tbuckley/cabot-search huggingface dataset:
Pigeon fancier's lung
Authors: A M. Ward, P A E White, D. Leung
Journal: BMJ (1997)

More widespread public debate on rationing is essentialEditor-We find it significant that none of the clinicians who contributed to the conference "Rationing in the NHS: Time to Get Real" signed the open letter to Frank Dobson. 1 In the letter, rationing is defined as occurring when not all health services can be provided to everybody who might benefit from them, a definition so broad that it can be said always to have existed.Yet most British clinicians would not recognise the examples given as rationing.A young woman with high cholesterol as a single risk factor for coronary heart disease may be "denied" drug treatment and given dietary advice instead simply because the risks of side effects outweigh the marginal benefit; this is rational, not rationing.Again, "denying" magnetic resonance imaging for uncomplicated migraine in a young person has nothing to do with cost: the risks of iatrogenic anxiety and distress are far greater than any possible benefit from such intervention.The authors do the cause of so called smart rationing a disservice by these examples.This debate is too important to be "dumbed down" in this way.Whenever rationing is discussed there is a tension between those whose professional discipline (health economics, medical ethics, or policy analysis) allows them to work with broad underlying principles and those who are constantly brought face to face with the limitations of these principles through daily contact with patients.The former are much more likely to believe that it is possible and appropriate to base all rationing decisions on a series of well argued principles.Life for the latter is far messier: it is often impossible to apply broad principle to individual cases, let alone find a "currency of comparison" 2 that will enable the claims of, for example, a dying older person on an understaffed geriatric ward to be ranked against those of a patient with multiple sclerosis who might benefit from interferon beta.Struggling to make these sorts of comparisons is painful; the examples given in the open letter tax no one and thereby offer false hope of easy solutions.It is because the choices are difficult that more widespread public debate is essential.Only through such a debate can we all, as citizens, realise what is happening to the NHS, consider if that is the NHS that we want, and decide how much of our taxes an NHS worthy of the name deserves.
Inhibition of estrogen receptor negative breast cancer cell growth by a new class of peroxisome proliferator-activated receptor γ agonists
Authors: Kathryn E. Vanderlaag, Kelcey Walker, Ismael Samudio, Stephen Safe
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

3856 

A series of 1,1-bis(3’-indolyl)-1-(p-substituted phenyl)methanes activate peroxisome proliferator-activated receptor γ (PPARγ) and inhibit growth of estrogen receptor (ER)-positive breast cancer cells. The most active methylene-substituted diindolylmethane (DIM) compounds contained p-CF3 (DIM-p-pPhCF3), p-tbutyl (DIM-C-pPhtBu) and p-C6H5 (DIM-C-pPhC6H5) substituents and the effects of these compounds on proliferation of ER-negative MDA-MB-231 and MDA-MB-453 breast cancer cells were investigated. The PPARγ-active methylene substituted DIMs inhibited growth of both ER-negative cell lines and the concentrations required for 50% growth inhibition (IC50) were 1-5 μM. MDA-MB-453 cells were treated for 96 hours with DMSO, 1 or 5 uM DIM-C-pPhC6H5. FACS analysis showed that the percentage of cells in G0/G1, G2/M and S phase was 73.8, 7.54 and 18.7% respectively in DMSO (solvent) treated cells whereas these percentages were 86.3, 5.46 and 8.23% respectively after treatment with 5 μM DIM-C-pPhC6H5. No significant changes were observed in cells treated with 1 μM DIM-C-pPhC6H5, however the higher concentration significantly blocked G0/G1 to S phase progression. MDA-MB-231 cells treated for 12 hours with 1-10 μM DIM-C-pPhCF3 were also investigated in cell cycle progression studies. The percentage of cells in G0/G1, G2/M and S phase with DMSO treatment were 57.3, 14.8, 27.9% respectively and 71.5, 13.7, 14.7% with 10 μM DIM-C-pPhCF3 treatment. No substantial differences were seen with 1 or 5 μM treatment of DIM-C-pPhCF3 in MDA-MB-231 cells. The PPARγ-active compounds had minimal effects on expression of cyclin D1 and cyclin-dependent kinase inhibitors p21 and p27 in MDA-MB-453 cells whereas both p21 and p27 protein were induced in MDA-MB-231 cells. Other cell context-dependent mechanisms of growth inhibition are currently being investigated.
Optogenetics: 10 years after ChR2 in neurons—views from the community
Authors: Antoine Adamantidis, Silvia Arber, Jaideep S Bains, Ernst Bamberg, Antonello Bonci, György Buzsáki, Jessica A Cardin, Rui M Costa, Yang Dan, Yukiko Goda, Ann M Graybiel, Michael Häusser, Peter Hegemann, John R Huguenard, Thomas R Insel, Patricia H Janak, Daniel Johnston, Sheena A Josselyn, Christof Koch, Anatol C Kreitzer, Christian Lüscher, Robert C Malenka, Gero Miesenböck, Georg Nagel, Botond Roska, Mark J Schnitzer, Krishna V Shenoy, Ivan Soltesz, Scott M Sternson, Richard W Tsien, Roger Y Tsien, Gina G Turrigiano, Kay M Tye, Rachel I Wilson
Journal: Nature Neuroscience (2015)
Molecular prediction of durable remission after first-line fludarabine-cyclophosphamide-rituximab in chronic lymphocytic leukemia
Authors: Davide Rossi, Lodovico Terzi-di-Bergamo, Lorenzo De Paoli, Michaela Cerri, Guido Ghilardi, Annalisa Chiarenza, Pietro Bulian, Carlo Visco, Francesca R. Mauro, Fortunato Morabito, Agostino Cortelezzi, Francesco Zaja, Francesco Forconi, Luca Laurenti, Ilaria Del Giudice, Massimo Gentile, Iolanda Vincelli, Marina Motta, Marta Coscia, Gian Matteo Rigolin, Alessandra Tedeschi, Antonino Neri, Roberto Marasca, Omar Perbellini, Carol Moreno, Giovanni Del Poeta, Massimo Massaia, Pier Luigi Zinzani, Marco Montillo, Antonio Cuneo, Valter Gattei, Robin Foà, Gianluca Gaidano
Journal: Blood (2015)
Alpha-1 Antitrypsin Deficiency and Lung Cancer Risk
Authors: María Torres-Durán, Alberto Ruano-Ravina, Isaura Parente-Lamelas, José Abal-Arca, Virginia Leiro-Fernández, Carmen Montero-Martínez, Carolina Pena, Olalla Castro-Añón, Antonio Golpe-Gómez, Francisco J. González-Barcala, Cristina Martínez, Rosirys Guzmán-Taveras, Mariano Provencio, María José Mejuto-Martí, Alberto Fernández-Villar, Juan Miguel Barros-Dios
Journal: Journal of Thoracic Oncology (2015)
Abstract 12763: Imatinib Mesylate Attenuates Hypertensive Cardiovascular Remodeling in Spontaneously Hypertensive Rats
Authors: Sang-Hyun Ihm, Eun-Ho Choo, Ok-Ran Kim, Myung Hee Kim, Hee Jung Lee, Hyo Eun Park, Kiyuk Chang, Chan-Seok Park, Hee-Yeol Kim, Wook-Sung Chung, Ki-Bae Seung, Jae-Hyung Kim
Journal: Circulation (2011)
Improved Patient Satisfaction, Adherence and Health-Related Quality of Life with Deferasirox (Exjade®) in β-Thalassemia Patients Previously Receiving Other Iron Chelation Therapies.
Authors: John B. Porter, Miranda Athanasiou-Metaxa, Donald K. Bowden, Jacques Troncy, Dany Habr, Gabor Domokos, Bernard Roubert, Diana Rofail, Adam Gater, Jean-François Baladi, M. Domenica Cappellini
Journal: Blood (2009)
Adverse events due to chemotherapy in emergency room
Authors: S. Serrano Solares, M. Vidal, A. Ferrer, M. Tobeña, E. Millastre, M. Ruiz Echarri, I. Pajares, D. Lopez, A. Tres, J. Lambea
Journal: Journal of Clinical Oncology (2009)

e20701 Background: High rates of mortality due to cancer make necessary improve oncologic treatments. Relationship between adverse events and chemotherapy schedule and dose is well known thanks to large observational studies. Our study´s objective is to estimate the prevalence of chemotherapy adverse events in oncologic patients attended in Emergency room. Methods: From October 2007 to October 2008 560 patients were recollected. It was revised tumors location and stage, chemotherapy schedule and date of the last treatment, diagnosis and therapheutic in Emergency. Results: 87 of the 560 patients (15%) were attended in Emergency room because of chemotherapy toxicity. The most common cause of consultation was fever (27 patients, 31%) followed by diarrhea (18 patients, 20.7%) and nausea-vomiting (12 patients, 13.8%). Most of the patients were being treated with classic chemotherapy schedules (70.1%). Comparing as a whole all the chemotherapy schedules there were not statistically significant differences due to toxicity between them. Nevertheless analyzing by subgroups we found there was no difference between toxicity in patients treated with classic chemotherapy and chemotherapy plus target agents (33.8% vs 5.5%, p=0.30), but there was differences between chemotherapy and target agents in monotherapy (33.8% vs 13.2%, p&lt;0.05). In 39 of the 87 patients (39%) admission was required with a good evolution in most of them. Conclusions: Adverse events due to chemotherapy is a common cause of consultation in Emergency room. In our sample new target agents did not add toxicity to classic chemotherapy and given as monotherapy they had really good tolerance. More randomized studies are necessary to do a better evaluation of adverse events due to new agents. No significant financial relationships to disclose.
Abstract 13662: Different Estimation of Arterial Age and Cardiovascular Risk by Test of Subclinical Atherosclerosis
Authors: Sebastian Graf, Gilles Chironi, Jean-Louis Megnien, Alain Simon
Journal: Circulation (2010)

Background: As individual's arterial age assessed from atherosclerosis burden may vary according to the test used, we compared arterial age estimated by testing coronary artery calcium (CAC), carot...
Abstract 16363: Contributions of Cardiovascular Disease Risk Factors to Racial/Ethnic Differences in Sleep Duration: Chicago Area Sleep Study
Authors: Mercedes R Carnethon, Kristen L Knutson, Jason Ng, Peter J de Chavez, Kwang-Youn Kim, Kiang Liu, Jeffrey J Goldberger, Phyllis Zee
Journal: Circulation (2011)

Introduction: Shortened sleep duration is associated with cardiovascular disease (CVD) risk factors (e.g., hypertension, obesity, diabetes). Epidemiologic studies in diverse samples describe shorte...
Abstract 16497: The Impact of Adiposity and Weight Loss on Intima Media Thickness in Adulthood
Authors: Marietta Charakida, Tauseef Khan, William Johnson, John Woodside, Diana Kuh, Nicholas Finer, Rebecca Hardy, John Deanfield
Journal: Circulation (2013)

Background: Increased adiposity has been associated with adverse cardiovascular (CV) outcome. We examined whether exposure to adiposity has a cumulative effect on carotid intima media thickness (cI...
Curcumin: An adjuvant chemotherapeutic for lung cancer
Authors: Sudip Sen, Himani Sharma, Neeta Singh
Journal: Cancer Research (2004)

2956  Lung cancer accounts for a major load (17%) of all cancer related deaths worldwide with more than half of all lung cancer patients in developing countries presenting in advanced stages (Stage IIIB and IV). Multiple studies have shown that new single agents like Vinorelbine are much less toxic but as effective as previously used Cisplatin based combinations. Hence, it is a realistic single drug option for patients with advanced Non Small Cell Lung Carcinoma (NSCLC). Apoptosis is a critical mechanism essential for the action of most chemotherapeutic agents. Thus a better understanding of the molecular mechanisms of apoptosis and augmentation in chemotherapy and chemo-adjuvant therapies are needed. The objective of this study was to investigate whether efficacy of Vinorelbine as an anticancer drug in lung cancer can be enhanced by pretreatment with chemopreventive agent Curcumin. Lung squamous cell carcinoma cells (H520) were cultured in DMEM with 10% FCS. They were treated with a dose of 25μM Curcumin and/or 0.1 μg/ml Vinorelbine for 24 hours each. Apoptosis was detected by morphological examination, TUNEL assay and flowcytometry. Apoptosis and its related proteins were studied by Western blotting and Caspase-3 activity assay. 39% & 24% apoptosis were seen on treatment of H520 cells with Vinorelbine & Curcumin respectively for 24 hours. Priming with Curcumin for 24 hours augmented the Vinorelbine induced apoptosis to 61%. Protein expression analysis revealed that Curcumin & Vinorelbine decreased antiapoptotic Bcl-XL by 34% & 50% respectively, whereas their combination caused a 63% decrease. Proapoptotic Bcl-Xs was increased by 86% by Curcumin & 110% by Vinorelbine and their combination caused a 220% increase. Antiapoptotic Bcl-2 was decreased by 42% and 10% by Curcumin & Vinorelbine alone, while their combination caused a 50% reduction in the same protein. Bax, another pro-apoptotic protein was up-regulated by 64% and 328% by Curcumin & Vinorelbine alone, while their combination caused a 514% upregulation. Cox-2 was decreased by 40% & 8% on Curcumin & Vinorelbine treatments while their combination decreased it by 41%. The uncleaved fragment of Poly-ADP ribose polymerase (PARP) was decreased by 27% and 61% by Curcumin & Vinorelbine alone while their combination caused a 92% decrease. The activity of downstream effector caspase, Caspase-3, corroborated the above results. The findings demonstrate that Vinorelbine induces apoptosis which can be augmented by prior treatment with Curcumin in lung cancer H520 cells. The observations suggest that Bax, Bcl-2, Bcl-XL, Bcl-Xs and Cox-2 are ideal targets for chemotherapy & chemosensitization. It is hoped that less toxic and targeted therapies will provide relief particularly in patients suffering from advanced lung cancer.
Abstract 1697: Normal Right Ventricle Anatomy and Function in a Longitudinally Followed Cohort Free of Hypertension and Cardiovascular Disease: A Cardiovascular Magnetic Resonance Study of the Framingham Heart Study Offspring Cohort
Authors: Garima Arora, Philmon Gona, Carol J Salton, Michael L Chuang, Rahul R Jhaveri, Raghava S Velagaleti, Susan B Yeon, Christopher J O'Donnell, Warren J Manning
Journal: Circulation (2009)
Modulation of extracellular receptor kinase (ERK) by radiation
Authors: Mukesh K. Nyati, Divya Maheshwari, Vinay Arora, Mary A. Davis, Theodore S. Lawrence
Journal: Cancer Research (2004)

1298   Signal-transduction genes such as EGFR and RAS, which encode components of the MAPK pathway, are frequently over-expressed or mutated in a variety of cancers. A majority of colorectal cancers carry either a RAS or a BRAF mutation. The BRAF gene codes for a serine/threonine kinase just downstream from RAS that activates p42/44 ERK via phosphorylation. In some instances, ionizing radiation activates the EGFR via its phosphorylation, which is a major effector of the p42/44 mitogen-activated protein kinase (MAPK/ERK) pathway. This pathway has been proposed to be involved in cell proliferation or repopulation after radiation. We wished to understand the significance of the EGFR and MAPK pathways in radiation-induced cell death and/or survival. For this purpose we chose a panel of cell lines including SW620 colorectal cell line, MDA-MB-468 breast carcinoma, A431 epidermoid carcinoma, normal skin fibroblasts and ATM cells. SW620 cells do not express EGFR (absent by immunoblotting and RT-PCR), while both MDA-MB-468 and A-431 have EGFR amplification and overexpression. The surviving fractions of SW620 and MDA-MB-468 cells irradiated with 2 Gy were 0.37 ± 0.05 and 0.32 ± 0.06, respectively. Cells were irradiated with 2-8 Gy. Phospho p42/44-ERK levels were assessed by immunoblotting at various time interval post irradiation. We found that p42/44 ERK levels were decreased in a dose dependent manner relative to control within 5 min of irradiation in SW620, MDA-MB-468 and fibroblasts. In these cells the p42/44 ERK levels recovered by 2h at 2 or 4 Gy dose levels. However we found as reported before, that in confluent A-431 cells the p42/44 ERK levels were increased within 2 min post irradiation, the levels returned to baseline by 20 min. In contrast the pERK activity was not affected in ATM cells. These results demonstrate that p42/44 ERK can be modulated by ionizing radiation, but that this effect is independent of EGFR. These findings suggest that it will be critical to measure downstream effects, rather than simply EGFR presence or activation, in determining the effect of radiation on signal transduction.
P0369 : Circulating SCCA-IgM complex is a useful biomarker to predict the outcome of therapy in HCC patients
Authors: F. Morisco, M. Guarino, G.G. Di Costanzo, A. Gallotta, G. Fassina, R. Tortora, C. Tuccillo, R. Granata, I. Loperto, F. Auriemma, N. Caporaso
Journal: Journal of Hepatology (2015)
Anti-tumoral and anti-osteolytic activity of zoledronic acid (ZA) in a preclinical model of neuroblastoma bone invasion
Authors: Hongjun Peng, Yasuyoshi Sohara, Hiroyuki Shimada, Maria L. Mouchess, Rex A. Moats, Marvin D. Nelson, Susan G. Groshen, C. Patrick Reynolds, Yves A. Declerck
Journal: Cancer Research (2006)

4334   Metastasis to the bone is seen in 56% of patients with neuroblastoma and is a major factor of mortality and morbidity. Using a murine model of bone invasion, we have previously reported that neuroblastoma cells invade the bone by activating osteoclasts. Here we investigated the anti-tumor and anti-osteolytic activities of zoledronic acid (ZA), a nitrogen containing bisphosphonate, in a murine xenotransplant model.  Nu/nu  mice were injected into the femur with CHLA-255 and SMS-SAN human neuroblastoma cells(2×10 5 ) and treated with ZA (4 μg/mouse/day). Whereas all mice in the control group (receiving an i.p. injection on sterile 0.9% NaCl) showed radiological evidence of cortical breach or pathological fracture of the femur (grade IV radiological lesion) by 10 to 12 weeks, 60% of the mice in the treated group were free of a grade 4 radiological lesion 15 weeks after tumor cell injection. A histological analysis of the femur of these mice 3 weeks after treatment revealed a 50% decrease in the amount of osteoclasts in the treated group (p 2  in the treated group vs. 80 ± 45 TUNEL pos. cells/mm 2  in the control group, p in vitro. The data revealed a dose dependent increase in Annexin V positive cells and a decrease on BrdU positive cells in the presence of ZA at concentrations ranging from 6.25 to 100 μM. We then demonstrated that ZA induced apoptosis through the activation of caspase 3 and the downregulation of the pro-apoptotic Bcl-2 protein. The data thus demonstrates that ZA has a dual anti-tumor and anti-osteoclast activity and provides evidence to support the use of ZA in the treatment of children with neuroblastoma bone metastasis.
Abstract 726: Cardiac Sympathetic Nerve System Abnormality Predicts Long-Term Outcome in Patients with Paroxysmal Atrial Fibrillation who did not have Conventional Risk Factors
Authors: Yasushi Akutsu, Kyouichi Kaneko, Yusuke Kodama, Hui-Ling Li, Jumpei Suyama, Akira Shinozuka, Takehiko Gokan, Youichi Kobayashi
Journal: Circulation (2008)

Backgrounds: A history of structural heart disease, heart failure, or stroke increases mortality in patients with atrial fibrillation (AF). However, a useful marker for predicting mortality is not clarified in AF patients without those conventional risks. We recently reported cardiac sympathetic nerve system (SNS) abnormality as a predictor of arrhythmogenic mortality. We hypothesized that SNS abnormality would be associated with increased mortality in patients with paroxysmal AF who didn’t have conventional risk factors. Methods and Results: Iodine-123 metaiodobenzylguanidine scintigraphy was performed to measure Heart/Mediastinum (H/M) ratio as SNS activity in 48 patients (mean ± standard deviation, age: 65 ± 14 years, 65% males) with paroxysmal AF who didn’t have structural heart disease, heart failure, or stroke. P wave dispersion on 12-lead ECG and left atrial dimension on echocardiography were also measured to evaluate structural and electrical properties. Over 11 years follow up, 15 patients (31.3%) transited to permanent AF, and 12 (25%) had cardio/cerebrovascular events. SNS abnormality (defines as H/M ratio &lt;2.7) was a powerful predictor of vascular events (50% in 9 of 18 patients with SNS abnormality vs 10% in 3 of 30 patients without those, p=0.0008). After adjustment for potential confounding variables such as age, gender, P wave dispersion, left atrial dimension, transit to permanent AF, and medications, SNS abnormality remained predictive of vascular events with hazard ratio of 6.9 [95% confidence interval, 1.9 to 25.7 (p=0.004)]. Conclusion: SNS abnormality is predictive of mortality in patients with paroxysmal AF who did not have conventional risk.
Gene Therapy Restores Hair Cell Stereocilia Morphology in Inner Ears of Deaf Whirler Mice
Authors: Wade W Chien, Kevin Isgrig, Soumen Roy, Inna A Belyantseva, Meghan C Drummond, Lindsey A May, Tracy S Fitzgerald, Thomas B Friedman, Lisa L Cunningham
Journal: Molecular Therapy (2015)

Hereditary deafness is one of the most common disabilities affecting newborns. Many forms of hereditary deafness are caused by morphological defects of the stereocilia bundles on the apical surfaces of inner ear hair cells, which are responsible for sound detection. We explored the effectiveness of gene therapy in restoring the hair cell stereocilia architecture in the whirlin mouse model of human deafness, which is deaf due to dysmorphic, short stereocilia. Wild-type whirlin cDNA was delivered via adeno-associated virus (AAV8) by injection through the round window of the cochleas in neonatal whirler mice. Subsequently, whirlin expression was detected in infected hair cells (IHCs), and normal stereocilia length and bundle architecture were restored. Whirlin gene therapy also increased inner hair cell survival in the treated ears compared to the contralateral nontreated ears. These results indicate that a form of inherited deafness due to structural defects in cochlear hair cells is amenable to restoration through gene therapy. Hereditary deafness is one of the most common disabilities affecting newborns. Many forms of hereditary deafness are caused by morphological defects of the stereocilia bundles on the apical surfaces of inner ear hair cells, which are responsible for sound detection. We explored the effectiveness of gene therapy in restoring the hair cell stereocilia architecture in the whirlin mouse model of human deafness, which is deaf due to dysmorphic, short stereocilia. Wild-type whirlin cDNA was delivered via adeno-associated virus (AAV8) by injection through the round window of the cochleas in neonatal whirler mice. Subsequently, whirlin expression was detected in infected hair cells (IHCs), and normal stereocilia length and bundle architecture were restored. Whirlin gene therapy also increased inner hair cell survival in the treated ears compared to the contralateral nontreated ears. These results indicate that a form of inherited deafness due to structural defects in cochlear hair cells is amenable to restoration through gene therapy.
Monoclonal Antibodies in Multiple Myeloma Come of Age
Authors: Noopur Raje, Dan L. Longo
Journal: New England Journal of Medicine (2015)

Multiple myeloma is a cancer of plasma cells that has an estimated incidence of 26,850 new patients in 2015 in the United States.1 In the past few years, dramatic progress has been made in the treatment of this disease. New classes of drugs, including proteasome inhibitors (e.g., bortezomib and carfilzomib) and immunomodulatory agents (e.g., lenalidomide and pomalidomide), have improved response rates and survival significantly, and it now appears that immunotherapy is likely to lead to even greater advances.Results regarding the use of daratumumab, an antibody directed against CD38, in patients with relapsed, refractory multiple myeloma are now reported in . . .