tbuckley/cabot-search huggingface dataset:
Safety, tolerability and potential efficacy of injection of autologous adipose-derived stromal vascular fraction in the fingers of patients with systemic sclerosis: an open-label phase I trial
Authors: Brigitte Granel, Aurélie Daumas, Elisabeth Jouve, Jean-Robert Harlé, Pierre-Sébastien Nguyen, Christian Chabannon, Nathalie Colavolpe, Jean-Charles Reynier, Romain Truillet, Stéphanie Mallet, Antoine Baiada, Dominique Casanova, Laurent Giraudo, Laurent Arnaud, Julie Veran, Florence Sabatier, Guy Magalon
Journal: Annals of the Rheumatic Diseases (2014)

Background In patients with systemic sclerosis (scleroderma, SSc), impaired hand function greatly contributes to disability and reduced quality of life, and is insufficiently relieved by currently available therapies. Adipose tissue-derived stromal vascular fraction (SVF) is increasingly recognised as an easily accessible source of regenerative cells with therapeutic potential in ischaemic or autoimmune diseases. We aimed to measure for the first time the safety, tolerability and potential efficacy of autologous SVF cells local injections in patients with SSc with hand disability. Methods We did an open-label, single arm, at one study site with 6-month follow-up among 12 female SSc patients with Cochin Hand Function Scale score &gt;20/90. Autologous SVF was obtained from lipoaspirates, using an automated processing system, and subsequently injected into the subcutaneous tissue of each finger in contact with neurovascular pedicles. Primary outcome was the number and the severity of adverse events related to SVF-based therapy. Secondary endpoints were changes in hand disability and fibrosis, vascular manifestations, pain and quality of life from baseline to 2 and 6 months after cell therapy. Findings All enrolled patients had surgery, and there were no dropouts or patients lost to follow-up. No severe adverse events occurred during the procedure and follow-up. Four minor adverse events were reported and resolved spontaneously. A significant improvement in hand disability and pain, Raynaud's phenomenon, finger oedema and quality of life was observed. Interpretation This study outlines the safety of the autologous SVF cells injection in the hands of patients with SSc. Preliminary assessments at 6 months suggest potential efficacy needing confirmation in a randomised placebo-controlled trial on a larger population. Funding GFRS (Groupe Francophone de Recherche sur la Sclérodermie). Clinical Trials number NCT01813279.
GATA4 and GATA5 are Potential Tumor Suppressors and Biomarkers in Colorectal Cancer
Authors: Debby M.E.I. Hellebrekers, Marjolein H.F.M. Lentjes, Sandra M. van den Bosch, Veerle Melotte, Kim A.D. Wouters, Kathleen L.J. Daenen, Kim M. Smits, Yoshimitsu Akiyama, Yasuhito Yuasa, Silvia Sanduleanu, Carolina A.J. Khalid-de Bakker, Daisy Jonkers, Matty P. Weijenberg, Joost Louwagie, Wim van Criekinge, Beatriz Carvalho, Gerrit A. Meijer, Stephen B. Baylin, James G. Herman, Adriaan P. de Bruïne, Manon van Engeland
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The transcription factors GATA4 and GATA5 are involved in gastrointestinal development and are inactivated by promoter hypermethylation in colorectal cancer. Here, we evaluated GATA4/5 promoter methylation as potential biomarkers for noninvasive colorectal cancer detection, and investigated the role of GATA4/5 in colorectal cancer. Experimental Design: Promoter methylation of GATA4/5 was analyzed in colorectal tissue and fecal DNA from colorectal cancer patients and healthy controls using methylation-specific PCR. The potential function of GATA4/5 as tumor suppressors was studied by inducing GATA4/5 overexpression in human colorectal cancer cell lines. Results: GATA4/5 methylation was observed in 70% (63/90) and 79% (61/77) of colorectal carcinomas, respectively, and was independent of clinicopathologic features. Methylation frequencies in normal colon tissues from noncancerous controls were 6% (5 of 88, GATA4; P &amp;lt; 0.001) and 13% (13 of 100, GATA5; P &amp;lt; 0.001). GATA4/5 overexpression suppressed colony formation (P &amp;lt; 0.005), proliferation (P &amp;lt; 0.001), migration (P &amp;lt; 0.05), invasion (P &amp;lt; 0.05), and anchorage-independent growth (P &amp;lt; 0.0001) of colorectal cancer cells. Examination of GATA4 methylation in fecal DNA from two independent series of colorectal cancer patients and controls yielded a sensitivity of 71% [95% confidence interval (95% CI), 55-88%] and specificity of 84% (95% CI, 74–95%) for colorectal cancer detection in the training set, and a sensitivity of 51% (95% CI, 37–65%) and specificity of 93% (95% CI, 84-100%) in the validation set. Conclusions: Methylation of GATA4/5 is a common and specific event in colorectal carcinomas, and GATA4/5 exhibit tumor suppressive effects in colorectal cancer cells in vitro. GATA4 methylation in fecal DNA may be of interest for colorectal cancer detection.
Systematic Assessment of Patients With Unexplained Cardiac Arrest
Authors: Andrew D. Krahn, Jeffrey S. Healey, Vijay Chauhan, David H. Birnie, Christopher S. Simpson, Jean Champagne, Martin Gardner, Shubhayan Sanatani, Derek V. Exner, George J. Klein, Raymond Yee, Allan C. Skanes, Lorne J. Gula, Michael H. Gollob
Journal: Circulation (2009)

Background— Cardiac arrest without evident cardiac disease may be caused by subclinical genetic conditions. Provocative testing to unmask a phenotype is often necessary to detect primary electrical disease, direct genetic testing, and perform family screening. Methods and Results— Patients with apparently unexplained cardiac arrest and no evident cardiac disease (normal cardiac function on echocardiogram, no evidence of coronary artery disease, and a normal ECG) underwent systematic evaluation that included cardiac magnetic resonance imaging, signal-averaged ECG, exercise testing, drug challenge, and selective electrophysiological testing. Diagnostic criteria were based on accepted criteria or provocation of the characteristic clinical features for long-QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, early repolarization, arrhythmogenic right ventricular cardiomyopathy, coronary spasm, and myocarditis. Sixty-three patients in 9 centers were enrolled (age 43.0±13.4 years, 29 women). A diagnosis was obtained in 35 patients (56%): Long-QT syndrome in 8, catecholaminergic polymorphic ventricular tachycardia in 8, arrhythmogenic right ventricular cardiomyopathy in 6, early repolarization in 5, coronary spasm in 4, Brugada syndrome in 3, and myocarditis in 1. Targeted genetic testing demonstrated evidence of causative mutations in 9 (47%) of 19 patients. Screening of 64 family members of these patients identified 15 affected individuals who were treated (24%). The remaining 28 patients (44%) were considered to have idiopathic ventricular fibrillation. Conclusions— Systematic clinical testing, including drug provocation and advanced imaging, results in unmasking of the cause of apparently unexplained cardiac arrest in &gt;50% of patients. This approach assists in directing genetic testing to diagnose genetically mediated arrhythmia syndromes, which results in successful family screening.
Selective blockade of mGlu5 metabotropic glutamate receptors is protective against acetaminophen hepatotoxicity in mice
Authors: Marianna Storto, Richard Teke Ngomba, Giuseppe Battaglia, Isabel Freitas, Patrizia Griffini, Plinio Richelmi, Ferdinando Nicoletti, Mariapia Vairetti
Journal: Journal of Hepatology (2003)
AID expression levels determine the extent of <i>cMyc</i> oncogenic translocations and the incidence of B cell tumor development
Authors: Makiko Takizawa, Helena Tolarová, Zhiyu Li, Wendy Dubois, Susan Lim, Elsa Callen, Sonia Franco, Maria Mosaico, Lionel Feigenbaum, Frederick W. Alt, André Nussenzweig, Michael Potter, Rafael Casellas
Journal: The Journal of Experimental Medicine (2008)

Immunoglobulin (Ig) isotype switching is a recombination event that changes the constant domain of antibody genes and is catalyzed by activation-induced cytidine deaminase (AID). Upon recruitment to Ig genes, AID deaminates cytidines at switch (S) recombination sites, leading to the formation of DNA breaks. In addition to their role in isotype switching, AID-induced lesions promote Igh-cMyc chromosomal translocations and tumor development. However, cMyc translocations are also present in lymphocytes from healthy humans and mice, and thus, it remains unclear whether AID directly contributes to the dynamics of B cell transformation. Using a plasmacytoma mouse model, we show that AID+/− mice have reduced AID expression levels and display haploinsufficiency both in the context of isotype switching and plasmacytomagenesis. At the Ig loci, AID+/− lymphocytes show impaired intra- and inter-switch recombination, and a substantial decrease in the frequency of S mutations and chromosomal breaks. In AID+/− mice, these defects correlate with a marked decrease in the accumulation of B cell clones carrying Igh-cMyc translocations during tumor latency. These results thus provide a causality link between the extent of AID enzymatic activity, the number of emerging Igh-cMyc–translocated cells, and the incidence of B cell transformation.
Increasing Incidence of Cutaneous Melanoma in Queensland, Australia
Authors: R. MacLennan, A. C. Green, G. R. C. McLeod, N. G. Martin
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Increasing Incidence of Cutaneous Melanoma in Queensland, Australia Get access R. MacLennan, R. MacLennan * Queensland Institute of Medical ResearchBrisbane, Australia *Correspondence to : Robert MacLennan, M.B., B.S., Queensland Institute of Medical Research, 300 Herston Rd., Brisbane, Old., Australia 4029. Search for other works by this author on: Oxford Academic PubMed Google Scholar A. C. Green, A. C. Green Queensland Institute of Medical ResearchBrisbane, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar G. R. C. McLeod, G. R. C. McLeod Queensland Melanoma Project, Princess Alexandra HospitalBrisbane Search for other works by this author on: Oxford Academic PubMed Google Scholar N. G. Martin N. G. Martin Queensland Institute of Medical ResearchBrisbane, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 18, 16 September 1992, Pages 1427–1432, https://doi.org/10.1093/jnci/84.18.1427 Published: 16 September 1992 Article history Received: 27 January 1992 Revision received: 01 June 1992 Accepted: 09 June 1992 Published: 16 September 1992
A role for gut-associated lymphoid tissue in shaping the human B cell repertoire
Authors: Anna Vossenkämper, Paul A. Blair, Niloufar Safinia, Louise D. Fraser, Lisa Das, Theodore J. Sanders, Andrew J. Stagg, Jeremy D. Sanderson, Kirstin Taylor, Fuju Chang, Lee M. Choong, David P. D’Cruz, Thomas T. MacDonald, Giovanna Lombardi, Jo Spencer
Journal: The Journal of Experimental Medicine (2013)

We have tracked the fate of immature human B cells at a critical stage in their development when the mature B cell repertoire is shaped. We show that a major subset of bone marrow emigrant immature human B cells, the transitional 2 (T2) B cells, homes to gut-associated lymphoid tissue (GALT) and that most T2 B cells isolated from human GALT are activated. Activation in GALT is a previously unknown potential fate for immature human B cells. The process of maturation from immature transitional B cell through to mature naive B cell includes the removal of autoreactive cells from the developing repertoire, a process which is known to fail in systemic lupus erythematosus (SLE). We observe that immature B cells in SLE are poorly equipped to access the gut and that gut immune compartments are depleted in SLE. Thus, activation of immature B cells in GALT may function as a checkpoint that protects against autoimmunity. In healthy individuals, this pathway may be involved in generating the vast population of IgA plasma cells and also the enigmatic marginal zone B cell subset that is poorly understood in humans.
Robotics, Motor Learning, and Neurologic Recovery
Authors: David J. Reinkensmeyer, Jeremy L. Emken, Steven C. Cramer
Journal: Annual Review of Biomedical Engineering (2004)

▪ Abstract Robotic devices are helping shed light on human motor control in health and injury. By using robots to apply novel force fields to the arm, investigators are gaining insight into how the nervous system models its external dynamic environment. The nervous system builds internal models gradually by experience and uses them in combination with impedance and feedback control strategies. Internal models are robust to environmental and neural noise, generalized across space, implemented in multiple brain regions, and developed in childhood. Robots are also being used to assist in repetitive movement practice following neurologic injury, providing insight into movement recovery. Robots can haptically assess sensorimotor performance, administer training, quantify amount of training, and improve motor recovery. In addition to providing insight into motor control, robotic paradigms may eventually enhance motor learning and rehabilitation beyond the levels possible with conventional training techniques.
Estrogen Signaling Is Active in Cartilaginous Tumors: Implications for Antiestrogen Therapy as Treatment Option of Metastasized or Irresectable Chondrosarcoma
Authors: Anne-Marie Cleton-Jansen, Hetty M. van Beerendonk, Hans J. Baelde, Judith V.G.M. Bovée, Marcel Karperien, Pancras C.W. Hogendoorn
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Chondrosarcoma is a malignant cartilaginous matrix–producing tumor that can be lethal in 10% to 50% of the patients. Surgery is the only effective treatment known as these tumors are notorious refractory to all types of conventional chemotherapy or radiotherapy. To identify a target for therapy, we want to determine whether estrogen signaling is active in chondrosarcoma because estrogen is important in the regulation of longitudinal growth that is initiated by chondrocyte proliferation and differentiation in the epiphyseal growth plate of long bones. Experimental Design: We studied protein expression of the estrogen receptor in 35 cartilaginous tumors as well as mRNA levels for the estrogen receptor and for aromatase, an enzyme for estrogen synthesis and another potential therapeutic target. Furthermore, the activity of aromatase was determined in vitro by the tritiated water release assay. Dose-response experiments with chondrosarcoma cultured cells were done with estrogen, androstenedione, and exemestane. Results: All chondrosarcomas tested showed mRNA and nuclear protein expression of the estrogen receptor. Also, aromatase mRNA was detected. The aromatase activity assay showed a functional aromatase enzyme in primary chondrosarcoma cultures and in a cell line. Growth of chondrosarcoma cell cultures can be stimulated by adding estrogen or androstenedione, which can be inhibited by exemestane. Conclusions: These results show, on the RNA, protein, and cell biological levels, that the ligand and the receptor are active in estrogen-mediated signal transduction. This observation implicates potential use of targeted drugs that interfere with estrogen signaling, such as those applied for treating breast cancer.
Sharing the Pain
Authors: M. James Lenhard, Raelene E. Maser
Journal: Diabetes Care (2003)

It finally happened. I finally had a chart audit that inspired me to tell others about it.

Most clinicians are accustomed to having their outpatient charts reviewed by a variety of representatives from managed care organizations, hospitals, and peer review organizations. When the medical records of patients with diabetes are reviewed, most surveys focus on several key quality measures. These usually include, as a minimum, the frequency of dilated eye exams and foot inspections, as well as HbA1c results.

Our office is accustomed to these chart reviews, and our marks are usually very high. A recent chart review found that I was providing good clinical care for my patients with diabetes based on these quality measures. In one area, however, I received a score of zero. It seems that I had not assessed any of my patients for pain. This was the first time that our charts had been reviewed for this specific feature, as well as the first time, in my personal experience, that pain assessment had been given equal importance to the standard benchmarks of diabetes care.

It is never exactly clear which charts are used for random review, but I examined the chart of one patient that I believe had been included in the chart review. In the history section I found the following notation: “Neuropathy - present for 3 years, bilateral lower extremities, epicritic > protopathic, worse at night.” I felt that this was a reasonable assessment of the patient’s neuropathic discomfort, but it didn’t …
Ecological associations between asthma prevalence and potential exposure to farming
Authors: L. Elliott, K. Yeatts, D. Loomis
Journal: European Respiratory Journal (2004)

Farming and exposure to livestock have been proposed as protective against the development of asthma in children. An ecological study was conducted to examine the support for these relationships in the USA. County-specific aggregate measures were used to examine the relationship between the prevalence of asthma and wheeze in 7th and 8th grade school children (aged 12-14 yrs) and selected measures of potential exposure to farming in the state of North Carolina. Binomial regression models were fitted to quantify these relationships, with adjustments for parental smoking, socioeconomic status, sex and race. Regression coefficients were reported for an increment of one interquartile range (IQR) in each indicator of exposure. The prevalence of asthma showed decreasing trends for most indicators of farm exposure. Regression results suggested that the largest decreases in asthma prevalence were associated with the number of farms (-5.0% per IQR increment), acreage of hay (-7.2% per IQR increment) and beef cattle (-7.8% per IQR increment). The pattern of results was similar for wheezing. In conclusion, the findings of this study are consistent with the hypothesis that certain farm exposures are protective against childhood asthma. Further research with individual-level data is needed to identify the specific protective exposures.
Abstract 3074: Success Rate Safety of CRT Devices Implantation : Results from the CARE-HF Trial.
Authors: Daniel Gras, Dietrick Böcker, Maurizzio Lunati, Hein J Wellens, Melanie Calvert, Nick Freemantle, Renaud Gervais, Lukas Kappenberger, Luigi Tavazzi, Erland Erdmann, John G Cleland, Claude Daubert
Journal: Circulation (2007)

Objectives: To assess procedural characteristics and adjudicated procedure-related (≤30 days) major adverse events among patients who underwent cardiac resynchronization therapy (CRT) implantation in the CARE-HF study. Background: The CARE-HF study shows that CRT improves symptoms and reduces morbidity and mortality in New York Heart Association (NYHA) class III/IV chronic heart failure (CHF) patients. However, safe and proper implantation of pacing systems remains key to effective CRT delivery. Methods: Generalized linear modeling was used to examine the relationships between 1 st implant success/failure and: NYHA class; beta-adrenergic blocker use; underlying ischemic versus non-ischemic heart disease; history of coronary artery bypass graft or valve surgery; left ventricular (LV) end-diastolic volume ≤ versus &gt;300 cm 3 ; and, influence of the participating study-centers. Results: Implantation was attempted in 404/409 patients assigned to CRT, and in 65/404 patients assigned to medical therapy. Among these 469 patients, 450 (95.9%) received a successfully implanted and activated device. Complications occurred within 24 h in 47 patients (10.0%), mainly lead dislodgments (n=10, 2.1%) and coronary sinus dissection/perforation (n=10, 2.1%), and between 24 h and 30 days in 26 patients (5.5%), mainly lead dislodgment (n=13, 2.8%). Mean LV lead stimulation threshold was significantly higher than at the right atrium or right ventricle, though remained stable, delivering effective and reliable CRT. Implanting experience was the only predictor of procedural outcome. Conclusions: Transvenous CRT system implantation, using a CS lead designed for long-term LV pacing, was safe and reliable. As implanting centers become more experienced, this success rate is expected to increase further.
Receptors for bradykinin in intact cultured human fibroblasts. Identification and characterization by direct binding study.
Authors: A A Roscher, V C Manganiello, C L Jelsema, J Moss
Journal: Journal of Clinical Investigation (1983)

Bradykinin receptors on cultured human fibroblasts were characterized using [2,3-prolyl-3,4-3H(N)]bradykinin as radioligand. During incubation with intact fibroblasts, intact [3H]bradykinin was lost much more rapidly at 37 degrees than at 4 degrees C as determined by bioassay, high-performance liquid chromatography, and ion-exchange chromatography, and is likely to be degraded. At 4 degrees, but not at 37 degrees C, bradykinin remained intact in the presence of 2 mM bacitracin, but not in the presence of soybean trypsin inhibitor or SQ-20881, an inhibitor of kininase II. Specific binding at 4 degrees C was saturable with a maximum number of binding sites of 230 +/- 18 fmol/mg protein (mean +/- SE, n = 4) and a dissociation constant of 4.6 +/- 0.5 nM (mean +/- SE, n = 4). Linear Scatchard plots, Hill coefficients close to unity (0.95-1.06), and the failure of excess bradykinin to influence dissociation kinetics are consistent with a single component binding system with no significant cooperativity. Na+ at physiological concentrations and Ca++ or Mg++ at 3-10 mM reduced binding by 25%. The relative potencies of bradykinin analogues and unrelated peptides in competing for [3H]bradykinin binding indicated a specificity of the binding sites consistent with that of a B2 type receptor. Potencies of the peptides in displacing [3H]bradykinin correlated with their abilities to release prostacyclin, determined as its metabolite 6-keto-PGF1 alpha. This system, the first in which bradykinin receptors on human cells have been characterized, should prove useful for investigation of the regulation of bradykinin-influenced biological processes.
Exhaled nitric oxide as a marker of asthma control in smoking patients
Authors: A. Michils, R. Louis, R. Peché, S. Baldassarre, A. Van Muylem
Journal: European Respiratory Journal (2009)

Exhaled nitric oxide fraction ( F eNO ), which is a reliable marker of eosinophilic airway inflammation, is partially suppressed by tobacco smoking. Consequently, its potential as a biomarker in asthma management has never been evaluated in smoking patients. In the present study, the authors tested the validity of F eNO to predict asthma control in this population. F eNO and the Asthma Control Questionnaire (ACQ) were recorded at least once in 411 nonsmoking (345 with at least two visits) and 59 smoking (51 with at least two visits) asthma patients. Despite similar mean ACQ scores (1.5 versus 1.7), F eNO was reduced in smoking asthmatics (18.1 ppb versus 33.7 ppb). A decrease in F eNO of &lt;20% precludes asthma control improvement in nonsmoking (negative predictive value (NPV) 78%) and in smoking patients (NPV 72%). An increase in F eNO &lt;30% is unlikely to be associated with deterioration in asthma control in both groups of patients (NPV = 86% and 84% in nonsmoking and smoking patients, respectively). It is concluded that, even in smokers, sequential changes in F eNO have a relationship with asthma control. The present study is the first to indicate that cigarette smoking does not obviate the clinical value of measuring F eNO in asthma among smokers.