tbuckley/cabot-search huggingface dataset:
The TRAF1/C5 region is a risk factor for polyarthritis in juvenile idiopathic arthritis
Authors: H M Albers, F A S Kurreeman, J J Houwing-Duistermaat, D M C Brinkman, S S M Kamphuis, H J Girschick, C Wouters, M A J Van Rossum, W Verduijn, R E M Toes, T W J Huizinga, M W Schilham, R t. Cate
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> Juvenile idiopathic arthritis (JIA) is a chronic disorder in which both genetic and environmental factors are involved. Recently, we identified the <i>TRAF1/C5</i> region (located on chromosome 9q33–34) as a risk factor for rheumatoid arthritis (RA) (p<sub>combined</sub> = 1.4×10<sup>−8</sup>). In the present study the association of the <i>TRAF1/C5</i> region with the susceptibility to JIA was investigated. <h3>Methods:</h3> A case–control association study was performed in 338 Caucasian patients with JIA and 511 healthy individuals. We genotyped the single nucleotide polymorphism rs10818488 as a marker for the <i>TRAF1/C5</i> region. <h3>Results:</h3> The A allele was associated with the susceptibility to rheumatoid factor-negative polyarthritis with an 11% increase in allele frequency (OR 1.54, 95% CI 1.09 to 2.18; p = 0.012). This association was stronger when combining subtypes with a polyarticular phenotype (OR 1.46, 95% CI 1.12 to 1.90; p = 0.004). In addition, we observed a trend towards an increase in A allele frequency in patients with extended oligoarthritis versus persistent oligoarthritis (49%, 38% respectively); p = 0.055. <h3>Conclusions:</h3> Apart from being a well replicated risk factor for RA, <i>TRAF1/C5</i> also appears to be a risk factor for the rheumatoid factor-negative polyarthritis subtype of JIA and, more generally, seems to be associated with subtypes of JIA characterised by a polyarticular course.
Short Communication: Genetic Ablation of L-Type Ca <sup>2+</sup> Channels Abolishes Depolarization-Induced Ca <sup>2+</sup> Release in Arterial Smooth Muscle
Authors: Miguel Fernández-Tenorio, Patricia González-Rodríguez, Cristina Porras, Antonio Castellano, Sven Moosmang, Franz Hofmann, Juan Ureña, José López-Barneo
Journal: Circulation Research (2010)

In arterial myocytes, membrane depolarization-induced Ca(2+) release (DICR) from the sarcoplasmic reticulum (SR) occurs through a metabotropic pathway that leads to inositol trisphosphate synthesis independently of extracellular Ca(2+) influx. Despite the fundamental functional relevance of DICR, its molecular bases are not well known.Biophysical and pharmacological data have suggested that L-type Ca(2+) channels could be the sensors coupling membrane depolarization to SR Ca(2+) release. This hypothesis was tested using smooth muscle-selective conditional Ca(v)1.2 knockout mice.In aortic myocytes, the decrease of Ca(2+) channel density was paralleled by the disappearance of SR Ca(2+) release induced by either depolarization or Ca(2+) channel agonists. Ca(v)1.2 channel deficiency resulted in almost abolition of arterial ring contraction evoked by DICR. Ca(2+) channel-null cells showed unaltered caffeine-induced Ca(2+) release and contraction.These data suggest that Ca(v)1.2 channels are indeed voltage sensors coupled to the metabolic cascade, leading to SR Ca(2+) release. These findings support a novel, ion-independent, functional role of L-type Ca(2+) channels linked to intracellular signaling pathways in vascular myocytes.
Nonuniform Recovery of Excitability in Ventricular Muscle
Authors: JAOK HAN, GORDON K. MOE
Journal: Circulation Research (1964)

Recovery of excitability of ventricular muscle was measured at numerous points in exposed dog ventricles at varying distances along six radial axes from a primary point of stimulation. Temporal dispersion of recovery of excitability at various points equidistant from the point of stimulation was minimal after a basic beat but was increased after an early premature beat. The degree of dispersion following a basic beat was increased by stimulation of the cardiac sympathetic nerves, administration of chloroform, ouabain intoxication, administration of higher doses of quinidine, myocardial ischemia, and hypothermia, but it was decreased by administration of sympathomimetic amines.
Arsenic Trioxide in Patients With Myelodysplastic Syndromes: A Phase II Multicenter Study
Authors: Norbert Vey, Andre Bosly, Agnes Guerci, Walter Feremans, Herve Dombret, Francois Dreyfus, David Bowen, Alan Burnett, Mike Dennis, Vincent Ribrag, Nicole Casadevall, Laurence Legros, Pierre Fenaux
Journal: Journal of Clinical Oncology (2006)

Purpose Evaluation of the safety and efficacy of arsenic trioxide in patients with myelodysplastic syndromes (MDS). Patients and Methods MDS patients diagnosed according to standard French-American-British criteria received a loading dose of 0.3 mg/kg per day of arsenic trioxide for 5 days followed by a maintenance dose of 0.25 mg/kg arsenic trioxide twice weekly for 15 weeks. Patients were divided into two cohorts: lower-risk MDS (International Prognostic Scoring System risk category low or intermediate 1) and higher-risk MDS (International Prognostic Scoring System risk category intermediate 2 or high). Modified International Working Group criteria were used for response evaluation. Results Of 115 patients enrolled and treated in the study, 67% of patients were transfusion dependent at baseline; median age was 68 years. Most treatment-related adverse events were mild to moderate. The overall rate of hematologic improvement (intent-to-treat) was 24 (19%) of 115, including one complete and one partial response in the higher-risk cohort. The hematologic response rates were 13 (26%) of 50 and 11 (17%) of 64 in patients with lower-risk and higher-risk MDS, respectively. Major responses were observed in all three hematologic lineages; 16% of RBC transfusion-dependent patients and 29% of platelet transfusion-dependent patients became transfusion independent. At data cut off, the median response duration was 3.4 months, with responses ongoing in nine patients. Conclusion Arsenic trioxide treatment consisting of an initial loading dose followed by maintenance therapy has moderate activity in MDS, inducing hematologic responses in both lower- and higher-risk patients. This activity combined with a manageable adverse effect profile warrants the additional study of arsenic trioxide, particularly in combination therapy, for the treatment of patients with MDS.
Epigenetic Changes in Prostate Cancer: Implication for Diagnosis and Treatment
Authors: Long-Cheng Li, Peter R. Carroll, Rajvir Dahiya
Journal: JNCI Journal of the National Cancer Institute (2005)

Prostate cancer is the most common noncutaneous malignancy and the second leading cause of cancer death among men in the United States. DNA methylation and histone modifications are important epigenetic mechanisms of gene regulation and play essential roles both independently and cooperatively in tumor initiation and progression. Aberrant epigenetic events such as DNA hypo- and hypermethylation and altered histone acetylation have both been observed in prostate cancer, in which they affect a large number of genes. Although the list of aberrantly epigenetically regulated genes continues to grow, only a few genes have, so far, given promising results as potential tumor biomarkers for early diagnosis and risk assessment of prostate cancer. Thus, large-scale screening of aberrant epigenetic events such as DNA hypermethylation is needed to identify prostate cancer-specific epigenetic fingerprints. The reversibility of epigenetic aberrations has made them attractive targets for cancer treatment with modulators that demethylate DNA and inhibit histone deacetylases, leading to reactivation of silenced genes. More studies into the mechanism and consequence of demethylation are required before the cancer epigenome can be safely manipulated with therapeutics as a treatment modality. In this review, we examine the current literature on epigenetic changes in prostate cancer and discuss the clinical potential of cancer epigenetics for the diagnosis and treatment of this disease.
318 PPARA polymorphisms and haplotypes in gallstone patients: Prevalence and gender associations
Authors: M. Montagnani, E. Ravaioli, R. Aldini, M.L. Bacchi-Reggianil, D. Festi, A. Colecchia, E. Azzaroli, R. Righetti, G. Mazzella, F. Minni, E. Roda
Journal: Journal of Hepatology (2006)
274 TIME TO PROGRESSION TO AFP AS A PREDICTOR OF SURVIVAL IN PATIENTS WITH HEPATOCELLULAR CARCINOMA TREATED WITH SORAFENIB
Authors: M. Varela, O. Castaño-Fernández, L. Blanco García, A. Mesa-Álvarez, R. Menéndez de Llano, S. Sanmartino, B. Argüelles, P. Martínez-Camblor, L.H. Luyando, M. Rodríguez
Journal: Journal of Hepatology (2013)
Detectable clonal mosaicism from birth to old age and its relationship to cancer
Authors: Cathy C Laurie, Cecelia A Laurie, Kenneth Rice, Kimberly F Doheny, Leila R Zelnick, Caitlin P McHugh, Hua Ling, Kurt N Hetrick, Elizabeth W Pugh, Chris Amos, Qingyi Wei, Li-e Wang, Jeffrey E Lee, Kathleen C Barnes, Nadia N Hansel, Rasika Mathias, Denise Daley, Terri H Beaty, Alan F Scott, Ingo Ruczinski, Rob B Scharpf, Laura J Bierut, Sarah M Hartz, Maria Teresa Landi, Neal D Freedman, Lynn R Goldin, David Ginsburg, Jun Li, Karl C Desch, Sara S Strom, William J Blot, Lisa B Signorello, Sue A Ingles, Stephen J Chanock, Sonja I Berndt, Loic Le Marchand, Brian E Henderson, Kristine R Monroe, John A Heit, Mariza de Andrade, Sebastian M Armasu, Cynthia Regnier, William L Lowe, M Geoffrey Hayes, Mary L Marazita, Eleanor Feingold, Jeffrey C Murray, Mads Melbye, Bjarke Feenstra, Jae H Kang, Janey L Wiggs, Gail P Jarvik, Andrew N McDavid, Venkatraman E Seshan, Daniel B Mirel, Andrew Crenshaw, Nataliya Sharopova, Anastasia Wise, Jess Shen, David R Crosslin, David M Levine, Xiuwen Zheng, Jenna I Udren, Siiri Bennett, Sarah C Nelson, Stephanie M Gogarten, Matthew P Conomos, Patrick Heagerty, Teri Manolio, Louis R Pasquale, Christopher A Haiman, Neil Caporaso, Bruce S Weir
Journal: Nature Genetics (2012)
Early life exposure to diagnostic radiation and ultrasound scans and risk of childhood cancer: case-control study
Authors: P. Rajaraman, J. Simpson, G. Neta, A. Berrington de Gonzalez, P. Ansell, M. S. Linet, E. Ron, E. Roman
Journal: BMJ (2011)

<b>Objective</b> To examine childhood cancer risks associated with exposure to diagnostic radiation and ultrasound scans in utero and in early infancy (age 0-100 days). <b>Design</b> Case-control study. <b>Setting</b> England and Wales. <b>Participants</b> 2690 childhood cancer cases and 4858 age, sex, and region matched controls from the United Kingdom Childhood Cancer Study (UKCCS), born 1976-96. <b>Main outcome measures</b> Risk of all childhood cancer, leukaemia, lymphoma, and central nervous system tumours, measured by odds ratios. <b>Results</b> Logistic regression models conditioned on matching factors, with adjustment for maternal age and child's birth weight, showed no evidence of increased risk of childhood cancer with in utero exposure to ultrasound scans. Some indication existed of a slight increase in risk after in utero exposure to x rays for all cancers (odds ratio 1.l4, 95% confidence interval 0.90 to 1.45) and leukaemia (1.36, 0.91 to 2.02), but this was not statistically significant. Exposure to diagnostic x rays in early infancy (0-100 days) was associated with small, non-significant excess risks for all cancers and leukaemia, as well as increased risk of lymphoma (odds ratio 5.14, 1.27 to 20.78) on the basis of small numbers. <b>Conclusions</b> Although the results for lymphoma need to be replicated, all of the findings indicate possible risks of cancer from radiation at doses lower than those associated with commonly used procedures such as computed tomography scans, suggesting the need for cautious use of diagnostic radiation imaging procedures to the abdomen/pelvis of the mother during pregnancy and in children at very young ages.
Access for what? Reflective consciousness
Authors: Michael Snodgrass, Scott A. Lepisto
Journal: Behavioral and Brain Sciences (2007)

Abstract Can phenomenality without access occur? We suggest that the crucial issue is not to show phenomenality that cannot be accessed, but whether phenomenality sometimes simply is not accessed. Considering this question leads to positing a distinct, second form of consciousness: Reflective consciousness. The most important form of access is then from phenomenal (first-order) to reflective (second-order) consciousness.
Hydrotropic oligomer-conjugated glycol chitosan as a carrier of paclitaxel: Synthesis, characterization, and in vivo biodistribution
Authors: G. Saravanakumar, Kyung Hyun Min, Dong Sik Min, Ah Young Kim, Chang-Moon Lee, Yong Woo Cho, Sang Cheon Lee, Kwangmeyung Kim, Seo Young Jeong, Kinam Park, Jae Hyung Park, Ick Chan Kwon
Journal: Journal of Controlled Release (2009)
Breast Image Analysis for Risk Assessment, Detection, Diagnosis, and Treatment of Cancer
Authors: Maryellen L. Giger, Nico Karssemeijer, Julia A. Schnabel
Journal: Annual Review of Biomedical Engineering (2013)

The role of breast image analysis in radiologists' interpretation tasks in cancer risk assessment, detection, diagnosis, and treatment continues to expand. Breast image analysis methods include segmentation, feature extraction techniques, classifier design, biomechanical modeling, image registration, motion correction, and rigorous methods of evaluation. We present a review of the current status of these task-based image analysis methods, which are being developed for the various image acquisition modalities of mammography, tomosynthesis, computed tomography, ultrasound, and magnetic resonance imaging. Depending on the task, image-based biomarkers from such quantitative image analysis may include morphological, textural, and kinetic characteristics and may depend on accurate modeling and registration of the breast images. We conclude with a discussion of future directions.
The PEF data plot: planning to get the message
Authors: M R Miller
Journal: Thorax (2005)

Work is needed to determine the best scaling for PEF data to enable patients and clinicians to get the most benefit from them

A large part of medical practice involves pattern recognition. A clinician may note that a few key aspects of a patient’s history, their demographic data, their clinical examination, and chest radiograph fit a pattern they recognise as making a particular diagnosis highly probable. This pattern involves more than one domain of data acquisition, and both within and between these domains our ability to recognise patterns may be affected by how the information is presented to us. If data are presented to us verbally, the ordering of this information may be crucial. For example, verbal instructions on how to get from ward A to ward B are easier to understand and use if they are given in consecutive order starting from ward A and ending up at ward B rather than the instructions coming in random order. The order in which a patient’s history is presented to a colleague is an example of this. The graphical presentation of tables of numbers may improve the usefulness of the data,1 especially if there is a shape in the data that conveys the signal and the time required to search the data for any signal is thereby reduced.2 In this issue of Thorax Reddel and colleagues3 question whether we are doing enough to present our patients’ peak expiratory flow (PEF) data in a manner that is likely to facilitate both clinicians and patients distinguishing the signal or message in the data from all the noise.

Research continues to add to our understanding of how the brain detects and learns patterns. Facial recognition and the interpretation of facial expression are key aspects of human interaction involving complex pattern recognition. …
Prevention of Contrast-Induced Nephropathy With Sodium Bicarbonate
Authors: Gregory J. Merten, W. Patrick Burgess, Lee V. Gray, Jeremiah H. Holleman, Timothy S. Roush, Glen J. Kowalchuk, Robert M. Bersin, Arl Van Moore, Charles A. Simonton III, Robert A. Rittase, H. James Norton, Thomas P. Kennedy
Journal: JAMA (2004)

ContextContrast-induced nephropathy remains a common complication of radiographic procedures. Pretreatment with sodium bicarbonate is more protective than sodium chloride in animal models of acute ischemic renal failure. Acute renal failure from both ischemia and contrast are postulated to occur from free-radical injury. However, no studies in humans or animals have evaluated the efficacy of sodium bicarbonate for prophylaxis against contrast-induced nephropathy.ObjectiveTo examine the efficacy of sodium bicarbonate compared with sodium chloride for preventive hydration before and after radiographic contrast.Design, Setting, and PatientsA prospective, single-center, randomized trial conducted from September 16, 2002, to June 17, 2003, of 119 patients with stable serum creatinine levels of at least 1.1 mg/dL (≥97.2 µmol/L) who were randomized to receive a 154-mEq/L infusion of either sodium chloride (n = 59) or sodium bicarbonate (n = 60) before and after iopamidol administration (370 mg iodine/mL). Serum creatinine levels were measured at baseline and 1 and 2 days after contrast.InterventionsPatients received 154 mEq/L of either sodium chloride or sodium bicarbonate, as a bolus of 3 mL/kg per hour for 1 hour before iopamidol contrast, followed by an infusion of 1 mL/kg per hour for 6 hours after the procedure.Main Outcome MeasureContrast-induced nephropathy, defined as an increase of 25% or more in serum creatinine within 2 days of contrast.ResultsThere were no significant group differences in age, sex, incidence of diabetes mellitus, ethnicity, or contrast volume. Baseline serum creatinine was slightly higher but not statistically different in patients receiving sodium bicarbonate treatment (mean [SD], 1.71 [0.42] mg/dL [151.2 {37.1} µmol/L] for sodium chloride and 1.89 [0.69] mg/dL [167.1 {61.0} µmol/L] for sodium bicarbonate; P = .09). The primary end point of contrast-induced nephropathy occurred in 8 patients (13.6%) infused with sodium chloride but in only 1 (1.7%) of those receiving sodium bicarbonate(mean difference, 11.9%; 95% confidence interval [CI], 2.6%-21.2%; P = .02). A follow-up registry of 191 consecutive patients receiving prophylactic sodium bicarbonate and meeting the same inclusion criteria as the study resulted in 3 cases of contrast-induced nephropathy (1.6%; 95% CI, 0%-3.4%).ConclusionHydration with sodium bicarbonate before contrast exposure is more effective than hydration with sodium chloride for prophylaxis of contrast-induced renal failure.
Properties of antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. I. In vivo activity and immunochemical characterization.
Authors: T Takemori, T Tada
Journal: The Journal of Experimental Medicine (1975)

An antigen-specific suppressive T-cell factor was extracted from physically disrupted thymocytes and spleen cells of mice that had been immunized with soluble protein antigens. The factor, when inoculated into syngeneic normal mice, could induce a significant suppression of IgG antibody response against a hapten coupled to the carrier protein by which the donor of the suppressor factor was immunized. The suppressor factor was found only effective in suppressing the antibody response of syngeneic or H-2 histocompatible recipients. The suppressive T-cell factor was removed by absorption with immunoadsorbent composed of the relevant antigen, but not with any of those of anti-immunoglobulin antibodies. The factor was successfully removed by alloantibodies with specificity for the K end (H-2K, I-A and I-B) of the H-2 complex of the donor strain, but not by those for the D end (I-C, SsSlp, and H-2D). The activity was removed by absorption with a heterologous antithymocyte serum. The mol wt of the suppression T-cell factor was between 35,000 and 60,000 as determined by Sephadex G-200 gel filtration. The suppressive T-cell factor was found to be a heat-liable protein.
Fractional Flow Reserve–Guided PCI versus Medical Therapy in Stable Coronary Disease
Authors: Bernard De Bruyne, Nico H.J. Pijls, Bindu Kalesan, Emanuele Barbato, Pim A.L. Tonino, Zsolt Piroth, Nikola Jagic, Sven Möbius-Winkler, Gilles Rioufol, Nils Witt, Petr Kala, Philip MacCarthy, Thomas Engström, Keith G. Oldroyd, Kreton Mavromatis, Ganesh Manoharan, Peter Verlee, Ole Frobert, Nick Curzen, Jane B. Johnson, Peter Jüni, William F. Fearon
Journal: New England Journal of Medicine (2012)

The preferred initial treatment for patients with stable coronary artery disease is the best available medical therapy. We hypothesized that in patients with functionally significant stenoses, as determined by measurement of fractional flow reserve (FFR), percutaneous coronary intervention (PCI) plus the best available medical therapy would be superior to the best available medical therapy alone.In patients with stable coronary artery disease for whom PCI was being considered, we assessed all stenoses by measuring FFR. Patients in whom at least one stenosis was functionally significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus the best available medical therapy (PCI group) or the best available medical therapy alone (medical-therapy group). Patients in whom all stenoses had an FFR of more than 0.80 were entered into a registry and received the best available medical therapy. The primary end point was a composite of death, myocardial infarction, or urgent revascularization.Recruitment was halted prematurely after enrollment of 1220 patients (888 who underwent randomization and 332 enrolled in the registry) because of a significant between-group difference in the percentage of patients who had a primary end-point event: 4.3% in the PCI group and 12.7% in the medical-therapy group (hazard ratio with PCI, 0.32; 95% confidence interval [CI], 0.19 to 0.53; P<0.001). The difference was driven by a lower rate of urgent revascularization in the PCI group than in the medical-therapy group (1.6% vs. 11.1%; hazard ratio, 0.13; 95% CI, 0.06 to 0.30; P<0.001); in particular, in the PCI group, fewer urgent revascularizations were triggered by a myocardial infarction or evidence of ischemia on electrocardiography (hazard ratio, 0.13; 95% CI, 0.04 to 0.43; P<0.001). Among patients in the registry, 3.0% had a primary end-point event.In patients with stable coronary artery disease and functionally significant stenoses, FFR-guided PCI plus the best available medical therapy, as compared with the best available medical therapy alone, decreased the need for urgent revascularization. In patients without ischemia, the outcome appeared to be favorable with the best available medical therapy alone. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT01132495.).
Ability of a new infant formula prepared from partially hydrolyzed bovine whey to induce anaphylactic sensitization: evaluation in a guinea pig model
Authors: G. L. Piacentini, A. Bertolini, E. Spezia, T. Piscione, A. L. Boner
Journal: Allergy (1994)

In the present study we evaluated the allergenicity and immunogenicity of a whey partially hydrolysate formula (PHF) in a guinea pig model. Nine groups of 10 guinea pigs received either a conventional milk formula (CMF) or PHF for 37 days. After intravenous (i.v.) challenge with either α‐lactoglobulin (β‐L) or ultracentrifuged (u)CMF, animals fed CMF showed, respectively, 80% and 100®0 fatal reactions, whereas animals fed PHF showed no reactions when i.v. challenged both with (3‐L and uPHF. Eighty percent fatal reactions, and 10%, respectively, of severe and mild reactions have been observed in the CMF‐fed, casein‐challenge group. In contrast, only one (10%) mild reaction occurred in the PHF‐fed, casein‐challenged group. When challenged with u‐pasteurized cow's milk (uPCM), CMF‐fed animals showed 86% fatal reactions and 14% mild reactions, whereas PHF‐fed ones presented 70% no reactions, 20%, mild reactions, and one (10%) fatal reaction. Animals fed CMF showed a significantly higher level of specific IgG against cow's milk antigens than PHF‐fed ones, which, however, presented higher levels of antibodies than a water‐supplemented control group. The present results confirm that PHF is less sensitizing than CMF in a guinea pig model.