tbuckley/cabot-search huggingface dataset:
Functional studies of BCL11A: characterization of the conserved BCL11A-XL splice variant and its interaction with BCL6 in nuclear paraspeckles of germinal center B cells
Authors: Hui Liu, Gregory C Ippolito, Jason K Wall, Teresa Niu, Loren Probst, Baeck-Seung Lee, Karen Pulford, Alison H Banham, Luke Stockwin, Arthur L Shaffer, Louis M Staudt, Chhaya Das, Martin JS Dyer, Philip W Tucker
Journal: Molecular Cancer (2006)

Abstract Background Chromosomal aberrations of BCL11A at 2p16.1 have been reported in a variety of B-cell malignancies and its deficiency in mice leads to a profound block in B-cell development. Results Alternative pre-mRNA splicing of BCL11A produces multiple isoforms sharing a common N-terminus. The most abundant isoform we have identified in human lymphoid samples is BCL11A-XL , the longest transcript produced at this locus, and here we report the conservation of this major isoform and its functional characterization. We show that BCL11A-XL is a DNA-sequence-specific transcriptional repressor that associates with itself and with other BCL11A isoforms, as well as with the BCL6 proto-oncogene. Western blot data for BCL11A-XL expression coupled with data previously published for BCL6 indicates that these genes are expressed abundantly in germinal-center-derived B cells but that expression is extinguished upon terminal differentiation to the plasma cell stage. Although BCL11A-XL/BCL6 interaction can modulate BCL6 DNA binding in vitro , their heteromeric association does not alter the homomeric transcriptional properties of either on model reporter activity. BCL11A-XL partitions into the nuclear matrix and colocalizes with BCL6 in nuclear paraspeckles. Conclusion We propose that the conserved N-terminus of BCL11A defines a superfamily of C2HC zinc-finger transcription factors involved in hematopoietic malignancies.
Screening for Asymptomatic Carotid Artery Stenosis: U.S. Preventive Services Task Force Recommendation Statement
Authors: Michael L. LeFevre
Journal: Annals of Internal Medicine (2014)

Update of the 2007 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for carotid artery stenosis.The USPSTF commissioned a systematic review to synthesize the evidence on the accuracy of screening tests, externally validated risk-stratification tools, the benefits of treatment of asymptomatic carotid artery stenosis with carotid endarterectomy (CEA) or carotid angioplasty and stenting (CAAS), the benefits from medications added to current standard medical therapy, and the harms of screening and treatment with CEA or CAAS.This recommendation applies to adults without a history of transient ischemic attack, stroke, or other neurologic signs or symptoms.The USPSTF recommends against screening for asymptomatic carotid artery stenosis in the general adult population. (D recommendation).
Randomized Phase III Trial of Erlotinib Versus Docetaxel As Second- or Third-Line Therapy in Patients With Advanced Non–Small-Cell Lung Cancer: Docetaxel and Erlotinib Lung Cancer Trial (DELTA)
Authors: Tomoya Kawaguchi, Masahiko Ando, Kazuhiro Asami, Yoshio Okano, Masaaki Fukuda, Hideyuki Nakagawa, Hidenori Ibata, Toshiyuki Kozuki, Takeo Endo, Atsuhisa Tamura, Mitsuhiro Kamimura, Kazuhiro Sakamoto, Michihiro Yoshimi, Yoshifumi Soejima, Yoshio Tomizawa, Shun-ichi Isa, Minoru Takada, Hideo Saka, Akihito Kubo
Journal: Journal of Clinical Oncology (2014)

To investigate the efficacy of erlotinib versus docetaxel in previously treated patients with advanced non-small-cell lung cancer (NSCLC) in an epidermal growth factor receptor (EGFR) -unselected patient population.The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), response rate, safety, and analyses on EGFR wild-type tumors. Patients with stage IIIB or IV NSCLC, previous treatment with one or two chemotherapy regimens, evaluable or measurable disease, and performance status of 0 to 2 were eligible.From August 2009 to July 2012, 150 and 151 patients were randomly assigned to erlotinib (150 mg daily) and docetaxel (60 mg/m(2) every 3 weeks), respectively. EGFR wild-type NSCLC was present in 109 and 90 patients in the erlotinib and docetaxel groups, respectively. Median PFS for erlotinib versus docetaxel was 2.0 v 3.2 months (hazard ratio [HR], 1.22; 95% CI, 0.97 to 1.55; P = .09), and median OS was 14.8 v 12.2 months (HR, 0.91; 95% CI, 0.68 to 1.22; P = .53), respectively. In a subset analysis of EGFR wild-type tumors, PFS for erlotinib versus docetaxel was 1.3 v 2.9 months (HR, 1.45; 95% CI, 1.09 to 1.94; P = .01), and OS was 9.0 v 10.1 months (HR, 0.98; 95% CI, 0.69 to 1.39; P = .91), respectively.Erlotinib failed to show an improvement in PFS or OS compared with docetaxel in an EGFR-unselected patient population.
Implications of the Tobacco Industry Documents for Public Health and Policy
Authors: Lisa Bero
Journal: Annual Review of Public Health (2003)

▪ Abstract The release of previously secret internal tobacco industry documents has given the public health community unprecedented insight into the industry's motives, strategies, tactics, and data. The documents provide information that is not available from any other source and describe the history of industry activities over the past 50 years. The documents show that the tobacco industry has been engaged in deceiving policy makers and the public for decades. This paper begins with a brief history of the tobacco industry documents and describes the methodological challenges related to locating and analyzing an enormous number of poorly indexed documents. It provides an overview of selected important findings of document research conducted to date, including analyses of industry documents on nicotine and addiction, product design, marketing and promotion, passive smoke, and internal activities. The paper concludes with a discussion of the implications of tobacco document research for public health and the application of such research to fields other than tobacco control.
Copper Content and Exchange in Mammalian Hearts
Authors: ERNEST PAGE, JUDY EARLEY, LAWRENCE P. McCALLISTER, CHANTAL BOYD
Journal: Circulation Research (1974)

Determination of the copper (Cu) content of rat, rabbit, and mouse hearts proved to be a sensitive microassay for mitochondrial content and membrane area of mitochondrial cristae per unit myocardial cell volume. The direction of variations in Cu content correlated well with variations in membrane area of mitochondrial cristae determined by morphometry of electron micrographs during normal postnatal growth, ventricular hypertrophy after aortic constriction, and thyroxin-stimulated myocardial cell growth. Right and left ventricular and interventricular septal Cu contents per unit dry weight were the same, did not vary during postnatal growth, and significantly exceeded atrial Cu content. Among different mammalian species, ventricular Cu content per unit dry weight tended to vary inversely with adult animal size and thus with adult resting heart rate. The existence of mechanisms for transport of 67 Cu across the myocardial cell plasma membrane and for incorporation of 67 Cu into mitochondrial cristae from an intracellular precursor pool was demonstrated by injecting 67 Cu-labeled blood serum into rats.
Cancer patients requiring interruption of long‐term warfarin because of surgery or chemotherapy induced thrombocytopenia: The use of fixed sub‐therapeutic doses of low‐molecular weight heparin
Authors: Giorgia Saccullo, Alessandra Malato, Simona Raso, Marco Santoro, Valentina Zammit, Alessandra Casuccio, Sergio Siragusa
Journal: American Journal of Hematology (2012)

Abstract No data are available regarding the management of cancer patients requiring interruption of long‐term vitamin‐K antagonist (VKA) therapy. For this purpose, we tested the efficacy and safety of fixed doses of low‐molecular weight heparin (LMWH) in substitution of VKA because of invasive procedures or chemotherapy‐induced thrombocytopenia. In cancer patients on VKA, therapy was discontinued 5 ± 1 days before surgery or chemotherapy. Heparin was given at prophylactic dosage in patients at low risk and at fixed subtherapeutic doses (3,800 or 4,000 UI anti‐FXa, b.i.d.) in those at high‐risk for thrombosis. LMWH was reinitiated 12 hr after surgery and VKA the day after. In patients receiving chemotherapy, LMWH was reinitiated 12/24 hr after obtaining a stable platelet count ≥ 30,000 mmc 3 and VKA after a stable platelet count ≥ 50,000 mmc 3 . Thromboembolism and major bleeding events were recorded from the time of VKA suspension to 30 ± 2 days postprocedure or until the next chemotherapy. Overall, 156 patients (56.4% at low risk and 43.5% at high risk for thrombosis) were enrolled; 34.6% underwent major surgery, 40.4% nonmajor surgery, and 25% chemotherapy. Thrombotic events occurred in five patients [3.2%, 95% confidence interval (CI): 1.41–7.27], four belonging to the high‐risk and one to the low‐risk group. Major bleeding occurred in five patients (3.2%, 95 CI: 1.41–7.27), all belonging to the high‐risk group (three during major surgery and two during chemotherapy). In conclusion, LMWH given at fixed subtherapeutic is a feasible and relatively safe approach for bridging therapy in cancer patients on long‐term VKA. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.
Updated Analysis of SWOG-Directed Intergroup Study 0116: A Phase III Trial of Adjuvant Radiochemotherapy Versus Observation After Curative Gastric Cancer Resection
Authors: Stephen R. Smalley, Jacqueline K. Benedetti, Daniel G. Haller, Scott A. Hundahl, Norman C. Estes, Jaffer A. Ajani, Leonard L. Gunderson, Bryan Goldman, James A. Martenson, J. Milburn Jessup, Grant N. Stemmermann, Charles D. Blanke, John S. Macdonald
Journal: Journal of Clinical Oncology (2012)

Surgical resection of gastric cancer has produced suboptimal survival despite multiple randomized trials that used postoperative chemotherapy or more aggressive surgical procedures. We performed a randomized phase III trial of postoperative radiochemotherapy in those at moderate risk of locoregional failure (LRF) following surgery. We originally reported results with 4-year median follow-up. This update, with a more than 10-year median follow-up, presents data on failure patterns and second malignancies and explores selected subset analyses.In all, 559 patients with primaries ≥ T3 and/or node-positive gastric cancer were randomly assigned to observation versus radiochemotherapy after R0 resection. Fluorouracil and leucovorin were administered before, during, and after radiotherapy. Radiotherapy was given to all LRF sites to a dose of 45 Gy.Overall survival (OS) and relapse-free survival (RFS) data demonstrate continued strong benefit from postoperative radiochemotherapy. The hazard ratio (HR) for OS is 1.32 (95% CI, 1.10 to 1.60; P = .0046). The HR for RFS is 1.51 (95% CI, 1.25 to 1.83; P < .001). Adjuvant radiochemotherapy produced substantial reduction in both overall relapse and locoregional relapse. Second malignancies were observed in 21 patients with radiotherapy versus eight with observation (P = .21). Subset analyses show robust treatment benefit in most subsets, with the exception of patients with diffuse histology who exhibited minimal nonsignificant treatment effect.Intergroup 0116 (INT-0116) demonstrates strong persistent benefit from adjuvant radiochemotherapy. Toxicities, including second malignancies, appear acceptable, given the magnitude of RFS and OS improvement. LRF reduction may account for the majority of overall relapse reduction. Adjuvant radiochemotherapy remains a rational standard therapy for curatively resected gastric cancer with primaries T3 or greater and/or positive nodes.
Beliefs about hydration and physiology drive drinking behaviours in runners
Authors: James M Winger, Jonathan P Dugas, Lara R Dugas
Journal: British Journal of Sports Medicine (2010)

Exercise-associated hyponatraemia (EAH) is a dilutional hyponatraemia that is caused primarily by the intake of hypotonic fluid beyond the dictates of thirst and exacerbated by the syndrome of inappropriate antidiuretic hormone secretion as well as an inability to mobilise osmotically inactive sodium stores. Runners who drink more than to their thirst do so for a reason, and understanding and curtailing this behaviour will probably decrease the incidence of this highly preventable condition.To determine the beliefs about fluid replacement held by runners and whether these beliefs are reflected in hydration behaviours.An online survey was filled out by 197 runners solicited by personal solicitation, e-mail and flyers distributed at three local races in autumn 2009.Most runners (58%) drink only when thirsty. Runners drinking to a set schedule are significantly older, more experienced and faster than those drinking when thirsty. Gastrointestinal distress is the most frequently cited (71.5%) reason to avoid overhydration. Runners have a poor understanding of the physiological consequences of hydration behaviours that frequently reflect messages of advertising.Runners at highest risk of EAH exhibit behaviour that is shaped by their beliefs about the benefits and risks of hydration. These beliefs are frequently based on misconceptions about basic exercise physiology.
What Don't We Know About Colonoscopy? New Study Raises Questions About Practice, Biology, and More
Authors: R. Twombly
Journal: JNCI Journal of the National Cancer Institute (2009)

The study offered two surprises. Researchers in Toronto found that although a history of colonoscopy appeared to be associated with a lower risk of death from colorectal cancer, the drop was not as dramatic as has been assumed. Physicians have long told their patients that the screening procedure probably prevents 90% of colon cancer incidence — suggesting by inference that the mortality reduction could be as high. But this study found that roughly 67% of deaths were prevented. And that is an important finding, because the study, published in the January 6 issue of the Annals of Internal Medicine , is the fi rst population-based, case-control study of colonoscopy to look at mortality reduction. No randomized mortality studies have been carried out to date; the landmark National Polyp Study looked only at colon cancer incidence in people screened with a colonoscopy. But even more surprising was the fi nd- ing that the reduction in death was only from cancers detected in the left side of the colon. The death rate from right-sided colon tumors was the same whether or not a person had a colonoscopy. There certainly seems to be a dra- matic difference between the effectiveness of colonoscopy for prevention of mortal- ity on the left side versus the right side, said the study's lead researcher, Nancy Baxter , M.D., a colorectal surgeon and researcher at St. Michael's Hospital and an investigator at the Institute for Clinical and Evaluative Sciences. That's not to say that colonoscopies don't fi nd colorec- tal cancers.  clearly fi nds cancers on the right side, Baxter said. It just doesn't seem to prevent colorectal cancer deaths on the right side. Whereas some gastroenterologists who perform colonoscopies complained that the study was fl awed, others said that the fi nd- ings raised important questions and should, at least, be seen as a wake-up call for physi- cians who perform these tests. What this article basically does is it
An Experimental Inquiry INTO THE RELATIONSHIP OF ACTION TO DOSE ESPECIALLY WITH REFERENCE TO REPEATED ADMINISTRATION OF INDACONITINE
Authors: J. T. Cash
Journal: BMJ (1908)

A&TkouGH the consideration of of dose, as well as of the principles of readministration in the treatment of caes calling for more or less prolonged medication, are of ppime importance therapeutically, it must be admitted that they have scarcely received the amount of attention to which they are obviously entitled.Stokvisasserts that'thee is perhaps no part of our science which does not defy our aspirations to precision more than the Posology, whilst Harnack laments the inattention of medical practitioners towards such an Important question, remarkng that there exists a surprising carelessness and caprice in the matter.Sir Benjamin Brodie receognized the error of the assertion, which Is even to-day ocasiaon-
Prognostic Significance of Nottingham Histologic Grade in Invasive Breast Carcinoma
Authors: Emad A. Rakha, Maysa E. El-Sayed, Andrew H.S. Lee, Christopher W. Elston, Matthew J. Grainge, Zsolt Hodi, Roger W. Blamey, Ian O. Ellis
Journal: Journal of Clinical Oncology (2008)

The three strongest prognostic determinants in operable breast cancer used in routine clinical practice are lymph node (LN) stage, primary tumor size, and histologic grade. However, grade is not included in the recent revision of the TNM staging system of breast cancer as its value is questioned in certain settings.This study is based on a large and well-characterized consecutive series of operable breast cancer (2,219 cases), treated according to standard protocols in a single institution, with a long-term follow-up (median, 111 months) to assess the prognostic value of routine assessment of histologic grade using Nottingham histologic grading system.Histologic grade is strongly associated with both breast cancer-specific survival (BCSS) and disease-free survival (DFS) in the whole series as well as in different subgroups based on tumor size (pT1a, pT1b, pT1c, and pT2) and LN stages (pN0 and pN1 and pN2). Differences in survival were also noted between different individual grades (1, 2, and 3). Multivariate analyses showed that histologic grade is an independent predictor of both BCSS and DFS in operable breast cancer as a whole as well as in all studied subgroups.Histologic grade, as assessed by the Nottingham grading system, provides a strong predictor of outcome in patients with invasive breast cancer and should be incorporated in breast cancer staging systems.
Clinical Impact of Discordance in Serum Albumin Measurements on Myeloma International Staging System
Authors: Prashant Kapoor, Christine L.H. Snozek, Colin Colby, Dirk R. Larson, Jerry A. Katzmann, S. Vincent Rajkumar, Philip R. Greipp
Journal: Journal of Clinical Oncology (2008)

Fig 1.Comparison of survival curves of myeloma patients staged by the International Staging System using chemistry (bromcresol green [BCG]) albumin and electrophoretic (protein electrophoresis [PEL]) albumin (group A patients: stage I based on BCG albumin but stage II based on PEL albumin; group B patients: stage II based on BCG albumin but stage I based on PEL albumin).
<i>cis</i> Element Decoy Against Nuclear Factor-κB Attenuates Development of Experimental Autoimmune Myocarditis in Rats
Authors: Osamu Yokoseki, Jun-ichi Suzuki, Hiroshi Kitabayashi, Noboru Watanabe, Yuko Wada, Motokuni Aoki, Ryuichi Morishita, Yasufumi Kaneda, Toshio Ogihara, Hideki Futamatsu, Yasushi Kobayashi, Mitsuaki Isobe
Journal: Circulation Research (2001)

Nuclear factor-kappaB (NFkappaB) plays a significant role in the coordinated transactivation of cytokine, inducible NO synthase (iNOS), and adhesion molecule genes. Although inflammation is an essential pathological feature of myocarditis, the role of NFkappaB in this process remains obscure. We examined the role of NFkappaB in the progression of rat experimental autoimmune myocarditis (EAM) and tested the hypothesis that NFkappaB blockade with a decoy against the cis element of NFkappaB can prevent the progression of EAM. Lewis rats were immunized with purified porcine cardiac myosin to establish EAM on day 0. NFkappaB decoy was infused into the rat coronary artery on day 0 (group NF0), 7 (group NF7), or 14 (group NF14) and harvested on day 21. Scrambled decoy was infused on day 0 (group SD0), 7 (group SD7), or 14 (group SD14) and served for control groups. The ratios of myocarditis-affected areas to the ventricular cross-sectional area of all treatment groups were significantly lower than those of the control groups (group NF0, 33+/-18% versus SD0, 53+/-14%; group NF7, 19+/-15% versus SD7, 50+/-16%; and group NF14, 34+/-10% versus SD14, 52+/-14%). Immunohistochemical and immunoblot analyses showed expression of ICAM-1, iNOS, IL-2, and TNFalpha in myocardium of scrambled decoy groups, and this expression was effectively suppressed by NFkappaB decoy treatment. Thus, we found that NFkappaB is a key regulator in the progression of EAM and that in vivo transfection of NFkappaB decoy reduces the severity of EAM.
Analysis of impaired in vitro immunoglobulin synthesis in rheumatoid arthritis.
Authors: I Jokinen, K Poikonen, T Mottonen, P Hannonen, M Oka, J Ilonen, H M Surcel, R Karttunen, H Arvilommi
Journal: Annals of the Rheumatic Diseases (1990)

Decreased immunoglobulin production in pokeweed mitogen driven lymphocyte cultures has been reported in rheumatoid arthritis (RA). Here various activators and experimental designs have been used to determine the contribution of B cells, T cells, or monocytes to this low response. Sixty patients with RA and paired controls were studied at the onset of disease and again six months later. Concentrations of IgA, IgG, and IgM in cultures of RA peripheral blood mononuclear cells stimulated with thymus dependent activators were already decreased at the onset of the disease. Six months later RA mononuclear cells produced even lower concentrations of immunoglobulin. In contrast, stimulation with a T cell independent activator showed that RA B lymphocytes had retained normal potential to synthesise immunoglobulin. Poor helper function was indicated by costimulation experiments and cultures of mixed mononuclear cells from patients and controls. This notion was supported also by the fact that phytohaemagglutinin induced interleukin-2 production by RA mononuclear cells was less than half of the control values. Nonspecific suppressor activity was similar in RA and controls. Monocyte functions were normal when tested by addition of indomethacin or 2-mercaptoethanol to the mitogen activated cultures. The defect in mitogen stimulated immunoglobulin production in vitro of RA mononuclear cells thus was more pronounced with time and probably reflects impaired mediator associated help in the differentiation of B lymphocytes into immunoglobulin secreting cells.