tbuckley/cabot-search huggingface dataset:
Transcriptional and posttranslational regulation of cre recombinase by ru486 as the basis for an enhanced inducible expression system
Authors: Stephanos Kyrkanides, Jen-nie H Miller, William J Bowers, Howard J Federoff
Journal: Molecular Therapy (2003)

Genetic studies often require the employment of an inducible expression system, whereby the expression of a particular gene can be regulated by the exogenous administration of an inert ligand. Cre/loxP-based systems have been previously described as the basis for inducible expression systems by exerting site-specific DNA recombination. In our effort to enhance the properties of the RU486-responsive CrePr1 construct, we have developed the dual GLVP/CrePr system, in which RU486 confers activity control at both the transcriptional and the posttranslational level of CrePr1. This was achieved by placing CrePr1 transcriptional regulation under the control of the RU486-sensitive chimeric regulator GLVP. Stable cell lines harboring the dual GLVP/CrePr as well as the single CrePr1 system were developed. Our results indicate that the dually regulated system is highly inducible by RU486 while maintaining minimal basal activity ("leakage"), characteristics that can be employed in the development of transgenic mice in which genetic pathways can be turned on or turned off after exogenous administration of RU486 at physiologically inert doses.
Response to Letter Regarding Article, “Prevalence, Characteristics, and Outcomes of Patients Presenting With Cardiogenic Unilateral Pulmonary Edema”
Authors: David Attias, Nicolas Mansencal, Aurélie Delos, Roland N′Guetta, Olivier Dubourg, Bertran Auvert, Antoine Vieillard-Baron, François Jardin, Pascal Lacombe
Journal: Circulation (2011)

Pulmonary Edema"First, we thank Dr Lacout et al for their interest in and comments concerning our report that described the prevalence, characteristics, and outcomes of patients presenting with cardiogenic unilateral pulmonary edema (UPE). 1 As detailed in the Methods section, this was not a study that included all patients with acute respiratory failure referred to our hospital, but a retrospective study that included patients with a final diagnosis of acute cardiogenic pulmonary edema.Thus, patients who presented with pulmonary embolism could not be included in our study.We agree with Lacout et al about the potential usefulness of a computed tomography (CT) scan for patients presenting with acute chest pain.However, it is difficult to propose the use of a CT scan for patients with dyspnea and suspected heart failure; indeed, a CT scan may be deleterious in these patients.Moreover, current guidelines 2 do not mention a CT scan as a potential first-line examination for these patients, and echocardiography is probably the most useful first-line examination in this case.Furthermore, determination of levels of natriuretic peptides is probably of more help as a complement to a careful physical examination.In the case of patients who present with radiological features of UPE, we used to perform transthoracic echocardiography first in our institution.Indeed, we found that UPE was systematically associated with severe mitral regurgitation, and that the correct diagnosis of acute heart failure was achieved thanks to transthoracic echocardiography, with or without transesophageal echocardiography.Thus, transthoracic echocardiography may have several uses for patients with UPE: to detect severe mitral regurgitation, to assess left ventricular systolic or diastolic dysfunction, and to rule out another diagnosis of acute dyspnea.In the case of UPE, and in the absence of left ventricular dysfunction and/or mitral regurgitation, transthoracic echocardiography may be used to detect signs of acute Cor pulmonale, such as right ventricular dilatation with paradoxical septal motion and a right ventricular/left ventricular area ratio Ͼ0.6, 3 and may prompt consideration for a CT scan to reveal potential pulmonary embolism.In very rare cases, and when echocardiography is silent, we agree with Lacout et al that clinicians should consider that a CT scan may be of use for patients presenting with UPE.
Intracellular application of guanosine-5'-O-(3-thiotriphosphate) induces exocytotic granule fusion in guinea pig eosinophils.
Authors: O Nüsse, M Lindau, O Cromwell, A B Kay, B D Gomperts
Journal: The Journal of Experimental Medicine (1990)

The mechanism of eosinophil secretion was studied in guinea pig eosinophils by measuring release of hexosaminidase from cell suspensions (greater than 98% pure) permeabilized with streptolysin-O and by whole-cell patch-clamp capacitance measurements. It is shown that release of eosinophil granule components occurs by an exocytotic mechanism in which individual granules fuse with the plasma membrane. Exocytosis can be induced by intracellular application of the nonhydrolyzable GTP analog guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S), suggesting the involvement of a GTP-binding protein. The activation is modulated by the intracellular calcium concentration, with activation by GTP-gamma-S inducing transient elevations in the concentration of Ca2+. Thus, the nature and regulation of the release mechanism appear to be very similar to that of the mast cell and neutrophil.
Prenatal Organochlorine Compound Exposure, Rapid Weight Gain, and Overweight in Infancy
Authors: Michelle A. Mendez, Raquel Garcia-Esteban, Mónica Guxens, Martine Vrijheid, Manolis Kogevinas, Fernando Goñi, Silvia Fochs, Jordi Sunyer
Journal: Environmental Health Perspectives (2010)

Although it has been hypothesized that fetal exposure to endocrine-disrupting chemicals may increase obesity risk, empirical data are limited, and it is uncertain how early in life any effects may begin.We explored whether prenatal exposure to several organochlorine compounds (OCs) is associated with rapid growth in the first 6 months of life and body mass index (BMI) later in infancy.Data come from the INMA (Infancia y Medio-Ambiente) Child and Environment birth cohort in Spain, which recruited 657 women in early pregnancy. Rapid growth during the first 6 months was defined as a change in weight-for-age z-scores > 0.67, and elevated BMI at 14 months, as a z-score ≥ the 85th percentile. Generalized linear models were used to estimate the risk of rapid growth or elevated BMI associated with 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene (DDE), hexachlorobenzene, β-hexachlorohexane, and polychlorinated biphenyls in first-trimester maternal serum.After multivariable adjustment including other OCs, DDE exposure above the first quartile was associated with doubling of the risk of rapid growth among children of normal-weight (BMI < 25 kg/m2), but not overweight, mothers. DDE was also associated with elevated BMI at 14 months (relative risk per unit increase in log DDE = 1.50; 95% confidence interval, 1.11-2.03). Other OCs were not associated with rapid growth or elevated BMI after adjustment.In this study we found prenatal DDE exposure to be associated with rapid weight gain in the first 6 months and elevated BMI later in infancy, among infants of normal-weight mothers. More research exploring the potential role of chemical exposures in early-onset obesity is needed.
Bone morphogenetic protein-6 production in human osteoblastic cell lines. Selective regulation by estrogen.
Authors: D J Rickard, L C Hofbauer, S K Bonde, F Gori, T C Spelsberg, B L Riggs
Journal: Journal of Clinical Investigation (1998)

Bone morphogenetic proteins (BMPs) induce differentiation of osteoblast and chondroblast lineage cells from uncommitted mesenchymal precursors. Because estrogen has potent osteochondrogenic actions, we investigated its effect on BMP production in two estrogen-responsive, human immortalized cell lines (hFOB/ER3 and hFOB/ER9) that display the mature osteoblast phenotype. These cell lines were produced by stable transfection of the estrogen receptor (ER) gene into immortalized fetal osteoblasts at low ( approximately 800 ER/ nucleus) and at high ( approximately 3, 900 ER/nucleus) levels, respectively. As assessed by reverse transcriptase PCR, treatment with 17beta-estradiol (10(-)10 - 10(-)7 M) increased steady-state levels of BMP-6 mRNA dose dependently by twofold in the hFOB/ER3 cells and by over threefold in the hFOB/ER9 cells. Messenger RNA levels for transforming growth factors-beta1 and -beta2 and BMPs-1 through -5 and -7 levels were unchanged. The results were confirmed by sequence determination of the PCR product and by Northern blot analysis for total RNA. 17beta-estradiol increased BMP-6 protein production sixfold by Western analysis. Cotreatment with antiestrogens (ICI 182,780 or 4-hydroxytamoxifen) antagonized the effects of 17beta-estradiol. These data suggest that some of the skeletal effects of estrogen on bone and cartilage may be mediated by increased production of BMP-6 by osteoblasts.
The Chemical Feast: The Ralph Nader Study Group Report on Food Protection and the Food and Drug Administration
Authors: James Harvey Young
Journal: JAMA (1971)

Sixteen of Ralph Nader's bright and idealistic young allies—law, medical, and graduate students—spent the summer of 1969 interviewing Food and Drug Administration personnel and examining FDA records. This report renders their judgment of the agency's role as protector of the nation's food supply: in virtually every respect an "appalling failure." Concerned by the ecological crisis and moved by a strong antiestablishment bias, these "raiders" hold that food laws have been enacted and enforced so as to benefit industry rather than consumers. We would be better off without the 2,000 or 3,000 food additives now in use. The faintest hint of danger should be enough to ban use of an additive. FDA's "naive faith" in the food industry's professed goal of acting to benefit the consumer causes the agency to squander its power in back-room meetings with food tycoons and to rely on a "ludicrous" voluntary compliance system instead of on
MicroRNA regulation of tumorigenesis, cancer progression and interpatient heterogeneity: towards clinical use
Authors: S Patrick Nana-Sinkam, Carlo M Croce
Journal: Genome biology (2014)

In the past two decades, microRNAs have emerged as crucial mediators of organ development and human disease. Here, we discuss their role as drivers or suppressors of the hallmarks of cancer during tumorigenesis and progression, in defining interpatient heterogeneity and the promise of therapeutic application.
Soluble Tumor Necrosis Factor Receptor 1 Is Strongly and Independently Associated With Serum Homocysteine in Nonobese Japanese Type 2 Diabetic Patients
Authors: Ataru Taniguchi, Mitsuo Fukushima, Yoshikatsu Nakai, Minako Ohgushi, Akira Kuroe, Michihiro Ohya, Yutaka Seino
Journal: Diabetes Care (2006)

The major clinical consequence of type 2 diabetes is mortality and morbidity from atherosclerotic vascular disease. With regards to the risk factors responsible for the evolution of atherosclerosis, Bierman (1) estimated that typical risk factors, including smoking, cholesterol, and blood pressure, can account for no more than 30% of excess cardiovascular risk factors in diabetic patients. Thus, other factors seem to play a key role in the progression of atherosclerosis in diabetes.

One potential factor is homocysteine. Homocysteine has been shown …
The Simultaneous Use of Telomerase, Cytokeratin 20 and CD4 for Bladder Cancer Detection in Urine
Authors: Salvatore Siracusano, Benedetta Niccolini, Roberto Knez, Anna Tiberio, Elena Benedetti, Serena Bonin, Stefano Ciciliato, Giovanni L. Pappagallo, Emanuele Belgrano, Giorgio Stanta
Journal: European Urology (2004)
Microsatellite instability has a positive prognostic impact on stage II colorectal cancer after complete resection: results from a large, consecutive Norwegian series
Authors: M.A. Merok, T. Ahlquist, E.C. Røyrvik, K.F. Tufteland, M. Hektoen, O.H. Sjo, T. Mala, A. Svindland, R.A. Lothe, A. Nesbakken
Journal: Annals of Oncology (2012)

Microsatellite instability (MSI) was suggested as a marker for good prognosis in colorectal cancer in 1993 and a systematic review from 2005 and a meta-analysis from 2010 support the initial observation. We here assess the prognostic impact and prevalence of MSI in different stages in a consecutive, population-based series from a single hospital in Oslo, Norway.Of 1274 patients, 952 underwent major resection of which 805 were included in analyses of MSI prevalence and 613 with complete resection in analyses of outcome. Formalin-fixed tumor tissue was used for PCR-based MSI analyses.The overall prevalence of MSI was 14%, highest in females (19%) and in proximal colon cancer (29%). Five-year relapse-free survival (5-year RFS) was 67% and 55% (P = 0.030) in patients with MSI and MSS tumors, respectively, with the hazard ratio (HR) equal to 1.60 (P = 0.045) in multivariate analysis. The improved outcome was confined to stage II patients who had 5-year RFS of 74% and 56% respectively (P = 0.010), HR = 2.02 (P = 0.040). Examination of 12 or more lymph nodes was significantly associated with proximal tumor location (P < 0.001).MSI has an independent positive prognostic impact on stage II colorectal cancer patients after complete resection.
Identification of the membrane receptor for the complement fragment C3d by means of a monoclonal antibody.
Authors: K Iida, L Nadler, V Nussenzweig
Journal: The Journal of Experimental Medicine (1983)

The B2 antigen characterized by means of a monoclonal antibody (14) is a 140,000 Mr protein expressed only in certain stages of the differentiation of lymphocytes of the B lineage. Here we examine the relationship between B2 and the membrane complement receptor type 2 (CR2) for the complement fragment C3d (11, 12), which is also associated only with B cells. Both phenotypic markers are distributed in a similar manner among B cell malignancies and, as shown here, among established cell lines. A polypeptide with binding affinity for C3d was isolated from the membrane of B2-positive cells, i.e., tonsil lymphocytes and Raji cells. We found that this C3d-binding protein not only had the same Mr and isoelectric point (pI) as the B2 antigen, but that it was recognized by the monoclonal antibody to B2. However, anti-B2 does not mask the ligand-binding site of CR2 since it does not prevent the interaction of the purified 140,000 Mr polypeptide with immobilized C3d. Rosette formation between tonsil lymphocytes and erythrocyte intermediates bearing C3d was specifically inhibited by anti-B2. In the case of Raji cells, rosette formation was strongly inhibited only when the lymphocytes were sequentially treated with anti-B2 and with a polyclonal antibody against mouse Ig. In short, B2 and CR2 have a similar distribution among normal and malignant cells, have the same Mr and pI under denaturing conditions, and react with a single monoclonal antibody. We conclude that B2 is identical to CR2.
B7-06: Mass Spectrometry Profiling of Low Molecular Weight Platelet Proteome for the Detection of Lung Cancer Specific Biomarkers
Authors: Luigi De Petris, Maria Pernemalm, Eva Brandèn, Hirsh Koyi, Jenny Forshed, Birgitta Sundelin, Rolf Lewensohn, Janne Lehtiö
Journal: Journal of Thoracic Oncology (2007)
Cardiac imaging using a phased array ultrasound system. I. System design.
Authors: O T vonRamm, F L Thurstone
Journal: Circulation (1976)

A new two-dimensional, real-time, high resolution ultrasound imaging system is described. This system uses a linear array of ultrasound transducers to generate tomographic images of the heart in a circular sector format. Phased array techniques allow rapid steering of the ultrasound beam so that images are produced at the rate of 20 per second, or more, while maintaining a resolution of 2-4 mm throughout the field of view.
Government must do more to explain benefits of centralised database
Authors: G. Iacobucci
Journal: BMJ (2014)

The UK government should be wary of rolling out its national centralised database of patients’ medical records until it has averted the current “crisis of confidence” in the plans, the Royal College of General Practitioners has warned.

The “care.data” programme is being launched to assist in medical research and monitor NHS trends and performance more closely, by linking patients’ GP records with information already collected from acute trusts through hospital episode statistics (HES).1

But the scheme has attracted criticism from campaigners and some GPs, who are concerned that holding patients’ confidential data on a national …
Best lung function equations for the very elderly selected by survival analysis
Authors: Martin R. Miller, Mikael Thinggaard, Kaare Christensen, Ole F. Pedersen, Torben Sigsgaard
Journal: European Respiratory Journal (2014)

We evaluated which equations best predicted the lung function of a cohort of nonagenarians based on which best accounted for subsequent survival. In 1998, we measured lung function, grip strength and dementia score (Mini Mental State Examination (MMSE)) in a population-based sample of 2262 Danes born in 1905. Mortality was registered to 2011 when only five (0.2%) subjects were alive. In half the cohort, we recorded forced expiratory volume in 1 s (FEV 1 ). Complete data were available in 592 subjects with results expressed as standardised residuals (SR) using various prediction equations. Cox proportional hazard regression found lower FEV 1 SR was a predictor of mortality having controlled for MMSE, grip strength and sex. The US National Health and Nutrition Examination Survey (NHANES) III (1999) equations gave a better spread of median survival by FEV 1 SR quartile: 3.94, 3.65, 3.51 and 2.61 years with a hazard ratio for death of 1, 1.16, 1.32 and 1.60 respectively, compared with equations derived with the inclusion of elderly subjects. We conclude that extrapolating from NHANES III equations to predict lung function in nonagenarians gave better survival predictions from spirometry than when employing equations derived using very elderly subjects with possible selection bias. These findings can help inform how future lung function equations for the elderly are derived.
399 ELASTOGRAPHY-BASED ASSOCIATION STUDY OF THE FUNCTIONAL FAS PROMOTER POLYMORPHISM −670A&gt;G AND THE DEVELOPMENT OF ADVANCED FIBROSIS IN A COHORT OF PATIENTS WITH CHRONIC LIVER DISEASES
Authors: F. Grünhage, M. Krawczyk, R. Goebel, T. Sauerbruch, F. Lammert
Journal: Journal of Hepatology (2010)
Use of mobile phones in hospitals
Authors: Stuart W G Derbyshire, Adam Burgess
Journal: BMJ (2006)

Mobile phones are widely used, but their use is still restricted in certain places including petrol stations, some areas in hospitals, and aircraft. Restrictions have been justified on the grounds of public safety, but the reasons behind these restrictions are often unclear. In hospitals, patients, visitors, and staff routinely breeze through wards with their mobile phones switched on. As yet we have no evidence that this behaviour has serious consequences for patients. The lack of such evidence has encouraged the Medicines and Healthcare products Regulatory Agency (MHRA) to advise more selective restrictions on the use of mobile phones in hospitals (box).1 While welcoming this relaxation, we wonder why it has taken so long to happen and why it has the feeling of extracting a generous concession. The liberalisation sits alongside proposed new restrictions, such as a ban on the use of camera phones in patient areas. The regulations also fail to criticise the previous ones, which were overcautionary. Paradoxically, the new rules may be even more restrictive than the old ones.
French cardiovascular mortality did not increase during 1996 European football championship
Authors: L Toubiana
Journal: BMJ (2001)

EDITOR—Witte et al found a significant increase in mortality from coronary heart disease and stroke in Dutch men aged ≥45 on the day that the Dutch team was eliminated by the French from the 1996 European football championship compared with the five days before and after the match (relative risk 1.51; 95% confidence interval 1.08 to 2.09).1 We reassessed this hypothesis using corresponding French data.

The match had an audience of 4.7 million television viewers in France (around 8% of the French population). We performed the same time series analysis as Witte et al on …
TCT-447 Usefulness of Polyzene-F nanocoated stent to facilitate reendothelialization and reduce thrombus formation. In vivo results of stented rabbit iliac arteries
Authors: Luc Maillard, Delphine Corseaux, Alexandre Altié, Alexandre Ung, Joel Courageot, Emmanuel Teiger, eric van belle
Journal: Journal of the American College of Cardiology (2014)
Canadian government almost swamped by ciprofloxacin
Authors: David Spurgeon
Journal: BMJ (2001)

Canada's federal government has narrowly avoided having to pay for twice as much of the antibiotic ciprofloxacin (Cipro) as it thinks it needs to protect its citizens in the case of an outbreak of anthrax.

The federal health department circumvented its own drug patent rules when it ordered about 900 000 tablets of the medication from a generic drug manufacturer, Apotex. The patent, held by Bayer AG, does …
Sometimes appendicitis can wait
Authors: Olivier Turrini, Vincent Moutardier, Norbert Vey, Jérome Guiramand, Bernard Lelong, Jean‐Robert Delpero
Journal: American Journal of Hematology (2004)

To the Editor: Cerebrovascular accident (CVA) is a rare feature of childhood SCA (about 10% of children).Tang et al. [1] reported an odds ratio of 4 for a pair of alleles of a microsatellite locus within the site of the angiotensinogen gene (AGT) [
Genome Evolution and Developmental Constraint in Caenorhabditis elegans
Authors: Cristian I. Castillo-Davis, Daniel L. Hartl
Journal: Molecular Biology and Evolution (2002)

It has been hypothesized that evolutionary changes will be more frequent in later ontogeny than early ontogeny because of developmental constraint. To test this hypothesis, a genomewide examination of molecular evolution through ontogeny was carried out using comparative genomic data in Caenorhabditis elegans and Caenorhabditis briggsae. We found that the mean rate of amino acid replacement is not significantly different between genes expressed during and after embryogenesis. However, synonymous substitution rates differed significantly between these two classes. A genomewide survey of correlation between codon bias and expression level found codon bias to be significantly correlated with mRNA expression (rs = −0.30 and P < 10−131) but does not alone explain differences in dS between classes. Surprisingly, it was found that genes expressed after embryogenesis have a significantly greater number of duplicates in both the C. elegans and C. briggsae genomes (P < 10−20 and P < 10−13) when compared with early-expressed and nonmodulated genes. A similarity in the distribution of duplicates of nonmodulated and early-expressed genes, as well as a disproportionately higher number of early pseudogenes, lend support to the hypothesis that this difference in duplicate number is caused by selection against gene duplicates of early-expressed genes, reflecting developmental constraint. Developmental constraint at the level of gene duplication may have important implications for macroevolutionary change.
Strike Me Dead!
Authors: Joel E. Holloway
Journal: JAMA (1985)

To the Editor.—  In the Jan 11, 1985, issue, the authors of the article, Lightning Injury With Survival in Five Patients, 1 state the following: Reports of lightning injuries range from the anecdotal to collective reviews of large numbers of patients injured in natural electrocutions. I bring to the attention of the authors and the editors that if someone is electrocuted he dies. If someone is merely injured, the term electrocution is incorrect.
Hinchingbrooke Hospital's reply to "inadequate" rating on patient care
Authors: S. Hamilton
Journal: BMJ (2015)

Over the past three years there have been many positive changes to the quality of services (for example, the colorectal department) and to the number of services offered by Hinchingbrooke (provision of in-house urology; ear, nose, and throat; and plastic and hand surgery).

Recent data on mortality show that it is significantly lower than in other hospitals and the overall trend for mortality is reducing.1 We have had no …