tbuckley/cabot-search huggingface dataset:
Abstract 13006: Electrophysiologic Characteristics of the Focal Discharges Critical for the Initiation of Atrial Fibrillation and its Relation to the Complex Fractionated Electrogram Region: Three-dimensional Analysis Using Non-contact Mapping
Authors: Hiroshige Yamabe, Kenji Morihisa, Koji Enomoto, Hisanori Kanazawa, Hisao Ogawa
Journal: Circulation (2010)

Background:  It has not been well clarified how the atrial fibrillation (AF) was initiated by the focal discharge. Also, it is not clear what characteristics of focal discharge are prerequisite for the initiation of AF.   Objectives:  The purpose of this study was to define the electrophysiologic characteristics of focal discharges which initiate the random wave propagation at AF onset and clarify the mechanism of AF initiation, especially in relation to the complex fractionated atrial electrograms (CFAE) region.   Methods:  Nineteen patients with paroxysmal AF (17 men, mean age 57 years) in whom the spontaneous AF onset was observed during non-contact mapping (EnSite 3000) of the left atrium were included. To define the electrophysiologic characteristics of focal discharge critical for the initiation of random wave propagation, we analyzed the left atrial activation following focal discharges at AF onset. The coupling interval, left atrial activation time and atrial activation sequence were compared between focal discharges which initiated random wave propagation (AF-D) and those did not (non-AF-D).   Results:  There were 32 spontaneous AF onset episodes. All of these AF were initiated by the focal repetitive discharges (8.6±8.6 beats), derived from pulmonary vein (PV) (n=17) and from non-PV CFAE region (n=15). The mean coupling interval of AF-D was significantly shorter than that of non-AF-D (179.3±33.2 vs. 216.6±44.8 msec, p=0.0005). The left atrial activation time of AF-D was significantly longer than that of non-AF-D (151.3±35.1 vs. 82.6±16.5 msec, p   Conclusions:  A critically short coupling interval of focal discharge and subsequent prolonged left atrial activation time, associated with localized conduction block in the CFAE region, were the crucial factors for the initiation of random wave propagation at the onset of AF.
Central apnea following rapid onset and progression of hypoxemia. A pilot animal study
Authors: Elizaveta Baranova, Zhanna Donina, Nina Aleksandrova
Journal: European Respiratory Journal (2014)

Objectives: Acute effects of progressive hypoxia include central apnea attributed to respiratory and cardiovascular collapse, but the relative contributions of the central and peripheral effects in producing collapse of cardiorespiratory system is unclear.

Aims: The purpose of this study is to examine the influence of acute progressive hypoxia on respiratory effort and cardiovascular variability during prompt gradual decrease oxygen content from normoxia up to gasping and apnea.

Methods: We studied the dynamic response of tidal volume (VT), breathing rate (BR), minute lung ventilation (MLV), esophageal pressure (Pes), inspiratory occlusion pressure (P0.1), arterial oxygen saturation (SpO2), heart rate (HR), mean arterial blood pressure (MAP) in anesthetized Wistar rats. The inspired oxygen concentration (FIO2 ) decreased to 3% within 10 min.

Results: The rapid reduction FIO2 up to 6% O2 cause hyperventilation with concomitant hypocapnia. Further reduction FIO2 (up to 3-4% O2)producesharp decrease MAP to 50±12%(P<0.05), HR to 27 ± 6% (P<0.05), gasping respiration and apnea. However Pes and P0.1prior to the point of apnea was higher than the initial values by 47 ± 8 % and 52±6% (P <0.05 respectively).

Conclusions: We conclude that the decline respiratory effort did not have time to develop during the rapid onset and progression of hypoxemia in our model. Apnea results from direct inhibitory effect of hypoxia and concomitant hypocapnia on the respiratory and vasomotor centers.
Abstract 3505: Regulation of Cyclin A1 promoter by the Wilms tumor gene, WT1
Authors: Sony Pandey, Mustafa Moazam, Steven J. Kuerbitz, Gail C. Fraizer
Journal: Cancer Research (2014)

Abstract Cyclin A1(CCNA1) is a unique type of Cyclin A expressed predominantly in highly proliferative tissues such as the testis and bone marrow. In hematopoietic cells CCNA1 expression has been observed in CD34+ progenitor cells, leukemia stem cells and leukemia cell lines. Similarly, Wilms tumor 1 (WT1) gene expression has been observed in these highly proliferative, undifferentiated cells. Regulation of CCNA1 expression is poorly understood, but the CCNA1 gene promoter is a highly GC-rich TATA-less sequence, containing three potential WT1 binding sites. Chromatin immunoprecipitation analysis of two of the three sites revealed binding of the WT1 protein to chromatin in K562 leukemia cells. To assess the role of WT1 in CCNA1 regulation, activation of the CCNA1 promoter by WT1 was measured using luciferase reporter constructs in K562 cells. The distal construct (-1180/+145 ) contains two potential WT1 sites, and the activity of this reporter construct was up-regulated by WT1 co-transfection. In contrast, the proximal (-454/+145) promoter region contains no canonical WT1 binding sites. Suprisingly, the proximal promoter was also up-regulated by WT1 co-transfection. Transcription factor binding site analysis revealed 6 GC boxes -within the core promoter region of the proximal promoter construct that we predicted could serve as non-canonical WT1 binding sites. To determine the importance of these GC boxes for WT1 binding, we treated K562 cells with Mithramycin A, which blocks binding at GC rich sequences. We found that Mithramycin A treatment decreased the activity of both the distal and proximal promoter constructs. Finally we demonstrated that WT1 mediated activation of CCNA1 promoter required an intact DNA binding domain, as a mutant WT1 expression construct lacking the zinc finger domain failed to activate any of the CCNA1 promoter constructs. Overall these results show that WT1 binding can up-regulate the CCNA1 promoter. This observation supports our previous finding that overexpressing WT1 in K562 cells increased CCNA1 mRNA. These data suggest that elevated WT1 expression could mediate increased CCNA1 expression in leukemia cells and thereby enhance proliferation. Overall, our results are consistent with the hypothesis that both WT1 and CCNA1 behave as oncogenes in leukemia. Citation Format: Sony Pandey, Mustafa Moazam, Steven J. Kuerbitz, Gail C. Fraizer. Regulation of Cyclin A1 promoter by the Wilms tumor gene, WT1. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3505. doi:10.1158/1538-7445.AM2014-3505
Cutaneous amalgam tattoo in a dental professional: an unreported occupational argyria
Authors: A. Rumayor Piña, M. Martínez Martínez, V.H. Toral Rizo, M. Ajudarte Lopes, O. Paes de Almeida
Journal: British Journal of Dermatology (2012)

Funding sources: This work was supported by the Brazilian Federal Agency of Support and Evaluation of Postgraduate Education (CAPES). Conflicts of interest: none declared. Madam, Amalgam tattoo is the most common exogenous pigmentation of the oral mucosa1, 2; surprisingly, there are no reports of similar lesions on the skin. It is caused by traumatic implantation of amalgam fragments into the oral mucosa following dental treatment, particularly when amalgam fillings are removed with high‐speed instruments. Amalgam tattoo occurs mostly in the gingiva and alveolar mucosa. Clinically it presents as an asymptomatic bluish to black macule, eventually observed by the patient or discovered during routine dental treatment. Histologically it shows brown to black aggregates of granules interspersed among collagen fibres and around blood vessels. Most cases show a slight inflammatory response, and eventually a foreign body granulomatous reaction is found.1–4 Cases of cutaneous localized argyria are uncommon, and are usually attributed to trauma, acupuncture, topical silver‐based medication or use of pieces of jewellery such as earrings.5–7 We report a case of cutaneous amalgam tattoo caused by implantation of amalgam particles on the skin of the eyebrow of a dental surgeon.
MENINGOCOCCIC MENINGITIS: REPORT ON 165 CASES
Authors: Andrew H. Meyer
Journal: Annals of Internal Medicine (1945)

Article1 April 1945MENINGOCOCCIC MENINGITIS: REPORT ON 165 CASESANDREW H. MEYERANDREW H. MEYERSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-22-4-543 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptDuring the period from July 1942 through May 1944, 165 cases of meningococcic meningitis were seen at the Highland-Alameda County Hospital. As this is a relatively large series, it was decided to report the group, especially since the mortality in the proved cases was 4 per cent.Of these 165 cases, the spinal fluid showed meningococci on direct smear in 120 instances and positive cultures in an additional 30 instances, making a total of 150 cases in which the etiology was proved. The additional 15 cases were included because purulent spinal fluid was demonstrated, and they occurred during epidemic periods... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Oakland, California*Received for publication July 19, 1944. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1945Volume 22, Issue 4Page: 543-545KeywordsEtiologyMeningitisMortality ePublished: 1 December 2008 Issue Published: 1 April 1945 PDF downloadLoading ...
A point mutation in PTPRC is associated with the development of multiple sclerosis
Authors: Marc Jacobsen, Dorothee Schweer, Andreas Ziegler, Rami Gaber, Sabine Schock, Reinhard Schwinzer, Kurt Wonigeit, Ralf-Björn Lindert, Orhun Kantarci, Janet Schaefer-Klein, Hayo I. Schipper, Wolfgang H. Oertel, Fedor Heidenreich, Brian G. Weinshenker, Norbert Sommer, Bernhard Hemmer
Journal: Nature Genetics (2000)
Idiopathic sustained left ventricular tachycardia: clinical and electrophysiologic characteristics.
Authors: T Ohe, K Shimomura, N Aihara, S Kamakura, M Matsuhisa, I Sato, H Nakagawa, A Shimizu
Journal: Circulation (1988)

Electrophysiologic studies were performed in 16 patients 11 to 45 years old (mean 33 years) with idiopathic sustained (lasting more than 5 min) ventricular tachycardia (VT) originating from the left ventricle. Endocardial mapping during VT showed that the earliest site of activation was at the apical inferior portion of the left ventricle in 14 patients whose QRS morphology during VT showed a right bundle branch block pattern and left-axis deviation, but at the apical anterosuperior portion of the left ventricle in two patients whose QRS morphology during VT showed a right bundle branch block and right-axis deviation. Single programmed ventricular stimulation induced VT in 13 patients, and rapid ventricular pacing induced VT in the remaining three patients. Rapid ventricular pacing terminated VT in all patients. The relationship between the coupling interval and the echo interval was inverse in all eight patients with a wide VT inducible zone. Entrainment was recognized in three of six patients. The initiation of VT by constant pacing depended on the number of pacing beats but not the duration of pacing in all four patients tested. Intravenous verapamil terminated the VT in 13 of 14 patients. Long-term oral verapamil was also effective in all five patients who required long-term oral therapy for their symptoms associated with VT. In conclusion (1) idiopathic left ventricular tachycardia has unique electrocardiographic, electrophysiologic, and electropharmacological properties, (2) the electrophysiologic characteristics suggest that the mechanism is reentry, and (3) verapamil is effective in both the short- and long-term treatment of VT.
Bet v 1 and its homologous food allergen Api g 1 stimulate dendritic cells from birch pollen‐allergic individuals to induce different Th‐cell polarization
Authors: U. Smole, S. Wagner, N. Balazs, C. Radauer, M. Bublin, G. Allmaier, K. Hoffmann‐Sommergruber, H. Breiteneder
Journal: Allergy (2010)

Bet v 1 is the most relevant sensitizing protein for birch pollen (BP)-allergic individuals. Its homologues from plant foods are mainly involved in allergic reactions caused by IgE cross reactivity. We aimed to evaluate the polarizing effect of dendritic cells (DCs) pulsed with Bet v 1, Mal d 1, Api g 1 or Dau c 1 on Th-cell responses.Immature DCs were generated from peripheral blood monocytes of BP-allergic and healthy donors by culture with GM-CSF and IL-4 and subsequently pulsed with allergens in combination with maturation factors. Cell surface markers were analysed by FACS. Mature DCs were co-cultured with autologous Th cells and T-cell proliferation and cytokine profiles were determined.In co-culture, mature allergen-pulsed DCs induced autologous Th cells of BP-allergic donors to proliferate significantly more than those of healthy individuals. Exposure of DCs from BP-allergic donors to Bet v 1 resulted in a robust Th2 skewing with significantly higher quantities of IL-5 and elevated IL-13 compared to maturation factors. In contrast, Api g 1-primed DCs from BP allergics significantly enhanced the production of the Th1 cytokine IFN-γ and significantly down-regulated IL-13 compared to maturation factors. In healthy donors, no significant cytokine production could be detected.Bet v 1 in contrast to homologous food allergens seems to possess distinct molecular features that enable it to condition DCs from BP-allergic donors to induce allergen-specific T-cell proliferation and Th2 polarization.
Tam Olarak Rezeke Edilen Evre IA Küçük Hücreli Dışı Akciğer Kanseri Hastalarında Uzun Süreli Sonuçlar ve Geç Rekürrens
Authors: Ryo Maeda, Junji Yoshida, Genichiro Ishii, Keiju Aokage, Tomoyuki Hishida, Mitsuyo Nishimura, Yutaka Nishiwaki, Kanji Nagai
Journal: Journal of Thoracic Oncology (2010)
Control of commensal microbiota by the adaptive immune system
Authors: Husen Zhang, Xin M Luo
Journal: Gut Microbes (2015)

The symbiotic relationship between the mammalian host and gut microbes has fascinated many researchers in recent years. Use of germ-free animals has contributed to our understanding of how commensal microbes affect the host. Immunodeficiency animals lacking specific components of the mammalian immune system, on the other hand, enable studying of the reciprocal function-how the host controls which microbes to allow for symbiosis. Here we review the recent advances and discuss our perspectives of how to better understand the latter, with an emphasis on the effects of adaptive immunity on the composition and diversity of gut commensal bacteria.
Abstract 12188: Intensive Glycemic Control in Patients With Acute Coronary Syndrome: Evidence From a Meta-Analysis
Authors: Partha Sardar, Ramez Nairooz, Saurav Chatterjee, Jacob A Udell, Dharam J Kumbhani, Mikhail N Kosiborod, John Ryan, Debabrata Mukherjee, Darren K McGuire
Journal: Circulation (2014)

Introduction: Hyperglycemia is associated with unfavorable prognosis in patients with acute coronary syndrome (ACS). Studies with intensive glycemic control in ACS patients have provided inconsistent results. A meta-analysis was performed to evaluate the effectiveness and safety of intensive glycemic control in patients with ACS. Methods: Search of PubMed, Cochrane CENTRAL, EMBASE, EBSCO, Web of Science and CINAHL databases from their inception through April 2014, identifying randomized controlled trials (RCTs) comparing the effects of intensive versus standard glucose management in patients with ACS. We calculated summary random-effect odds ratios (OR) and 95% confidence intervals (CI). Results: Results from 10 RCTs comprising 2,621 patients were analyzed. All-cause mortality between intensive versus standard glucose management groups did not differ significantly (OR 1.00, 95% CI 0.75-1.34). Similarly, no significant differences were observed between the comparator groups for the odds of cardiac mortality (OR 0.87, 95% CI, 0.67 to 1.12), recurrent myocardial infarction (OR 1.07, 95% CI, 0.76 to 1.52), or stroke (OR 1.20, 95% CI, 0.60 to 2.40). The risk of hypoglycemia (OR 5.95, 95% CI, 2.73 to 12.97; p&lt;0.001) was significantly higher with intensive compared with standard glucose management. Conclusions: Intensive glucose control compared with standard care in ACS patients did not reduce mortality or morbidity, but significantly increased the risk of hypoglycemia. These data from prior clinical trials should be interpreted in the context of their significant methodological limitations.
Veterans' Pain a Vital SignAIDS Vaccine TrialFruit Fly GenomeCervical CancerVeterans' Pain a Vital SignAIDS Vaccine TrialFruit Fly GenomeCervical Cancer
Authors: Joan Stephenson
Journal: JAMA (1999)

The US Department of Veterans Affairs (VA) is instructing physicians and nurses who treat veterans to regard pain as a "fifth vital sign" to be routinely assessed along with blood pressure, pulse, temperature, and respiration.
Abstract 2719: Use of abiraterone against a luminal androgen receptor breast cancer cell line
Authors: Krishna A. Rao, Vishnu Modur, Sumana Ghosh
Journal: Cancer Research (2014)

Abstract Background: Data from this pre-clinical model suggests that the LAR TNBC subtype is unique and may respond to novel hormonal agents such as bicalutamide or abiraterone. The LAR subtype represents 11 % of all TNBC (which represent 20% of all breast cancers). Thus, positive studies of abiraterone could potentially extend the application of abiraterone to an additional 2% of all breast cancer patients, who could be treated in the metastatic, neoadjuvant, and adjuvant setting (for five years) with hormonal maintenance therapy. We, therefore, conducted studies of abiraterone on LAR TNBC cell line, MDA-MB-453. . Methods: i). Cell proliferation- Cell proliferation will be done by plating 500,000 cells in triplicate Petri dishes and measuring cell number over a six day period between parent cells and cellstreated with the following varying concentrations of abiraterone: 100 ng/ml, 250 ng/ml, and 400 ng/ml. ii).Cell cycle effects- Cells were incubated for 24 hours with abiraterone and then lifted from the plate with trypsin/EDTA (0.5%/0.1%) and fixed overnight in 80% ethanol. This was followed by staining in PBS with 10 ug/ml of propidium iodide for twenty minutes at room temperature. Flow cytometry was performed in our facility, and data was obtained on the percentage of the cell population in various points of the cell cycle. iii). Apoptosis and necrosis assay (Annexin-V-PI assay)- Cells were harvested at 72 hours post-seeding and incubation with abiraterone and washed with ice-cold PBS, followed by staining with 1ug/ml of PI and 5ul of Alexa Fluor® 488 annexin V in 100ul of annexin binding buffer (10 mM Hepes/NaOH, pH 7.4, 140 mM NaCl, 2.5 mM CaCl2). After the incubation at room temperature for 15 minutes, 400ul of ice-cold annexin binding buffer was added and stained cells were analyzed by Becton-Dickinson FACSCalibur Flow Cytometer. Results: Abiraterone caused a significant impact on cell proliferation and promoted apoptosis in the MDA-MB-453 population. Cell cycle effects were also noted with abiraterone treatment. Conclusion: Abiraterone has activity against MDA-MB-453, a breast cancer cell line known to express luminal androgen receptor. The results suggest that further studies may be warranted with this agent against this unique subtype of breast cancer. Citation Format: Krishna A. Rao, Vishnu Modur, Sumana Ghosh. Use of abiraterone against a luminal androgen receptor breast cancer cell line. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2719. doi:10.1158/1538-7445.AM2014-2719
Abstract 17913: Inhibition of CETP by Dalcetrapib Results in a Modest Increase in Cholesterol Efflux Capacity Associated With an Increase in Large HDL Particles, but Does Not Impact Carotid Intima-Media Thickness in a dal-PLAQUE-2 Substudy
Authors: David Rhainds, Marie Boule, Sonia Alem, Mathieu R Brodeur, Daniel Charpentier, Olivier Gingras, Malorie Chabot-Blanchet, Marie-Claude Guertin, Guillaume Lettre, Eric Rhéaume, Jean-Claude Tardif
Journal: Circulation (2014)

Inhibition of cholesteryl ester transfer protein (CETP) is an approach aiming at raising HDL-cholesterol levels and reducing cardiovascular risk. The dal-PLAQUE-2 phase III study recruited 988 subjects with stable coronary artery disease. Its primary objective was to evaluate the effect of dalcetrapib on the progression of carotid atherosclerotic disease measured by intima-media thickness after one year of therapy. As dalcetrapib showed a neutral effect on cardiovascular risk in the dal-OUTCOMES study, our objective was to evaluate its effect on cIMT and markers of HDL mass, lipoprotein subclass distribution and HDL function. All subjects from dal-PLAQUE-2 who had provided serum samples at baseline and one year were included in our substudy of 193 subjects on placebo and 186 subjects on dalcetrapib. Comparisons between groups at one year were made by ANCOVA after adjustment for baseline levels. No significant differences between groups for all variables considered were observed at baseline. Dalcetrapib reduced CETP activity as measured by a fluorescent method by 30% after 1 year (p&lt;0.001), which resulted in increases in HDL-cholesterol and apoA-I levels by 32% and 11%, respectively (both p&lt;0.001). Dalcetrapib markedly increased the concentration of large HDL particles measured by NMR profiling (+59%, p&lt;0.001), at the expense of small HDL particles (-9.5%, p&lt;0.001). Cholesterol efflux capacity of serum was measured from J774 macrophages under basal conditions and after cAMP stimulation. Dalcetrapib increased basal and stimulated efflux by 7.1% and 5.5% (both p&lt;0.001), but was without effect on the ABCA1-dependent component (p=0.26). Despite these effects, dalcetrapib had no impact on mean and maximal cIMT (p=0.98 and p=0.85). While the change in cIMT was inversely correlated with basal cholesterol efflux in the placebo group (Spearman r=-0.163, p&lt;0.05), such a relationship was not found in the dalcetrapib group. Moreover, the change in total HDL particles concentration was inversely correlated with change in cIMT (r=0.181, p&lt;0.05) in the placebo arm only. In conclusion, dalcetrapib raised HDL-C and larger HDL, but this had minimal effects on cholesterol efflux capacity of patients’ serum and had a neutral effect on carotid artery plaque burden.
FDA Seeks Genome-Based Drug Data
Authors: Tracy Hampton
Journal: JAMA (2004)

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