tbuckley/cabot-search huggingface dataset:
Ethical considerations in the design and execution of the National and Hispanic Health and Nutrition Examination Survey (HANES).
Authors: D K Wagener
Journal: Environmental Health Perspectives (1995)

The purpose of this article is to describe some ethical considerations that have arisen during the design and implementation of the health examination surveys conducted by the National Center for Health Statistics of the Centers for Disease Control and Prevention. Three major areas of concern are discussed: sharing information from the study, banking and using banked tissue samples, and obligations for future testing of subjects. Specific concerns of sharing information include: when to inform, whom to inform, maintaining confidentiality, and how to inform individuals. Specific concerns of determining when sera will be banked and using banked samples include: depletion of samples for quality control, obtaining informed consent for unanticipated uses, access by others, and requests for batches of samples. Finally, specific concerns regarding future testing of subjects include: retesting for verification, retesting for interpretation, testing for different risk factors, and follow-up. Although existing surveys can provide experience or even suggest guidelines, the uniqueness of any new survey will generate unique ethical problems, requiring the careful formulation of unique solutions.
Clinical Significance of Ploidy in Carcinoma of Cervix: Its Relation to Prognosis
Authors: N. B. Atkin, B. M. Richards
Journal: BMJ (1962)

MEDIBLNoRrHL 1445 within the hepatic duct for the relief of obstruction by extrinsic carcinoma (cf.Cattell, 1943 ; Grey Turner, 1955; McGoon and Clagett
Abstract 1046: AS1411 activity is regulated by epidermal growth factor receptor signaling pathway.
Authors: Elsa M. Reyes-Reyes, Francesca R. Salipur, Paula J. Bates
Journal: Cancer Research (2013)

Abstract The anticancer AS1411 agent is a G-rich phosphodiester oligodeoxynucleotide, which forms a stable quadruplex structure and binds specifically to nucleolin as an aptamer. It efficiently inhibits proliferation and induces cell death in many types of cancer cells, but has little effect on normal cells. We have also shown that AS1411 is taken up by macropinocytosis and stimulates further macropinocytosis by a nucleolin-dependent mechanism in several cancer cells. AS1411 activity correlates with stimulated macropinocytosis, suggesting this hyperstimulation of macropinocytosis may explain the unusual cancer cell death caused by AS1411. Macropinocytosis is a ligand-independent endocytic pathway that is normally activated by growth factor receptor stimulation. On the other hand, nucleolin has been reported that can enhance growth factor signaling by binding directly to some growth factor receptors. Therefore in this study, we determine the participation of growth factor signaling pathway in AS1411-induced macropinocytosis and cell death. Pre-incubation of DU145 cells with a specific EGFR inhibitor, but not PDGFR or JAK2 inhibitors, significantly inhibited the stimulation of AS1411-mediated macropinocytosis, suggesting that AS1411 activates EGFR signaling pathways. This was confirmed by observing that DU145 cells treated with AS1411 induced tyrosine phosphorylation of EGFR and activation of its downstream effectors, including p38, PI3K and Rac1. Furthermore, AS1411 seem to induce the interaction between EGFR and nucleolin in accord with EGFR activation. We also found that the activation of EGFR signaling pathway by AS1411 might regulate its cancer cellular response. Simulation of macropinocytosis by AS1411 was significantly inhibited in DU145 cells pre-treated with pharmacological inhibitors of Rac1 or PI3K, but not by Src inhibitor. Moreover the ability of AS1411 to inhibit cell proliferation and induce cell death was reduced by an EGFR-neutralizing antibody (cetuximab) or by downregulating the expression of Rac1 using siRNAs. These results indicate that AS1411 mediates the activation of EGFR signaling pathway to induce cancer cell death, and suggest that AS1411 might redirect EGFR signaling pathway from a cell survival signal to a cell death signal. Citation Format: Elsa M. Reyes-Reyes, Francesca R. Salipur, Paula J. Bates. AS1411 activity is regulated by epidermal growth factor receptor signaling pathway. [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 1046. doi:10.1158/1538-7445.AM2013-1046
IS MEMBRANOUS DYSMENORRHEA CAUSED BY ENDOMETRITIS
Authors: K. I. SANES
Journal: JAMA (1913)

In this paper I shall use the term "menstrual membrane" instead of membranous dysmenorrhea because we are interested in all the membranes passed during the menstrual period, and since not all are accompanied by pain, the term "membranous dysmenorrhea" cannot cover them all. I shall use the term "membranous dysmenorrhea" only when I wish to convey the idea of a membrane passed with pain. Before taking up the question of the relation of the menstrual membrane to endometritis, it is essential to consider the histology of the endometrium. <h3>HISTOLOGY OF ENDOMETRIUM</h3> The description of the endometrium as given by the anatomists is not uniform. In the old description the endometrium was considered as a definite and unchangeable structure. The picture of the endometrium most commonly met was considered to be the normal one and any deviation from it was looked on as pathologic. Milnes Marshall<sup>1</sup>and Heape,<sup>2</sup>independently of each other, reported a classification of the endometrial
Development of a human T-T cell hybridoma secreting B cell growth factor.
Authors: J L Butler, A Muraguchi, H C Lane, A S Fauci
Journal: The Journal of Experimental Medicine (1983)

The success of long-term culture of normal human and murine B cells has been hampered by the limited availability of soluble factors capable of maintaining proliferation of activated B lymphocytes. Previous experiments using various culture-derived supernatants in a human system were unable to separate the activities of B cell growth factor (BCGF) and interleukin 2 (IL-2) by immunochemical means. Thus, purified factors with BCGF activity in the absence of IL-2 activity have not been available for study. In the present study, normal human peripheral blood T cells were fused with the hypoxanthine/aminopterin/thymidine-sensitive human T-leukemic cell line, CEM-6. Supernatants from the resulting hybrid cells were tested for the ability to maintain proliferation of normal human B cells in a recently described assay system for human BCGF. Hybrids demonstrating BCGF activity were cloned by limiting dilution. One hybrid clone, 2B11, continued to support proliferation of B cells in both long-term cultures and 6-d assays at a level significantly above that seen with conventionally produced growth factors. No IL-2 activity was found in the supernatant from hybrid 2B11. The hybridoma supernatant was fractionated by gel filtration, and maximum proliferation of B cells was supported by the 18-20,000 mol wt protein fraction. Thus, a human T-T cell hybridoma that has BCGF activity in the absence of any demonstrable IL-2 activity has been developed. Human T-T cell hybridomas secreting discrete immunoregulatory factors should prove to be powerful tools in dissecting the mechanisms of immunoregulation of human lymphocyte function.
Those who believe in alternative theories of AIDShave little room for manoeuvre
Authors: S. W G Derbyshire
Journal: BMJ (1997)

Interferon beta in multiple sclerosis Reducing frequency and severity of relapses will be of great clinical benefitEditor-Richard G Richards's editorial on interferon beta in multiple sclerosis deals with the "clinical cost effectiveness" of the drug in the disease, but it lacks a fair balance, emphasising the cost effectiveness and minimising the clinical effectiveness of the drug. 1 Richards states that "the studies showed no evidence of any reduction in the more clinically relevant endpoint-the progression of disability, which should be the goal of treatment."This is his personal judgment and does not reflect the needs and wishes of patients with multiple sclerosis and their families.Multiple sclerosis is a distressing, humiliating, and often long drawn out disease with no cure.For this reason, quality of life, for the patients and their families, is paramount.A drug that can reduce the frequency and severity of relapses, whether or not it diminishes the progression of the disease, will be of great clinical benefit to many patients, improving their situation physically, psychologically, and socially.Surely happiness, feeling better, and increased health have great value.This is what many of us believe that the practice of our profession is about.
Suppressor of cytokine signaling 3 (SOCS3) expression and hepatitis C virus–related chronic hepatitis: Insulin resistance and response to antiviral therapy
Authors: Marcello Persico, Mario Capasso, Eliana Persico, Monica Svelto, Roberta Russo, Daniela Spano, Lori Crocè, Vincenzo La Mura, Francesco Moschella, Flora Masutti, Roberto Torella, Claudio Tiribelli, Achille Iolascon
Journal: Hepatology (2007)

Abstract The response to antiviral therapy is lower in hepatitis C virus (HCV) patients with genotype 1 than in those with genotype 2. Overexpression of the suppressor of cytokine signaling 3 (SOCS3) gene in liver tissue is associated with a poorer treatment outcome in patients with chronic hepatitis C viral genotype 1. Also, insulin resistance has been implicated in nonresponse to an anti-HCV treatment. To understand why HCV genotype 1 patients respond differently, we investigated SOCS3 gene expression, metabolic syndrome (MS), and the response to therapy in a cohort of patients with HCV-related hepatitis. A total of 198 patients (108 with genotype 1 and 90 with genotype 2) treated with pegylated interferon plus ribavirin were consecutively enrolled in the study. We measured SOCS3 expression in Epstein-Barr virus–transformed lymphoblastoid cell lines derived from peripheral lymphocytes of a subset of 130 patients. MS was more frequent in genotype 1 patients than in genotype 2 patients ( P &lt; 0.01). Nonresponders ( P &lt; 0.01), MS ( P &lt; 0.001), and genotype 1 ( P &lt; 0.001) were significantly related to SOCS3 overexpression. However, SOCS3 levels were higher in nonresponders also, regardless of the genotype ( P &lt; 0.01). In a univariate analysis, the genotype ( P &lt; 0.001), age ( P &lt; 0.001), SOCS3 ( P &lt; 0.001), and MS ( P &lt; 0.001) were significantly related to the response to therapy. However, in a multivariate analysis, SOCS3 was the only independent predictor of the response (odds ratio = 6.7; P &lt; 0.005). Conclusion: We speculate that SOCS3 expression per se may influence the response to antiviral therapy and that the genotype 1b virus might induce its up-regulation. This may account for the different responses to therapy between genotype 1–infected and genotype 2–infected patients. (HEPATOLOGY 2007.)
Aircraft noise is linked to raised risk of cardiovascular disease
Authors: Z. Kmietowicz
Journal: BMJ (2013)

Exposure to high levels of aircraft noise is associated with an increased risk of cardiovascular disease, studies from the United Kingdom and United States published in the BMJ have found.

In the first study UK researchers compared hospital admissions and death rates for stroke, coronary heart disease, and cardiovascular disease from 2001 to 2005 in 12 London boroughs and nine districts west of London. These areas, which are home to 3.6 million people, experienced annual average daytime noise levels of at least 50 dB from Heathrow in 2001.

The researchers found that in areas with the highest levels of daytime noise (>63 dB) the risk of hospital admission was 20% to 30% higher than in areas with the lowest noise (≤51 dB) for stroke (relative risk 1.24 (95% confidence interval 1.08 to 1.43)), coronary heart …
Which comes first: the antigen or the adjuvant?
Authors: Sallie R. Permar, Herman F. Staats
Journal: Journal of Clinical Investigation (2014)

Recent attempts to develop an HIV-1 vaccine indicate that viral replication can be limited by the induction of viral-specific T cell responses; however, recent trials of vaccine candidates designed to target CD8+ T cell responses were unsuccessful. In this issue, Sui and colleagues used a nonhuman primate model to investigate the effect of various vaccine adjuvants on the efficacy of SIV immunization. Unexpectedly, Sui et al. discovered that animals given adjuvant alone in the absence of SIV antigen exhibited a pronounced decrease in viral load following viral challenge. Vaccination with viral antigens combined with adjuvant correlated with the expansion of a population of cells with similarity to myeloid-derived suppressor cells (MDSCs) that may have suppressed vaccine-elicited T cell responses. Together, these results suggest that both innate and adaptive vaccine-elicited immune responses will need to be considered in future HIV-1 vaccine development.
Increased serum corticosterone and glucose in offspring of chromium(III)-treated male mice.
Authors: Robert Y S Cheng, W Gregory Alvord, Douglas Powell, Kazimierz S Kasprzak, Lucy M Anderson
Journal: Environmental Health Perspectives (2002)

Preconceptional carcinogenesis occurs in animals and is suspected for humans--for example, after occupational metals exposure. Several characteristics in animal models, including high frequency and non-Mendelian inheritance patterns, have suggested an epigenetic mechanism, possibly involving hormone changes in offspring. To test this hypothesis, we treated male mice with chromium(III) chloride, a preconceptional carcinogen, 2 weeks before mating, in two separate experiments. Their 10-week-old offspring showed highly significant increases in average serum corticosterone and glucose, compared with control offspring. Average serum levels of insulin-like growth factor 1 (IGF1) showed more modest possible increases. A previous microarray experiment identified hepatic insulin-like growth factor binding protein 1 (IGF BP1) gene expression as consistently changed in correlation with serum corticosterone levels. In the present study, hepatic IGF BP1 mRNA correlated with serum IGF1 in male offspring of chromium-treated fathers, but not in controls; serum glucose correlated positively with hepatic IGF BP1 in chromium-group offspring but negatively in controls. These results support the hypothesis that preconceptional exposure effects may alter hormones, metabolism, and control of tissue gene expression, probably through epigenetic mechanisms. Risk of neoplasia may be influenced by these changes.
Definitive Treatment of Intractable Plantar Ulcers
Authors: Joseph E. Murray
Journal: JAMA (1966)

Although most plantar ulcers respond to conservative therapy, such as protective padding, metatarsal supports, and gait correction, a few persist and constitute a major medical, social, and economic disability. These intractable plantar defects can be speedily and successfully treated by relatively simple surgical techniques, such as split grafts and pedicle flaps, either local or distant. These techniques were used in the management of 15 patients with chronic plantar ulcers.
Abstract 1796: SAR302503: A Jak2 inhibitor with antitumor activity in solid tumor models
Authors: Rita Greco, Raelene Hurley, Fangxian Sun, Lu Yang, Qunyan Yu, Juliet Williams, Marion Dorsch, Pamela Cohen, Francisco Adrián
Journal: Cancer Research (2012)

Abstract Numerous studies have recognized the critical role of STAT3 in malignant transformation and tumor progression. Constitutive STAT3 activation is frequently found in cancer cell lines and tumor samples and it is usually linked to the presence of IL-6. Autocrine or paracrine IL-6 loops have been described to provide tumor cells with the ability to proliferate, survive, migrate and metastasize. At the molecular level, IL-6 binding to its receptor results in activation of Jak/STAT3 signaling and other signaling cascades, namely PI3K/Akt, MEK/ERK1-2, with a well established role in cancer. We have evaluated the ability of SAR302503, a selective Jak2 inhibitor entering a PhIII clinical trial in myelofibrosis patients, to block these pathways in a panel of ∼20 tumor cell lines representing different cancer types (prostate, breast, lung, colorectal, pancreas, hepatocellular, etc). A 45 minutes treatment with different concentrations of SAR302503 (0.1-10 µM) was sufficient to block both basal or IL-6 induced STAT3 phosphorylation in a dose dependent manner. Compound concentrations equal or greater than 0.1 µM were able to reduce the phosphorylation levels of STAT3 by an extent greater than 50% in all the cell lines included in the study. The impact of SAR302503 in tumor cell proliferation and survival was evaluated using different assays including clonogenic assays. Complete inhibition of colony formation was achieved at concentrations of SAR302503 below 1 µM in most of the cell lines. The antitumor activity of SAR302503 was evaluated in mice xenotransplanted subcutaneously with DU145 human prostate cancer cells. Oral administration of SAR302503 for 10 days resulted in significant dose dependent tumor growth inhibition, near to stasis at the highest dose (T/C=19% at 100 mg/kg, bid). In summary, we demonstrate that SAR302503 negatively impacts the proliferation and survival of different solid tumor cells and our data supports a role for a selective Jak2 inhibition in treating solid tumors with activated Jak/STAT signaling. 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 1796. doi:1538-7445.AM2012-1796
Serum Cardiac Glycoside Assay Based upon Displacement of <sup>3</sup> H-Ouabain from Na-K ATPase
Authors: GARY BROOKER, ROGER W. JELLIFFE, Victoria Cochran, Sabine Sauer
Journal: Circulation (1972)

An assay of serum digoxin and other cardiac glycosides by displacement of 3 H-ouabain from Na-K ATPase is described. It is rapidly set up by any laboratory with a liquid scintillation counter. It can also assay digitalis leaf, digitoxin, and gitalin (Gitaligin), and has uncovered unsuspected administration of them. The assay takes less than 1 hour. No quench correction of counts is required. One technician can assay 30 samples/day with results that afternoon. No interfering compounds have been found in over 1,800 assays. It is unaffected by lung scans. Incidence of toxicity from digoxin is 10%, 25%, and 50% at serum levels of 1.4, 2.0, and 2.9 ng/ml, respectively. Toxic levels of digitalis and digitoxin are usually over 40 ng/ml. Serum digoxin levels are also highly correlated with computed total-body concentrations of digoxin, obtained from data of dosage, route of administration, and the patient's weight and renal function. Physicians may now select a serum digoxin level and computed total-body concentration of digoxin which are associated with an incidence of arrhythmias which they feel is reasonable for the urgency of each patient's clinical situation. These selected serum levels are associated with specific loading and maintenance dosage regimens, individualized to that patient's body weight, renal function, and route of digoxin administration.
Intensity of Testing and Invasive Procedures-Reply
Authors: David E. Wennberg
Journal: JAMA (1996)

<h3>In Reply.</h3> —Whether patients with known or suspected noncardiac vascular disease should have evaluation for coronary artery disease is an important clinical question. Patients with peripheral vascular disease are at a high risk for fatal and nonfatal cardiac events.<sup>1</sup>While significant work has been done concerning the preoperative cardiac evaluation in patients undergoing noncardiac vascular surgery,<sup>2</sup>debate continues about how to manage these patients even after the extent of their disease is known.<sup>3</sup>Finally, there is no consensus about whether case finding and risk stratification is either appropriate or costeffective in the population being evaluated in a vascular laboratory. Thus, the question of the use of exercise testing raised by Dr Crouse and colleagues is relevant. Unfortunately, our data could not allow us to discern between those undergoing testing for symptoms and those undergoing testing for case finding and stratification. However, the use of exercise testing in the setting
R990G polymorphism of calcium-sensing receptor does produce a gain-of-function and predispose to primary hypercalciuria
Authors: G. Vezzoli, A. Terranegra, T. Arcidiacono, R. Biasion, D. Coviello, M.L. Syren, V. Paloschi, S. Giannini, G. Mignogna, A. Rubinacci, A. Ferraretto, D. Cusi, G. Bianchi, L. Soldati
Journal: Kidney International (2007)
Abstract 3360: Epithelial-mesenchymal transition (EMT) stimulates tumor cells to produce invadopodia-like protrusions in collagen matrix, suppressing cell growth
Authors: Jun Oyanagi, Shouichi Higashi, Kaoru Miyazaki
Journal: Cancer Research (2011)

Abstract Epithelial tumor cells often change their epithelial phenotype to mesenchymal one when they invade into surrounding stromal tissue. This change, called epithelial-mesenchymal transition (EMT), is thought to be a crucial event in tumor progression. EMT is known to be regulated by environmental factors. However, it is unclear how EMT contributes to invasive growth of tumor cells. To address this question, we characterized EMT-induced tumor cells under various conditions in vitro. EMT was induced in three human carcinoma cell lines of the lung, pancreas and stomach by treating with TGF-beta and/or TNF-alpha. The EMT treatment of these cell lines induced expression of the invasion marker laminin gamma2 chain and MT1-MMP, in addition to other well-known phenotypes such as the morphological change and vimentin expression. EMT induction enhanced cell motility in monolayer culture. Although EMT cells showed comparable cell growth with the control cells in monolayer culture, their growth rates were extremely suppressed in collagen gel and soft agar culture conditions. Most characteristically, EMT-induced tumor cells commonly and markedly extended invadopodia-like protrusions in collagen gel. Such protrusion formation in collagen gel was effectively blocked by the TGF-beta/Smad pathway inhibitor SB431542 but scarcely suppressed by the synthetic and natural MMP inhibitors, TAPI-1 and TIMP-2, respectively. These data suggest that EMT may enhance interstitial tumor infiltration without cell growth by promoting prominent invadopodia formation and cell motility. The TGF-beta-induced cytoskeletal change seems to play a more critical role than MMP expression in the tumor invasion. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3360. doi:10.1158/1538-7445.AM2011-3360