tbuckley/cabot-search huggingface dataset:
Recurrent Melanocytic Nevi and Melanomas in Dermoscopy
Authors: Andreas Blum, Rainer Hofmann-Wellenhof, Ashfaq A. Marghoob, Giuseppe Argenziano, Horacio Cabo, Cristina Carrera, Bianca Costa Soares de Sá, Eric Ehrsam, Roger González, Josep Malvehy, Ausilia Maria Manganoni, Susana Puig, Olga Simionescu, Masaru Tanaka, Luc Thomas, Isabelle Tromme, Iris Zalaudek, Harald Kittler
Journal: JAMA Dermatology (2013)

IMPORTANCE Differentiating recurrent nevi from recurrent melanoma is challenging. OBJECTIVE To determine dermoscopic features to differentiate recurrent nevi from melanomas. DESIGN, SETTING, AND PARTICIPANTS Retrospective observational study of 15 pigmented lesion clinics from 12 countries; 98 recurrent nevi (61.3%) and 62 recurrent melanomas (38.8%) were collected from January to December 2011. MAIN OUTCOMES AND MEASURES Scoring the dermoscopic features, patterns, and colors in correlation with the histopathologic findings. RESULTS In univariate analysis, radial lines, symmetry, and centrifugal growth pattern were significantly more common dermoscopically in recurrent nevi; in contrast, circles, especially if on the head and neck area, eccentric hyperpigmentation at the periphery, a chaotic and noncontinuous growth pattern, and pigmentation beyond the scar's edge were significantly more common in recurrent melanomas. Patients with recurrent melanomas were significantly older than patients with recurrent nevi (mean [SD] age, 63.1 [17.5] years vs 30.2 [12.4] years) (P<.001), and there was a significantly longer time interval between the first procedure and the second treatment (median time interval, 25 vs 8 months) (P<.001). In a multivariate analysis, pigmentation beyond the scar's edge (P=.002), age (P<.001), and anatomic site (P=.002) were significantly and independently associated with the diagnosis of recurrent melanoma in dermoscopy. CONCLUSIONS AND RELEVANCE Dermoscopically, pigmentation beyond the scar's edge is the strongest clue for melanoma. Dermoscopy is helpful in evaluating recurrent lesions, but final interpretation requires taking into account the patient age, anatomic site, time to recurrence, growth pattern, and, if available, the histopathologic findings of the first excision.
ROS accumulation and IGF-IR inhibition contribute to fenofibrate/PPARα -mediated inhibition of Glioma cell motility in vitro
Authors: Justyna Drukala, Katarzyna Urbanska, Anna Wilk, Maja Grabacka, Ewa Wybieralska, Luis Del Valle, Zbigniew Madeja, Krzysztof Reiss
Journal: Molecular Cancer (2010)

Abstract Background Glioblastomas are characterized by rapid cell growth, aggressive CNS infiltration, and are resistant to all known anticancer regimens. Recent studies indicate that fibrates and statins possess anticancer potential. Fenofibrate is a potent agonist of peroxisome proliferator activated receptor alpha (PPARα) that can switch energy metabolism from glycolysis to fatty acid β-oxidation, and has low systemic toxicity. Fenofibrate also attenuates IGF-I-mediated cellular responses, which could be relevant in the process of glioblastoma cell dispersal. Methods The effects of fenofibrate on Glioma cell motility, IGF-I receptor (IGF-IR) signaling, PPARα activity, reactive oxygen species (ROS) metabolism, mitochondrial potential, and ATP production were analyzed in human glioma cell lines. Results Fenofibrate treatment attenuated IGF-I signaling responses and repressed cell motility of LN-229 and T98G Glioma cell lines. In the absence of fenofibrate, specific inhibition of the IGF-IR had only modest effects on Glioma cell motility. Further experiments revealed that PPARα-dependent accumulation of ROS is a strong contributing factor in Glioma cell lines responses to fenofibrate. The ROS scavenger, N-acetyl-cysteine (NAC), restored cell motility, improved mitochondrial potential, and increased ATP levels in fenofibrate treated Glioma cell lines. Conclusions Our results indicate that although fenofibrate-mediated inhibition of the IGF-IR may not be sufficient in counteracting Glioma cell dispersal, PPARα-dependent metabolic switch and the resulting ROS accumulation strongly contribute to the inhibition of these devastating brain tumor cells.
Thyrotoxicosis, sumatriptan and coronary artery spasm
Authors: S. Bassi, R. Amersey, R. Henderson, G K. Morris
Journal: Journal of the Royal Society of Medicine (2004)

The anti-migraine agent sumatriptan sometimes causes chest tightness, presumed to be secondary to coronary artery spasm. Another proposed factor in coronary artery spasm is thyrotoxicosis. The combination may be hazardous.
Myosin Crossbridge Activation of Cardiac Thin Filaments
Authors: Richard L. Moss, Maria Razumova, Daniel P. Fitzsimons
Journal: Circulation Research (2004)

At the level of the myofibrillar proteins, activation of myocardial contraction is thought to involve switch-like regulation of crossbridge binding to the thin filaments. A central feature of this view of regulation is that Ca 2+ binding to the low-affinity (≈3 μmol/L) site on troponin C alters the interactions of proteins in the thin filament regulatory strand, which leads to movement of tropomyosin from its blocking position on the thin filament and binding of crossbridges to actin. Although Ca 2+ binding is a critical step in initiating contraction, this event alone does not account for the activation dependence of contractile properties of myocardium. Instead, activation is a highly cooperative process in which initial crossbridge binding to the thin filaments recruits additional crossbridge binding to actin as well as increased Ca 2+ binding to troponin C. This review addresses possible roles of thin filament cooperativity in myocardium as a process that modulates the activation dependence of force and the rate of force development and also possible mechanisms by which cooperative signals are transmitted along the thick filament. Emerging evidence suggests that such mechanisms could contribute to the regulation of fundamental mechanical properties of myocardium and alterations in regulation that underlie contractile disorders in diseases such as cardiomyopathies.
Slow walking speed and cardiovascular death in well functioning older adults: prospective cohort study
Authors: J. Dumurgier, A. Elbaz, P. Ducimetiere, B. Tavernier, A. Alperovitch, C. Tzourio
Journal: BMJ (2009)

<b>Objective</b> To study the relation between low walking speed and the risk of death in older people, both overall and with regard to the main causes of death. <b>Design</b> Prospective cohort study. <b>Setting</b> Dijon centre (France) of the Three-City study. <b>Participants</b> 3208 men and women aged ≥65 living in the community, recruited from 1999 to 2001, and followed for an average of 5.1 years. <b>Main outcome measures</b> Mortality, overall and according to the main causes of death, by thirds of baseline walking speed (measured at maximum speed over six metres), adjusted for several potential confounders; Kaplan-Meier survival curves by thirds of baseline walking speed. Vital status during follow-up. Causes of death. <b>Results </b>During 16 414 person years of follow-up, 209 participants died (99 from cancer, 59 from cardiovascular disease, 51 from other causes). Participants in the lowest third of baseline walking speed had an increased risk of death (hazard ratio 1.44, 95% confidence interval 1.03 to 1.99) compared with the upper thirds. Analyses for specific causes of death showed that participants with low walking speed had about a threefold increased risk of cardiovascular death (2.92, 1.46 to 5.84) compared with participants who walked faster. There was no relation with cancer mortality (1.03, 0.65 to 1.70). In stratified analyses, cardiovascular mortality was increased across various strata defined by sex, median age, median body mass index (BMI), and level of physical activity. <b>Conclusion </b>Slow walking speed in older people is strongly associated with an increased risk of cardiovascular mortality.
One-Year Outcome of Subacromial Corticosteroid Injection Compared With Manual Physical Therapy for the Management of the Unilateral Shoulder Impingement Syndrome
Authors: Daniel I. Rhon, Robert B. Boyles, Joshua A. Cleland
Journal: Annals of Internal Medicine (2014)

Corticosteroid injections (CSIs) and physical therapy are used to treat patients with the shoulder impingement syndrome (SIS) but have never been directly compared.To compare the effectiveness of 2 common nonsurgical treatments for SIS.Randomized, single-blind, comparative-effectiveness, parallel-group trial. (ClinicalTrials.gov: NCT01190891).Military hospital-based outpatient clinic in the United States.104 patients aged 18 to 65 years with unilateral SIS between June 2010 and March 2012.Random assignment into 2 groups: 40-mg triamcinolone acetonide subacromial CSI versus 6 sessions of manual physical therapy.The primary outcome was change in Shoulder Pain and Disability Index scores at 1 year. Secondary outcomes included the Global Rating of Change scores, the Numeric Pain Rating Scale scores, and 1-year health care use.Both groups demonstrated approximately 50% improvement in Shoulder Pain and Disability Index scores maintained through 1 year; however, the mean difference between groups was not significant (1.5% [95% CI, -6.3% to 9.4%]). Both groups showed improvements in Global Rating of Change scale and pain rating scores, but between-group differences in scores for the Global Rating of Change scale (0 [CI, -2 to 1]) and pain rating (0.4 [CI, -0.5 to 1.2]) were not significant. During the 1-year follow-up, patients receiving CSI had more SIS-related visits to their primary care provider (60% vs. 37%) and required additional steroid injections (38% vs. 20%), and 19% needed physical therapy. Transient pain from the CSI was the only adverse event reported.The study occurred at 1 center with patients referred to physical therapy.Both groups experienced significant improvement. The manual physical therapy group used less 1-year SIS-related health care resources than the CSI group.Cardon Rehabilitation Products through the American Academy of Orthopaedic Manual Physical Therapists.
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci
Authors: Eli A Stahl, Soumya Raychaudhuri, Elaine F Remmers, Gang Xie, Stephen Eyre, Brian P Thomson, Yonghong Li, Fina A S Kurreeman, Alexandra Zhernakova, Anne Hinks, Candace Guiducci, Robert Chen, Lars Alfredsson, Christopher I Amos, Kristin G Ardlie, Anne Barton, John Bowes, Elisabeth Brouwer, Noel P Burtt, Joseph J Catanese, Jonathan Coblyn, Marieke J H Coenen, Karen H Costenbader, Lindsey A Criswell, J Bart A Crusius, Jing Cui, Paul I W de Bakker, Philip L De Jager, Bo Ding, Paul Emery, Edward Flynn, Pille Harrison, Lynne J Hocking, Tom W J Huizinga, Daniel L Kastner, Xiayi Ke, Annette T Lee, Xiangdong Liu, Paul Martin, Ann W Morgan, Leonid Padyukov, Marcel D Posthumus, Timothy R D J Radstake, David M Reid, Mark Seielstad, Michael F Seldin, Nancy A Shadick, Sophia Steer, Paul P Tak, Wendy Thomson, Annette H M van der Helm-van Mil, Irene E van der Horst-Bruinsma, C Ellen van der Schoot, Piet L C M van Riel, Michael E Weinblatt, Anthony G Wilson, Gert Jan Wolbink, B Paul Wordsworth, Cisca Wijmenga, Elizabeth W Karlson, Rene E M Toes, Niek de Vries, Ann B Begovich, Jane Worthington, Katherine A Siminovitch, Peter K Gregersen, Lars Klareskog, Robert M Plenge
Journal: Nature Genetics (2010)
The Role of Electroporation in Defibrillation
Authors: Ayman Al-Khadra, Vladimir Nikolski, Igor R. Efimov
Journal: Circulation Research (2000)

Abstract —Electric shock is the only effective therapy against ventricular fibrillation. However, shocks are also known to cause electroporation of cell membranes. We sought to determine the impact of electroporation on ventricular conduction and defibrillation. We optically mapped electrical activity in coronary-perfused rabbit hearts during electric shocks (50 to 500 V). Electroporation was evident from transient depolarization, reduction of action potential amplitude, and upstroke dV/dt. Electroporation was voltage dependent and significantly more pronounced at the endocardium versus the epicardium, with thresholds of 229±81 versus 318±84 V, respectively ( P =0.01, n=10), both being above the defibrillation threshold of 181.3±45.8 V. Epicardial electroporation was localized to a small area near the electrode, whereas endocardial electroporation was observed at the bundles and trabeculas throughout the entire endocardium. Higher-resolution imaging revealed that papillary muscles (n=10) were most affected. Electroporation and conduction block thresholds in papillary muscles were 281±64 V and 380±79 V, respectively. We observed no arrhythmia in association with electroporation. Further, preconditioning with high-energy shocks prevented reinduction of fibrillation by 50-V shocks, which were otherwise proarrhythmic. Endocardial bundles are the most susceptible to electroporation and the resulting conduction impairment. Electroporation is not associated with proarrhythmic effects and is associated with a reduction of vulnerability.
Synthesis, characterization, and evaluation of a novel inhibitor of WNT/β-catenin signaling pathway
Authors: Zhao Yan, Zhongling Zhu, Jinghui Wang, Jian Sun, Yihui Chen, Guang Yang, Wenting Chen, Yuheng Deng
Journal: Molecular Cancer (2013)

Wnt/β-catenin signaling is a highly conserved pathway in organism evolution and is important in many biological processes. Overactivation of Wnt/β-catenin signaling is closely related to tumor development and progression. To identify potent small molecules that can fight aberrant Wnt/β-catenin-mediated cancer, we synthesized a novel pyrazoline derivative (N-(4-hydroxybenzyl)-1,3,4-triphenyl-4,5-dihydro-1H-pyrazole-5-carboxamide, BHX) to block Wnt signaling, and determined the absolute configuration of its precursor (ethyl 1,3,4-triphenyl-4,5-dihydro-1H-pyrazole-5-carboxylate). We then evaluated the inhibitory effect of BHX in vitro and in vivo. Cell proliferation was assessed in three human cancer cell lines (A549, HT29, and MGC803) in the presence and absence of BHX using MTS assays. BHX effectively inhibited A549, HT29, and MGC803 cell proliferation with IC50 of 5.43 ± 1.99, 6.95 ± 0.24, and 7.62 ± 1.31 μM, respectively. BHX significantly induced apoptosis and G1 phase arrest in A549 and MGC803 cells. The β-catenin protein level was markedly reduced in A549 and MGC803 cells under BHX treatment. The inhibitory effect of BHX in vivo was investigated using a mouse xenograft model. A549 xenograft growth was suppressed by 50.96% in nude mice treated continuously with 100 mg/kg BHX for 21 d. Weight remained almost unchanged, which indicates the low toxicity of the compound. Our data suggest that BHX is a new drug candidate for cancer treatment because of its potent effect on the Wnt/β-catenin pathway and low toxicity.
THE TREATMENT OF ACUTE INFECTIOUS HEPATITIS. CONTROLLED STUDIES OF THE EFFECTS OF DIET, REST, AND PHYSICAL RECONDITIONING ON THE ACUTE COURSE OF THE DISEASE AND ON THE INCIDENCE OF RELAPSES AND RESIDUAL ABNORMALITIES 1
Authors: Thomas C. Chalmers, Richard D. Eckhardt, William E. Reynolds, Joaquin G. Cigarroa, Norman Deane, Robert W. Reifenstein, Clifford W. Smith, Charles S. Davidson, Mary A. Maloney, Merme Bonnel, Marian Niiya, Alice Stang, Ann McD. O'Brien
Journal: Journal of Clinical Investigation (1955)

1202 6.5 The Interval Between Discharge and Fol- low-up Examination 1202 6.6 Comparisons of Treatment Groups at the Time of Follow-up Examinations 1202 6.7 Results of Additional Follow-up Examina- tions 1204 6.8 Comparisons of Post-Hepatitis Patients with "Normal" Soldiers 1205 6.9 Summary 1206 Part Seven: Retrospective Analyses of the Effects of Rest and Diet 7.1 Relation of the Stage and Severity of Ill- ness to the Effects of Rest 1207 7.2 The Effects of Pre-hospitalization Activity on the Duration of Subsequent Illness 1207 7.3 Relation of the Stage and Severity of Ill- ness to the Effects of Diet 1207 Part Eight: General Summary, Discussion and Recommendations 8.
Phase II Study of Alemtuzumab in Combination With Pentostatin in Patients With T-Cell Neoplasms
Authors: Farhad Ravandi, Ahmed Aribi, Susan O'Brien, Stefan Faderl, Dan Jones, Alessandra Ferrajoli, Xuelin Huang, Sergernne York, Sherry Pierce, William Wierda, Dimitrios Kontoyiannis, Srdan Verstovsek, Barbara Pro, Luis Fayad, Michael Keating, Hagop Kantarjian
Journal: Journal of Clinical Oncology (2009)

Purpose To examine the efficacy and safety of the combination of alemtuzumab and pentostatin in patients with T-cell neoplasms. Patients and Methods We treated 24 patients with a variety of T-cell leukemias and lymphomas with a combination of alemtuzumab 30 mg intravenously (IV) three times weekly for up to 3 months and pentostatin 4 mg/m 2 IV weekly for 4 weeks followed by alternate weekly administration for up to 6 months. Prophylactic antibiotics including antiviral, antifungal, and antibacterial agents were administered during the treatment and for 2 months after its completion. Results The median age of patients was 57 years (range, 21 to 79 years). Eight patients were previously untreated, and 16 had a median of two prior therapies (range, one to six regimens). Thirteen patients responded to treatment (11 complete responses [CRs] and two partial responses), for an overall response rate of 54%. The median response duration was 19.5 months. Monoclonal T-cell receptor chain gene rearrangements were detected by polymerase chain reaction in bone marrow of 20 of 22 evaluable patients and became negative in five of seven evaluable patients in CR. Opportunistic infections caused by pathogens associated with severe T-cell dysfunction were common. Conclusion The combination of alemtuzumab and pentostatin is feasible and effective in T-cell neoplasms. Although infections, including cytomegalovirus reactivation, are a concern, they may be minimized with adequate prophylactic antibiotic therapy.
Gene-Environment Interaction Signatures by Quantitative mRNA Profiling in Exfoliated Buccal Mucosal Cells
Authors: Simon D. Spivack, Gregory J. Hurteau, Ritu Jain, Shalini V. Kumar, Kenneth M. Aldous, John F. Gierthy, Laurence S. Kaminsky
Journal: Cancer Research (2004)

Exfoliated cytologic specimens from mouth (buccal) epithelium may contain viable cells, permitting assay of gene expression for direct and noninvasive measurement of gene-environment interactions, such as for inhalation (e.g., tobacco smoke) exposures. We determined specific mRNA levels in exfoliated buccal cells collected by cytologic brush, using a recently developed RNA-specific real-time quantitative reverse transcription-PCR strategy. In a pilot study, metabolic activity of exfoliated buccal cells was verified by 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium assay in vitro. Transcriptional activity was observed, after timed in vivo exposure to mainstream tobacco smoke resulted in induction of CYP1B1 in serially collected buccal samples from the one subject examined. For a set of 11 subjects, mRNA expression of nine genes encoding carcinogen- and oxidant-metabolizing enzymes qualitatively detected in buccal cells was then shown to correlate with that in laser-microdissected lung from the same individuals (Chi2 = 52.91, P < 0.001). Finally, quantitative real-time reverse transcription-PCR assays for seven target gene (AhR, CYP1A1, CYP1B1, GSTM1, GSTM3, GSTP1, and GSTT1) and three reference gene [glyceraldehyde-3-phosphate dehydrogenase (GAPDH), beta-actin, and 36B4] transcripts were performed on buccal specimens from 42 subjects. In multivariate analyses, gender, tobacco smoke exposure, and other factors were associated with the level of expression of CYP1B1, GSTP1, and other transcripts on a gene-specific basis, but substantial interindividual variability in mRNA expression remained unexplained. Within the power limits of this pilot study, gene expression signature was not clearly predictive of lung cancer case or control status. This noninvasive and quantitative method may be incorporated into high-throughput human applications for probing gene-environment interactions associated with cancer.
High-Frequency Periodic Sources Underlie Ventricular Fibrillation in the Isolated Rabbit Heart
Authors: Jay Chen, Ravi Mandapati, Omer Berenfeld, Allan C. Skanes, José Jalife
Journal: Circulation Research (2000)

Abstract —The mechanism(s) underlying ventricular fibrillation (VF) remain unclear. We hypothesized that at least some forms of VF are not random and that high-frequency periodic sources of activity manifest themselves as spatiotemporal periodicities, which drive VF. Twenty-four VF episodes from 8 Langendorff-perfused rabbit hearts were studied using high-resolution video imaging in conjunction with ECG recordings and spectral analysis. Sequential wavefronts that activated the ventricles in a spatially and temporally periodic fashion were identified. In addition, we analyzed the lifespan and dynamics of wavelets in VF, using a new method of phase mapping that enables identification of phase singularity points (PSs), which flank individual wavelets. Spatiotemporal periodicity was found in 21 of 24 episodes. Complete reentry on the epicardial surface was observed in 3 of 24 episodes. The cycle length of discrete regions of spatiotemporal periodicity correlated highly with the dominant frequency of the optical pseudo-ECG ( R 2 =0.75) and with the global bipolar electrogram ( R 2 =0.79). The lifespan of PSs was short (14.7±14.4 ms); 98% of PSs existed for &lt;1 rotation. The mean number of waves entering (6.50±0.69) exceeded the mean number of waves that exited our mapping field (4.25±0.56; P &lt;0.05). These results strongly suggest that ongoing stable sources are responsible for the majority of the frequency content of VF and therefore play a role in its maintenance. In this model, multiple wavelets resulting from wavebreaks do not appear to be responsible for the sustenance of this arrhythmia, but are rather the consequence of breakup of high-frequency activation from a dominant reentrant source.
Albumin-mediated transport of rose bengal by perfused rat liver. Kinetics of the reaction at the cell surface.
Authors: E L Forker, B A Luxon
Journal: Journal of Clinical Investigation (1983)

Rapid dissociation of organic anions from plasma albumin maximizes the presentation of free ligand to the cell surface and thus favors its efficient hepatic extraction. Even assuming these optimal conditions, however, taurocholate and rose bengal have hepatic extraction fractions that are higher than can be accounted for by spontaneous dissociation of their albumin-ligand complexes. In this study we developed a transport model that attributes this behavior to sites on the hepatocyte plasma membrane that bind the albumin-ligand complexes, promoting the transport of ligand into the hepatocyte. Fitting this model to rose bengal removal rates measured over a wide range of albumin concentrations yields estimates of the number of cell surface sites and their affinity for albumin. These estimates are in good agreement with those reported by Weisiger, Gollan, and Ockner for the binding of ligand-free albumin to isolated hepatocytes. We conclude that both experiments measure the same phenomenon and, accordingly, that the binding of albumin to the cell surface is the functional equivalent of albumin-mediated transport.