tbuckley/cabot-search huggingface dataset:
Risks of Presymptomatic Direct-to-Consumer Genetic Testing
Authors: Justin P. Annes, Monica A. Giovanni, Michael F. Murray
Journal: New England Journal of Medicine (2010)

Geneticists have long cited the risks of direct-to-consumer (DTC) genetic testing, highlighting the danger for consumers who make complex medical decisions without adequate clinical guidance. On May 10, 2010, the Food and Drug Administration (FDA) voiced its concern by sending a letter informing Pathway Genomics that its DNA testing and interpretation service "appears to meet the definition of a device" and may therefore require FDA approval.1 The letter was prompted by the announcement by Pathway Genomics and Walgreens of the impending marketing of an over-the-counter testing kit to analyze genetic risk and provide information regarding more than 70 diseases or . . .
Abstract 1571: Developing antigen-specific Th1 epitope based vaccines by excluding immunosuppressive peptide sequences
Authors: Denise L. Cecil, Gregory E. Holt, Dan Herendeen, Ekram Gad, Lauren Rastetter, Kyong Hwa Park, Mary L. Disis
Journal: Cancer Research (2012)

Abstract We have determined that IGFBP-2 is immunogenic in ovarian cancer. Our aim is to develop a multi-epitope vaccine that will elicit Th1 immunity to IGFBP-2. Antigen specific Th1 can modulate the tumor microenvironment to enhance cross priming, supporting the proliferation of cytotoxic T cells which are capable of eradicating ovarian cancer cells. Although some clinical benefit has been demonstrated with this strategy, recent ex vivo analyses of human PBMC have described the presence of antigen-specific CD4+ T regulatory cell (Tregs) in cancer patients that were not detected in healthy individuals. Thus, we questioned if we could optimize our vaccine to include only Th1-stimulating epitopes. Using a combined scoring system from five algorithms for predicting class II binding to determine Th epitopes, we identified 14 IGFBP-2 peptides. Th1 immunogenicity (IFN-gamma) and potential immunosuppression (IL-10) was evaluated by ELISPOT for 40 different donors. Twenty-two percent of the donors only responded with IL-10 secretion to any peptide, 22% only responded with IFN-gamma and 53% of the patients had a mixed IFN-gamma and IL-10 response. To determine which peptides would induce a predominantly Th1 response in the greatest number of people, we used a ratio of IFN-gamma to IL-10 and analyzed both the magnitude and frequency of ELISPOT responses for each of peptides using the following algorithm: (corrected mean SPW) x (percent of responding donors). The peptides were then ranked from highest IL-10 response to highest IFN-gamma response. Interestingly, 6 of the 14 peptides demonstrated a preference to secrete IFN-gamma over IL-10 and are only located in the N-terminus (amino acids 1-163) of IGFBP-2; the remaining potentially immunosuppressive peptides are located in the C-terminus (amino acids 164-328). Vaccination with p1-163 in MMTV-neu mice demonstrated a robust Th1 response (p=0.03) and concomitant inhibition of tumor growth by 70% compared to adjuvant only control animals, p164-328-vaccinated or full length protein-vaccinated mice (p&amp;lt;0.001 for all). Vaccination with p164-328 or full length protein did not inhibit tumor growth. These data suggest that more effective vaccines can be designed when both Th1 epitopes and immunosuppressive epitopes are screened simultaneously and epitopes that are most likely to induce robust Th1 responses in the majority of individuals can be identified and included as vaccine components. 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 1571. doi:1538-7445.AM2012-1571
Resolved Splenic Accumulation of Tc-99m HMDP After Recovery of Disseminated Intravascular Coagulation in a Patient With Rhabdomyosarcoma
Authors: KAZUYOSHI SUGA, NAOFUMI MATSUNAGA, TAKERO KAWAMURA, AKIKO HARA, NORIHIKO KUME
Journal: Clinical Nuclear Medicine (1999)

Unusual, intense splenic radioactivity was seen on bone scintigraphy with Tc-99m HMDP in a 14-year-old boy with alveolar rhabdomyosarcoma complicated by disseminated intravascular coagulation. Abnormal splenic radioactivity was resolved after recovery from the disseminated intravascular coagulation. During treatment of disseminated intravascular coagulation and tumors, the patient received repeated blood transfusions, resulting in iron overload, but this did not prevent the abnormal splenic uptake from resolving. This case indicates that disseminated intravascular coagulation may be a cause of splenic accumulation of bone-seeking agents, and that abnormal splenic uptake can be resolved.
… and good-bye!
Authors: T. Rösch
Journal: Endoscopy (2013)

To say good-bye after more than 20 years of work for one specific journal may resemble the inevitable farewell of dinosaurs due to climatic changes, but the least I can say is that have I greatly enjoyed my time with Endoscopy. The different colleagues I had the honor and pleasure to work with, especially during the last team, contributed enormously to the pleasure of learning. The mixture of differing mentalities, elder and wise endoscopists and young, sharp-edged researchers, together with the cooperation with authors and reviewers from around the globe, has been an exhilarating and stimulating experience.
Elizabeth Mary Pope
Authors: D. Chantrey
Journal: BMJ (2014)

Elizabeth Mary Pope (“Liz”) was a dedicated, respected, and much loved general practitioner; an enthusiastic sportswoman; a devoted Christian; and a loving and much loved wife, daughter, sister, aunty, and friend. Her sudden and unexpected death has left the world and darker place.

Liz was born in Stoke on Trent. She lived and went to school there and in Cambridge, Wordesley, Kingswinford, and Shifnal, before going to Leicester University where she studied dedicine.

When she graduated, Liz married Trevor Pope (from Bridgnorth) and they lived in Tasley. Liz took up a post of house officer and then senior house officer at Shrewsbury Royal Infirmary. She then moved to the outskirts of Yeovil in Somerset, where she worked as a GP. Some seven years ago she moved back to Shropshire and became a GP partner in the Three Villages Medical Practice, in the Amblecote and Wollaston areas of Stourbridge. She was a respected member of the GP team in that practice and was loved and liked by her patients, for whom Liz always had time to listen , sympathise, and care with great skill and compassion. Liz was also a member of the clinical commissioning …
Kaposi's Sarcoma–Associated Herpesvirus DNA Sequences in Prostate Tissue and Human Semen
Authors: Paolo Monini, Laura de Lellis, Marina Fabris, Franco Rigolin, Enzo Cassai
Journal: New England Journal of Medicine (1996)

Sequences of a novel herpesvirus, Kaposi's sarcoma–associated herpesvirus (KSHV), have been identified in Kaposi's sarcoma tissue, but it is not known whether the virus is transmitted by sexual contact.
A8.06 Microrna-125b expression in PBMCS is inversely associated with disease activity in patients with early rheumatoid arthritis
Authors: V Hruskova, R Jandova, L Vernerova, H Mann, K Prajzlerova, M Filkova, K Pavelka, J Vencovsky, L Senolt
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> MicroRNAs (miRNAs) are small RNAs that regulate gene expression by targeting mRNA. It was proved that some miRNAs are significantly deregulated in rheumatoid arthritis (RA). MicroRNA-125b negatively regulates expression of TNF-α, which plays a crucial role in RA pathogenesis. The aim of this study was to evaluate the expression of miRNA-125b in peripheral blood mononuclear cells (PBMCs) and its association with disease activity and treatment response in early RA patients. <h3>Materials and methods</h3> A total of 58 (42 females; mean age 54.3 ± 16.4 years) early RA patients and 54 (41 females; mean age 50.9 ± 15.11 years) healthy controls (HC) were studied. Total RNA was isolated from PBMCs collected from patients before and after three months of glucocorticoid/disease modifying antirheumatic drugs treatment and from HC. The expression of miRNA-125b was determined by quantitative PCR. RNU44 was used for normalisation. Disease activity was defined using 28-Joint Count Disease activity Score (DAS28-ESR). The expression of miRNA-125b was studied in order to predict treatment response characterised by achieving remission or alternatively low disease activity (DAS28 &lt;&nbsp;3.2). <h3>Results</h3> The expression of miRNA-125b was significantly lower in early RA patients compared to HC (p = 0.001) and increased after three months of therapy (p = 0.006), mainly in responders (p = 0.019). At baseline, miRNA-125b expression negatively correlated with DAS28 (r&nbsp;= -0.462; p = 0.0003). In addition, baseline miRNA-125b expression predicted treatment response after three months which was performed by ROC curve analysis (AUC: 0.663 [95% CI 0.520 to 0.805]; p = 0.048). <h3>Conclusion</h3> Monitoring of miRNA-125b could be used as a &nbsp;biomarker of disease activity and treatment response in &nbsp;early RA. <h3>Acknowledgement</h3> IGA project No NT 14498; GAUK-367615.
Intense 18F-Fluoride Accumulation in Liver Metastases From a Neuroendocrine Tumor After Peptide Receptor Radionuclide Therapy
Authors: Cyprian Świętaszczyk, Vikas Prasad, Richard P. Baum
Journal: Clinical Nuclear Medicine (2012)

A 48-year-old female patient with a liver-metastasizing neuroendocrine tumor of pancreas underwent restaging with 18F-fluoride PET/CT after peptide receptor radionuclide therapy. The study detected 4 intense activity enhancements in the liver. These corresponded to 4 of altogether 9 liver metastatic lesions. The fluoride-positive lesions were calcified. Additionally, in pretherapeutic PET scans with 18F-FDG as well as with 68Ga-DOTA-NOC, they presented with doughnut sign and with more avid accumulation of 18F-FDG.
Stat Bite Cancer Incidence in Blue-Collar Workers by Industry
Authors: N. E. L. Hall
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Stat Bite Cancer Incidence in Blue-Collar Workers by Industry Get access Nancy E. L. Hall, Ph.D. Nancy E. L. Hall, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 23, 7 December 1994, Page 1749, https://doi.org/10.1093/jnci/86.23.1749 Published: 07 December 1994
Abstract 5259: Ubiquitination and degradation of EGFR mutants by C-terminus hsp70 interacting protein (CHIP) in non-small cell lung cancer (NSCLC).
Authors: Jeong Eun Lee, Kang Won Jang, Hye Rim Cha, Jo-ock Kim, Sung Soo Jung, Dong Il Park, Myoung Rin Park, Chaeuk Chung
Journal: Cancer Research (2013)

Abstract Several somatic mutations in the kinase domain of the epidermal growth factor receptor (EGFR), including L858R and exon 19 deletions, are predictive markers for EGFR tyrosine kinase inhibitor treating non-small cell lung cancer (NSCLC), especially adenocarcinoma. The mutational activation of EGFR is stabilized by Hsp90. Therefore Hsp90 inhibition may promote ubiquitin-mediated degradation of EGFR mutants. C-terminus hsp70 interacting protein (CHIP) has been shown to negatively regulate Hsp70 and Hsp90 function and to convert Hsp90 complexes from a chaperone function to one that promotes the ubiquitination and degradation of interacting proteins. Here, we report a novel interaction of EGFR mutants with an E3 ubiquitin ligase CHIP, which can ubiquitinate, and destabilize EGFR mutants. In CHO cells expressing either wild-type or mutant EGFR, inhibition of expression of its mutants: L858R, G719S and del L747_E749del, occurred following overexpression with CHIP, whereas diminution of wild-type EGFR was not in CHIP transfected cells. In full-down assay, CHIP especially interacted with G719S and del L747_E749del, but not L858R, and simultaneously induced ubiquitination of its proteins. Similarly, EGFR proteins in NSCLC cell lines harboring EGFR mutations, PC9, were also declined by CHIP mediated ubiquitination and degradation compared with the protein in wild-type cells. In EGFR mutant cell lines, CHIP inhitibited cell proliferation as well as depletion of phosphor-Akt and ERK. These data suggest that CHIP regulates and stabilizes EGFR mutants and that CHIP may be a novel regulator and marker in EGFR-mutants NSCLC. We confirmed these results by tumor xenograft model. Based on above findings, we conclude that CHIP is a new modulator in EGFR mutant pathway in NSCLC. Citation Format: Jeong Eun Lee, Kang Won Jang, Hye Rim Cha, Jo-ock Kim, Sung Soo Jung, Dong Il Park, Myoung Rin Park, Chaeuk Chung. Ubiquitination and degradation of EGFR mutants by C-terminus hsp70 interacting protein (CHIP) in non-small cell lung cancer (NSCLC). [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 5259. doi:10.1158/1538-7445.AM2013-5259 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
AB0007 The CD226 gene is not involved in giant cell arteritis in the spanish caucasian population
Authors: A. Serrano, D. Carmona, J.A. Miranda-Filloy, S. Castañeda, L. Rodríguez-Rodríguez, I. Morado, C. Gόmez-Vaquero, R. Solans, B. Sopeña, R. Blanco, A. Unzurrunzaga, N. Ortego-Centeno, B. Marí-Alfonso, E. de Miguel, A. Hidalgo-Conde, J. Martín, M.A. González-Gay
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> <i>CD226</i> genetic variants have been associated with a number of autoimmune diseases. <h3>Objectives</h3> The aim of this study was to investigate the potential implication of the <i>CD226</i> loci in the susceptibility to and main clinical manifestations of giant cell arteritis (GCA). <h3>Methods</h3> A Spanish Caucasian cohort of 455 patients diagnosed with biopsy-proven GCA and 1414 healthy controls were included in the study. Three <i>CD226</i> polymorphisms, rs727088, rs34794968 and rs763361, were genotyped using the TaqMan® allelic discrimination technology. PLINK software was used for the statistical analyses. <h3>Results</h3> No significant association between the <i>CD226</i> polymorphisms and susceptibility to GCA was found (rs727088: <i>P</i>=0.92, OR=1.01 CI 95% 0.86-1.18; rs34794968: <i>P</i>=0.61, OR=1.04 CI 95% 0.89-1.22; rs763361: <i>P</i>=0.88, OR=0.99 CI 95% 0.84-1.16). Similarly, when patients were stratified according to the specific clinical features of GCA such as polymyalgia rheumatica, visual ischemic manifestations or irreversible occlusive disease, no association was observed either between the case subgroups and the control set or between GCA patients with and without the specific features of the disease. Furthermore, the haplotype analysis revealed no significant association with the disease. <h3>Conclusions</h3> Our results show that the <i>CD226</i> gene does not play a relevant role in the susceptibility to GCA and clinical manifestations of this vasculitis. <h3>References</h3> Hafler JP, Maier LM, Cooper JD, Plagnol V, Hinks A, Simmonds MJ, et al. CD226 Gly307Ser association with multiple autoimmune diseases. Genes Immun. 2009; 10:5-10. Lofgren SE, Delgado-Vega AM, Gallant CJ, Sanchez E, Frostegard J, Truedsson L, et al. A 3’-untranslated region variant is associated with impaired expression of CD226 in T and natural killer T cells and is associated with susceptibility to systemic lupus erythematosus. Arthritis Rheum. 2010; 62:3404-3414. Salvarani C, Cantini F, Boiardi L, Hunder GG. Polymyalgia rheumatica and giant-cell arteritis. N Engl J Med. 2002; 347:261-271. Gonzalez-Gay MA, Vazquez-Rodriguez TR, Lopez-Diaz MJ, Miranda-Filloy JA, Gonzalez-Juanatey C, Martin J, et al. Epidemiology of giant cell arteritis and polymyalgia rheumatica. Arthritis Rheum. 2009; 61:1454-1461. <h3>Disclosure of Interest</h3> None Declared
The Pathogenesis of Acute Pulmonary Edema Associated with Hypertension
Authors: Sanjay K. Gandhi, John C. Powers, Abdel-Mohsen Nomeir, Karen Fowle, Dalane W. Kitzman, Kevin M. Rankin, William C. Little
Journal: New England Journal of Medicine (2001)

Patients with acute pulmonary edema often have marked hypertension but, after reduction of the blood pressure, have a normal left ventricular ejection fraction (≥0.50). However, the pulmonary edema may not have resulted from isolated diastolic dysfunction but, instead, may be due to transient systolic dysfunction, acute mitral regurgitation, or both.
Save the Children and GSK join forces to develop drugs for children in developing countries
Authors: S. Mayor
Journal: BMJ (2013)

The charity Save the Children and the drug company GlaxoSmithKline have established a partnership to work together to develop drugs to treat some of the leading causes of deaths in children in developing countries.

The two organisations are working together to prioritise areas for research, plan projects, and share expertise and resources to accelerate the development and availability of drugs and technologies to improve the health of children.

For the first time a member of Save the Children has a place on a new paediatric research and development board to help plan projects for development, and GSK will work with the charity’s healthcare teams on the ground to reach children in remote areas.

“GSK is really engaging with us, focusing on the areas of greatest need and working jointly on projects in the world’s poorest countries,” explained Simon Wright, head of child survival at Save the Children. …
¿PUEDE EL TRATAMIENTO TÓPICO ADYUVANTE ACORTAR LA DURACIÓN DE LA FULGURACIÓN CON ARGÓN PLASMA EN LA RECTITIS RÁDICA?
Authors: B Merino Rodríguez, C González Asanza, J García Lledó, L Pérez Carazo, P De Gracia Celia, C Padilla, A Ahumada, G Perez Rial, A Caballero, Ó Nogales Rincón, P Menchén Fernández Pacheco
Journal: Endoscopy (2013)

Introducción: La rectitis rádica es una complicación a largo plazo de la radioterapia para el cáncer pélvico. Objetivo: Comparar la eficacia y seguridad de dos regímenes de tratamiento: agentes locales tras la coagulación con argón-plasma (APC) vs. APC sólo en pacientes con rectitis post-radioterapia. Material y Método: (60 pacientes) y el cáncer de cérvix (2 pacientes). Los pacientes fueron aleatorizados para recibir 5-aminosalicilatos/sucralfato/budesonida durante 4 semanas más APC o sólo APC. APC se repite cada 8 semanas si es necesario después de la primera sesión. Usando un sistema de puntuación establecido, los pacientes se clasificaron en tres grupos: sin enfermedad, con enfermedad leve y grave antes, a las 16 semanas después del tratamiento inicial de APC (1,5 – 2 l/min, 25 – 40 W) y después de 48 semanas. El éxito se definió como el cese de la hemorragia o una reducción significativa que no requiere tratamiento adicional. Resultados: 62 pacientes (edad media 68,4 años). Todos presentaban sangrado rectal, 26,8 meses de media (rango 7 – 100 meses) tras la radioterapia. Al inicio del estudio no se detectaron diferencias significativas entre ambos grupos: agentes locales + APC (30 pacientes) y APC sólo (32 pacientes). Al año, Se objetivó una mejoría en la escala clínica en ambos grupos no estadísticamente significativa. Hubo diferencias en el número de sesiones (2, 15 vs. 4, 2) y la duración del tratamiento (1, 2 vs. 4, 45meses) a favor del grupo con agentes locales+ APC (no estadísticamente significativas). No hubo complicaciones. Conclusiones: APC es seguro y eficaz para el tratamiento de la rectitis rádica. El tratamiento adyuvante no influye en el resultado clínico o endoscópico, pero podría reducir la duración del tratamiento. Es necesario realizar estudios con mayor número de pacientes para confirmarlo.
Diagnosis of Coliform Infection in Acutely Dysuric Women
Authors: Walter E. Stamm, George W. Counts, Katherine R. Running, Stephen Fihn, Marvin Turck, King K. Holmes
Journal: New England Journal of Medicine (1982)

We reevaluated conventional criteria for diagnosing coliform infection of the lower urinary tract in symptomatic women by obtaining cultures of the urethra, vagina, midstream urine, and bladder urine. The traditional diagnostic criterion, ≥105 bacteria per milliliter of midstream urine, identified only 51 per cent of women whose bladder urine contained coliforms. We found the best diagnostic criterion to be ≥102 bacteria per milliliter (sensitivity, 0.95; specificity, 0.85). Although isolation of <105 coliforms per milliliter of midstream urine has had a low predictive value in previous studies of asymptomatic women, the predictive value of the criterion of ≥102 per milliliter was high (0.88) among symptomatic women in whom the prevalence of coliform infection exceeded 50 per cent. In view of these findings, clinicians and microbiologists should alter their approach to the diagnosis and treatment of women with acute symptomatic coliform infection of the lower urinary tract. (N Engl J Med. 1982; 307:463–8.)
Abstract 5405: PPARγ-agonist can render bladder tumor sensitive to EGFR inhibition
Authors: Jose J. Mansure, Konrad Szymanski, Roland Nassim, Joice Rocha, Saad Aldousari, Simone Chevalier, Wassim Kassouf
Journal: Cancer Research (2010)

Abstract Abstract Purpose: The two signalling molecules that are extremely attractive for targeted therapy are the epidermal growth factor receptor (EGFR) and the peroxisome proliferator-activated receptor γ (PPARγ). We evaluate the integration of combined drugs against these targets in the management of bladder cancer therapy. Methods: The effect of EGFR inhibitor (Gefitinib) and PPARγ-agonist DIM-C, on cell growth, were screened in a panel of 9 human urothelial carcinoma cell lines derived from well-differentiated superficial bladder tumors as well as from high-grade invasive tumors. Cell proliferation was determined with an MTT assay after incubation with varying concentrations of the targeted agents (10-3 to 102 mM) for 72 h. Antiproliferative effects of combined therapy (Gefitinib and DIM-C) compared to each drug alone were monitored in vitro, by MTT assays. Levels of expression of EGFR and PPARγ were evaluated by Western Blot analysis at baseline and after pre-treatment with EGFR inhibitor (Gefitinib). Immunofluorescence was then used to determine PPARγ nuclear accumulation mediated by Gefitinib. In vivo, the effect of Gefitinib, DIM-C alone and combined were determined in nude mice bearing human KU-7 subcutaneous xenografts. Results: Several bladder cancer cell lines were demonstrated to be relatively resistant to Gefitinib. Induction of PPARγ expression was observed in response to different concentrations of Gefitinib for 24 h. Moreover, nuclear accumulation of PPARγ was observed following its upregulation. MTT assay shows that PPARγ agonist significantly sensitized bladder cancer cell lines that were resistant to EGFR inhibition in a schedule-specific manner. These findings were confirmed in vivo where combination therapy maximally inhibited tumor growth in contrast to each treatment alone when compared to control (p&amp;lt;0.04). Conclusions: Preliminary results suggest that PPARγ-agonist DIM-C can render bladder tumor sensitive to EGFR inhibition and combination efficacy might be achieved in a schedule-specific manner. 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 5405.