tbuckley/cabot-search huggingface dataset:
TMEM16A/ANO1 Channels Contribute to the Myogenic Response in Cerebral Arteries
Authors: Simon Bulley, Zachary P. Neeb, Sarah K. Burris, John P. Bannister, Candice M. Thomas-Gatewood, Wanchana Jangsangthong, Jonathan H. Jaggar
Journal: Circulation Research (2012)

Rationale: Pressure-induced arterial depolarization and constriction (the myogenic response) is a smooth muscle cell (myocyte)-specific mechanism that controls regional organ blood flow and systemic blood pressure. Several different nonselective cation channels contribute to pressure-induced depolarization, but signaling mechanisms involved are unclear. Similarly uncertain is the contribution of anion channels to the myogenic response and physiological functions and mechanisms of regulation of recently discovered transmembrane 16A (TMEM16A), also termed Anoctamin 1, chloride (Cl − ) channels in arterial myocytes. Objective: To investigate the hypothesis that myocyte TMEM16A channels control membrane potential and contractility and contribute to the myogenic response in cerebral arteries. Methods and Results: Cell swelling induced by hyposmotic bath solution stimulated Cl − currents in arterial myocytes that were blocked by TMEM16A channel inhibitory antibodies, RNAi-mediated selective TMEM16A channel knockdown, removal of extracellular calcium (Ca 2+ ), replacement of intracellular EGTA with BAPTA, a fast Ca 2+ chelator, and Gd 3+ and SKF-96365, nonselective cation channel blockers. In contrast, nimodipine, a voltage-dependent Ca 2+ channel inhibitor, or thapsigargin, which depletes intracellular Ca 2+ stores, did not alter swelling-activated TMEM16A currents. Pressure-induced (−40 mm Hg) membrane stretch activated ion channels in arterial myocyte cell–attached patches that were inhibited by TMEM16A antibodies and were of similar amplitude to recombinant TMEM16A channels. TMEM16A knockdown reduced intravascular pressure-induced depolarization and vasoconstriction but did not alter depolarization-induced (60 mmol/L K + ) vasoconstriction. Conclusions: Membrane stretch activates arterial myocyte TMEM16A channels, leading to membrane depolarization and vasoconstriction. Data also provide a mechanism by which a local Ca 2+ signal generated by nonselective cation channels stimulates TMEM16A channels to induce myogenic constriction.
Immunological Function in Dystrophia Myotonica
Authors: D. I. Grove, S. J. O Callaghan, T. O. Burston, I. J. Forbes
Journal: BMJ (1973)

Humoral and cellular immunity have been investigated in 15 patients with dystrophia myotonica. No abnormalities in total serum levels of the five major immunoglobulin classes were found but there was a rise in the mean serum level of beta(1)A complement. Altogether, 54% of patients failed to make antibody to tetanus toxoid as compared with 1% of controls: 13% of patients failed to make antibody to Salmonella typhi H antigen as compared with no failure of this function in control subjects. There was a reduced uptake of tritiated thymidine by whole blood lymphocyte cultures spontaneously, while in the presence of phytohaemagglutinin (PHA) and both autologous and fetal calf serum the uptake was normal. It is suggested that there may be a wider derangement of immunological function in dystrophia myotonica than previously thought.
A STUDY OF HUMAN SKIN GRAFTED UPON THE CHORIO-ALLANTOIS OF CHICK EMBRYOS
Authors: Ernest W. Goodpasture, Beverly Douglas, Katherine Anderson
Journal: The Journal of Experimental Medicine (1938)

Human skin grafted upon the chorio-allantoic membrane of chick embryos adheres and becomes nourished for as long as 10 days. Occasionally regrafts upon a second egg have succeeded and thus prolonged the vitality of the graft to 14 days. In successful experiments the epithelium of the chorio-allantois fuses with that of the graft, the collagen fibers of the corium interlace with those of the membrane after the separation or disappearance of the ectodermal layer, and the blood vessels of the chick anastomose, and unite by intervening pools of extravasated blood, with those of the graft. This vascular communication between the two tissues is largely responsible for the nourishment of the graft by affording a plasmatic circulation. Gradually there is a partial revascularization of the graft by an ingrowth of blood vessels from the chick membrane. Human skin grafts were susceptible to experimental infection by several viruses.
Increase of angiotensin II type 1 receptor auto-antibodies in Huntington’s disease
Authors: De-Hyung Lee, Harald Heidecke, Alexandra Schröder, Friedemann Paul, Rolf Wachter, Rainer Hoffmann, Gisa Ellrichmann, Duska Dragun, Anne Waschbisch, Johannes Stegbauer, Peter Klotz, Ralf Gold, Ralf Dechend, Dominik N Müller, Carsten Saft, Ralf A Linker
Journal: Molecular Neurodegeneration (2014)

In the recent years, a role of the immune system in Huntington's disease (HD) is increasingly recognized. Here we investigate the presence of T cell activating auto-antibodies against angiotensin II type 1 receptors (AT1R) in all stages of the disease as compared to healthy controls and patients suffering from multiple sclerosis (MS) as a prototype neurologic autoimmune disease. As compared to controls, MS patients show higher titers of anti-AT1R antibodies, especially in individuals with active disease. In HD, anti-AT1R antibodies are more frequent than in healthy controls or even MS and occur in 37.9% of patients with relevant titers ≥ 20 U/ml. In a correlation analysis with clinical parameters, the presence of AT1R antibodies in the sera of HD individuals inversely correlated with the age of onset and positively with the disease burden score as well as with smoking and infection. These data suggest a dysfunction of the adaptive immune system in HD which may be triggered by different stimuli including autoimmune responses, infection and possibly also smoking.
Emergence and global spread of epidemic healthcare-associated Clostridium difficile
Authors: Miao He, Fabio Miyajima, Paul Roberts, Louise Ellison, Derek J Pickard, Melissa J Martin, Thomas R Connor, Simon R Harris, Derek Fairley, Kathleen B Bamford, Stephanie D'Arc, Jon Brazier, Derek Brown, John E Coia, Gill Douce, Dale Gerding, Hee Jung Kim, Tse Hsien Koh, Haru Kato, Mitsutoshi Senoh, Tom Louie, Stephen Michell, Emma Butt, Sharon J Peacock, Nick M Brown, Tom Riley, Glen Songer, Mark Wilcox, Munir Pirmohamed, Ed Kuijper, Peter Hawkey, Brendan W Wren, Gordon Dougan, Julian Parkhill, Trevor D Lawley
Journal: Nature Genetics (2012)
Phase II Study of Docetaxel and S-1 Combination Therapy for Advanced or Recurrent Gastric Cancer
Authors: Kazuhiro Yoshida, Motoki Ninomiya, Norihisa Takakura, Naoki Hirabayashi, Wataru Takiyama, Yuji Sato, Satoru Todo, Masanori Terashima, Mitsukazu Gotoh, Jyunnichi Sakamoto, Masahiko Nishiyama
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To evaluate the efficacy and toxicity of docetaxel in combination with a novel oral 5-fluorouracil analogue S-1 for patients with advanced or recurrent gastric cancer. Experimental Design: Patients with advanced or recurrent adenocarcinoma of the stomach and up to one previous chemotherapy regimen were treated with i.v. docetaxel 40 mg/m2 on day 1 and oral S-1 80 mg/m2/d on days 1 to 14 every 3 weeks. Results: Forty-eight patients (median age, 65 years; range, 25-75 years) received a total of 272 treatment cycles (median, 4; range, 1-17). No complete responses and 27 partial responses were observed for an overall response rate of 56.3% [95% confidence interval (95% CI), 38-66%]. Eighteen patients (37.5%) had stable disease and three patients (6.3%) had progressive disease as best response. The tumor control rate (complete response + partial response + stable disease) was 93.8% (95% CI, 83-98%). Median overall survival was 14.3 months (95% CI, 10.7-20.3 months) and median time to tumor progression was 7.3 months (95% CI, 4.3-10.0 months). The most common grade 3 to 4 hematologic toxicities were neutropenia (58.3%), leukopenia (41.7%), febrile neutropenia (8.3%), and anemia (8.3%). The most common grade 3 nonhematologic toxicities included anorexia (14.6%), stomatitis (8.3%), and nausea (6.3%). No grade 4 nonhematologic toxicities were reported and all treatment-related toxicities were resolved. Conclusion: Docetaxel/S-1 combination is highly active and well tolerated in advanced or recurrent gastric cancer. Further investigation in randomized studies is warranted.
FOXA1 Expression in Breast Cancer—Correlation with Luminal Subtype A and Survival
Authors: Sunil Badve, Dmitry Turbin, Mangesh A. Thorat, Akira Morimiya, Torsten O. Nielsen, Charles M. Perou, Sandi Dunn, David G. Huntsman, Harikrishna Nakshatri
Journal: Clinical Cancer Research (2007)

Abstract Purpose: FOXA1, a forkhead family transcription factor, is essential for optimum expression of ∼50% of estrogen receptor α (ERα):estrogen responsive genes. FOXA1 is expressed in breast cancer cells. It segregates with genes that characterize the luminal subtypes in DNA microarray analyses. The utility of FOXA1 as a possible independent prognostic factor has not been determined in breast cancers. Materials and Methods: A tissue microarray comprising tumors from 438 patients with 15.4 years median follow-up was analyzed for FOXA1 expression by immunohistochemistry. Interpretable FOXA1 expression obtained in 404 patients was analyzed along with other prognostic factors like tumor grade, size, nodal status, ER, progesterone receptor (PR), and HER2/neu. Results: FOXA1 expression (score &amp;gt;3) was seen in 300 of 404 breast cancers and it correlated with ER (P = 0.000001), PR (P = 0.00001), and luminal A subtype (P = 0.000001). Loss of expression was noted with worsening tumor grade (P = 0.001). Univariate analysis showed nodal status (P = 0.0000012), tumor size (P = 0.00001), FOXA1 (P = 0.0004), and ER (P = 0.012) to be predictors of breast cancer–specific survival. Multivariate analysis showed only nodal status (P = 0.001) and tumor size (P = 0.039) to be significant prognostic factors, whereas FOXA1 (P = 0.060) and ER (P = 0.131) were not significant. In luminal subtype A patient subgroup, FOXA1 expression was associated with better cancer-specific survival (P = 0.024) and in ER-positive subgroup, it was better predictor of cancer-specific survival (P = 0.009) than PR (P = 0.213). Conclusion: FOXA1 expression correlates with luminal subtype A breast cancer and it is significant predictor of cancer-specific survival in patients with ER-positive tumors. Prognostic ability of FOXA1 in these low-risk breast cancers may prove to be useful in clinical treatment decisions.
15 years of tracking physiotherapy evidence on PEDro, where are we now?
Authors: Steven J Kamper, Anne M Moseley, Robert D Herbert, Christopher G Maher, Mark R Elkins, Catherine Sherrington
Journal: British Journal of Sports Medicine (2015)

Healthcare systems across the globe have begun the transition to evidence-based practice. The degree to which the transition has occurred can be debated but, it is underpinned by a large and rapidly growing volume of research. However, this research is only useful if it is reliable, comprehensive and accessible.

The Physiotherapy Evidence Database (PEDro; http://www.pedro.org.au) recently celebrated 15 years of existence. PEDro is a free resource that indexes published randomised controlled trials (RCT), systematic reviews and clinical practice guidelines relevant to physiotherapy. The first physiotherapy RCT was published in 1929 and the first physiotherapy systematic review in 1982. Since then there has been exponential growth in the number of published RCTs and systematic reviews relevant to physiotherapy (figure 1). This editorial reflects on what PEDro tells us about the evidence base for physiotherapy and sports physiotherapy in particular.



Figure 1 
Growth in the number of published randomised controlled trials (RCTs), reviews and guidelines indexed on PEDro.



As of October 2014, PEDro indexes 23 049 RCTs, 5039 systematic reviews and 512 clinical practice guidelines. The largest number of studies are in the musculoskeletal subdiscipline (7676), followed by cardiothoracics (5334) and gerontology (4105). This volume of studies and the ongoing increase in rate of publication points to a substantial commitment to physiotherapy research.

There are 1325 sports physiotherapy studies (1098 RCTs, 222 systematic reviews and 5 practice guidelines); this is the second lowest of the 10 subdisciplines. The low number of studies is surprising given the high profile of sports physiotherapy. The rate of publications …
Report of EULAR Standing Committee on Epidemiology and Health Services Research: Lisbon, June 2003
Authors: S van der Linden
Journal: Annals of the Rheumatic Diseases (2003)

In recent years at the EULAR annual congresses the standing committee has put together several interactive workshops on methodological issues in clinical epidemiology. This year we offered a mini-symposium on practical issues in descriptive epidemiological studies in the EULAR region. The symposium aimed at obtaining knowledge on various available sources, methods, and screening instruments; understanding the goals, advantages, and pitfalls of the various methods; contributing to the improvement and updating of knowledge …
Membrane Trafficking of G Protein–Coupled Receptors
Authors: Christopher M. Tan, Ashley E. Brady, Hilary Highfield Nickols, Qin Wang, Lee E. Limbird
Journal: The Annual Review of Pharmacology and Toxicology (2004)

G protein-coupled receptors (GPCRs) modulate diverse physiological and behavioral signaling pathways by virtue of changes in receptor activation and inactivation states. Functional changes in receptor properties include dynamic interactions with regulatory molecules and trafficking to various cellular compartments at various stages of the life cycle of a GPCR. This review focuses on trafficking of GPCRs to the cell surface, stabilization there, and agonist-regulated turnover. GPCR interactions with a variety of newly revealed partners also are reviewed with the intention of provoking further analysis of the relevance of these interactions in GPCR trafficking, signaling, or both. The disease consequences of mislocalization of GPCRs also are described.
Testicular Cancer Survivorship: Research Strategies and Recommendations
Authors: L. B. Travis, C. Beard, J. M. Allan, A. A. Dahl, D. R. Feldman, J. Oldenburg, G. Daugaard, J. L. Kelly, M. E. Dolan, R. Hannigan, L. S. Constine, K. C. Oeffinger, P. Okunieff, G. Armstrong, D. Wiljer, R. C. Miller, J. A. Gietema, F. E. van Leeuwen, J. P. Williams, C. R. Nichols, L. H. Einhorn, S. D. Fossa
Journal: JNCI Journal of the National Cancer Institute (2010)

Testicular cancer represents the most curable solid tumor, with a 10-year survival rate of more than 95%. Given the young average age at diagnosis, it is estimated that effective treatment approaches, in particular, platinum-based chemotherapy, have resulted in an average gain of several decades of life. This success, however, is offset by the emergence of considerable long-term morbidity, including second malignant neoplasms, cardiovascular disease, neurotoxicity, nephrotoxicity, pulmonary toxicity, hypogonadism, decreased fertility, and psychosocial problems. Data on underlying genetic or molecular factors that might identify those patients at highest risk for late sequelae are sparse. Genome-wide association studies and other translational molecular approaches now provide opportunities to identify testicular cancer survivors at greatest risk for therapy-related complications to develop evidence-based long-term follow-up guidelines and interventional strategies. We review research priorities identified during an international workshop devoted to testicular cancer survivors. Recommendations include 1) institution of lifelong follow-up of testicular cancer survivors within a large cohort setting to ascertain risks of emerging toxicities and the evolution of known late sequelae, 2) development of comprehensive risk prediction models that include treatment factors and genetic modifiers of late sequelae, 3) elucidation of the effect(s) of decades-long exposure to low serum levels of platinum, 4) assessment of the overall burden of medical and psychosocial morbidity, and 5) the eventual formulation of evidence-based long-term follow-up guidelines and interventions. Just as testicular cancer once served as the paradigm of a curable malignancy, comprehensive follow-up studies of testicular cancer survivors can pioneer new methodologies in survivorship research for all adult-onset cancer.
Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial
Authors: Jeffrey L Lennox, Edwin DeJesus, Adriano Lazzarin, Richard B Pollard, Jose Valdez Ramalho Madruga, Daniel S Berger, Jing Zhao, Xia Xu, Angela Williams-Diaz, Anthony J Rodgers, Richard JO Barnard, Michael D Miller, Mark J DiNubile, Bach-Yen Nguyen, Randi Leavitt, Peter Sklar
Journal: The Lancet (2009)
Activation of STAT3 by the Hepatitis C Virus Core Protein Leads to Cellular Transformation
Authors: Takafumi Yoshida, Toshikatsu Hanada, Takeshi Tokuhisa, Ken-ichiro Kosai, Michio Sata, Michinori Kohara, Akihiko Yoshimura
Journal: The Journal of Experimental Medicine (2002)

The signal transducer and activator of transcription (STAT) family proteins are transcription factors critical in mediating cytokine signaling. Among them, STAT3 is often constitutively phosphorylated and activated in human cancers and in transformed cell lines and is implicated in tumorigenesis. However, cause of the persistent activation of STAT3 in human tumor cells is largely unknown. The hepatitis C virus (HCV) is a major etiological agent of non-A and non-B hepatitis, and chronic infection by HCV is associated with development of liver cirrhosis and hepatocellular carcinoma. HCV core protein is proposed to be responsible for the virus-induced transformation. We now report that HCV core protein directly interacts with and activates STAT3 through phosphorylation of the critical tyrosine residue. Activation of STAT3 by the HCV core in NIH-3T3 cells resulted in rapid proliferation and up-regulation of Bcl-XL and cyclin-D1. Additional expression of STAT3 in HCV core-expressing cells resulted in anchorage-independent growth and tumorigenesis. We propose that the HCV core protein cooperates with STAT3, which leads to cellular transformation.
Abnormal regulation of renal 25-hydroxyvitamin D-1 alpha-hydroxylase activity in the X-linked hypophosphatemic mouse.
Authors: B Lobaugh, M K Drezner
Journal: Journal of Clinical Investigation (1983)

Abnormal vitamin D metabolism has been suspected in patients with X-linked hypophosphatemic rickets (XLH) and X-linked hypophosphatemic mice (Hyp-mice), the murine homologue of the human disease. We compared 25(OH)D-1 alpha-hydroxylase activity in the Hyp-mouse kidney to that in normal and phosphate-depleted mouse kidney. Weanling normal and Hyp-mice were fed a 0.6% phosphorus diet; phosphate-depleted mice received a 0.02% phosphorus diet. At 8-10 wk of age the serum phosphorus values in Hyp (3.35 +/- 0.12 mg/dl) and phosphate-depleted mice (3.83 +/- 0.56) were not significantly different. Despite the similar magnitude of phosphate depletion, however, the maximum levels of 25(OH)D-1 alpha-hydroxylase activity were disparate: phosphate-depleted mouse kidney had profoundly increased activity compared to normal (17.04 +/- .104 vs. 4.96 +/- 0.23 fmol 1,25(OH)2D3 produced/mg kidney per min) while Hyp-mouse kidney had a fourfold lesser increment (8.18 +/- 0.62). These data indicate that phosphate depletion is a potent stimulus of 25(OH)D-1 alpha-hydroxylase activity in the (C57BL6J) mouse. Moreover, the results show that abnormal regulation of 25(OH)D-1 alpha-hydroxylase activity is manifest in the Hyp-mouse.
Transcranial Magnetic Stimulation in the Treatment of Depression
Authors: Ari A Gershon, Pinhas N Dannon, Leon Grunhaus
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Transcranial magnetic stimulation (TMS) is a noninvasive and easily tolerated method of altering cortical physiology. The authors evaluate evidence from the last decade supporting a possible role for TMS in the treatment of depression and explore clinical and technical considerations that might bear on treatment success. METHOD: The authors review English-language controlled studies of nonconvulsive TMS therapy for depression that appeared in the MEDLINE database through early 2002, as well as one study that was in press in 2002 and was published in 2003. In addition, the authors discuss studies that have examined technical, methodological, and clinical treatment parameters of TMS. RESULTS: Most data support an antidepressant effect of high-frequency repetitive TMS administered to the left prefrontal cortex. The absence of psychosis, younger age, and certain brain physiologic markers might predict treatment success. Technical parameters possibly affecting treatment success include intensity and duration of treatment, but these suggestions require systematic testing. CONCLUSIONS: TMS shows promise as a novel antidepressant treatment. Systematic and large-scale studies are needed to identify patient populations most likely to benefit and treatment parameters most likely to produce success. In addition to its potential clinical role, TMS promises to provide insights into the pathophysiology of depression through research designs in which the ability of TMS to alter brain activity is coupled with functional neuroimaging.
Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1β production
Authors: Hendrik Poeck, Michael Bscheider, Olaf Gross, Katrin Finger, Susanne Roth, Manuele Rebsamen, Nicole Hannesschläger, Martin Schlee, Simon Rothenfusser, Winfried Barchet, Hiroki Kato, Shizuo Akira, Satoshi Inoue, Stefan Endres, Christian Peschel, Gunther Hartmann, Veit Hornung, Jürgen Ruland
Journal: Nature Immunology (2009)
Early Salvage Radiotherapy After Radical Prostatectomy
Authors: Christopher Parker, Charles Catton, Matthew R. Sydes
Journal: Journal of Clinical Oncology (2009)

It follows that giving adju-vant radiotherapy to all patients with high-risk features will causemore treatment-related morbidity than salvage radiotherapy givenonlytothosewhorelapse.Giventhatanadjuvantpolicywillbemoretoxicthanaselectiveearlysalvagepolicy,andthatitisunclearwhetheradjuvant treatment is more effective, we regard early salvage radio-therapyasthestandardofcare.Thompsonetal
Acupuncture and asthma: a review of controlled trials.
Authors: J Kleijnen, G ter Riet, P Knipschild
Journal: Thorax (1991)

BACKGROUND: Published controlled trials of acupuncture in asthma have often contained a small number of subjects and the results are contradictory. Controlled trials have been reviewed to determine whether clearer conclusions could be obtained by assessing as many studies as possible according to methodological criteria. METHODS: A literature search produced 13 trials on the efficacy of acupuncture in the treatment of patients with asthma. These studies were reviewed on the basis of 18 predefined methodological criteria. A maximum of 100 points for study design could be earned in three main categories: (a) adequate study population, (b) adequate intervention, and (c) adequate measurement of effects. RESULTS: The quality of even the eight better studies (more than 50% of the maximum score) proved to be mediocre. No study earned more than 72% of the maximum score. The results from the better studies are highly contradictory. CONCLUSIONS: Claims that acupuncture is effective in the treatment of asthma are not based on the results of well performed clinical trials.
Effect of -irradiation with 188 Re-filled long-balloon on reference segments
Authors: Bon Kwon Koo, Myoung-Mook Lee, Woo-Young Chung, In-Ho Chai, Hyosoo Kim, Byoung-Hee Oh, Young-Bae Park, Yun-Shik Choi
Journal: Journal of the American College of Cardiology (2003)