tbuckley/cabot-search huggingface dataset:
miRNA-196b inhibits cell proliferation and induces apoptosis in HepG2 cells by targeting IGF2BP1
Authors: Magali Rebucci, Audrey Sermeus, Elodie Leonard, Edouard Delaive, Marc Dieu, Maude Fransolet, Thierry Arnould, Carine Michiels
Journal: Molecular Cancer (2015)

Tumor hypoxia is one of the features of tumor microenvironment that contributes to chemoresistance. miRNAs have recently been shown to play important roles in tumorigenesis and drug resistance. Moreover, hypoxia also regulates the expression of a series of miRNAs. However, the interaction between chemoresistance, hypoxia and miRNAs has not been explored yet. The aim of this study is to understand the mechanisms activated/inhibited by miRNAs under hypoxia that induce resistance to chemotherapy-induced apoptosis. TaqMan low-density array was used to identify changes in miRNA expression when cells were exposed to etoposide under hypoxia or normoxia. The effects of miR-196b overexpression on apoptosis and cell proliferation were studied in HepG2 cells. miR-196b target mRNAs were identified by proteomic analysis, luciferase activity assay, RT-qPCR and western blot analysis. Results showed that hypoxia down-regulated miR-196b expression that was induced by etoposide. miR-196b overexpression increased the etoposide-induced apoptosis and reversed the protection of cell death observed under hypoxia. By a proteomic approach combined with bioinformatics analyses, we identified IGF2BP1 as a potential target of miR-196b. Indeed, miR-196b overexpression decreased IGF2BP1 RNA expression and protein level. The IGF2BP1 down-regulation by either miR-196b or IGF2BP1 siRNA led to an increase in apoptosis and a decrease in cell viability and proliferation in normal culture conditions. However, IGF2BP1 silencing did not modify the chemoresistance induced by hypoxia, probably because it is not the only target of miR-196b involved in the regulation of apoptosis. In conclusion, for the first time, we identified IGF2BP1 as a direct and functional target of miR-196b and showed that miR-196b overexpression reverses the chemoresistance induced by hypoxia. These results emphasize that the chemoresistance induced by hypoxia is a complex mechanism.
Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus
Authors: Timothy R D J Radstake, Olga Gorlova, Blanca Rueda, Jose-Ezequiel Martin, Behrooz Z Alizadeh, Rogelio Palomino-Morales, Marieke J Coenen, Madelon C Vonk, Alexandre E Voskuyl, Annemie J Schuerwegh, Jasper C Broen, Piet L C M van Riel, Ruben van 't Slot, Annet Italiaander, Roel A Ophoff, Gabriela Riemekasten, Nico Hunzelmann, Carmen P Simeon, Norberto Ortego-Centeno, Miguel A González-Gay, María F González-Escribano, Paolo Airo, Jaap van Laar, Ariane Herrick, Jane Worthington, Roger Hesselstrand, Vanessa Smith, Filip de Keyser, Fredric Houssiau, Meng May Chee, Rajan Madhok, Paul Shiels, Rene Westhovens, Alexander Kreuter, Hans Kiener, Elfride de Baere, Torsten Witte, Leonid Padykov, Lars Klareskog, Lorenzo Beretta, Rafaella Scorza, Benedicte A Lie, Anna-Maria Hoffmann-Vold, Patricia Carreira, John Varga, Monique Hinchcliff, Peter K Gregersen, Annette T Lee, Jun Ying, Younghun Han, Shih-Feng Weng, Christopher I Amos, Fredrick M Wigley, Laura Hummers, J Lee Nelson, Sandeep K Agarwal, Shervin Assassi, Pravitt Gourh, Filemon K Tan, Bobby P C Koeleman, Frank C Arnett, Javier Martin, Maureen D Mayes
Journal: Nature Genetics (2010)
Military Medicine From World War II to Vietnam
Authors: VADM Donald L. Custis
Journal: JAMA (1990)

PERHAPS more than most physicians, I have had an unpredictable medical career—little of it developed according to plan. Although as early as I can remember my goal was medical school, I never intended a vocation in military surgery or executive medicine. War in Europe broke out in September 1939, the year I graduated from college. I was an early draft registrant and, on entering Northwestern University Medical School in Chicago, had applied for a reserve navy commission. Two years remained before the tranquility of our sheltered academic environment would be shattered by the unforeseen and disastrous Japanese raid on Pearl Harbor. It was not at all apparent in the 1930s that modern medicine would begin with my generation. Nuclear medicine, for example, came with an atomic age born of the war, which also ushered in the space age and an explosion of medical technology. Nor could I have imagined that
Roundworms in Fishes and so-called "Herring-worm Disease"
Authors: H. H. Williams
Journal: BMJ (1965)

Raynaud's Phenomenon-;ohnston et al.bEDICAmJOURA from the finger-tips, especially if associated with resorption of the terminal phalanges, points towards some other disease process, in particular systemic scleroderma.Flat (macular) polygonal telangiectases on the hands are unusual in patients with Raynaud's phenomenon.In this series they occurred in the patients with systemic scleroderma, and in very small numbers (one to three) in five patients with confirmed primary Raynaud's phenomenon.We believe that in patients with Raynaud's phenomenon, macular telangiectases may be the most valuable early clinical sign of incipient or overt systemic scleroderma if present on the hands, but are of less significance if found on the face alone.Brachial arteriography is not helpful in distinguishing severe primary Raynaud's phenomenon from early systemic scleroderma.This procedure was performed pre-operatively on four of the patients initially diagnosed as having primary Raynaud's phenomenon who later developed systemic sclero- derma.In two the arteriograms were normal, and in two digital-arterial blocks were demonstrated, but there was no
Functional Viability Profiles of Breast Cancer
Authors: Rachel Brough, Jessica R. Frankum, David Sims, Alan Mackay, Ana M. Mendes-Pereira, Ilirjana Bajrami, Sara Costa-Cabral, Rumana Rafiq, Amar S. Ahmad, Maria Antonietta Cerone, Rachael Natrajan, Rachel Sharpe, Kai-Keen Shiu, Daniel Wetterskog, Konstantine J. Dedes, Maryou B. Lambros, Teeara Rawjee, Spiros Linardopoulos, Jorge S. Reis-Filho, Nicholas C. Turner, Christopher J. Lord, Alan Ashworth
Journal: Cancer Discovery (2011)

Abstract The design of targeted therapeutic strategies for cancer has largely been driven by the identification of tumor-specific genetic changes. However, the large number of genetic alterations present in tumor cells means that it is difficult to discriminate between genes that are critical for maintaining the disease state and those that are merely coincidental. Even when critical genes can be identified, directly targeting these is often challenging, meaning that alternative strategies such as exploiting synthetic lethality may be beneficial. To address these issues, we have carried out a functional genetic screen in &amp;gt;30 commonly used models of breast cancer to identify genes critical to the growth of specific breast cancer subtypes. In particular, we describe potential new therapeutic targets for PTEN-mutated cancers and for estrogen receptor–positive breast cancers. We also show that large-scale functional profiling allows the classification of breast cancers into subgroups distinct from established subtypes. Significance: Despite the wealth of molecular profiling data that describe breast tumors and breast tumor cell models, our understanding of the fundamental genetic dependencies in this disease is relatively poor. Using high-throughput RNA interference screening of a series of pharmacologically tractable genes, we have generated comprehensive functional viability profiles for a wide panel of commonly used breast tumor cell models. Analysis of these profiles identifies a series of novel genetic dependencies, including that of PTEN-null breast tumor cells upon mitotic checkpoint kinases, and provides a framework upon which additional dependencies and candidate therapeutic targets may be identified. Cancer Discovery; 1(3); 260–73. © 2011 AACR. Read the Commentary on this article by Beijersbergen and Bernards, p. 205 This article is highlighted in the In This Issue feature, p. 189
Cancer Following Radiotherapy for Peptic Ulcer
Authors: M. L. Griem, R. A. Kleinerman, J. D. Boice, M. Stovall, D. Shefner, J. H. Lubin
Journal: JNCI Journal of the National Cancer Institute (1994)

Radiotherapy for peptic ulcer was used between 1937 and 1965 to control excessive gastric acid secretions (mean dose, 14.8 Gy). Patients with this benign condition live many years after treatment and are at risk for late effects.Our purpose was to investigate the risk of death from cancer following radiotherapy for peptic ulcer.A mortality study was conducted of 3609 patients with peptic ulcer; 1831 were treated with radiation and 1778 were treated by other means. Extensive methods were used to trace patients. Radiation doses to specific organs were reconstructed from the original radiotherapy records.Nearly 70% of patients were found to have died. The average period of observation was 21.5 years (maximum 51 years). Compared with the general population, patients treated with or without radiation were at significantly increased risk of dying of cancer and non-malignant diseases of the digestive system. Risk of death due to heart disease was slightly higher following radiotherapy. Cancers of the stomach, pancreas, lung, and prostate were increased in both irradiated and nonirradiated patients. Radiotherapy was linked to significantly high relative risks (RRs) for all cancers combined (RR = 1.53; 95% confidence interval [CI] = 1.3-1.8), for cancers of the stomach (RR = 2.77; 95% CI = 1.6-4.8), pancreas (RR = 1.87; 95% CI = 1.0-3.4), and lung (RR = 1.70; 95% CI = 1.2-2.4), and for leukemia (RR = 3.28; 95% CI = 1.0-10.6). Radiation combined with surgery, or given to treat gastric ulcer, appeared to increase the risk of stomach cancer 10-fold, which was greater than the sum of individual effects. Patients with gastric ulcers were at higher risk for stomach cancer than patients with duodenal ulcers.Patients with peptic ulcer are at increased risk of dying of cancer, related in part to lifestyle factors and treatment. Radiotherapy and surgery together appear to induce carcinogenic processes that greatly enhance the development of stomach cancer. The risk of radiation-induced stomach cancer was 0.25 extra deaths per 10,000 persons per year per Gy, somewhat lower than reported in other studies. High-dose radiation may have increased the risk of pancreatic cancer, a condition rarely found elevated in irradiated populations, but misclassified death notices may have contributed to the excess. Cancer mortality remained high for up to 50 years, indicating that radiation damage may persist to the end of life.
Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution
Authors: Z. Yang
Journal: Molecular Biology and Evolution (1998)

An excess of nonsynonymous substitutions over synonymous ones is an important indicator of positive selection at the molecular level. A lineage that underwent Darwinian selection may have a nonsynonymous/synonymous rate ratio (dN/dS) that is different from those of other lineages or greater than one. In this paper, several codon-based likelihood models that allow for variable dN/dS ratios among lineages were developed. They were then used to construct likelihood ratio tests to examine whether the dN/dS ratio is variable among evolutionary lineages, whether the ratio for a few lineages of interest is different from the background ratio for other lineages in the phylogeny, and whether the dN/dS ratio for the lineages of interest is greater than one. The tests were applied to the lysozyme genes of 24 primate species. The dN/dS ratios were found to differ significantly among lineages, indicating that the evolution of primate lysozymes is episodic, which is incompatible with the neutral theory. Maximum-likelihood estimates of parameters suggested that about nine nonsynonymous and zero synonymous nucleotide substitutions occurred in the lineage leading to hominoids, and the dN/dS ratio for that lineage is significantly greater than one. The corresponding estimates for the lineage ancestral to colobine monkeys were nine and one, and the dN/dS ratio for the lineage is not significantly greater than one, although it is significantly higher than the background ratio. The likelihood analysis thus confirmed most, but not all, conclusions Messier and Stewart reached using reconstructed ancestral sequences to estimate synonymous and nonsynonymous rates for different lineages.
Improved Pregnancy Outcome in Type 1 Diabetic Women With Microalbuminuria or Diabetic Nephropathy
Authors: Lene Ringholm Nielsen, Peter Damm, Elisabeth R. Mathiesen
Journal: Diabetes Care (2008)

To describe pregnancy outcome in type 1 diabetic women with normoalbuminuria, microalbuminuria, or diabetic nephropathy after implementation of an intensified antihypertensive therapeutic strategy.Prospective study of 117 pregnant women with type 1 diabetes. Antihypertensive therapy, mainly methyldopa, was given to obtain blood pressure <135/85 mmHg and urinary albumin excretion <300 mg/24 h. Blood pressure and A1C were recorded during pregnancy. The pregnancy outcome was compared with recently published studies of pregnant women with microalbuminuria or diabetic nephropathy.Antihypertensive therapy was given in 14 of 100 women with normoalbuminuria, 5 of 10 women with microalbuminuria, and all 7 women with diabetic nephropathy. Mean systolic blood pressure during pregnancy was 120 mmHg (range 101-147), 122 mmHg (116-135), and 135 mmHg (111-145) in women with normoalbuminuria, microalbuminuria, and diabetic nephropathy, respectively (P = 0.0095). No differences in mean diastolic blood pressure or A1C were detected between the groups. No women with microalbuminuria developed preeclampsia. The frequency of preterm delivery was 20% in women with normoalbuminuria and microalbuminuria in contrast to 71% in women with diabetic nephropathy (P < 0.01) where the median gestational age was 258 days (220-260). Compared with previous studies using less stringent antihypertensive therapeutic strategy and less strict metabolic control, gestational age was longer and birth weight was larger in our study.With intensified antihypertensive therapy and strict metabolic control, comparable pregnancy outcome was seen in type 1 diabetic women with microalbuminuria and normoalbuminuria. Although less severe than in previous studies, diabetic nephropathy was associated with more adverse pregnancy outcome.
ILCOR Advisory Statement: Resuscitation of the Newly Born Infant
Authors: John Kattwinkel, Susan Niermeyer, Vinay Nadkarni, James Tibballs, Barbara Phillips, David Zideman, Patrick Van Reempts, Martin Osmond
Journal: Circulation (1999)

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Lymphoid priming in human bone marrow begins before expression of CD10 with upregulation of L-selectin
Authors: Lisa A Kohn, Qian-Lin Hao, Rajkumar Sasidharan, Chintan Parekh, Shundi Ge, Yuhua Zhu, Hanna K A Mikkola, Gay M Crooks
Journal: Nature Immunology (2012)
Predictors of Health-related Quality of Life and Adjustment to Prostate Cancer During Active Surveillance
Authors: Lara Bellardita, Tiziana Rancati, Maria Francesca Alvisi, Daniela Villani, Tiziana Magnani, Cristina Marenghi, Nicola Nicolai, Giuseppe Procopio, Sergio Villa, Roberto Salvioni, Riccardo Valdagni
Journal: European Urology (2013)
Book: Curbing the epidemic: governments and the economics of tobacco control
Authors: S. Chapman
Journal: BMJ (2000)

Eds Prabat Jha, Frank J Chaloupka World Bank, £16, pp 122 ISBN 0 8213 4519 2 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> If you have been dining with conservative economists lately you may have heard something like this after the fourth port: "Tobacco is a wonderful thing. People start in their youth, contribute easily collectable tax for 40-50 years, and then about half have the decency to die around retirement age, thus saving the government the cost of their pensions and of treating their degenerative diseases in their final … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
Quantitative structure-activity relationships (QSARs) for estrogen binding to the estrogen receptor: predictions across species.
Authors: W Tong, R Perkins, R Strelitz, E R Collantes, S Keenan, W J Welsh, W S Branham, D M Sheehan
Journal: Environmental Health Perspectives (1997)

The recognition of adverse effects due to environmental endocrine disruptors in humans and wildlife has focused attention on the need for predictive tools to select the most likely estrogenic chemicals from a very large number of chemicals for subsequent screening and/or testing for potential environmental toxicity. A three-dimensional quantitative structure-activity relationship (QSAR) model using comparative molecular field analysis (CoMFA) was constructed based on relative binding affinity (RBA) data from an estrogen receptor (ER) binding assay using calf uterine cytosol. The model demonstrated significant correlation of the calculated steric and electrostatic fields with RBA and yielded predictions that agreed well with experimental values over the entire range of RBA values. Analysis of the CoMFA three-dimensional contour plots revealed a consistent picture of the structural features that are largely responsible for the observed variations in RBA. Importantly, we established a correlation between the predicted RBA values for calf ER and their actual RBA values for human ER. These findings suggest a means to begin to construct a more comprehensive estrogen knowledge base by combining RBA assay data from multiple species in 3D-QSAR based predictive models, which could then be used to screen untested chemicals for their potential to bind to the ER. Another QSAR model was developed based on classical physicochemical descriptors generated using the CODESSA (Comprehensive Descriptors for Structural and Statistical Analysis) program. The predictive ability of the CoMFA model was superior to the corresponding CODESSA model.
HURLER'S SYNDROME: A GENETIC STUDY OF CLONES IN CELL CULTURE WITH PARTICULAR REFERENCE TO THE LYON HYPOTHESIS
Authors: B. Shannon Danes, Alexander G. Bearn
Journal: The Journal of Experimental Medicine (1967)

Clones of skin fibroblasts from normal individuals, patients with different mucopolysaccharidoses, and certain of their relatives have been examined for cellular metachromasia and cellular uronic acid. All the clones derived from affected individuals and heterozygous carriers in families with the autosomal forms of Hurler's syndrome showed marked metachromasia and increased cellular uronic acid. Since only one cell population was demonstrated in clones derived from heterozygous carriers, no evidence for autosomal inactivation was obtained. Clones derived from affected individuals with the X-linked recessive form of Hurler's syndrome contained uniform populations of metachromatic staining cells which demonstrated increased cellular uronic acid. Clones derived from the noncarrier fathers showed no cellular metachromasia or increased cellular uronic acid. Clones derived from the heterozygous mothers and sisters showed two populations both qualitatively and quantitatively. On the average, 72% of these clones were metachromatic and demonstrated an increased uronic acid content; 28% of the clones showed no metachromasia and the uronic acid content was similar to that found in normal individuals. The appearance of two distinct cell populations in clones derived from females heterozygous for the X-linked recessive form of Hurler's syndrome provides evidence in favor of the Lyon hypothesis.
Prognostic Value of CD133 Caused by Mutant K-Ras and B-Raf—Response
Authors: Kristel Kemper, Jan Paul Medema
Journal: Clinical Cancer Research (2012)

In their letter to the editor, Fornaro and colleagues address important issues regarding our findings on CD133 as a prognostic marker for colorectal cancer.

We would like to thank them for correctly pointing out the lack of important clinical parameters that have been shown to determine prognosis
THE PASSAGE OF MENINGOCOCCIC AGGLUTININS FROM THE BLOOD TO THE SPINAL FLUID OF THE MONKEY
Authors: Harold L. Amoss, Frederick Eberson
Journal: The Journal of Experimental Medicine (1919)

Agglutinins for the meningococcus were not found in the spinal fluid of normal monkeys which had received antimeningococcic serum intravenously. The intraspinal injection of isotonic salt solution, normal horse serum, or a culture of living meningococci allows agglutinins for the meningococcus to pass from the blood to the spinal fluid of the passively immunized monkey; and the rate of the passage is affected by the severity of the inflammation induced in the meninges. The rates of elimination from the blood and spinal canal of meningococcic antibodies, as shown by the agglutination reaction, were compared in monkeys treated with immune serum (a) intraspinally, (b) intravenously, and (c) intraspinally and intravenously in combination. (a) When immune serum is given intraspinally the agglutinins are very much diminished after 8 hours and practically disappear at 12 hours. They appear in the blood at the 4th hour after injection and quickly diminish. (b) After intravenous injection of immune serum, when the meninges are inflamed, agglutinins appear in the spinal fluid in small amounts in about 12 hours and increase to the 25th hour. More than one-half of the agglutinins disappear from the blood within 8 hours and remain in low concentration at 25 hours. (c) After combined intraspinal and intravenous injection the agglutinins remain in higher concentration in the spinal fluid and for a longer time than by method (a) or (b). The curve descends after 12 hours, and agglutinins are present at 25 hours. They remain in maximum concentration in the blood for 25 hours.
Genetic and Environmental Influences on Trauma Exposure and Posttraumatic Stress Disorder Symptoms: A Twin Study
Authors: Murray B. Stein, Kerry L. Jang, Steven Taylor, Philip A. Vernon, W. John Livesley
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Posttraumatic stress disorder (PTSD) develops in only a subset of persons exposed to traumatic stress, suggesting the existence of stressor and individual differences that influence risk. In this study the authors examined the heritability of trauma exposure and PTSD symptoms in male and female twin pairs of nonveteran volunteers. METHOD: Scores on a traumatic events inventory and a DSM-IV PTSD symptom inventory were examined in 222 monozygotic and 184 dizygotic twin pairs. Biometrical model fitting was conducted by using standard statistical methods. RESULTS: Additive genetic, common environmental, and unique environmental effects best explained the variance in exposure to assaultive trauma (e.g., robbery, sexual assault), whereas exposure to nonassaultive trauma (e.g., motor vehicle accident, natural disaster) was best explained by common and unique environmental influences. PTSD symptoms were moderately heritable, and the remaining variance was accounted for by unique environmental experiences. Correlations between genetic effects on assaultive trauma exposure and on PTSD symptoms were high. CONCLUSIONS: Genetic factors can influence the risk of exposure to some forms of trauma, perhaps through individual differences in personality that influence environmental choices. Consistent with symptoms in combat veterans, PTSD symptoms after noncombat trauma are also moderately heritable. Moreover, many of the same genes that influence exposure to assaultive trauma appear to influence susceptibility to PTSD symptoms in their wake.