tbuckley/cabot-search huggingface dataset:
Abstract 4274: Characterization and drug sensitivity testing of HTS compatible cancer microtissues
Authors: Marianne M. Helbling, Maren Drewitz, Manuela Bieri, Carina Lotz, Lorenza Wyder, Francois Lehembre, Jan Lichtenberg, Wolfgang Moritz, Urs Regenass, Jens M. Kelm
Journal: Cancer Research (2011)

Abstract The tumor microenvironment strongly effects the drug response. Although the advantages of organotypic 3D-cell-culture models are known for years, complex production and readout processes impede the implementation in an industrial setting. This study, presents for the first time a novel multi-well platform in a standard 96-well format to produce organotypic, scaffold-free cancer microtissues models and its implementation in an automated screening process. This technology allows to produce either homotypic or heterotypic tumor microtissues in a hanging-drop culture by liquid top-loading similar to standard 96-well plates. The core piece of the well is a microfluidic channel connecting an inlet funnel at the top and an outlet funnel at the bottom of the plate, where a hanging drop is formed and stabilized by a combination of capillary and surface-tension forces. The use of this technology enables the automated production of microtissues with a very narrow size distribution below 10% on plate and batch-to-batch. 3 cancer microtissue models were developed from two colon cancer and one breast cancer cell lines and characterized in terms of their proliferative capacity and growth characteristics. Process parameters for media exchange, addition of compounds, microtissue-size variances and implementation of cell-based viability assays (ATP, LDH and size) were established. As a proof of concept, a whole screening process using four reference compounds was performed in comparison to classical monolayer cultures underlining the different behavior of both cell-culture models. Finally, four novel compounds that inhibit tumor cell proliferation in monolayer cultures, were tested for their potential in a 3-D system. Overall, we could demonstrate that organotypic microtissues can be implemented into an automated screening process using standard liquid-handling robotics. The use of this system in drug development may strengthen the predictive force of the in-vitro evaluation of novel drug candidates and reduce drug failure in clinics. 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 4274. doi:10.1158/1538-7445.AM2011-4274
PSEUDO-HYSTERICAL APHONIA.Read in the Section on Laryngology and Otology, at the Forty-fifth Annual Meeting of the American Medical Association, held in San Francisco, June 5-8, 1894.
Authors: F. B. EATON
Journal: JAMA (1894)

Typical hysterical aphonia is described in our treatises as a form of bilateral adductor paralysis of the larynx, usually of neurotic origin; sometimes more exactly, as paralysis of the lateral crico arytenoid muscles. As such, its etiology, symptomatology and treatment, as generally accepted, are familiar to all laryngologiste. Some writers describe associated laryngeal conditions, such as hoarseness from acute cold; others loss of power of artic ulation. The inference is that the neurotic feature is not the only etiologic one. Indeed, many cases of this affection appear to be the result of a number of abnormal factors, though the prominent indication to be met and the one most influencing the physician in his attitude toward the complaint is the functional, hysterical, nervous one; it overshadows all the others, and treatment is directed toward its removal too often without due consideration of other important constitutional and local conditions. I am satisfied
Schemes that reward GPs for prescribing generics may breach EU law
Authors: C. Dyer
Journal: BMJ (2010)

A ruling expected next month from the European Court of Justice in Luxembourg could deprive the NHS of millions of pounds in savings on drugs budgets.

If the judges follow the opinion of the court’s advocate general Niilo Jaaskinen, schemes that reward GPs in England and Wales for prescribing cheaper generic drugs instead of branded medicines will be held to breach European Union law.

The European Court was asked to rule on the issue by the High Court in London, which was hearing a challenge by the Association of the British Pharmaceutical Industry (ABPI) …
Relation between estrogen replacement therapy and restenosis after percutaneous coronary interventions
Authors: Jeanne E. O'Brien, Eric D. Peterson, Gordon P. Keeler, Lisa G. Berdan, E. Magnus Ohman, David P. Faxon, Alice K. Jacobs, Eric J. Topol, Robert M. Califf
Journal: Journal of the American College of Cardiology (1996)

We attempted to determine the relation between estrogen replacement therapy and the rate of restenosis after coronary angioplasty and atherectomy.Although estrogen replacement therapy in women has been associated with a reduction in cardiovascular events and improvement in endothelial function, no study has examined whether estrogen reduces restenosis rates after percutaneous coronary interventions.A total of 204 women enrolled in the Coronary Angioplasty Versus Excisional Atherectomy Trial with angiographic follow-up were contacted, and their menopausal and estrogen replacement status was determined. Late loss in minimal lumen diameter, late loss index, minimal lumen diameter, rate of restenosis > 50% and actual percent of stenosis were compared in estrogen users and nonusers by quantitative coronary angiography at 6-month follow-up.Late loss in minimal lumen diameter was significantly less in women using estrogen than in nonusers (-0.13 vs. -0.46 mm, p = 0.01). A regression analysis of the determinants of late loss in minimal lumen diameter revealed that estrogen use was the single most important predictor of subsequent late loss (F = 13.38, p = 0.0006). Formal testing revealed a highly significant interaction between the use of estrogen and intervention (angioplasty or atherectomy). Women undergoing atherectomy who received estrogen had a significantly lower late loss index (0.06 vs. -0.63, p = 0.002), less late loss (0.06 vs. -0.61 mm, p = 0.0006), larger minimal lumen diameter (p = 0.044) and lower restenosis rates (p = 0.038 for > 50% stenosis) than those not using estrogen. In contrast, estrogen had minimal effects on restenosis end points after angioplasty.This study demonstrates the potential for estrogen replacement therapy to reduce angiographic measures of restenosis in postmenopausal women after coronary intervention, particularly in those undergoing atherectomy.
Tc-99m-Diphosphonate Distribution in a Patient with Hypercalcemia and Metastatic Calcifications
Authors: GUILLERMO L. ARBONA, SADI ANTONMATTEI, MARC R. TETALMAN, JOHN D. SCHEU
Journal: Clinical Nuclear Medicine (1980)

ARBONA, GUILLERMO L. M.D.; ANTONMATTEI, SADI M.D.; TETALMAN, MARC R. M.D.; SCHEU, JOHN D. Ph.D. Author Information
Rat-Bite Fever
Authors: JAMES S. COLE
Journal: Annals of Internal Medicine (1969)

Three cases of rat-bite fever, resulting from the bite of laboratory rats, were observed in a 6-month period. In two cases, Streptobacillus moniliformis was obtained from blood culture. Extracellular spiral organisms, presumably Spirillum minus, were observed on peripheral blood smear in the third case. All cases responded promptly to penicillin therapy. The occurrence of three cases in 6 months suggests that this disease may be commoner than is currently appreciated. Extreme care must be taken when handling laboratory rats.
World Bank is urged to end support for social health insurance schemes
Authors: A. Gulland
Journal: BMJ (2013)

The World Bank should stop encouraging developing countries to set up health insurance schemes in the drive to ensure universal access to healthcare, the charity Oxfam has urged.

In a report published on 9 October the charity says that social health insurance schemes, promoted by the World Bank and other organisations as effective ways of ensuring universal access to healthcare, “have low coverage, are costly to administer, and exclude the poor.”1

Social health insurance schemes work by taking a percentage from an employee’s wage and then pooling health revenues so that they can be distributed throughout the population. The report says that they are successful in high income countries where rates of employment are high but are not …
Association Between Anthropometric Parameters and Measurements of Liver Stiffness by Transient Elastography
Authors: Grace Lai–Hung Wong, Henry Lik–Yuen Chan, Paul Cheung–Lung Choi, Anthony Wing–Hung Chan, Angeline Oi–Shan Lo, Angel Mei–Ling Chim, Vincent Wai–Sun Wong
Journal: Clinical Gastroenterology and Hepatology (2012)
OP15 * LACTATE DEHYDROGENASE A (LDHA) AND CHILDHOOD MEDULLOBLASTOMA
Authors: C. Valvona, L. Donovan, S. Higgins, H. L. Fillmore, G. J. Pilkington
Journal: Neuro-Oncology (2014)

INTRODUCTION: Medulloblastomas (MBs) are the most common type of solid, malignant childhood brain tumour. Recently, integrated genomics has identified four distinct sub-groups of which display different demographics, and clinical outcomes. Approximately 30% of MB patients present with metastatic spread at the time of diagnosis. Group 3 are considered the most metastatic, carry the worst prognosis and characteristically overexpress c-Myc. C-Myc, is involved in the initiation of several genes responsible for tumour growth and metabolism. Lactate dehydrogenase A (LDHA), a downstream target of c-Myc is often de-regulated in metastatic and invasive tumours. We have begun to investigate the role of LDHA and lactate on MB metabolism. METHOD: LDHA protein was examined in three medulloblastoma cell lines using Immunocytochemistry (ICC) and western blot analysis (WB). To investigate the role of LDHA in MB cell lines, LDHA was inhibited either by shRNA or with sodium oxamate. Metabolic assays and analysis include lactate and pyruvate assays. RESULTS: The three MB cell lines demonstrated varying levels of LDHA protein however ICC analysis showed consistency in localisation of LDHA in cytoplasmic and nuclear areas. Successful knockdown of LDHA protein using shRNA was confirmed with WB analysis. Knockdown of LDHA resulted in decreased lactate levels. LDHA inhibition by sodium oxamate also caused a decrease in lactate levels in a time and concentration dependent manner. Interestingly, pyruvate levels also decreased when LDHA was inhibited. CONCLUSION: Targeting medulloblastoma metabolism, such as LDHA, warrants further investigation to determine if this approach will affect not only metabolism but also cancer cell spread.
The Nonhuman Primate as a Model of Growth Hormone Physiology in the Human Being*
Authors: MARK D. WHEELER, DENNIS M. STYNE
Journal: Endocrine Reviews (1988)

OVER the last three decades investigators have provided an exponential increase in our knowledge of the mechanisms controlling primate GH secretion and action. Starting from (1) the first demonstration of the efficacy of primate GH in promoting growth in GHdeficient human beings, continuing through (2) the advent of RIAs that greatly simplified the measurement of GH and (3) allowed a profusion of physiological studies of GH secretion, proceeding to (4) the realization of the importance of intermediary growth factors in accomplishing the ultimate effects of GH, and arriving at (5) the isolation of the hypothalamic factors regulating GH secretion and (6) the cloning of the genes for GH and its regulators, this field of study has matured at a rapid rate. Much of the information has been obtained from clinical studies in human beings, but animal studies have been instrumental in many areas where human studies are ethically or practically impossible.
PAX5/TEL Acts as a Transcriptional Repressor Causing Down-modulation of CD19, Enhances Migration to CXCL12, and Confers Survival Advantage in pre-BI Cells
Authors: Grazia Fazio, Chiara Palmi, Antonius Rolink, Andrea Biondi, Giovanni Cazzaniga
Journal: Cancer Research (2008)

Abstract PAX5 is a transcription factor essential for B-cell development. Recently, it has been found as a frequent target of aberrancies in childhood acute lymphoblastic leukemia (ALL; 30% of B cell ALL cases), showing monoallelic loss, point mutations, or chromosomal translocations. The role of these aberrancies is still poorly understood. We previously cloned the PAX5/TEL fusion gene in a patient affected by B-cell precursor ALL with a t(9;12) translocation. This is the first report investigating the molecular and functional roles of PAX5/TEL protein in vitro from murine wild-type pre-BI cells. We showed that PAX5/TEL protein acts as an aberrant transcription factor with repressor function, recruiting mSin3A, down-regulating B220, CD19, BLNK, MB-1, FLT3, and μ heavy chain expression, thus suggesting a block on B-cell differentiation. In a PAX5-deficient context, the presence of PAX5/TEL did not replace PAX5 functions. PAX5/TEL protein enhances cell migration towards CXCL12, with the overexpression of CXCR4. Moreover, the presence of the fusion gene overcomes interleukin-7 withdrawal and interferes with transforming growth factor-β1 pathway, inducing resistance and conferring cells an advantage in proliferation and survival. Thus, in vitro, the PAX5/TEL protein has a dominant effect on wild-type PAX5, interferes with the process of B-cell differentiation and migration, and induces resistance to apoptosis. Taken together, these phenomena likely represent key events in the process of B-cell transformation. [Cancer Res 2008;68(1):181–9]
Multicenter Evaluation of Infant Lung Function Tests as Cystic Fibrosis Clinical Trial Endpoints
Authors: Stephanie D. Davis, Margaret Rosenfeld, Gwendolyn S. Kerby, Lyndia Brumback, Margaret H. Kloster, James D. Acton, Andrew A. Colin, Carol K. Conrad, Meeghan A. Hart, Peter W. Hiatt, Peter J. Mogayzel, Robin C. Johnson, Stephanie L. Wilcox, Robert G. Castile
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

The conducting of clinical trials in infants with cystic fibrosis (CF) has been hindered by lack of sensitive outcome measures.To evaluate safety, feasibility, and ability to detect abnormalities in lung function of serial pulmonary function tests (PFTs) in infants with CF.Multicenter observational study using a commercial device, rigorous training, ongoing quality control, and over-reading of data by an independent panel. Raised volume rapid thoracoabdominal compression technique and plethysmography were performed at enrollment and at 6 and 12 months, with an additional 1-month reproducibility visit.A total of 342 procedures were performed in 100 infants with CF at 10 centers. FRC measurements were acceptable at a higher proportion of study visits (89%) than raised volume (72%) or fractional lung volume (68%) measurements. Average Z scores for many parameters differed significantly from historical control values. Mean (95% confidence interval) Z scores were: -0.52 (-0.78 to -0.25) for forced expiratory flow at 75% (FEF₇₅) for FVC; 1.92 (1.39-2.45) for FRC; 1.22 (0.68-1.76) for residual volume; 0.87 (0.60-1.13) for FRC/total lung capacity; and 0.66 (0.27-1.06) for residual volume/total lung capacity. For future multicenter clinical trials using infant PFTs as primary endpoints, minimum detectable treatment effects are presented for several sample sizes.In this 10-center study, key PFT measures were significantly different in infants with CF than in historical control subjects. However, infant PFTs do not yet appear ready as primary efficacy endpoints for multicenter clinical trials, particularly at inexperienced sites, based on acceptability rates, variability, and potentially large sample sizes required to detect reasonable treatment effects.
Cognitive test can predict risk of mental illness in teenagers, say scientists
Authors: K. Chinthapalli
Journal: BMJ (2012)

Adolescents with a particular genetic variant and a history of an abusive family life are worse at judging emotions and at an increased risk of developing depression and anxiety, says new research.1

The University of Cambridge psychiatrists who conducted the research interviewed 238 teenagers, then conducted cognitive tests and looked at variations in a gene for serotonin transport, 5-HTTLPR. A shorter variant of this gene, the SS allele, is present in 18% of the population and is known to increase the risk of depression in adults with a history of adverse social …
Abstract B8: Correlation of the expression of hepcidin mRNA and the serum iron, ferritin, and TIBC levels in hepatocellular carcinoma
Authors: Smita C. Pawar
Journal: Clinical Cancer Research (2010)

Abstract Background: The present study correlated the expression of hepcidin mRNA and the levels of serum iron, ferritin, and TIBC in hepatocellular carcinoma (HCC). Methods: Samples of cancerous and noncancerous liver tissue were taken from patients with HCC who underwent hepatectomy. Expression of hepcidin mRNA was evaluated by realtime PCR, and compared in tumors differing in their degree of differentiation and number of tumors. Correlations between hepcidin expression and the serum concentration of hepcidin were evaluated, together with the expression of the serum concentration of biochemical markers of iron metabolism. Results: Hepcidin mRNA expression in non-cancerous and cancerous tissues was 1791.6 (34.3- 25187.4) and 58.7 (1.93235.8), respectively (P &amp;lt; 0.0001). There were no significant differences in hepcidin expression among tumors differing in their degree of differentiation and number of tumors. The serum concentration of hepcidin did not correlate with hepcidin-mRNA expression. The serum iron level was found to be normal (125.4 ± 21.4 mg/dL). The serum ferritin level was also found to be normal 193.5(14.0-232.9 ng/mL). TIBC was (284.8 ±28.3 ng/mL). There were significant correlations between the serum levels of hepcidin and iron, hepcidin-25 and ferritin and hepcidin and TIBC. Conclusion: The serum hepcidin concentration was correlated with the levels of serum iron and ferritin, but not with the level of hepcidin mRNA expression in either cancerous or non- cancerous liver tissue. Hepcidin is produced in patients with HCC, from non-cancerous liver tissue, even though production is inhibited in cancerous tissue. Expression of hepcidin mRNA is constitutively suppressed in cancerous, but not in non-cancerous liver tissue of patients with HCC. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B8.
Drowning From Seizure While Bathing
Authors: Kenneth H. Geiger
Journal: JAMA (1980)

<h3>To the Editor.—</h3> In a recent letter to your journal, Riley and Brannon (242:2761, 1979) described a patient who died of a head injury after falling from a top bunk bed during a seizure. I recently became aware of a patient who drowned while taking a bath, as a result of having a seizure. In addition to cautioning seizure patients against swimming alone, I now advise them to take showers rather than baths.
Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk
Authors: Jianfeng Xu, S. Lilly Zheng, Akira Komiya, Josyf C. Mychaleckyj, Sarah D. Isaacs, Jennifer J. Hu, David Sterling, Ethan M. Lange, Gregory A. Hawkins, Aubrey Turner, Charles M. Ewing, Dennis A. Faith, Jill R. Johnson, Hiroyoshi Suzuki, Piroska Bujnovszky, Kathleen E. Wiley, Angelo M. DeMarzo, G. Steven Bova, Baoli Chang, M. Craig Hall, David L. McCullough, Alan W. Partin, Vahan S. Kassabian, John D. Carpten, Joan E. Bailey-Wilson, Jeffrey M. Trent, Jill Ohar, Eugene R. Bleecker, Patrick C. Walsh, William B. Isaacs, Deborah A. Meyers
Journal: Nature Genetics (2002)
Risk-Adjustment Methods Based on Health Status and Functional Status-Reply
Authors: Jinnet B. Fowles
Journal: JAMA (1997)

<h3>In Reply.</h3> —Dr Allman suggests that self-reported survey information should be used for risk adjustment for persons older than 65 years. He suggests that self-reported functional status measures perform just as well, if not better, than claims-based systems. Although the SF-36 model did predict health care expenditures within 5% of actual expenses for a higher proportion of "high-risk" groups than did adjustment using ambulatory care groups, we found that performance of risk-adjustment systems varied depending on the measure of predictive accuracy chosen. Taking this factor into account and considering issues of administrative feasibility, we concluded that a claims-based or encounter-based system is preferable to a survey-based method. Allman correctly suggests that some issues of administrative feasibility, such as surveying illiterate and non-English-speaking subjects, can be overcome. Even so, significant feasibility problems remain for survey-based risk adjusters. For example, the suggestion that SF-36 data be collected every 5 years does not correspond to
Endoscopic closure of postoperative esophageal leaks with a novel over-the-scope clip system
Authors: J. Pohl, M. Borgulya, D. Lorenz, C. Ell
Journal: Endoscopy (2010)

Management of esophageal anastomotic leaks is associated with high morbidity and mortality and remains an interdisciplinary challenge. We describe the first two cases of endoscopic closure of postoperative leaks following gastrectomy and primary repair after spontaneous acute esophageal perforation, using the over-the-scope clip (OTSC) system (Ovesco Endoscopy GmbH, Tübingen, Germany). Both leaks were successfully sealed with one clip. While one patient recovered without reintervention, in the other patient the postoperative leak reappeared following clip displacement 13 days later.
Repair and Regeneration: The Scientific Basis for Surgical Practice
Authors: Nelson R. Niles
Journal: JAMA (1969)

The original three-day symposium, of which this book is the published record, was probably instructive and memorable. However, published symposia generally lack the clarity of presentation found in textbooks and the oratorical power that accompanied delivery. Editors generally fail to request their contributors to adapt their materials into a form suitable for a book. Some reduction in the quantity of data seems desirable to make the whole more easily understood as well as to reduce the high price. The book includes discussions of bacterial inflammation and immunology, biological factors in skin repair, formation and repair of connective tissue, wound healing and remodeling, and some clinical aspects of wounds. Several thrills await the industrious uninformed reader. The principles of induction, scar contraction, and wound nutrition stand out. The enigma of the genesis of wound healing becomes somewhat clearer with the evidence of Bullough on chalones and of Grobstein on interactions between
Prognostic Value of Multislice Computed Tomography Coronary Angiography in Patients With Known or Suspected Coronary Artery Disease
Authors: Gabija Pundziute, Joanne D. Schuijf, J. Wouter Jukema, Eric Boersma, Albert de Roos, Ernst E. van der Wall, Jeroen J. Bax
Journal: Journal of the American College of Cardiology (2006)