tbuckley/cabot-search huggingface dataset:
SAT0290 Altered Microrna Expression and Regulation in GIANT Cell Arteritis
Authors: S. Wade, M. Connolly, L. O'Neill, J. Mc Cormick, D. Veale, C. Murphy, E. Molloy, U. Fearon
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Giant cell arteritis (GCA) is a common form of primary vasculitis characterised by dysfunctional vessels and inflammatory infiltration leading to luminal occlusion. It is now evident that these processes may be altered by a class of small non-coding RNAs or microRNA (miRNA), which exert their biological function through suppression of specific target genes. Abnormal miRNA expression has been demonstrated in cancer and chronic inflammatory arthritis, however to date miRNA have not been examined in GCA. <h3>Objectives</h3> This study examines expression and regulation of miRNA in GCA. <h3>Methods</h3> Temporal artery (TA) sections from patients positive and negative for GCA were assessed by immunohistology. Peripheral blood mononuclear cells (PBMC) from GCA positive (n=10), GCA negative (n=2) and healthy controls (n=4) were collected and expression of miR-155, miR-146a, miR-125a-3p/-5p and miR-323-3p were quantified using the Qiagen miRNA isolation kit (Qiagen) and Taqman PCR. To examine possible factors involved in regulating miRNA expression, GCA positive PBMC were cultured with candidate stimuli including Toll-like receptor (TLR) ligands- Pam3CSK4 (1 ng/ml), LPS (100 ng/ml) and pro-inflammatory cytokines- IL-1β (1 ng/ml) and TNFα (10 ng/ml). Total RNA was isolated and individual miRNA quantified by Taqman assay. In parallel IL-6, IL-8 and IL-10 were quantified in cultured supernatants by ELISA. <h3>Results</h3> Increased miR-155 levels were demonstrated in GCA positive PBMC compared to healthy controls and GCA negative PBMC (p&lt;0.05). No difference in expression of miR-125a-5p or miR-146a was observed. MiR-323-3p and miR-125a-3p were undetectable in all samples. Pam3CSK4 and IL-1β significantly induced miR-155 and miR-146 (p&lt;0.05), while TNFα induced miR-146a expression (P&lt;0.05) with no effect observed for LPS. In parallel, Pam3CSK4 and/or IL-1β significantly induced IL-6, IL-8 and IL-10 protein expression. Finally <i>in silico</i> analysis was used to identify putative microRNA targets which included IL-6R, IL-6 gp130 and TRAF3. <h3>Conclusions</h3> This study demonstrates for the first time increased expression and regulation of miRNA in patients positively diagnosed for GCA suggesting potential therapeutic regulation for the treatment of GCA. <h3>Disclosure of Interest</h3> S. Wade: None declared, M. Connolly: None declared, L. O9Neill: None declared, J. Mc Cormick: None declared, D. Veale Grant/research support: Abbvie,MSD,Pfizer,Roche, Consultant for: Pfizer,Roche, Speakers bureau: Abbott, MSD,Pfzier, Roche, C. Murphy: None declared, E. Molloy: None declared, U. Fearon: None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5559
Enhancing Nephrology Career Interest through the ASN Kidney TREKS Program
Authors: Laura J. Maursetter, Lauren D. Stern, Stephen M. Sozio, Ankit B. Patel, Reena Rao, Hitesh H. Shah, Katlyn Leight, Mark D. Okusa, Mark L. Zeidel, Mark G. Parker
Journal: Journal of the American Society of Nephrology (2016)

The Kidney Tutored Research and Education for Kidney Students (TREKS) Program is a product of the American Society of Nephrology (ASN) Workforce Committee that seeks to connect medical and graduate students to nephrology. This program starts with a weeklong camp–like course introducing participants to renal physiology through classic and modern experiments. Next, each student is matched with a nephrology mentor at his or her home institution to foster a better understanding of a nephrology career. Lastly, the students are encouraged to participate in scholarly activities and attend the ASN Kidney Week. Now in its third year, with a total of 84 participants, survey data suggest early success of the program, with a self–reported 40% increased interest in nephrology fellowship and/or research careers. In addition, students give high ratings to the course components and mentorship pairings. Continued student tracking will be necessary to determine the long–term program effect.
The Rapid-Rocking Bed: Its Effect on the Ventilation of Poliomyelitis Patients with Respiratory Paralysis
Authors: Fred Plum, G. Donald Whedon
Journal: New England Journal of Medicine (1951)

RECENT improvements in the management of respiratory insufficiency in patients with acute poliomyelitis have considerably reduced mortality in this stage of the disease. As a result, increasing numbers of patients have required artificial respiration for long periods after the acute febrile stage of poliomyelitis has passed. Although tank-type "iron-lung" respirators are life-saving for acutely ill patients, their continued use over periods of many weeks or months is associated with certain disadvantages. These include fixation and fibrosis of the diaphragm, restriction of motion of the extremities and difficulty in inducing patients to rely on their own recovering ventilatory mechanisms. A device . . .
P198Chronic, atherosclerosis-like ischemia model in hypercholesterolemic rabbits reveals a challenge for angiogenic gene therapy
Authors: P Korpisalo, JP Hytonen, J Taavitsainen, S Tarvainen, S Yla-Herttuala
Journal: Cardiovascular Research (2014)

Introduction: Angiogenic gene therapy has shown potential for treatment of peripheral ischemic diseases in animal models but unfortunately clinical trials have failed to show consistent improvements in patients. We hypothesized that the differential outcomes of animal and clinical trials could be explained by pathological differences between animal models and human disease.
Ondansetron Leads Antiemetic Research
Authors: F. X. Mahaney
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Ondansetron Leads Antiemetic Research Get access Francis X. Mahaney, Jr. Francis X. Mahaney, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 3, 3 February 1993, Pages 184–185, https://doi.org/10.1093/jnci/85.3.184 Published: 03 February 1993
1325 RIFAXIMIN IN NON-ALCOHOLIC STEATOHEPATITIS: AN OPEN-LABEL PILOT STUDY
Authors: J.F.L. Cobbold, S.N. Wai, J. Stove, F. Shojaee-Moradie, J. Fitzpatrick, E.L. Thomas, J.D. Bell, R.D. Goldin, S.D. Taylor- Robinson, M.S. Yee, Q.M. Anstee, M.R. Thursz
Journal: Journal of Hepatology (2013)
P372Electrophysiological changes in chronic heart failure rat hearts induced by vagal nerve stimulation
Authors: EG Tolkacheva, J Ippolito, SW Lee, C Maes, BH Kenknight, X Xie
Journal: Cardiovascular Research (2014)

Intermittent vagal nerve stimulation (VNS) has recently been shown to reduce arrhythmia in animals and humans with chronic heart failure (CHF). The electrophysiological changes underpinning these benefits remain largely uncharacterized. Therefore, we aimed to investigate the electrophysiological remodeling resulting from long-term intermittent VNS therapy in the CHF rat. Myocardial infarction (MI) was induced via LAD ligation in n=10 male Sprague-Dawley rats (250-300g). Rats were randomized into two groups: MI-SS rats (n = 5) were implanted with non-functional VNS stimulators, and MI-VNS rats (n = 5) were implanted with functional VNS stimulators and received chronic intermittent VNS treatment during 12 weeks. In Sham rats (n = 4) neither MI nor VNS were performed. At 13 weeks, hearts were explanted and Langendorff perfused. Optical mapping of right ventricle (RV) during periodic pacing and right atrium (RA) during sinus rhythm was then performed. First, we confirmed that long-term intermittent VNS therapy has clear antiarrhythmic benefits. Indeed, our results demonstrate that no MI-VNS rats (0/5) exhibited ventricular fibrillation, compared to Sham (2/4) and MI-SS (5/5) rats. Nevertheless, the maximum slope of the RV action potential duration (APD) restitution curve was larger (2.07±0.63) in MI-VNS rats compared to MI-SS (0.65±0.19, p<0.05) and Sham (0.59±0.13, p<0.05) rats. Most importantly, all MI-VNS rats displayed mean APD restitution slope greater than 1, while none of MI-SS or Sham rats had slope exceeding 1 (p < 0.05). Furthermore, MI-VNS rats exhibited significantly lower RV APD heterogeneity index (0.225±0.032) compared to MI-SS (0.538±0.107) rats. However, long-term intermittent VNS does not affect APD, and has moderate-to-no effect on conduction velocity of electrical propagation in RV. In RA during sinus rhythm, MI-VNS rats showed significantly larger APD (27.74±0.59 ms) compared to MI-SS (23.53±0.39 ms, p<0.05), but not different from Sham (26.41 ± 0.42, p=NS). However, APD heterogeneity indexes for both MI-VNS (0.562±0.038) and MI-SS (0.542±0.017) rats were similar, but significantly higher when compared to Sham (0.331±0.055). Our results suggest that the VNS therapy prevents VF through a remodeling of the electrophysiological properties of the myocardium.
Early Deposition of Aluminum in Bone in Diabetic Patients on Hemodialysis
Authors: Dennis L. Andress, Jeffrey B. Kopp, Norma A. Maloney, Jack W. Coburn, Donald J. Sherrard
Journal: New England Journal of Medicine (1987)

Aluminum-associated bone disease is a special problem in uremic patients on hemodialysis. We have observed this disorder in uremic patients with insulin-dependent diabetes soon after the start of dialysis treatments. We therefore studied bone biopsy specimens from 18 diabetic patients on hemodialysis to determine whether aluminum accumulates on bone surfaces at an accelerated rate in diabetes. We also measured the rates of bone formation, because lower rates may enhance the accumulation of aluminum on bone surfaces. As compared with 18 nondiabetic controls with uremia who were matched for age and duration of dialysis, the patients with diabetes had a higher rate of aluminum accumulation on bone surfaces (2.1 +/- 0.7 vs. 0.4 +/- 0.2 percent per month, P less than 0.01) and a lower rate of bone formation (117 +/- 50 vs. 396 +/- 81 microns 2 per square millimeter per day, P less than 0.01). Also, the patients with diabetes whose cumulative aluminum intake exceeded 0.5 kg had higher serum aluminum levels after an infusion of deferoxamine, as compared with controls matched for aluminum intake (P less than 0.01). These measurements reflected a higher aluminum content in the whole body in patients with diabetes. We suggest that the enhanced rate of aluminum accumulation on bone surfaces in uremic patients with diabetes occurs as a result of a low rate of bone formation and an increased accumulation of aluminum in the whole body.
Pseudo-Supernumerary Right Kidney
Authors: LIONEL S. ZUCKIER, NASRIN GHESANI, PAUL L. SAMUELS, BLANCHE J. SKURNICK
Journal: Clinical Nuclear Medicine (2003)

ZUCKIER, LIONEL S. M.D.; GHESANI, NASRIN; SAMUELS, PAUL L.; SKURNICK, BLANCHE J. Author Information
SAT0015 The negative effects of glucocorticoids on bone are primarily mediated by genes involved in osteoblast differentiation and bone remodelling
Authors: K.I. Blankenstein, T.C. Brennan-Speranza, K. Lyon, C.R. Dunstan, F. Buttgereit, H. Zhou, M.J. Seibel
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Long-term and high-dose treatment with glucocorticoids causes bone loss and can lead to secondary osteoporosis in both human and mice. The molecular mechanisms underlying the adverse effects of glucocorticoids on bone are not well understood. We recently demonstrated that osteoblast-targeted disruption of glucocorticoid signalling attenuates glucocorticoid-induced bone loss in mice, indicating that the detrimental skeletal effects of glucocorticoids are predominantly mediated by osteoblasts. <h3>Objectives</h3> To further determine the role of the osteoblast in glucocorticoid-induced bone loss, we aimed to elucidate the effects of glucocorticoids on the gene expression profile in bone cells. <h3>Methods</h3> Seven-week old male CD1 outbred mice were subcutaneously implanted with slow-release pellets containing either 1.5 mg corticosterone (CS) or placebo (PLC) over 28 days. Blood was obtained weekly and osteocalcin serum levels were measured by IRMA. RNA was isolated from tibia at endpoint (day 28) and Affymetrix Gene Array analysis (GeneSpring GX) was performed to assess changes in expression of genes associated with osteoblast differentiation and the regulation of bone remodelling. Genes considered to be regulated were at least 1.5-fold differentially expressed. Quantitative RT-PCR was employed to validate the gene array results on a selection of genes. <h3>Results</h3> By comparing gene expression profiles in RNA from mice treated with corticosterone or placebo, we found that corticosterone specifically regulated 391 genes. To further investigate the genes targeted by corticosterone treatment we performed gene ontology analysis with the aid of heat maps. We found that the expression of genes implicated in osteoblast differentiation and the regulation of bone remodelling was downregulated in mice treated with corticosterone compared to placebo. We observed a downregulation of the osteoblast markers Runx2, Colα1, osteocalcin and sclerostin in corticosterone-treated mice compared to placebo. In addition BMP4 and BMP7 followed the same pattern. Genes that were most profoundly downregulated in the array analysis were validated by qRT-PCR. Consistent with mRNA levels, osteocalcin serum levels were suppressed to almost undetectable levels. <h3>Conclusions</h3> These results confirm that glucocorticoids primarily target genes involved in osteoblast differentiation and the regulation of bone remodelling. Gene expression profile analyses may point to the pathways involved in the negative effects of glucocorticoids on bone. <h3>References</h3> Henneicke et al., doi:10.1016/j.bone.2011.06.013 (2011) Chrousos et al., Ann N Y Acad Sci. 1179: 153–166 (2009) Ezzat Y, Hamdy K, Int J Rheum Dis. 2010 Aug;13(3):259-65 <h3>Disclosure of Interest</h3> None Declared
Abstract 1953: Rapid quantitation of circulating microRNAs using a novel detection technology.
Authors: Dominik Duelli, Jaime Palma, Don Weldon, Justin Doong, Grace Johnston, Fellars Stacey, Michelle Hastings
Journal: Cancer Research (2013)

Abstract The rapid implementation of quantifying microRNAs (miRNAs) in body fluids for diagnosis and prognosis could be improved by designing more rapid approaches. The current mainstream approach is quantitative reverse transcriptase PCR (qRT-PCR). Barriers for the applicability are lengthy time requirement for isolation and amplification of miRNAs, and polymerase inhibitors that copurify with miRNA, and compromise the accuracy of the approach. Here we provide an approach using a nano-particle technology that overcomes these limitations. This technology is based on the principle that a fluorophore-containing oligonucletide sequence is fluorescently silent unless displaced from a quencher by a specific substrate RNA. Once displacement occurs, the resulting fluorescence provides a measure of RNA concentration in the reaction. Our approach allows for the direct and rapid quantification of circulating miRNAs with minimal processing of blood plasma/serum and is done without the use of enzymes. Using circulating miRNAs with established roles in cancer and quality control, miR-16, miR-21 and miR-22 and miR-451, we identified optimal temperature, detergent and solvent-extraction parameters, to quantify accurately these miRNAs in plasma using a microplate fluorometer within an hour after plasma preparation. The stringency of our conditions can discriminate wild type from a single-basepair mismatch RNA, and is specific for mature miRNAs. Furthermore, this approach facilitates measurement of samples collected in heparin, an anticoagulant that severely inhibits polymerases used for qRT-PCR. This approach creates the possibility for rapid blood tests to quantify miRNA-associated events in real-time, and provides greater public access to miRNA studies by reducing the cost and time requirement of current accurate approaches of miRNA quantitation. Citation Format: Dominik Duelli, Jaime Palma, Don Weldon, Justin Doong, Grace Johnston, Fellars Stacey, Michelle Hastings. Rapid quantitation of circulating microRNAs using a novel detection technology. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1953. doi:10.1158/1538-7445.AM2013-1953
Oral Rigosertib (ON 01910.Na) Treatment Produces An Encouraging Rate Of Transfusion Independence In Lower Risk Myelodysplastic Syndromes (MDS) Patients; A Genomic Methylation Profile Is Associated With Responses
Authors: Azra Raza, Benjamin Tycko, Sangmin Lee, Naomi Galili, Abdullah Ali, Andrew Eisenberger, John G. Mears, Aref Al-Kali, Raoul Tibes, Gary Spitzer, Francois Wilhelm, Siddhartha Mukherjee
Journal: Blood (2013)
Abstract C72: A mechanistic link between whole-chromosome aneuploidy and DNA damage
Authors: Karen Crasta, Luigi Nezi, Morgan Hennessy, Lisa Cameron, Yunfeng Pan, Dipanjan Chowdhury, David Pellman
Journal: Cancer Research (2009)

Abstract Cancer is associated with aneuploidy— both structural defects in chromosomes and abnormal numbers of intact chromosomes. The contribution of chromosome breaks to tumorigenesis is well accepted because of the possibility of generating cancer-causing mutations. However, the role of alterations of intact chromosome numbers remains a subject of debate, principally because mechanisms by which whole chromosome aneuploidy would affect cancer pathogenesis are poorly understood. We now have evidence to support one mechanism by which whole chromosome aneuploidy can lead to DNA breaks, via mis-segregation of chromosomes into micronuclei, structures commonly observed in cancer cells. Micronuclei containing intact chromosomes can form after mitotic errors, when the nuclear envelope reforms around a lagging chromosome. We have developed procedures to monitor the fate of micronuclei. Strikingly, whole chromosome-containing micronuclei develop evidence of DNA breaks during the first S phase after they are formed. Blocking DNA replication blocks the formation of these breaks. Defective DNA replication may be due to defective nucleocytoplasmic transport because micronuclei display a marked defect in assembling nuclear pore complexes. These findings suggest one mechanism by which mitotic errors result in DNA damage and thus potentially promote tumorigenesis. Citation Information: Cancer Res 2009;69(23 Suppl):C72.
Time Course and Diagnostic Accuracy of Glial and Neuronal Blood Biomarkers GFAP and UCH-L1 in a Large Cohort of Trauma Patients With and Without Mild Traumatic Brain Injury
Authors: Linda Papa, Gretchen M. Brophy, Robert D. Welch, Lawrence M. Lewis, Carolina F. Braga, Ciara N. Tan, Neema J. Ameli, Marco A. Lopez, Crystal A. Haeussler, Diego I. Mendez Giordano, Salvatore Silvestri, Philip Giordano, Kurt D. Weber, Crystal Hill-Pryor, Dallas C. Hack
Journal: JAMA Neurology (2016)

Glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) have been widely studied and show promise for clinical usefulness in suspected traumatic brain injury (TBI) and concussion. Understanding their diagnostic accuracy over time will help translate them into clinical practice.To evaluate the temporal profiles of GFAP and UCH-L1 in a large cohort of trauma patients seen at the emergency department and to assess their diagnostic accuracy over time, both individually and in combination, for detecting mild to moderate TBI (MMTBI), traumatic intracranial lesions on head computed tomography (CT), and neurosurgical intervention.This prospective cohort study enrolled adult trauma patients seen at a level I trauma center from March 1, 2010, to March 5, 2014. All patients underwent rigorous screening to determine whether they had experienced an MMTBI (blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale score of 9-15). Of 3025 trauma patients assessed, 1030 met eligibility criteria for enrollment, and 446 declined participation. Initial blood samples were obtained in 584 patients enrolled within 4 hours of injury. Repeated blood sampling was conducted at 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180 hours after injury.Diagnosis of MMTBI, presence of traumatic intracranial lesions on head CT scan, and neurosurgical intervention.A total of 1831 blood samples were drawn from 584 patients (mean [SD] age, 40 [16] years; 62.0% [362 of 584] male) over 7 days. Both GFAP and UCH-L1 were detectible within 1 hour of injury. GFAP peaked at 20 hours after injury and slowly declined over 72 hours. UCH-L1 rose rapidly and peaked at 8 hours after injury and declined rapidly over 48 hours. Over the course of 1 week, GFAP demonstrated a diagnostic range of areas under the curve for detecting MMTBI of 0.73 (95% CI, 0.69-0.77) to 0.94 (95% CI, 0.78-1.00), and UCH-L1 demonstrated a diagnostic range of 0.30 (95% CI, 0.02-0.50) to 0.67 (95% CI, 0.53-0.81). For detecting intracranial lesions on CT, the diagnostic ranges of areas under the curve were 0.80 (95% CI, 0.67-0.92) to 0.97 (95% CI, 0.93-1.00)for GFAP and 0.31 (95% CI, 0-0.63) to 0.77 (95% CI, 0.68-0.85) for UCH-L1. For distinguishing patients with and without a neurosurgical intervention, the range for GFAP was 0.91 (95% CI, 0.79-1.00) to 1.00 (95% CI, 1.00-1.00), and the range for UCH-L1 was 0.50 (95% CI, 0-1.00) to 0.92 (95% CI, 0.83-1.00).GFAP performed consistently in detecting MMTBI, CT lesions, and neurosurgical intervention across 7 days. UCH-L1 performed best in the early postinjury period.