tbuckley/cabot-search huggingface dataset:
Validation of ultrasound imaging for Achilles entheseal fibrocartilage in bovines and description of changes in humans with spondyloarthritis
Authors: Sibel Zehra Aydin, Emine Bas, Onur Basci, Emilio Filippucci, Richard J Wakefield, Çiğdem Çelikel, Mustafa Karahan, Pamir Atagunduz, Mike Benjamin, Haner Direskeneli, Dennis McGonagle
Journal: Annals of the Rheumatic Diseases (2010)

Entheseal fibrocartilage (EF) derangement is hypothesised to be pivotal to the pathogenesis of spondyloarthritis. Ultrasound is useful for visualisation of the enthesis but its role in EF visualisation is uncertain. This work aimed to demonstrate face and content validity of ultrasound for EF visualisation both by bovine histological evaluation and EF imaging in spondyloarthritis.Achilles enthesis of 18 bovine hindfeet was visualised using a MyLab 70 ultrasound machine. The presence of tissue with EF characteristics was documented and histological confirmation was performed on five randomly selected sections using Masson trichrome staining. Ultrasound of the Achilles tendon (AT) was performed in 19 patients with spondyloarthritis and 21 healthy controls (HC).The bovine EF could be visualised in all cases and seen as a thin, uncompressible, well-defined, anechoic layer between the hyperechoic bone and the hyperechoic fibrils of the enthesis both in longitudinal and transverse scans. This region corresponded to EF on histological examination. The same pattern of low signal corresponding to EF location was seen in 17/19 patients and all HC. Discontinuities of the anechoic layer around the erosions and enthesophytes were observed in the spondyloarthritis group. The thickness of the anechoic layer was not significantly different in spondyloarthritis and HC (0.5 ± 0.1 vs 0.5 ± 0.2 mm, p=0.9) whereas the thickness of the EF was greater in men (0.6 ± 0.2 vs 0.5 ± 0.1 mm; p=0.009) compared with women.Ultrasound can visualise EF of the AT insertion, which can be abnormal in cases of spondyloarthritis. This has implications for a better understanding of enthesopathy.
Studies on Components of RNA in Cardiac Muscle with Emphasis on the Rapidly Labeled 4 to 18 S Fraction
Authors: B. I. POSNER, B. L. FANBURG
Journal: Circulation Research (1966)

Studies on RNA from cardiac muscle of rats were performed by labeling the RNA with 32 P, extracting it with phenol, and purifying it prior to fractionating and analyzing it on a sucrose density gradient. The major components of RNA found had sedimentation values of 28, 18, and 4 S. Early 32 P-labeled RNA ranged in size from 4 to &gt; 45 S. Characterization of RNA from 4 to 18 S showed it to be more rapidly labeled and to have a higher turnover rate than 28 S RNA, to be located, at least in part, in the microsomes, and to have a base composition lower in guanine and cytosine content than 28 S RNA. Labeling of 4 to 18 S and 28 S RNA was equally inhibited by actinomycin. The possibility that 4 to 18 S RNA may represent a portion of messenger RNA in cardiac muscle is considered.
Upregulation of MAPK Negative Feedback Regulators and RET in Mutant ALK Neuroblastoma: Implications for Targeted Treatment
Authors: Irina Lambertz, Candy Kumps, Shana Claeys, Sven Lindner, Anneleen Beckers, Els Janssens, Daniel R. Carter, Alex Cazes, Belamy B. Cheung, Marilena De Mariano, An De Bondt, Sara De Brouwer, Olivier Delattre, Jay Gibbons, Isabelle Janoueix-Lerosey, Geneviève Laureys, Chris Liang, Glenn M. Marchall, Michael Porcu, Junko Takita, David Camacho Trujillo, Ilse Van Den Wyngaert, Nadine Van Roy, Alan Van Goethem, Tom Van Maerken, Piotr Zabrocki, Jan Cools, Johannes H. Schulte, Jorge Vialard, Frank Speleman, Katleen De Preter
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Activating ALK mutations are present in almost 10% of primary neuroblastomas and mark patients for treatment with small-molecule ALK inhibitors in clinical trials. However, recent studies have shown that multiple mechanisms drive resistance to these molecular therapies. We anticipated that detailed mapping of the oncogenic ALK-driven signaling in neuroblastoma can aid to identify potential fragile nodes as additional targets for combination therapies. Experimental Design: To achieve this goal, transcriptome profiling was performed in neuroblastoma cell lines with the ALKF1174L or ALKR1275Q hotspot mutations, ALK amplification, or wild-type ALK following pharmacologic inhibition of ALK using four different compounds. Next, we performed cross-species genomic analyses to identify commonly transcriptionally perturbed genes in MYCN/ALKF1174L double transgenic versus MYCN transgenic mouse tumors as compared with the mutant ALK-driven transcriptome in human neuroblastomas. Results: A 77-gene ALK signature was established and successfully validated in primary neuroblastoma samples, in a neuroblastoma cell line with ALKF1174L and ALKR1275Q regulable overexpression constructs and in other ALKomas. In addition to the previously established PI3K/AKT/mTOR, MAPK/ERK, and MYC/MYCN signaling branches, we identified that mutant ALK drives a strong upregulation of MAPK negative feedback regulators and upregulates RET and RET-driven sympathetic neuronal markers of the cholinergic lineage. Conclusions: We provide important novel insights into the transcriptional consequences and the complexity of mutant ALK signaling in this aggressive pediatric tumor. The negative feedback loop of MAPK pathway inhibitors may affect novel ALK inhibition therapies, whereas mutant ALK induced RET signaling can offer novel opportunities for testing ALK-RET oriented molecular combination therapies. Clin Cancer Res; 21(14); 3327–39. ©2015 AACR.
Natural Killer Cells Activity and Neuroimmunological Treatment of Cancer
Authors: Fuad Lechin, Bertha van der Dijs, Alex E. Lechin
Journal: Clinical Cancer Research (2004)

We read with great interest the article by Krause et al. [(1)][1] . They report on the role played by activated natural killer cells in the treatment of colon and lung cancer patients. With respect to the above, we would like to inform readers of our experience with this issue.

In 1987, we found
Eliglustat compared with imiglucerase in patients with Gaucher's disease type 1 stabilised on enzyme replacement therapy: a phase 3, randomised, open-label, non-inferiority trial
Authors: Timothy M Cox, Guillermo Drelichman, Renata Cravo, Manisha Balwani, Thomas Andrew Burrow, Ana Maria Martins, Elena Lukina, Barry Rosenbloom, Leorah Ross, Jennifer Angell, Ana Cristina Puga
Journal: The Lancet (2015)
Pharmacodynamic Effect of Cilostazol Plus Standard Clopidogrel Versus Double-Dose Clopidogrel in Patients With Type 2 Diabetes Undergoing Percutaneous Coronary Intervention
Authors: Young-Hoon Jeong, Udaya S. Tantry, Yongwhi Park, Tae Jung Kwon, Jeong Rang Park, Seok-Jae Hwang, Kevin P. Bliden, Eun-Ha Koh, Choong Hwan Kwak, Jin-Yong Hwang, Sunjoo Kim, Paul A. Gurbel
Journal: Diabetes Care (2012)

OBJECTIVE To determine the effect of adding cilostazol (100 mg b.i.d.) to standard-dose clopidogrel (75 mg/d) (TRIPLE) compared with double-dose clopidogrel (150 mg/d) (DOUBLE) and the influence of the cytochrome P450 (CYP2C19*2/*3, CYP3A5*3)and ATP-binding cassette subfamily B1(ABCB1 C3435T) genetic polymorphisms in type 2 diabetes (T2DM) patients. RESEARCH DESIGN AND METHODS T2DM patients were treated with TRIPLE (n = 41) or DOUBLE (n = 39) after percutaneous coronary intervention. Conventional aggregometry and VerifyNow were performed at baseline and at 30 days. The primary end point was absolute change in 20-μM ADP-induced maximal platelet aggregation (ΔMPA20) between baseline and switching values. RESULTS TRIPLE versus DOUBLE showed greater ΔMPA20 (22.9 ± 11.6 vs.12.7 ± 15.5%; difference, 10.2% [95% CI 4.2–16.3]; P &amp;lt; 0.001). Carriage of one (β coefficient, −5.4%; P = 0.162) and two CYP2C19 loss-of-function allele(s) (−8.3%; P = 0.007) were associated with lower ΔMPA20 in DOUBLE–treated patients, but not in TRIPLE-treated patients. CONCLUSIONS Among T2DM patients, adding cilostazol achieves greater platelet inhibition compared with clopidogrel (150 mg/d), which is not influenced by genetic polymorphisms.
Sensitive and specific assays for routine serological diagnosis of epidermolysis bullosa acquisita
Authors: Lars Komorowski, Ralf Müller, Artem Vorobyev, Christian Probst, Andreas Recke, Marcel F. Jonkman, Takashi Hashimoto, Soo-Chan Kim, Richard Groves, Ralf J. Ludwig, Detlef Zillikens, Winfried Stöcker, Enno Schmidt
Journal: Journal of the American Academy of Dermatology (2012)
The Histone Demethylase, Jmjd1a, Interacts With the Myocardin Factors to Regulate SMC Differentiation Marker Gene Expression
Authors: Kashelle Lockman, Joan M. Taylor, Christopher P. Mack
Journal: Circulation Research (2007)

We and others have previously shown that the myocardin transcription factors play critical roles in the regulation of smooth muscle cell (SMC) differentiation marker gene expression. In a yeast 2-hybrid screen for proteins that interact with myocardin-related transcription factor-A (MRTF-A), we identified the histone 3 lysine 9 (H3K9)-specific demethylase, Jmjd1a. GST pull-down assays demonstrated that Jmjd1a bound all 3 myocardin family members, and further mapping studies showed that the jumonjiC domain of Jmjd1a was sufficient to mediate this interaction. Overexpression of Jmjd1a in multipotential 10T1/2 cells decreased global levels of di-methyl H3K9, stimulated the SM alpha-actin and SM22 promoters, and synergistically enhanced MRTF-A- and myocardin-dependent transactivation. Using chromatin immunoprecipitation assays, we also demonstrated that TGF-beta-mediated upregulation of SMC differentiation marker gene expression in 10T1/2 cells was associated with decreased H3K9 dimethylation at the CArG-containing regions of the SMC differentiation marker gene promoters. Importantly, knockdown of Jmjd1a in 10T1/2 cells and primary rat aortic SMCs by retroviral delivery of siRNA attenuated TGF-beta-induced upregulation of endogenous SM myosin heavy chain expression. These effects were concomitant with increased H3K9 dimethylation at the SMC differentiation marker gene promoters and with inhibition of MRTF-A-dependent transactivation of the SMC-specific transcription. These results suggest, for the first time, that SMC differentiation marker gene expression is regulated by H3K9 methylation and that the effects of the myocardin factors on SMC-specific transcription may involve the recruitment of Jmjd1a to the SMC-specific promoters.
Subpopulations of long-lived and short-lived T cells in advanced HIV-1 infection
Authors: Marc K. Hellerstein, Rebecca A. Hoh, Mary Beth Hanley, Denise Cesar, Daniel Lee, Richard A. Neese, Joseph M. McCune
Journal: Journal of Clinical Investigation (2003)

Antigenic stimulation of T cells gives rise to short-lived effector cells and long-lived memory cells. We used two stable isotope-labeling techniques to identify kinetically distinct subpopulations of T cells and to determine the effect of advanced infection with HIV-1. Long-term deuterated water (2H2O) incorporation into DNA demonstrated biphasic accrual of total and of memory/effector (m/e)–phenotype but not naive-phenotype T cells, consistent with the presence of short-lived and longer-lived subpopulations within the m/e-phenotype T cell pool. These results were mirrored by biphasic die-away kinetics in m/e- but not naive-phenotype T cells after short-term 2H-glucose labeling. Persistent label retention was observed in a subset of m/e-phenotype T cells (presumably memory T cells), confirming the presence of T cells with very different life spans in humans. In advanced HIV-1 infection, much higher proportions of T cells were short-lived, compared to healthy controls. Effective long-term anti-retroviral therapy restored values to normal. These results provide the first quantitative evidence that long-lived and quiescent T cells do indeed predominate in the T cell pool in humans and determine T cell pool size, as in rodents. The greatest impact of advanced HIV-1 infection is to reduce the generation of long-lived, potential progenitor T cells.
Questionnaires in asthma epidemiology
Authors: NA Rosario, FP Ferrari
Journal: European Respiratory Journal (1998)

:In epidemiological studies of asthma, questionnaires arewidely accepted methods of identifying affected subjects.International Study of Asthma and Allergies in Childhood(ISAAC) is an international project aiming to determinethe prevalence of asthma, allergic rhinitis and eczema inchildren living in different countries [1].The written questionnaire includes questions on respi-ratory symptoms such as frequency and severity of whe-ezing and cough. It ends with a question about diagnosedasthma.Published results of the worldwide ISAAC study poin-ted to a large variation in the prevalence of self-reportedsymptoms of asthma [2–4]. The question concerningwhether the child had ever had asthma ranged 1.6– 28.2%.In our town, physicians are reluctant to diagnose childrenas having asthma, if they have recurrent wheezing.The frequency of asthma in Curitiba was 6.5 and 8.6%,respectively for 6-7 and 13–14 yr olds using the ISAACquestionnaire. This is definitely an underestimation of theprevalence of asthma.Thus, to assess a more realistic prevalence, we selectedquestions that could be considered strongly suggestive ofa diagnosis of asthma. They are presented in table 1.This cumulative frequency was then named probableasthma. Although there is a tendency to pick up moresevere asthma, it may not detect all cases of asthma. How-ever, it is more informative than relying on the questionhave you ever had asthma? We suggest that probableasthma is closer to actual figures and may be helpful incomparing point prevalence of active asthma in differentcountries.
Role of Physical Activity and Diet After Colorectal Cancer Diagnosis
Authors: Erin L. Van Blarigan, Jeffrey A. Meyerhardt
Journal: Journal of Clinical Oncology (2015)

This review summarizes the evidence regarding physical activity and diet after colorectal cancer diagnosis in relation to quality of life, disease recurrence, and survival. There have been extensive reports on adiposity, inactivity, and certain diets, particularly those high in red and processed meats, and increased risk of colorectal cancer. Only in the past decade have data emerged on how such lifestyle factors are associated with outcomes in colorectal cancer survivors. Prospective observational studies have consistently reported that physical activity after colorectal cancer diagnosis reduces mortality. A meta-analysis estimated that each 15 metabolic equivalent task-hour per week increase in physical activity after colorectal cancer diagnosis was associated with a 38% lower risk of mortality. No randomized controlled trials have been completed to confirm that physical activity lowers risk of mortality among colorectal cancer survivors; however, trials have shown that physical activity, including structured exercise, is safe for colorectal cancer survivors (localized to metastatic stage, during and after treatment) and improves cardiorespiratory fitness and physical function. In addition, prospective observational studies have suggested that a Western dietary pattern, high carbohydrate intake, and consuming sugar-sweetened beverages after diagnosis may increase risk of colorectal cancer recurrence and mortality, but these data are limited to single analyses from one of two US cohorts. Additional data from prospective studies and randomized controlled trials are needed. Nonetheless, on the basis of the available evidence, it is reasonable to counsel colorectal cancer survivors to engage in regular physical activity and limit consumption of refined carbohydrates, red and processed meats, and sugar-sweetened beverages.
Bendamustine in Combination With Rituximab for Previously Untreated Patients With Chronic Lymphocytic Leukemia: A Multicenter Phase II Trial of the German Chronic Lymphocytic Leukemia Study Group
Authors: Kirsten Fischer, Paula Cramer, Raymonde Busch, Sebastian Böttcher, Jasmin Bahlo, Jöerg Schubert, Karl H. Pflüger, Silke Schott, Valentin Goede, Susanne Isfort, Julia von Tresckow, Anna-Maria Fink, Andreas Bühler, Dirk Winkler, Karl-Anton Kreuzer, Peter Staib, Matthias Ritgen, Michael Kneba, Hartmut Döhner, Barbara F. Eichhorst, Michael Hallek, Stephan Stilgenbauer, Clemens-Martin Wendtner
Journal: Journal of Clinical Oncology (2012)

We investigated the safety and efficacy of bendamustine and rituximab (BR) in previously untreated patients with chronic lymphocytic leukemia (CLL).In all, 117 patients, age 34 to 78 years, 46.2% of patients at Binet stage C, and 25.6% of patients age 70 years or older received BR chemoimmunotherapy for first-line treatment of CLL. Bendamustine was administered at a dose of 90 mg/m(2) on days 1 and 2 combined with 375 mg/m(2) rituximab on day 0 of the first course and 500 mg/m(2) on day 1 during subsequent courses for up to six courses.Overall response rate was 88.0% (95% CI, 80.7% to 100.0%) with a complete response rate of 23.1% and a partial response rate of 64.9%. Ninety percent of patients with del(11q), 94.7% with trisomy 12, 37.5% with del(17p), and 89.4% with unmutated IGHV status responded to treatment. After a median observation time of 27.0 months, median event-free survival was 33.9 months, and 90.5% of patients were alive. Grade 3 or 4 severe infections occurred in 7.7% of patients. Grade 3 or 4 adverse events for neutropenia, thrombocytopenia, and anemia were documented in 19.7%, 22.2%, and 19.7% of patients, respectively.Chemoimmunotherapy with BR is effective and safe in patients with previously untreated CLL.
Protective Function of Transcription Factor TR3 Orphan Receptor in Atherogenesis
Authors: E. Karin Arkenbout, Vivian de Waard, Maaike van Bragt, Tanja A.E. van Achterberg, Jos M. Grimbergen, Bruno Pichon, Hans Pannekoek, Carlie J.M. de Vries
Journal: Circulation (2002)

Smooth muscle cells (SMCs) play a key role in intimal thickening in atherosclerosis and restenosis. The precise signaling pathways by which the proliferation of SMCs is regulated are largely unknown. The TR3 orphan receptor, the mitogen-induced nuclear orphan receptor (MINOR), and the nuclear receptor of T cells (NOT) are a subfamily of transcription factors belonging to the nuclear receptor superfamily and are induced in activated SMCs. In this study, we investigated the role of these transcription factors in SMC proliferation in atherogenesis.Multiple human vascular specimens at distinct stages of atherosclerosis (lesion types II to V by American Heart Association classification) derived from 14 different individuals were studied for expression of these transcription factors. We observed expression of TR3, MINOR, and NOT in neointimal SMCs, whereas no expression was detected in medial SMCs. Adenovirus-mediated expression of a dominant-negative variant of TR3, which suppresses the transcriptional activity of each subfamily member, increases DNA synthesis and decreases p27(Kip1) protein expression in cultured SMCs. We generated transgenic mice that express this dominant-negative variant or full-length TR3 under control of a vascular SMC-specific promoter. Carotid artery ligation of transgenic mice that express the dominant-negative variant of TR3 in arterial SMCs, compared with lesions formed in wild-type mice, results in a 3-fold increase in neointimal formation, whereas neointimal formation is inhibited 5-fold in transgenic mice expressing full-length TR3.Our results reveal that TR3 and possibly other members of this transcription factor subfamily inhibit vascular lesion formation. These transcription factors could serve as novel targets in the treatment of vascular disease.
A novel, possibly functional, single nucleotide polymorphism in the coding region of the thrombin-activatable fibrinolysis inhibitor (TAFI) gene is also associated with TAFI levels
Authors: Geert-Jan Brouwers, Hans L. Vos, Frank W. G. Leebeek, Saskia Bulk, Mark Schneider, Michael Boffa, Marlys Koschinsky, Nico H. van Tilburg, Michael E. Nesheim, Rogier M. Bertina, Encarnación B. Gómez Garcı́a
Journal: Blood (2001)
Differences in radiological/HRCT findings in eosinophilic bronchitis and asthma: implication for bronchial responsiveness
Authors: S-W Park
Journal: Thorax (2005)

Airway hyperresponsiveness in asthmatics is considered to be one of the major consequences of airway inflammation and remodelling. Airway responsiveness is normal in patients with eosinophilic bronchitis (EB), despite eosinophilic inflammation of the airways comparable to that which occurs in asthmatics. Comparisons between asthma and EB should clarify the changes in airway morphology that are related specifically to AHR in asthmatics.Eighteen asthmatic patients, 15 patients with EB, and 11 healthy subjects were recruited. Airway wall area percentage (WA%), centrilobular prominence, and air trapping were compared using thin slice section computed tomography.WA% was significantly greater in asthmatics than in patients with EB (72 (3.1)% v 54 (2.1)%, p = 0.032) and was similar in EB patients and controls (54 (2.1)% v 57 (1.8)%, p>0.05). Centrilobular prominence and air trapping were similar in EB patients and asthmatics and were significantly greater than in controls.WA% rather than air trapping or centrilobular prominence may be associated with the airway hyperresponsiveness that occurs in asthmatics but not in patients with EB.
Autonomic Control of Cardiac C-AMP
Authors: PAUL J. LARAIA, EDMUND H. SONNENBLICK
Journal: Circulation Research (1971)

Although catecholamines are known to increase cyclic adenosine 3'5'-monophosphate (C-AMP) in heart muscle, the relations of adrenergic and cholinergic mechanisms to inotropy and myocardial C-AMP levels and adenyl cyclase have not been defined. Accordingly, atrial and ventricular muscle preparations were studied in a myograph with a tension recorder. Adenyl cyclase, phosphodiesterase, and C-AMP were measured by chromatographic and isotopic methods. In atrial preparations, norepinephrine (10 -5 M ) increased tension by 80±10% (mean± SE ), adenyl cyclase by 40±10% and C-AMP by 75±12%, while carbamylcholine chloride (10 -4 M ) reduced tension by 65±10%, adenyl cyclase by 30±12% and C-AMP by 50±14%. The effects of carbamylcholine chloride on tension, adenyl cyclase, and C-AMP were blocked by atropine 10 -5 M . In paced ventricular (papillary) muscles, norepinephrine (10 -5 M ) increased tension by 70±10%, adenyl cyclase by 50±11% and CAMP by 90±17%. In contrast, carbamylcholine chloride (10 -5 M ) reduced tension by only 7±5%, adenyl cyclase by 12±8%, and C-AMP by 10±7%. These results demonstrate parallel changes in tension, adenyl cyclase, and C-AMP in atrium and ventricle. The failure of ventricular muscle to respond to carbamylcholine is mirrored by the adenyl cyclase system and C-AMP. Furthermore, the cholinergically mediated tension and adenyl cyclase changes in atria were specifically blocked by atropine. Thus these results relate the different effects of cholinergic agents on atrium and ventricle to adenyl cyclase and C-AMP, and suggest specific receptor localization in these two types of myocardia.