tbuckley/cabot-search huggingface dataset:
Abstract 2495: Quantitative screening of protein biomarkers of hepatocellular carcinoma by antibody array
Authors: Shuhong Luo, Ruochun Huang, Zhongsheng Wang, Yun-Ru Chen, Jinfei Lin, Ruo-Pan Huang
Journal: Cancer Research (2014)

Abstract Protein biomarkers can be key indicators for evaluating the presence or progression of a human disease or therapeutic response to treatment. We recently carried out a biomarker screening in hepatocellular carcinoma (HCC) using our antibody array platform. Using 25 pairs of HCC and adjacent control tissue samples, the expression levels of 274 proteins including growth factors, inflammation factors, angiogenesis, apoptosis factors and adhesion molecules, were examined using an antibody arrays. A panel of proteins demonstrating significant differences in expression levels between HCC and adjacent control samples was identified by significance analysis of microarrays (SAM) and Wilcoxon signed-rank test, combined with fold-change determination. Additionally, proteomic analysis algorithms were used to capture GO annotations and to construct signaling pathways and protein-protein interaction networks for these proteins. Proteins selected through these comprehensive analyses were designated as potential biomarkers and were well able to distinguish hepatocellular carcinoma tissue samples from paired, adjacent controls with cluster tools. The expression levels of several proteins were further evaluated by enzyme-linked immunosorbent assay (ELISA). Finally, we performed follow-up verification studies on selected proteins (Nidogen-1 and CEACAM-1) for detection of HCC in 164 pairs of serum samples from HCC patients and normal subjects with reverse phase protein array (RPPA). Our work reveals promising protein biomarkers for detection of HCC. Citation Format: Shuhong Luo, Ruochun Huang, Zhongsheng Wang, Yun-Ru Chen, Jinfei Lin, Ruo-Pan Huang. Quantitative screening of protein biomarkers of hepatocellular carcinoma by antibody array. [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 2495. doi:10.1158/1538-7445.AM2014-2495
Abstract 15080: Six Year Outcomes Following Endovascular Therapy with Nitinol Stenting in the Femoropopliteal Artery: Retrospective Multicenter Analysis for stenting of FemoroPopliteal lesions.
Authors: Tomoharu Dohi, Osamu Iida, Yoshimitsu Soga, Kenji Suzuki, Keisuke Hirano, Shinsuke Nanto, Masaaki Uematsu
Journal: Circulation (2011)

Background: Treatment strategy for patients presenting with femoropopliteal artery (FP) lesions remains controversial. Recently, nitinol stenting in the FP lesions has yielded improved mid-term res...
FGFR3 mutations in benign skin tumors
Authors: Arndt Hartmann, Christian Hafner, Johanna van Oers, Ellen Zwarthoff, Francisco Real, Michael Landthaler, Ferdinand Hofstaedter, Thomas Vogt
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

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Aims: Epidermal nevi (EN) of the non-epidermolytic type are common congenital skin lesions with an incidence of about 1 in 1,000 people, but their genetic basis remains elusive. Germline mutations of FGFR3 cause autosomal dominant skeletal disorders such as achondroplasia and thanatophoric dysplasia. Some of these patients also show acanthosis nigricans of the skin. In a mouse model, the expression of a mutant FGFR3 (249C) in the basal epidermis using the keratin 5 promoter caused verrucous skin tumors similar to seborrhoic keratoses (SK) and FGFR3 mutations were detected in 39% of SK in humans. Since EN and acanthosis nigricans share some clinical and histological features, we analyzed the presence of activating FGFR3 mutations in non-epidermolytic EN and in large series of SK of different histological subtypes.

Methods: We used a SNaPshot multiplex assay (van Oers et al., Clin Cancer Res 11:7743-7748, 2005) to screen for 11 previously described activating FGFR3 point mutations in thirty-three patients with 39 clinically and histologically confirmed EN of the non-epidermolytic type. In addition, 26 adenoid SK were screened. To evaluate the importance of FGFR3 mutations in individuals with large numbers of SK, 78 SK of four patients (19, 19, 21 and19 SK/patient, respectively) were also investigated for FGFR3 mutations.

Results: Activating FGFR3 mutations were identified, almost exclusively at codon 248 (R248C), in 11 of 33 (33%) patients with EN. The mutations were not present in adjacent normal skin, which was available in 4 patients. SK of the adenoid subtype showed with 81% (21/26 lesions) the highest frequency of FGFR3 mutations detected in any lesion so far. FGFR3 mutations were detected in 46 of 78 multifocal SK (59 %). However, the mutation frequency varied considerably in the patients, ranging from 26 % to 89 %. Four SK revealed a double and one a triple FGFR3 mutation. The differrent FGFR3 mutations were rather stochastically distributed among the patients, who showed at least four distinct mutated loci. Interestingly, all mutations detected in this series of human EN or SK were linked to a severe skeletal dysplasia phenotype in germline (thanatophoric dysplasia and SADDAN syndrome).

Conclusions: Our results provide evidence that a significant proportion of epidermal nevi is caused by a mosaicism of activating FGFR3 mutations in the human epidermis, resulting from a post-zygotic mutation in early embryonic development. The R248C mutation appears to be a hotspot for FGFR3 mutations in epidermal nevi.

FGFR3 mutations are also common in multiple SK with a varying mutation frequency between individuals but without specific intraindividual mutational hotspots. The mechanism leading to the high frequency of FGFR3 mutations in human SK and EN as well as details of FGFR3 signaling in mutant cells remains elusive.
Abstract 236: Regional Incidence and Outcome of Out-of-Hospital Cardiac Arrest Associated with Overdose
Authors: David D Salcido, Allison C Koller, Cesar D Torres, Aaron M Orkin, Rob H Schmicker, Laurie J Morrison, Graham Nichol, Shannon W Stephens, James J Menegazzi
Journal: Circulation (2014)

Introduction: The frequency of lethal overdose due to prescription and non-prescription drugs is increasing in North America. The contribution of drug overdose (OD) to regional variation in the incidence and outcome out-of-hospital cardiac arrest (OHCA) is unclear. Objective: To estimate overall and regional variation in incidence and outcomes of emergency medical services (EMS)-treated OD-OHCA cases across North America. Methods: The Resuscitation Outcomes Consortium (ROC) is a clinical research network with 10 regional clinical centers in United States (US) and Canada that uses uniform methods for surveillance of all EMS-treated OHCA in participating regions. Cases of OHCA from 2006 to 2010 were reviewed for evidence of association with or without OD. Incidence of OD-OHCA was calculated as the number of OD-OHCA in a region per 100,000 cumulative person-years, using 2000 US Census and 2006 Statistics Canada population counts. Patient and EMS characteristics as well as outcome were described. Multiple logistic regression was used to describe the association between OD status on return of spontaneous circulation (ROSC) and survival to hospital discharge, while adjusting for case characteristics and consortium center. Results: Included were 56,272 cases of OHCA. Regional incidence of OD-OHCA varied between 0.5 and 2.7 per 100,000 person years (p&lt;0.001), and proportion of OD-OHCA among all EMS-treated OHCA ranged from 0.9% to 3.8%. Table 1 shows outcomes and characteristics stratified by OD status; OD-OHCA were younger, less likely to be witnessed, and less likely to present with a shockable rhythm. Compared to non-OD, OD-OHCA was associated with ROSC (OR: 1.55; 95%CI: 1.35-1.78) and survival (OR: 2.14; 95%CI: 1.72-2.65). Conclusions: OD-OHCA are a small proportion of all OHCA, although incidence varied up to 5-fold across regions. OD-OHCA were more likely to survive than non-OD-OHCA.
Abstract 8520: Total beta-Adrenoceptor Knockout Slows Conduction and Reduces Inducible Arrhythmias in the Mouse Heart
Authors: Florian Stöckigt, Klara Brixius, Georg Nickenig, Lars Lickfett, Jan W Schrickel
Journal: Circulation (2011)

Introduction: Beta-Adrenocepors (ß-AR) play an important role in the neurohumoral regulation of cardiac function. Three β-AR subtypes (ß1, ß2 and ß3) have been described so far. Total deficiency of these adrenoceptors (TKO) results in cardiac hypotrophy and negative inotropy. We assessed the hypothesis that TKO leads to considerable changes in electrophysiological parameters. Methods: We performed in vivo electrophysiological studies using right heart catheterisation in 10 TKO mice at the age of 14 weeks. As controles served 10 wild type mice (WT) with identical genetic background (129SV). We analyzed standard ECG- and electrophysiological parameters and arrhythmia inducibility. Results: The surface ECG of TKO mice revealed a reduced heart rate (359.2 ± 20.9bpm vs. 461.1 ± 33.3bpm; p &lt;0.001) as well as prolonged P wave (17.5 ± 3.0ms vs. 15.1 ± 1.2ms; p=0.019) and PQ time (40.8 ± 2.4ms vs. 37.3 ± 3.0ms; p=0.013) compared to WT. Intracardiac ECG revealed a significantly prolonged infrahisian conductivity (12.9 ± 1.4ms vs. 6.8 ± 1.0ms; p &lt;0.001). Functional testing showed extended atrial and ventricular refractory periods in TKO (40.5 ± 15.5ms vs. 21.3 ± 5.8ms; p = 0.004; and 41.0 ± 9.7ms vs. 28.3 ± 6.6; p = 0.004, respectively). In TKO both the probability of induction of atrial fibrillation (12% vs. 24%; p &lt; 0.001) and the probability of induction of ventricular tachycardias (0% vs. 26%; p &lt; 0.001) were reduced. Conclusion: TKO results in significant prolongation in cardiac conduction times and refractory periods. This was accompanied by a highly significant reduction of atrial and ventricular arrhythmias. This finding confirms the importance of ß-AR in arrhythmogenesis and their role as therapeutic target.
The presence of ancient human T-cell lymphotropic virus type I provirus DNA in an Andean mummy
Authors: Hong-Chuan Li, Toshinobu Fujiyoshi, Hong Lou, Shinji Yashiki, Shunro Sonoda, Luis Cartier, Lautaro Nunez, Ivan Munoz, Satoshi Horai, Kazuo Tajima
Journal: Nature Medicine (1999)
Acute urinary retention in men
Authors: J. J Elkabir, A. Patel, J. A Vale, R. O'N Witherow, M. Emberton, K. Anson
Journal: BMJ (1999)

Editor—Emberton and Anson’s review of acute urinary retention was timely and informative.1 In part of it they focused on the use of finasteride to reduce the risk of the disease.2 We disagree with them that the continuous administration of finasteride for four years is probably warranted in men with large prostates, moderate to severe symptoms, and poor urinary flow rates.

Firstly, the cost implications are enormous. To prevent one event (acute urinary retention or prostatectomy) 15 patients would have to be treated for four years at a cost of £19 475.3 Secondly, the reduction in mean symptom scores with long term finasteride treatment is small (mean reduction 3.3 points) and not comparable with the results obtained after prostatectomy (mean reduction 19.4 points).4 Furthermore, what should happen after four years of treatment has not been established. Should finasteride treatment be stopped, with the probability of prostatic regrowth, or should patients take it for life? The answers are not known. We therefore conclude that long term finasteride is not efficient or cost effective in preventing acute urinary retention and that prostatectomy should remain first line treatment in such patients.

The review also describes patients with drained bladder volumes of more than 1 litre and low detrusor pressures who have a worse outcome (failure of catheter removal or failure of prostatectomy). Most urologists would describe this group as having chronic urinary retention, although there are no agreed criteria defining this condition. Uniform standards are urgently needed to evaluate data and therefore compare different treatments.
Percutaneous absorption and the surface area of occluded skin.
Authors: DAVID R. HARRIS, CHRISTOPHER M. PAPA, RAYMOND STANTON
Journal: British Journal of Dermatology (1974)

Scanning electron microscopy of samples of human skin occluded for 72 h, revealed that the hydrated stratum corneum not only swells, but develops multiple folds. Surface area estimations of such stratum corneum, utilizing stereo pairs of the photomicrographs, indicated a 37% increase over the normal, non‐occluded horny layer values. It is speculated that the increase in absorptive area contributes to the increased skin permeability following occlusion.
Using<i>in Vitro</i>High Throughput Screening Assays to Identify Potential Endocrine-Disrupting Chemicals
Authors: Daniel M. Rotroff, David J. Dix, Keith A. Houck, Thomas B. Knudsen, Matthew T. Martin, Keith W. McLaurin, David M. Reif, Kevin M. Crofton, Amar V. Singh, Menghang Xia, Ruili Huang, Richard S. Judson
Journal: Environmental Health Perspectives (2012)

Over the past 20 years, an increased focus on detecting environmental chemicals that pose a risk of adverse effects due to endocrine disruption has driven the creation of the U.S. Environmental Protection Agency (EPA) Endocrine Disruptor Screening Program (EDSP). Thousands of chemicals are subject to the EDSP; thus, processing these chemicals using current test batteries could require millions of dollars and decades. A need for increased throughput and efficiency motivated the development of methods using in vitro high throughput screening (HTS) assays to prioritize chemicals for EDSP Tier 1 screening (T1S).In this study we used U.S. EPA ToxCast HTS assays for estrogen, androgen, steroidogenic, and thyroid-disrupting mechanisms to classify compounds and compare ToxCast results to in vitro and in vivo data from EDSP T1S assays.We implemented an iterative model that optimized the ability of endocrine-related HTS assays to predict components of EDSP T1S and related results. Balanced accuracy was used as a measure of model performance.ToxCast estrogen receptor and androgen receptor assays predicted the results of relevant EDSP T1S assays with balanced accuracies of 0.91 (p < 0.001) and 0.92 (p < 0.001), respectively. Uterotrophic and Hershberger assay results were predicted with balanced accuracies of 0.89 (p < 0.001) and 1 (p < 0.001), respectively. Models for steroidogenic and thyroid-related effects could not be developed with the currently published ToxCast data.Overall, results suggest that current ToxCast assays can accurately identify chemicals with potential to interact with the estrogenic and androgenic pathways, and could help prioritize chemicals for EDSP T1S assays.
A Living Systematic Review of Nebulized Hypertonic Saline for Acute Bronchiolitis in Infants
Authors: Robert G. Badgett, Mohinder Vindhyal, Jason T. Stirnaman, C. Michael Gibson, Rim Halaby
Journal: JAMA Pediatrics (2015)

Results | The LTL (expressed in the telomere repeat copy number to the single gene copy number ratio) remained unchanged during and after the OC intake.In contrast, the LTL doubled while taking PioFluMet and returned to baseline after the PioFluMet intake was stopped (Figure).The LTL changes across treatment groups during 18 months related inversely to fasting insulinemia, body fat fraction by dual energy x-ray absorptiometry, and visceral and hepatic adiposity by magnetic resonance imaging (all r values were between -0.53 and -0.57; all P values were between 0.002 and 0.007).The ratio of circulating neutrophils to lymphocytes was first similar in treatment groups and remained similar in and between groups across 24 months.Noteworthy adverse effects were not encountered in either treatment group. 4scussion | Prolonged insulin sensitization (with PioFluMet) is emerging as a first approach with antiaging effects and includes a slow marked reversible increment of LTL in adolescent girls with HIAE.A comparably marked LTL increment was reported on initiating the treatment with sitagliptin in older Chinese adults with type 2 diabetes mellitus. 5In that study, telomere lengths were in the subnormal range at the start of treatment and increased to a healthy range within 2 months in parallel with improved glucose level control.In our young study population, telomere lengths were in the healthy range at the start of treatment and increased to the supranormal range after a longer intervention (12 to 18 months) in the absence of diabetes mellitus.Future studies should disclose whether other insulinsensitizing interventions (such as flutamide being replaced by spironolactone) can also elicit telomere lengthening in late adolescence and whether telomerase activity is up-regulated, either indirectly by a less adipose and more insulin-sensitive state or directly by components, such as pioglitazone, that can up-regulate the transcription of telomerase reverse transcriptase. 6Nevertheless, we may be closer to understanding why some insulin-sensitive women stay forever young.
Abstract 13891: Enhanced Sodium-Calcium Exchanger Current, Prolonged Action Potential Duration, and Early/Delayed-Afterdepolarization in Sorcin Knockout Heart
Authors: Xi Chen, Carmen R Valdivia, Craig Weber, Gerardo García-Rivas, Patricia A Powers, Hector H Valdivia
Journal: Circulation (2014)

Sorcin, a penta-EF-hand protein, plays a hypothetical role as a [Ca2+]i “sweeper” in cardiac excitation-contraction coupling based on the observations that sorcin a) decreases the open probability of RyRs, b) stimulates Na+-Ca2+exchanger (NCX) and SERCA2a, and c) accelerates L-type Ca2+ channel (LTCC) inactivation. However sorcin’s role on cardiac performance in health and disease are unknown. Thus, we have generated sorcin knockout (sorcin KO) mice. We show that sorcin KO mice a) have increased spontaneous Ca2+ release events (SCaEs) in cardiomyocytes; b) present ~2 fold expression of NCX and LTCC in heart; and c) are more susceptible to arrhythmia and death under stress. We investigated how SCaEs and increased NCX and LTCC expression in sorcin KO heart led to ventricular arrhythmias. Recording of NCX current showed that with 300nM isoproterenol (Iso), sorcin KO cardiomyocytes had significantly enhanced inward NCX current when clamped at -80 to -120mV (p
Fundamentals of Human Physiology for Students in the Medical Sciences.
Authors: William Barton Youmans
Journal: Annals of Internal Medicine (1958)

A commendable effort is made in this book to present the essential facts of human physiology for medical students within 540 pages. The effort has been, on the whole, successful, partly because of a good selection of illustrations and partly because of the exclusion of the usual quota of historical and theoretical material. It is also assumed that medical students will find the necessary collateral anatomic and biochemical information in other courses and that applied or clinical aspects of physiology are adequately dealt with elsewhere. The three parts of the book, following an introductory chapter on general principles, are devoted to nerve, muscle, junctional transmission, reflex action, central nervous system, and senses; circulation and respiration; and nutrition, digestion, metabolism, endocrinology, and excretion. A few disconcerting errors may be noted, but this book can be recommended to students and teachers of physiology in medical schools.
Abstract 11711: Valproic Acid, a Class [[Unable to Display Character: &amp;#1030;]] Histone Deacetylase Inhibitor, Suppresses the Development of Severe Pulmonary Hypertension in Rats
Authors: Beidi Lan, Emiko Hayama, Toshio Nakanishi
Journal: Circulation (2014)

Introduction: Pulmonary hypertension (PH) is a progressive vascular remodeling disease characterized by exuberant cell proliferation, apoptosis resistance, and inflammation that contributes to increased pulmonary arterial resistance. Histone deacetylases (HDACs) and histone acetyltransferases shift acetyl groups from histone and non-histone proteins and enhance gene transcription by post-translational modifications. Valproic acid, a class I HDAC inhibitor, is a widely used antiepileptic drug with low toxicity and also shows supportive efficacy in cancer treatment by inhibiting cancer cell proliferation and inflammation. Hypothesis: We assessed the hypothesis that HDAC inhibition may attenuate excessive cell proliferation and inflammation and improve vascular remodeling in a severe PH rat model. Methods: To compare the development of vascular remodeling, we assessed 6 rats that underwent a single monocrotaline injection, chronic hypoxic exposure, or a combination of both treatments. Valproic acid or vehicle was administered in rats with severe PH induced by the combination method to assess whether valproic acid has the ability to prevent severe PH development in the first 3 weeks or to reverse disease progression at 3-5 weeks. Results: The combination method induced PH of greater severity than that induced by any single stimulation in rats after 3 weeks. Compared with the vehicle-treated rats, valproic acid treatment blocked the elevation of right ventricular systolic pressure and right ventricle hypertrophy index (from 57 ± 3 to 49 ± 3 mmHg and from 46 ± 4 to 37 ± 3 %) in both the first 3 weeks and in the late treatment group (from 75 ± 2 to 61 ± 5mmHg and from 61 ± 7 to 48 ± 3 %, respectively; P &lt; 0.01). Valproic acid attenuated the muscularization ratio of peripheral pulmonary vascular, repressed proliferation and inflammation marker expression (PCNA and ED1), and enhanced apoptosis (cleaved caspase 3) in severe PH rats. Conclusions: These data indicate that a selective HDAC inhibitor may be effective in the treatment of PH.