tbuckley/cabot-search huggingface dataset:
Jagged-1 and DLL-4 stimulate the migration of T-cells via the NOTCH pathway
Authors: Thomas Zöggeler, Kathrin Watzinger, Christian Kähler
Journal: European Respiratory Journal (2013)

The Notch pathway is a signaling system, which regulates cell fates. It includes 4 different Notch receptors and 5 ligands, which are transmembrane proteins.T cells belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity.  We want to uncover, which role the notch signaling pathway plays in the pathogenesis of immunological processes.  T-cells were isolated from EDTA-anticoagulated venous blood, taken from healthy donors and with their informed consent. The isolation was carried out according to MACS isolation protocol (Miltenyi Biotec Bergisch Gladbach, Germany). For the chemotaxis experiments, a 48-well microchemotaxis chamber was used. The isolated T-cells migrated through a 5µm pore sized cellulose nitrate filter. Incubation time was 90 min, in a humified atmosphere. As chemokines were used fMLP,and gradients of DLL4, and Jag1. Migration depth of the cells in the filter was quantified microscopically by measuring the distance [µm] from the surface of the filters to the leading front of the cells. Findings are expressed as Chemotacitc Index (CI), which is the ratio between the distance cells migrated towards chemoattractants and that towards medium.  DLL4 and Jag1 significantly stimulated migration of the isolated T cells in a dose-dependent manner, revealing a maximal effect at [100ng] of both Notch ligands. The effect was comparable with maximal stimulation of migration elicited by the chemoattractant fMLP (10 -8  M).  Jag1 and DLL4 directly stimulate migration of T-cells. Thus, it can be suggested that Jag1 and DLL4 are involved in innate and adaptive immunological responses.
Identification of the Molecular Genetic Defect of Patients With Methemoglobin M Kankakee (M-Iwate), 87 (F8) His → Tyr: Evidence for an Electrostatic Model of M Hemoglobin Assembly
Authors: A. Ameri, V.F. Fairbanks, G.A. Yanik, F. Mahdi, S.N. Thibodeau, D.J. McCormick, L.A. Boxer, K.T. McDonagh
Journal: Blood (1999)
Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis
Authors: Romain Capoulade, Kwan L. Chan, Calvin Yeang, Patrick Mathieu, Yohan Bossé, Jean G. Dumesnil, James W. Tam, Koon K. Teo, Ablajan Mahmut, Xiaohong Yang, Joseph L. Witztum, Benoit J. Arsenault, Jean-Pierre Després, Philippe Pibarot, Sotirios Tsimikas
Journal: Journal of the American College of Cardiology (2015)
Standards in advertising
Authors: D. Millson, W. Clark, L. Dewulf, M Batterbury
Journal: BMJ (1999)

Deprivation and emergency admissions for cancersOther possible explanations for findings need to be explored Editor-The reasons for Pollock and Vickers's findings about the relation between deprivation and emergency admissions for cancers remain speculative. 1To impute the differences in care to failures of primary care seems unfair at this stage.The authors discuss a range of possible explanations, but many other could also be relevant.Day case treatment may require a certain level of facilities at home that are less commonly available in deprived areas.The presence of another adult at home may also be a prerequisite.Single people may be more likely to live in deprived areas; patients from deprived areas may be more likely to have a working partner who cannot afford to take time off work or who has a job where such absences would be unacceptable.Patients with lung cancer due to smoking (more common in areas where smoking is more prevalent) may be less likely to have an operable malignancy because of concomitant disease related to smoking.The authors mention this in their discussion, but limiting the study to inpatient finished consultant episodes with a primary diagnosis of any of the three cancers of interest does not give any information about comorbidity.I hope further research will be carried out to help elucidate the reasons behind the apparently inequitable access and treatment decisions that Pollock and Vickers have found.Both qualitative and quantitative research methods could be used to study patients' and professionals' experiences as patients pass through the system.Perhaps allocation of blame should wait until such results are available.
Abstract 315: Directly Targeting Myocardial Fibrosis with FT-011 Improves Cardiac Remodeling in Experimental Diabetic Cardiomyopathy
Authors: Henry Krum, Michael Zhang, Kim Connelly, Richard E Gilbert, Darren J Kelly
Journal: Circulation (2008)

The pathological accumulation of extracellular matrix (fibrosis) is a key contributor to cardiac dysfunction in diabetes and represents a major potential therapeutic target. The aim of this study w...
Public Health Surveillance using Emergency Medical Service logs - U.S.-Mexico land border, El Paso, Texas, 2009.
Authors: D. Fishbein, M. Sandoval, C. Wright, S. Herrera, S. Reese, T. Wilson, M. Escobedo, S. Waterman, S. Modi, J. Keir, H. Lipman, D. Sugerman
Journal: MMWR Morbidity and Mortality Weekly Report (2010)
Abstract 1733: EGF816, a novel covalent inhibitor of mutant-selective epidermal growth factor receptor, overcomes T790M-mediated resistance in NSCLC
Authors: Shailaja Kasibhatla, Jie Li, Celin Tompkins, Mei-Ting Vaillancourt, Jennifer Anderson, AnneMarie Culazzo Pferdekamper, Chun Li, Oliver Long, Mathew McNeill, Robert Epple, Debbie Liao, Eric Murphy, Steve Bender, Yong Jia, Gerald Lelais
Journal: Cancer Research (2014)

Abstract Non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations initially respond to EGFR tyrosine kinase inhibitors (TKI) but ultimately develop resistance to these therapies. The most common mechanism of resistance is a second site gate-keeper mutation within exon 20 of EGFR (T790M), followed by MET and other receptor tyrosine kinase amplification/activation. We developed a covalent mutant-selective EGFR inhibitor, EGF816 that potently inhibits both activating EGFR mutations as well as the T790M resistance mutation while sparing wild-type EGFR. EGF816 demonstrated strong tumor regressions in several EGFR activating and resistant tumor models in vivo. These include H1975 (L858R; T790M), HCC827 (exon 19 del) and H3255 (L858R) that are representative of the relevant clinical settings. In all of the models EGF816 inhibited tumor growth in a dose dependent manner and achieved regressions of established tumors at well tolerated doses. In single dose studies, EGF816 showed sustained inhibition of pEGFR, consistent with the irreversible binding mechanism of EGF816. EGF816 also performs exceptionally well in long term dosing studies providing durable responses in the preclinical models. Together, this data indicates that EGF816 exhibits excellent anti-tumor activity in the relevant patient derived tumor cell lines at well tolerated doses and is expected to provide long term duration of responses compared to current EGFR TKI therapy in the clinic. Citation Format: Shailaja Kasibhatla, Jie Li, Celin Tompkins, Mei-Ting Vaillancourt, Jennifer Anderson, AnneMarie Culazzo Pferdekamper, Chun Li, Oliver Long, Mathew McNeill, Robert Epple, Debbie Liao, Eric Murphy, Steve Bender, Yong Jia, Gerald Lelais. EGF816, a novel covalent inhibitor of mutant-selective epidermal growth factor receptor, overcomes T790M-mediated resistance in NSCLC. [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 1733. doi:10.1158/1538-7445.AM2014-1733
Abstract 9803: Relation of Vascular Growth Factors with CT-Derived Measures of Body Fat Distribution: The Framingham Heart Study
Authors: Bernhard M Kaess, Alison Pedley, Joseph M Massaro, Martin G Larson, Erin Corsini, Udo Hoffmann, Holly M Smith, Douglas B Sawyer, Ramachandran S Vasan, Caroline S Fox
Journal: Circulation (2011)

Background: Obesity is associated with cardiometabolic risk. However, the localization of excess body fat impacts on the accompanying morbidity. Given that angiogenesis is a key feature of adipogenesis, and that angiogenic factors correlate with cardiovascular risk, variation in the association of levels of circulating vascular growth factors (and their soluble receptors) with distinct body fat compartments may explain differences in the pathogenicity of regional fat depots. Methods and Results: We assessed relationships of four body fat compartments (visceral adipose tissue - VAT, subcutaneous adipose tissue - SAT, thoracic periaortic fat, pericardial fat) derived from computed tomography with serum levels of vascular endothelial growth factor (VEGF), the soluble VEGF receptor (sFlt-1), hepatocyte growth factor (HGF), angiopoietin-2 and its soluble receptor (sTie-2) using multivariable linear regression models in 1806 Framingham Third Generation participants (mean age 44.9 years, 44.5% women). VAT, SAT and periaortic fat were positively associated with VEGF (p=0.004, p&lt;0.0001 and p=0.03, respectively). HGF was positively associated with all assessed fat depots (all p&lt;0.0001). VAT and periaortic fat were weakly associated with sTie-2 (p=0.01 and p=0.03). For HGF, we observed effect modification by sex: associations of VAT, pericardial and periaortic fat with HGF were stronger in women than in men; in women, higher VAT and higher periaortic fat were jointly associated with higher HGF concentrations (p=0.02 and p=0.05, respectively). In women within the highest tertile of VAT, HGF levels increased with higher periaortic fat (p=0.0005; Figure ). Conclusions: We observed associations of several body fat compartments with circulating VEGF and HGF levels. In women, high VAT and high periaortic fat were jointly associated with greater HGF levels. Whether this finding will translate to elevated morbidity in this group warrants further evaluation.
La Obesidad y su Tratamiento.
Authors: Pedro Ballester
Journal: JAMA (1925)

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Glucocorticosteroid receptor (GCR) gene isoforms expression in bronchial asthma (BA) patients
Authors: Zhanna Mironova, Vasiliy Trofimov, Vasiliy Belash, Elena Iantchina, Anna Ulitina, Michael Dubina
Journal: European Respiratory Journal (2011)

Peculiarities of GCR function is one of mechanisms of steroid dependent asthma (SDBA). Most important isoforms are CRα and CRβ, formed due to alternative splicing of NR3C1 gene. Alternatively to CRα, CRβ is not linked to glucocorticosteroids (GCS), acting as inhibitor, which concurs with CRα for linking with hormone-responding element or coactivator. This mechanism may lead to steroid resistance (SR).  The aim of study was to evaluate the role of GCR isoforms in SDBA development.   Methods:  9 SDBA patients, 15 ones – with mild asthma (MBA), 7 – moderate BA and 7 healthy controls were included. In 10 MBA ones, inhaled GCS were primary administered. In this group blood samples were taken before and 2 weeks after start of treatment. In SDBA patients, having long history of inhaled and oral GCS, blood was taken once. Total RNA from peripheral blood cells was isolated using RIBO-zol-B nucleic acid extraction kit (CRIE, Russia). Level of CRα and CRβ expression was evaluated by RT-qPCR method.   Results:  No statistic difference between expression levels in BA and controls was found. CRα expression was higher in SDBA than in other asthmatics (243,0 vs 30,7; p=0,05). In MBA during the GCS treatment trend to CRα expression increase (from 9,3 to 94,5) and CRβ expression decrease (from 820,9 to 33,3) was revealed. Significantly increased CRα/CRβ ratio in MBA after treatment (from 0,5 to 17,7; p=0,022) was same as in SDBA (19,9).   Conclusions:  Level of CRβ expression, which didn9t change in SDBA, can be discussed as a marker of absence of SR. Sensitivity to GCS can be evaluated basing on initial domination of CRα expression in SDBA and increase of this indicator in MBA during the course of GCS treatment.
Abstract 18: Ultrasound Estimation of Cardiac Output in a Swine Model of Cardiac Arrest: Implications for Assessing Post Cardiac Arrest Syndrome.
Authors: Christian D McClung, Anthony Peduto, Scott T Youngquist, Mohammed A Hanif, Ekaterina Tzvetkova, Atman P Shah, John P Rosborough, James T Niemann
Journal: Circulation (2010)

Background: Post cardiac arrest syndrome (PCAS) is a dynamic process of physiologic compromise requiring repeated measures of the hemodynamic response to treatment. Ultrasound (U/S) provides a safe...
Role of bronchoscopy in non-HIV immunocompromised patients
Authors: Hugh Ip, Chris Kosky, Anne Collett
Journal: European Respiratory Journal (2011)

Background:  Non-HIV immuno-compromised patients with suspected chest sepsis commonly undergo bronchoscopy to aid microbiological diagnosis.   Aims:  Characterise non-HIV immuno-compromised patients undergoing bronchoscopy at a London hospital. To assess the diagnostic utility of this procedure with a focus on results leading to treatment changes.   Methods:  Clinical records of all patients undergoing bronchoscopies over a 14-month period were retrospectively reviewed. The diagnostic yield was calculated using the total number of bronchoscopies as the denominator. A positive result was defined as any positive culture (viral, fungal, bacterial) or diagnostic pathology. Using the clinical notes and prescription charts the percentage of treatment changes following bronchoscopy results was calculated.   Results:  43 bronchoscopies were carried out in this group. Underlying diagnoses were haematological malignancy (27), organ transplant (10), solid organ tumour (2), rheumatological (4). The most common indication was suspected infection (76.7%); fungal infection was suspected in 46.5%.The overall diagnostic yield was 51.2% (95% CI, 36.1-66.3%). Many of the positive samples were for virus (10) followed by positive bacterial cultures (8). Few samples were positive for fungus (2). Therapy was changed after 18.6% (95% CI, 6.8-30.4%) of all bronchoscopies. The total complication rate was 4.6% (95% CI, -1.7-11.1%); both cases due to controllable bleeding.   Conclusions:  The most common underlying diagnoses were haematological malignancies. Fungal chest infection was frequently suspected, but the fungal organism yield was low; treatment decisions were based on clinical and radiological findings. Total diagnostic yield was similar to published data.
Insights into the structure and function of GABA-benzodiazepine receptors: ion channels and psychiatry
Authors: C F Zorumski, K E Isenberg
Journal: American Journal of Psychiatry (1991)

As a result of combined biophysical and molecular biological studies, important insights into the structure and function of gamma-aminobutyric acid (GABA) receptors have been achieved. These insights have helped to define the role of GABA receptors in synaptic inhibition and the ion channel mechanisms by which different neuropsychiatric drugs work. The authors' goal is to describe the actions of GABA as a neurotransmitter and discuss the modulation of receptor function by different drugs.The authors focus on more recent studies of the structure and physiology of the receptor-ion channel complex and the relevance of these studies to psychiatry.The CNS effects of benzodiazepines, barbiturates, and alcohol have been linked to the GABA-chloride channel receptor complex. Multiple subunits of this complex have been cloned, sequenced, and expressed in heterologous systems. The results of cloning studies, coupled with membrane biophysics, have provided important insights into the structure and function of GABA receptors and their modulation by psychopharmacological agents.Future understanding of disease states, drug effects, and therapeutic successes and failures may be expressed in terms of differences in the structure and function of specific receptors and their associated ion channels. Furthermore, the ability to describe the molecular function of receptor subtypes offers the ability to tailor drug specificity by developing agents directed against a given receptor subtype. The current GABA studies also have important implications for the understanding of how neurotransmitter systems may be involved in illness.
Abstract 2564: Predictors of Early Stent Thrombosis in Patients with Acute Coronary Syndromes in the Drug-Eluting Stent Era: Analysis from the ACUITY trial
Authors: Jiro Aoki, Gregg W Stone, Roxana Mehran, Jeffery Moses, Michel E Bertrand, A. Michael Lincoff, E. Magnus Ohman, Harvey D White, Helen Parise, Martin B Leon, Alexandra J Lansky
Journal: Circulation (2007)

Objectives. The purpose of this study was to evaluate the incidence and predictors of early (&lt;30days) stent thrombosis (ST) in pts with acute coronary syndromes (ACS) in the drug-eluting stent (DES) era. Background. Predictors of ST, including detailed quantitative coronary angiographic (QCA) analysis parameters have not been carefully investigated in pts with ACS. Methods. In the prospective, multicenter ACUITY trial, a total of 7,179 pts with moderate and high risk ACS were treated with stents (66.4% of whom received at least 1 DES). Among these pts, core lab QCA was performed in 3,518 (49.0%) pts. Results. Within 30 days, 101 pts (1.4%) suffered definite or probable ST by the Academic Research Consortium (ARC) definition. Pts with ST were older and had a higher prevalence of diabetes mellitus, prior MI and renal insufficiency, higher TIMI risk scores and ST segment deviation compared to those without ST. By core lab QCA pts with ST were more likely to have greater overall coronary artery disease burden, procedural angiographic complications, suboptimal final angiographic results, implantation of ≥2 stents, and use of aspirin &lt;50% of time within 30 days. A final stent diameter stenosis &gt;20% and implantation of ≥2 stents were the strongest independent predictors of early ST (Table ). DES use was not significantly different between pts with and without ST (62.4% vs. 66.5%, P=0.40). Conclusions. Early ST in pts with ACS is frequent with both BMS and DES, and is predicted by use of multiple stents and suboptimal angiographic results. Avoiding multiple stents and improving operator technique and antiplatelet compliance may minimize the risk of early ST in ACS. Multivariate predictors of early ST
Sexual and physical abuse histories and psychiatric symptoms among male psychiatric outpatients
Authors: C Swett, J Surrey, C Cohen
Journal: American Journal of Psychiatry (1990)

Of 125 consecutive male patients at an adult psychiatric outpatient clinic, 48% reported histories of sexual abuse and/or physical abuse. The mean scores on the global severity index of the SCL-90-R at the first visit were significantly higher for those who reported histories of abuse than for those who had no such history. Childhood abuse also was associated with high levels of psychiatric symptoms in these men.
Abstract 1328: Selective Glutaredoxin (GRx1) Knockdown in H9c2 Cells Provides a Model for Age-Related Decreases in GRx1 in Rat Heart, and Increases Susceptibility to Oxidant Induced Apoptosis
Authors: Molly M Gallogly, Harish V Pai, David W Starke, Charles L Hoppel, Edward J Lesnefsky, John J Mieyal
Journal: Circulation (2007)

Clinical and animal studies show that hearts of the elderly are more susceptible to irreversible damage after ischemia-reperfusion (I/R) than adult hearts. We reasoned this was due in part to chang...
Fever and Rash in a Patient With Hepatitis
Authors: Meredith E. Clement, N. Lance Okeke, Charles B. Hicks
Journal: JAMA (2015)

A 56-year-old man with longstanding human immunodeficiency virus (HIV) infection presented with new-onset fatigue and malaise, fever, and a macular rash involving the palms and soles. What is the diagnosis?
Abstract 17104: Bicuspid Aortic Valve Thoracic Aortic Aneurysm is Associated With Apolipoprotein E and Osteopontin but Not Notch 1 Gene Dysregulation
Authors: Malcolm West, Maria Nataatmadja, Jennifer West, Sulistiana Prabowo, Homayoun Jalali
Journal: Circulation (2014)

Thoracic aortic aneurysm (TAA) develops in about 35% of those with bicuspid aortic valve (BAV) but the cause is unkown. Some studies have identified Notch1 gene mutations in BAV while expression of osteopontin ( OPN ) gene has been reported to be significantly elevated in BAV associated TAA. Furthermore OPN gene expression has been shown to regulate apoptosis and through a CD44 antigen dependent mechanism that regulates autophagy. Apolipoprotein E ( ApoE ) gene mutations have been correlated with atherosclerosis and with BAV stenosis however an association with development of TAA in BAV is not clear. We have previously shown using electron microscopy a significant increase of VSMC apoptosis and autophagy in BAV TAA. To determine the role of Notch1, OPN and ApoE gene function in BAV associated TAA we measured mRNA expression using RT PCR methods. Immunohistochemistry was used to analyse aortic wall degeneration and VSMC loss (OPN, CD44, apoptosis and autophagy). TAA tissue was obtained from 9 subjects (7M, 2F; 57±19yr) with BAV at the time of surgery. Samples of control aorta were obtained from 5 organ donor subjects (TAC; 2M, 3F; 54±13yr). There was significant increase in mRNA expression of OPN (1.42±0.69 vs 0.24±0.09; mean±SD, P≤0.05) and ApoE (1.38±0.55 vs 0.25±0.57; P≤0.05) but not Notch1 (1.24±0.16 vs 0.91±0.23) in BAV VSMC compared to controls. BAV VSMC apoptosis (≤ 30% of total VSMCs; caspase-3+) and autophagy (≥50% of total VSMCs; LC3+) was observed but not in controls. Notch1 protein staining was negligible but there was strong OPN expression in the subendothelial layer co-localised with inner elastic lamina degeneration. Focal OPN expression in medial layer was co-localised with VSMC apoptosis and some autophagy. CD44 expression in BAV TAA was minimal and no co-localisation was found with VSMC autophagy. In summary up-regulation of OPN and ApoE but not Notch1 mRNA was found in BAV TAA. This was associated with OPN protein up-regulation that co-localised with areas of VSMC apoptosis and autophagy in the absence of CD44. The findings suggest a potentially important role for OPN and ApoE gene function in VSMC death independent of CD44 in BAV associated TAA
Acid-Base and Electrolyte Disturbances in Anorexia Nervosa
Authors: Stanford E. Warren, Steven M. Steinberg
Journal: American Journal of Psychiatry (1979)

The literature on anorexia nervosa largely ignores the acid-base and electrolyte disturbances that may accompany this condition. In an attempt to assess the magnitude of these disturbances in anorexia nervosa the authors reviewed the laboratory profiles of 7 patients with the disease who were consecutively admitted to a hospital over a period of 8 years. Several acid-base and electrolyte disturbances were observed; the most frequent was chloride-responsive metabolic alkalosis. The authors suggest that all patients with anorexia nervosa receive diagnostic studies for these disturbances, including ECG and urinary electrolytes when necessary, so that abnormalities can be diagnosed and treated appropriately.