanics and Asians, all p&lt;0.05). Among women aged 45-65, MRs were 6.5 x higher in Native Americans (1,759 per 100,000) and 6.0 x higher in African Americans (1,686 per 100,000) than those among Asians (270 per 100,000). <h3>Conclusions</h3> We found marked age, sex and race-specific differences in MRs among Medicaid patients with SLE. MRs among SLE patients were highest among African and Native Americans, men vs. women and patients over age 45. <h3>References</h3> Centers for Disease Control and Prevention (CDC) Trendsin Deaths from Systemic Lupus Erythematosus--United States, 1979-1998. MMWE Morb Mortal Wkly Rep 2002;5:371-4. <h3>Disclosure of Interest</h3> None Declared
MYOCARDIAL EXTRACELLULAR VOLUME IS ELEVATED IN CANCER SURVIVORS TREATED WITH ANTHRACYCLINE-BASED CHEMOTHERAPY COMPARED TO CANCER-FREE PEERS AND NEWLY DIAGNOSED AND UNTREATED CANCER PATIENTS: A SINGLE-CENTER OBSERVATIONAL STUDY OF THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA) AND CARDIO-ONCOLOGY CARDIOVASCULAR MAGNETIC RESONANCE IMAGING STUDIES
Authors: Jennifer H. Jordan, Sujethra Vasu, Tim Morgan, Ralph D’Agostino, Giselle C. Melendez, Michael Hall, Craig Hamilton, Andrew Arai, Songtao Liu, Chia-Ying Liu, Joao Lima, David Bluemke, W. Hundley
Journal: Journal of the American College of Cardiology (2015)
False-Positive Ga-67 Citrate Scan Secondary to an Inguinal Hernia
Authors: WILLIAM FONG, EUGENE LIM
Journal: Clinical Nuclear Medicine (2002)

FONG, WILLIAM M.B.B.S., F.R.A.C.P.; LIM, EUGENE M.B.B.S., F.R.A.N.Z.C.R. Author Information