tbuckley/cabot-search huggingface dataset:
Abstract 279: Inositol Triphosphate Receptor Activation Alters the Electrical Properties of Human Ventricular Myocytes
Authors: Sergio Signore, João Ferreira-Martins, Kazuya Isobe, Ramaswamy Kannappan, Andrea Sorrentino, Mehrdad Shafaie, Elisabeth Steadman, Polina Goihberg, Christian Arranto, Fumihiro Sanada, Fabio Del Ben, Donato Cappetta, Ewa Wybieralska, Barbara Ogorek, Federica Del Monte, David A DAlessandro, Robert E Michler, Marcello Rota
Journal: Circulation Research (2012)

The recognition that ryanodine receptor (RyR) dysfunction is associated to arrhythmogenic diseases raises the possibility that alternative Ca2+ release channels alter the electrical properties of ventricular myocytes. The aim of this study was to determine whether inositol triphosphate receptor (IP3R)-mediated Ca2+ mobilization modulates Ca2+ cycling and electrical behavior in LV myocytes. Cells were obtained from human and mouse hearts and the expression and function of IP3Rs were evaluated. IP3Rs were identified in isolated myocytes by immunocytochemistry and Western blotting. In field-stimulated cells, IP3R activation via Gq-protein receptor agonists (ET-1, ATP) or enhancer of ligand affinity (thimerosal) increased diastolic Ca2+ and transient amplitude by 11% and 44%, respectively. Additionally, extra-systolic Ca2+ release and sustained Ca2+ elevations were detected. These effects were prevented by inhibition of IP3 production or by IP3R blockade. Importantly, myocytes obtained from mice infected in vivo with small hairpin RNA (shRNA) targeting IP3R type 2, failed to respond to Gq-protein receptor agonists. In patch-clamped human and mouse cells, changes in Ca2+ transient properties following IP3R activation were accompanied by a decrease in resting potential, action potential (AP) prolongation, and emergence of arrhythmic events. In mouse cardiomyocytes, assessment of excitation-contraction coupling gain and blockade of RyR channels under IP3R stimulation, excluded the contribution of RyRs to the effects induced by IP3R activation. In voltage-clamped cells, IP3R agonists promoted transient inward currents at the membrane potential of -70 mV and increased a nickel-sensitive current in the range of potentials corresponding to forward mode operation of the Na-Ca exchanger. To establish whether enhanced Ca2+ load was responsible for the altered electrical properties under IP3R activation, conditions buffering cytosolic Ca2+ levels were employed. Under these circumstances, IPR stimulation failed to prolong the AP and to induce arrhythmias. In conclusions, our observations demonstrate that Ca2+ mobilization via IP3Rs directly alters the electrical properties of human and rodent myocytes.
DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats
Authors: David Brocks, Christopher R Schmidt, Michael Daskalakis, Hyo Sik Jang, Nakul M Shah, Daofeng Li, Jing Li, Bo Zhang, Yiran Hou, Sara Laudato, Daniel B Lipka, Johanna Schott, Holger Bierhoff, Yassen Assenov, Monika Helf, Alzbeta Ressnerova, Md Saiful Islam, Anders M Lindroth, Simon Haas, Marieke Essers, Charles D Imbusch, Benedikt Brors, Ina Oehme, Olaf Witt, Michael Lübbert, Jan-Philipp Mallm, Karsten Rippe, Rainer Will, Dieter Weichenhan, Georg Stoecklin, Clarissa Gerhäuser, Christopher C Oakes, Ting Wang, Christoph Plass
Journal: Nature Genetics (2017)
Consistent Terminology Needed for Estimation of Outcomes of Prematurity—Reply
Authors: Jeanie L. Y. Cheong, Lex W. Doyle, Peter J. Anderson
Journal: JAMA Pediatrics (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Barriers to survivorship care in the Consortium for New England Childhood Cancer Survivors (CONNECCS).
Authors: Cindy L. Schwartz, Priay Hirway, Jeremy Ader, Heather Appleton Bradeen, Satkiran S. Grewal, Mary S Huang, Nina Kadan-Lottick, Naheed Usmani, Lisa Brazzamano Kenney
Journal: Journal of Clinical Oncology (2013)

10035 Background: Although long-term adverse consequences of childhood cancer treatment may be mitigated by screening, prevention, and interventions, many survivors do not take advantage of survivorship care. We hypothesized that patients who are at risk for poor compliance with long-term follow-up are identifiable at diagnosis. Methods: To identify factors associated with poor follow-up compliance, 7 CONNECCS institutions evaluated a childhood acute lymphoblastic leukemia (ALL) survivor cohort diagnosed 1996-99. Data collected included: diagnosis year, age, race, ethnicity, gender, insurance, distance from center, CNS disease, and risk classification. Primary endpoints were compliance with 5 and 10-year follow-up. Differences in compliance were tested using chi-squared or t-tests. Logistic regression (including institution as a clustering variable) was used to calculate adjusted odds ratios (OR). Results: At diagnosis, the 358 ALL patients were: female (47%), age= 6.5 + 4.6 years, white/non-Hispanic (84%), black non-Hispanic (7%), high-risk (52%), CNS involvement (10%), privately insured (68%). Private insurance (OR 4.0; 95% CI 2.1-7.8) significantly increased the odds of 5-year compliance. Compliance with 10-year follow-up increased with private insurance (OR 3.3; 95% CI 1.4-8.1) but decreased with CNS disease (OR 0.36; 95% CI 0.31- 0.42) and with years of age (OR 0.93; 95% CI 0.88- 0.96). Conclusions: We evaluated predictors of long-term follow-up based on disease/demographic characteristics at diagnosis to identify cohorts in need of early interventions. In this regional cohort, patients from lower socioeconomic background (without private insurance) at diagnosis were less likely to participate in long-term follow-up care at 5 and 10 years from diagnosis. Older survivors and those with CNS disease were less likely to be in follow-up at 10 years. Future studies should investigate reasons why follow-up compliance is affected by 1) private insurance at diagnosis, 2) older age, and 3) CNS disease. Remediable causes might include: understanding of risk, adolescence/young adult transitions, and healthcare access.
Intracellular trafficking of particles inside endosomal vesicles is regulated by particle size
Authors: Michihiko Aoyama, Yasuo Yoshioka, Yoshiyuki Arai, Haruna Hirai, Rio Ishimoto, Kazuya Nagano, Kazuma Higashisaka, Takeharu Nagai, Yasuo Tsutsumi
Journal: Journal of Controlled Release (2017)
Dyspepsia Prescribing by Primary Care Physicians (PCPS) – The Impact of an Open Access Urea Breath Test Service
Authors: HJ O'Connor, K Bennett, O Thornton, M Dobson, MJ Buckley, C O'Morain, A Qasim, J Feely
Journal: Endoscopy (2004)

Aims: The H Pylori Unit at the Adelaide & Meath Hospital provides an open access Urea breath test (UBT) service for PCP's. The aim was to assess the impact of UBT results on prescribing patterns by PCP's.
Protein kinase C ε expression correlates with the aggressiveness of human prostate cancer
Authors: Moammir H. Aziz, Nancy E. Dreckschmidt, Ajit K. Verma
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

339 

Prostate cancer (PCa) is the most common type of cancer in men and ranks second to lung cancer in cancer-related deaths. PCa first manifests as an androgen-dependent (AD) disease and can be treated with androgen-deprivation therapy. Despite the initial success of androgen ablation therapy, PCa progresses from AD to androgen-independent (AI). The hormone refractory invasive PCa is the end stage and accounts for the majority of PCa patient deaths. Defining the molecular mechanisms linking the transition of AD PCa to a hormone refractory PCa is essential in planning strategies in the management of PCa. We determined that Protein kinase Ce (PKCe) may be linked in vivo to the progression of human AI PCa and should be explored as a molecular target for the prevention and therapy of hormone refractory PCa. PKCe is among the PKC isoforms expressed in human and mouse prostate tissue. PKCe levels were determined by immunohistochemistry of human prostate tissue microarrays prepared from paraffin-fixed benign, hyperplastic and carcimona (Grades I-IV) specimens ([Table][1]). Results showed that PKCe was located predominantly in the cytoplasm of both benign (non-neoplastic) and malignant (neoplastic) epithelial cells. PKCe was uniformly distributed in cancer cells. PKCe was more densely located in the apical (luminal) side of the cytoplasm in normal epithelial cells. In addition, some cancer cells showed slight dense staining for PKCe in the nuclear membrane. Stromal cells were also positive for PKCe, but the intensity was lower than that in epithelial cells. The results of the level of the expression of PKCe are shown in the [table][1]. The level of expression of PKCe appear to correlate with the aggressiveness of PCa. Also, evidence from in vitro studies have demonstrated that PKCe, as compared to AD prostate cancer cell lines, is overexporessed in AI cell lines DU145 and PC3. Also, PKCe has also shown to transform the AD human prostate cancer cell line LNCaP to an AI variant, which forms tumors in castrated male nude mice. PKCe may be a molecular marker of AI PCa. [Table][1]: PKCe expression in human prostate specimens. The level of expression is denoted by the sign +. One + is the lowest and four + is the highest.



![Figure][2]  [1]: #F1
 [2]: pending:yes
Is the Mucosal Route of Administration Essential for Probiotic Function? Subcutaneous Administration is Associated with Attenuation of Murine Colitis and Arthritis
Authors: J McCarthy, B Sheil, L O'Mahony, MW Bennett, P Ryan, JJ Fitzgibbon, B Kiely, JK Collins, F Shanahan
Journal: Endoscopy (2004)

Background: We, and others have reported the prophylactic efficacy of oral consumption of probiotic lactobacilli in the IL-10 KO model of colitis. It has not been demonstrated that the oral route is essential for probiotic efficacy.
A C9ORF72 BAC mouse model recapitulates key epigenetic perturbations of ALS/FTD
Authors: Rustam Esanov, Gabriela Toro Cabrera, Nadja S. Andrade, Tania F. Gendron, Robert H. Brown, Michael Benatar, Claes Wahlestedt, Christian Mueller, Zane Zeier
Journal: Molecular Neurodegeneration (2017)

Amyotrophic Lateral Sclerosis (ALS) is a fatal and progressive neurodegenerative disorder with identified genetic causes representing a significant minority of all cases. A GGGGCC hexanucleotide repeat expansion (HRE) mutation within the C9ORF72 gene has recently been identified as the most frequent known cause of ALS. The expansion leads to partial heterochromatinization of the locus, yet mutant RNAs and dipeptide repeat proteins (DPRs) are still produced in sufficient quantities to confer neurotoxicity. The levels of these toxic HRE products positively correlate with cellular toxicity and phenotypic severity across multiple disease models. Moreover, the degree of epigenetic repression inversely correlates with some facets of clinical presentation in C9-ALS patients. Recently, bacterial artificial chromosomes (BAC) have been used to generate transgenic mice that harbor the HRE mutation, complementing other relevant model systems such as patient-derived induced pluripotent stem cells (iPSCs). While epigenetic features of the HRE have been investigated in various model systems and post-mortem tissues, epigenetic dysregulation at the expanded locus in C9-BAC mice remains unexplored.Here, we sought to determine whether clinically relevant epigenetic perturbations caused by the HRE are mirrored in a C9-BAC mouse model. We used complementary DNA methylation assessment and immunoprecipitation methods to demonstrate that epigenetic aberrations caused by the HRE, such as DNA and histone methylation, are recapitulated in the C9-BAC mice. Strikingly, we found that cytosine hypermethylation within the promoter region of the human transgene occurred in a subset of C9-BAC mice similar to what is observed in patient populations. Moreover, we show that partial heterochromatinization of the C9 HRE occurs during the first weeks of the mouse lifespan, indicating age-dependent epigenetic repression. Using iPSC neurons, we found that preventing R-loop formation did not impede heterochromatinization of the HRE.Taken together, these observations provide further insight into mechanism and developmental time-course of epigenetic perturbations conferred by the C9ORF72 HRE. Finally, we suggest that epigenetic repression of the C9ORF72 HRE and nearby gene promoter could impede or delay motor neuron degeneration in C9-BAC mouse models of ALS/FTD.
New Measurements of Oesophago-Gastric Junction Function
Authors: BP McMahon, J Frokjaer, P Kunwald, AM Drewes, H Gregersen
Journal: Endoscopy (2004)

Aims: To develop a method to biomechanically measure the competence of the sphincteric region at the oesophago-gastric junction (OGJ), which comprises the lower oesophageal sphincter (LOS) and the diaphragmatic hiatus.
Characterization of circRNA-Associated-ceRNA Networks in a Senescence-Accelerated Mouse Prone 8 Brain
Authors: Shuai Zhang, Dina Zhu, Hong Li, Hejian Li, Chengqiang Feng, Wensheng Zhang
Journal: Molecular Therapy (2017)

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Although many researchers have attempted to explain the origins of AD, developing an effective strategy in AD clinical therapy is difficult. Recent studies have revealed a potential link between AD and circRNA-associated-ceRNA networks. However, few genome-wide studies have identified the potential circRNA-associated-ceRNA pairs involved in AD. In this study, we systematically explored the circRNA-associated-ceRNA mechanism in a 7-month-old senescence-accelerated mouse prone 8 (SAMP8) model brain through deep RNA sequencing. We obtained 235 significantly dysregulated circRNA transcripts, 30 significantly dysregulated miRNAs, and 1,202 significantly dysregulated mRNAs. We then constructed the most comprehensive circRNA-associated-ceRNA networks in SAMP8 brain. GO analysis revealed that these networks were involved in regulating the development of AD from various angles, for instance, axon terminus (GO: 0043679) and synapse (GO: 0045202). Following rigorous selection, we discovered that the circRNA-associated-ceRNA networks in this AD mouse model were mainly involved in the regulation of Aβ clearance (Hmgb2) and myelin function (Dio2). This research is the first to provide a systematic dissection of circRNA-associated-ceRNA profiling in SAMP8 mouse brain. The selected circRNA-associated-ceRNA networks can profoundly affect the diagnosis and therapy of AD in the future.
TPF plus cetuximab induction chemotherapy followed by biochemoradiation with weekly cetuximab plus weekly cisplatin or carboplatin: a randomized phase II EORTC trial
Authors: P.M. Specenier, E. Remenar, J. Buter, D.L. Schrijvers, C. Bergamini, L.F. Licitra, A. Awada, P.M. Clement, C. Fortpied, J. Menis, J.B. Vermorken
Journal: Annals of Oncology (2017)
Evaluation of Diarrhoea Developing in an Inpatient Population: The Importance of Microbiological Investigations, Medications and Feeding
Authors: A McErlean, O Kelly, S Bergin, S Patchett, FE Murray
Journal: Endoscopy (2004)

The purpose of this study was to evaluate the investigations performed in an unselected group of inpatients in a tertiary referral hospital, who developed diarrhoea during their hospital stay.
Identification of liver-specific enhancer–promoter activity in the 3′ untranslated region of the wild-type AAV2 genome
Authors: Grant J Logan, Allison P Dane, Claus V Hallwirth, Christine M Smyth, Emilie E Wilkie, Anais K Amaya, Erhua Zhu, Neeta Khandekar, Samantha L Ginn, Sophia H Y Liao, Sharon C Cunningham, Natsuki Sasaki, Martí Cabanes-Creus, Patrick P L Tam, David W Russell, Leszek Lisowski, Ian E Alexander
Journal: Nature Genetics (2017)
Co‐Occurrence and Characteristics of Patients With Axial Spondyloarthritis Who Meet Criteria for Fibromyalgia
Authors: Gary J. Macfarlane, Maxwell S. Barnish, Ejaz Pathan, Kathryn R. Martin, Kirstie L. Haywood, Stefan Siebert, Jonathan Packham, Fabiola Atzeni, Gareth T. Jones
Journal: Arthritis & Rheumatology (2017)

To estimate the proportion of patients with axial spondyloarthritis (SpA) in a UK national biologics registry who met criteria for fibromyalgia (FM), and to delineate the characteristics of these patients.Two cohorts of patients are prospectively recruited from across 83 centers in the UK for the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS). All patients are required to meet Assessment of SpondyloArthritis international Society (ASAS) criteria for axial SpA. Patients are either newly starting biologic therapy (biologics cohort) or are naive to treatment with biologic agents (non-biologics cohort) at the time of recruitment, and all patients are followed up prospectively. At recruitment and follow-up, clinical information and measurements are recorded while patients complete the 2011 research criteria for FM and assessments of the level of disease activity and work impact.Of the patients registered in the BSRBR-AS, 1,504 (68% male) were eligible for the current analysis, of whom 311 (20.7%) met the 2011 research criteria for FM. Prevalence of FM was similar between patients who fulfilled the modified New York criteria for AS (19.7%) and those who fulfilled ASAS imaging criteria but not the modified New York criteria (25.2%); however, among those who fulfilled only the ASAS clinical criteria, the prevalence of FM was lower (9.5%). Patients who met FM criteria reported significantly worse disease activity, function, global severity scores, and quality of life, and were more likely to have moderate or severe levels of mood disorder and clinically important fatigue. Patients who met FM criteria reported experiencing work impairment around half their working time. Meeting FM criteria was not related to elevated C-reactive protein levels or most extraspinal manifestations, but was associated with a higher likelihood of having received biologic therapy.Developing management approaches that would address the significant unmet clinical needs of the 1 in 5 patients with axial SpA who meet criteria for FM should be a research priority.
The Impact of a Surgeon Led Endoluminal Ultrasonography Service
Authors: EI Eguare, P Neary, J Crosbie, SM Johnston, B McGovern, KC Conlon, FBV Keane
Journal: Endoscopy (2004)

Introduction: Endoluminal ultrasonography is useful, for assessing pelvic floor dysfunction (PFD), which has functional or neoplastic manifestations. Ultrasonography has reported accuracy for assessing tumour invasion, and lymph node involvement of, 75%-94% and 71% respectively.
Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1–Selected Advanced Non–Small-Cell Lung Cancer (BIRCH)
Authors: Solange Peters, Scott Gettinger, Melissa L. Johnson, Pasi A. Jänne, Marina C. Garassino, Daniel Christoph, Chee Keong Toh, Naiyer A. Rizvi, Jamie E. Chaft, Enric Carcereny Costa, Jyoti D. Patel, Laura Q.M. Chow, Marianna Koczywas, Cheryl Ho, Martin Früh, Michel van den Heuvel, Jeffrey Rothenstein, Martin Reck, Luis Paz-Ares, Frances A. Shepherd, Takayasu Kurata, Zhengrong Li, Jiaheng Qiu, Marcin Kowanetz, Simonetta Mocci, Geetha Shankar, Alan Sandler, Enriqueta Felip
Journal: Journal of Clinical Oncology (2017)

Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti–programmed death-ligand 1 (PD-L1) monoclonal antibody, in advanced non–small-cell lung cancer (NSCLC) across lines of therapy. Patients were selected on the basis of PD-L1 expression on tumor cells (TC) or tumor-infiltrating immune cells (IC). Patients and Methods Eligible patients had advanced-stage NSCLC, no CNS metastases, and zero to two or more lines of prior chemotherapy. Patients whose tumors expressed PD-L1 using the SP142 immunohistochemistry assay on ≥ 5% of TC or IC (TC2/3 or IC2/3 [TC or IC ≥ 5% PD-L1–expressing cells, respectively]) were enrolled. Atezolizumab 1,200 mg was administered intravenously every 3 weeks. Efficacy-evaluable patients (N = 659) comprised three cohorts: first line (cohort 1; n = 139); second line (cohort 2; n = 268); and third line or higher (cohort 3; n = 252). The primary end point was independent review facility–assessed objective response rate (ORR; Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1). Secondary end points included median duration of response, progression-free survival, and overall survival (OS). Results BIRCH met its primary objective of demonstrating a significant ORR versus historical controls. With a minimum of 12 months of follow-up, the independent review facility–assessed ORR was 18% to 22% for the three cohorts, and 26% to 31% for the TC3 or IC3 subgroup; most responses are ongoing. Responses occurred regardless of EGFR or KRAS mutation status. The median OS from an updated survival analysis (minimum of 20 month follow up) for cohort 1 was 23.5 months (26.9 months for TC3 or IC3 patients); the median OS in cohorts 2 and 3 was 15.5 and 13.2 months, respectively. The safety profile was similar across cohorts and consistent with previous atezolizumab monotherapy trials. Conclusion BIRCH demonstrated responses with atezolizumab monotherapy in patients with PD-L1–selected advanced NSCLC, with good tolerability. PD-L1 status may serve as a predictive biomarker for identifying patients most likely to benefit from atezolizumab.