tbuckley/cabot-search huggingface dataset:
Imaging flow cytometry for automated detection of hypoxia‐induced erythrocyte shape change in sickle cell disease
Authors: Eduard J. van Beers, Leigh Samsel, Laurel Mendelsohn, Rehan Saiyed, Kleber Y. Fertrin, Christine A. Brantner, Mathew P. Daniels, James Nichols, J. Philip McCoy, Gregory J. Kato
Journal: American Journal of Hematology (2014)

In preclinical and early phase pharmacologic trials in sickle cell disease, the percentage of sickled erythrocytes after deoxygenation, an ex vivo functional sickling assay, has been used as a measure of a patient's disease outcome. We developed a new sickle imaging flow cytometry assay (SIFCA) and investigated its application. To perform the SIFCA, peripheral blood was diluted, deoxygenated (2% oxygen) for 2 hr, fixed, and analyzed using imaging flow cytometry. We developed a software algorithm that correctly classified investigator tagged "sickled" and "normal" erythrocyte morphology with a sensitivity of 100% and a specificity of 99.1%. The percentage of sickled cells as measured by SIFCA correlated strongly with the percentage of sickle cell anemia blood in experimentally admixed samples (R = 0.98, P ≤ 0.001), negatively with fetal hemoglobin (HbF) levels (R = -0.558, P = 0.027), negatively with pH (R = -0.688, P = 0.026), negatively with pretreatment with the antisickling agent, Aes-103 (5-hydroxymethyl-2-furfural) (R = -0.766, P = 0.002), and positively with the presence of long intracellular fibers as visualized by transmission electron microscopy (R = 0.799, P = 0.002). This study shows proof of principle that the automated, operator-independent SIFCA is associated with predictable physiologic and clinical parameters and is altered by the putative antisickling agent, Aes-103. SIFCA is a new method that may be useful in sickle cell drug development.
Abstract 19640: Galectin-3 and Risk of Stroke: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort
Authors: Zubin Agarwal, Peter W Callas, Brett Kissela, Nancy Jenny, Suzanne E Judd, Neil Zakai, Mary Cushman
Journal: Circulation (2014)

Introduction:  Galectin-3 is a biomarker of atherosclerotic disease associated with risk of heart failure, and may therefore be a useful marker for stroke risk.   HYPOTHESIS:  Galectin-3 is associated with stroke risk in a biracial cohort.   METHODS:  REGARDS enrolled and examined 30,239 US participants in 2003-07 (41% black, 59% white, 55% living in the southeastern stroke belt). Baseline galectin-3 was measured in 594 subjects with incident stroke and a 947 participant cohort random sample (CRS). In the CRS, sample weighting was used to estimate baseline associations of galactin-3 with cardiovascular risk factors. Cox proportional hazards models were used to calculate hazard ratios (HR) of stroke by quartiles of galectin-3.   RESULTS:  In the CRS, baseline galectin-3 was higher with older age, black race, female sex, hypertension, diabetes mellitus, chronic kidney disease (estimated glomerular filtration rate  th  versus 1 st  quartile of galectin-3 had a 2.3-fold increased stroke risk (95% CI 1.6, 3.3). Adjustment for age, race, and sex attenuated this HR to 1.3 (CI 0.9, 1.8). There was a suggestive difference in results by age (p interaction galectin-3*age =0.08). Among those younger than age 64, baseline galectin-3 in the 2 nd -4 th  quartiles was associated with increased stroke risk in a fully adjusted model, but this was not the case among older participants (table).   CONCLUSION:  Galectin-3 was associated with incident stroke in younger, but not older individuals. More research is needed to determine the significance of this finding to stroke etiology.
Abstract 4278: Angiotensin II Receptor Antagonism and Transforming Growth Factor Beta and SMAD Signalling in Thoracic Aortic Aneurysm: Implications for Aneurysm Progression
Authors: Maria Nataatmadja, Jennifer West, Malcolm West
Journal: Circulation (2008)

Increased expression of transforming growth factor-beta (TGFβ) and Smad3 is associated with fibrosis and inflammatory cell infiltration in abdominal aortic aneurysm. In Smad3-null mice there is reduced extracellular matrix (ECM) deposition but enhanced neointimal hyperplasia in response to vascular injury suggesting a TGFβ/Smad3 role in ECM regulation and cell proliferation. In vitro studies show that exogenous TGFβ administration leads to phosphorylation and nuclear translocation of Smad3 while angiotensin II (AngII) induces fibrosis through TGFβ and Smad3 pathways. We investigated TGFβ/Smad3 signaling using immunohistochemical and cell culture studies in thoracic aortic aneurysm tissue derived from subjects with Marfan syndrome (MFS; 3M, 2F, 46±24yr, mean +/−SD) and bicuspid aortic valve malformation (BAV; (3M, 2F, 65±13yr) as well as normal aorta from organ donor subjects (3M, 2F 40±11yr). MFS and BAV tissue showed co-localisation of TGFβ1–3 and Smad3 in myofibroblasts, vascular smooth muscle cells (VSMCs) and chronic inflammatory cells in the subintimal layer and tunica media and in fibroblasts in tunica adventitia. In normal aortic wall there was minimal TGFβ and Smad3 staining. Cultured VSMCs (passage 1–5) from MFS and BAV showed nuclear Smad3 and strong cytoplasmic TGFβ1–3 expression in numerous vesicles and in areas of exocytosis and extracellular localisation. In control cells there was much weaker TGFβ1–3 staining compared to aneurysm derived cells. Smad3 staining in normal cells was located in the cytoplasm alone. Compared to normal tissue and cells AngII receptor type1 and 2 (ATR1 and 2) expression was increased in both aneurysm tissue and in cultured VSMCs derived from aneurysm. Cultured VSMCs were treated for 48h with the ATR1 antagonist losartan (10μM). This caused disappearance of TGFβ1–3 vesicle localisation and nuclear expression of Smad3. The findings of increased TGFβ1–3 and Smad3 expression in aneurysm tissue and cultured cells are consistent with aberrant TGFβ signalling and with activation of the Smad3 signalling pathway. Furthermore reduction in extracellular TGFβ and de-activation of Smad3 expression associated with losartan treatment supports a role for ATR1 antagonism in inhibition of aneurysm progression. Figure 1: Risk of IMH Conversion to Typical Dissection
Human fetal liver-derived CD7+CD2lowCD3-CD56- clones that express CD3 gamma, delta, and epsilon and proliferate in response to interleukin-2 (IL-2), IL-3, IL-4, or IL-7: implications for the relationship between T and natural killer cells
Authors: T Hori, JH Phillips, B Duncan, LL Lanier, H Spits
Journal: Blood (1992)
Into the Woods to End Global Hunger
Authors: M. J. Friedrich
Journal: JAMA (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 21178: Abacavir-based Antiretroviral Therapy is Associated with Long-term Increase incidence of Cardiovascular Events in HIV Patients with Presumable Cardiovascular Disease
Authors: Emad F Aziz, Balaji Pratap, Omar Wever-Pinzon, Fahad Javed, Carlos L Alviar, Kalyan K Bandavaram, Sejal Mehta, Venkat R Kakollu, Resmi Premji, Danielle Binler, Donald Kotler, Eyal Herzog
Journal: Circulation (2010)

Background: Antiretroviral therapy (ARV) with Abacavir is postulated to be associated with increased cardiovascular (CV) risk. We evaluated the long-term incidence of major adverse CV events (MACE)...
Abstract 19687: Morphological and Clinical Characteristics of Late and Young Age Onset Apical Hypertrophic Cardiomyopathy: Insight from a 13-Year Registry of Hypertrophic Cardomyopathy
Authors: Hyemoon Chung, Geu-Ru Hong, Jungwoo Son, In-Jeong Cho, Chi Young Shim, Hyuk-Jae Chang, Jong-Won Ha, Namsik Chung
Journal: Circulation (2014)

Background: Apical hypertrophic cardiomyopathy (ApHCM) might have different morphological and clinical features according to the age of disease onset, probably result from the distinct mechanism of pathogenesis. The aim of this study was to evaluated the morphological and clinical differences according to the age of disease onset in patients with ApHCM. Methods: This was a retrospective, observational study of 56 ApHCM patients (31 males, mean 65±9 years). Among 426 patients with diagnosed ApHCM from 2000 until 2013, we selected 56 patients who met the inclusion criteria: [[Unable to Display Character: &amp;#9332;]] patiens who diagnosed with ApHCM before 60 years old and current age &gt;60 years old, (group A, early onset, n=16); and [[Unable to Display Character: &amp;#9333;]] who diagnosed with ApHCM after 60 years old who had no evidence of apical hypertrophy confirmed by previous echocardiography (group B, late onset, n=40). Morphological LV feature was assessed by transthoracic echocardiography, which were divided into pure and mixed type. Furthermore, hemodynamic parameters and clinical events were also evaluated. Results: There were no differences in the presence of hypertension, LV systolic function and left atrial volume index between group A and B. However, early onset group A had more increased maximal wall thickness of LV apex (17.08±2.02 vs 15.43±1.68mm, p=0.005), and more incidence of pure type (100% (16/16) vs 56.8% (21/40), p=0.001) compare than late onset group B. Group B had older age (65±5 vs 72±4 years, p=0.001), increased LV end-diastolic dimension (51.25±2.32 vs 48.58±3.37mm, p=0.006), increased E/E’ (11.24±2.94 vs 14.60±6.37, p=0.049) with decreased E’ (5.61±1.34 vs 4.66±1.38cm/s, p=0.024) respectively.There were no significant differences in the risk of cardiovascular complication such as atrial fibrillation and stoke between group A and B. Conclusions: There was obvious different clinical characteristics according to the age of disease onset. Early onset ApHCM has typical morphological feature and relatively preserved LV diastolic function, compared with late onset ApHCM. Our result supports that late onset ApHCM was related to decreased LV diastolic function and increased LV wall thickness, which reflects the potential myocardial remodeling with aging.
EXTRATHYROIDAL HYPERMETABOLISM: CLASSIFICATION AND DISCUSSION INCLUDING THREE ILLUSTRATIVE CASE REPORTS
Authors: M BRUGER, V P HOLLANDER
Journal: Annals of Internal Medicine (1951)

Excerpt The problem presented by patients with elevated basal metabolic rates in whom careful study precludes a diagnosis of hyperthyroidism is exceedingly complex. Since the basal metabolism as measured is the sum of the rates of oxygen consumption of all the cells of the body (which number about 40 quintillion), and these in turn are controlled by physical, humoral, endocrine, pharmacologic and vegetative as well as central neural factors, the complexity is expected and understandable. Table 1 illustrates the many clinical, physiologic and physical factors the clinician must keep in mind when confronted with this problem. I. DISORDERS OF THE ENDOCRINE
Time trends in the prevalence of peanut allergy: three cohorts of children from the same geographical location in the UK
Authors: C. Venter, S. Hasan Arshad, J. Grundy, B. Pereira, C. Bernie Clayton, K. Voigt, B. Higgins, T. Dean
Journal: Allergy (2009)

Abstract Background: This article investigated the prevalence of peanut allergy in three cohorts of children born in the same geographical location, Isle of Wight, UK and seeks to determine whether the prevalence of peanut allergy has changed between 1994 and 2004. Methods: Three cohorts of children (age 3–4 years) born on the Isle of Wight, were assessed for peanut allergy and the outcomes compared: Cohort A: Born in 1989; reviewed at 4 years of age ( n = 2181). Cohort B: Born between 1994 and 1996; reviewed between 3 and 4 years of age ( n = 1273). Cohort C: Born between 2001 and 2002; reviewed at 3 years of age ( n = 891). Results: Peanut sensitization increased significantly from 1.3% in Cohort A to 3.3% ( P = 0.003) in Cohort B before falling back to 2.0% in Cohort C ( P = 0.145). Similarly, clinical peanut allergy increased significantly from 0.5% in Cohort A to 1.4% ( P = 0.023) in Cohort B, with a subsequent fall to 1.2% in Cohort C ( P = 0.850). Conclusions: Our data from three cohorts of 3‐ to 4‐year‐old children born in the same geographical area shows that peanut allergy prevalence has changed over time. Peanut sensitization and reported allergy in children born in 1994–1996 increased from 1989 but seems to have stabilized or slightly decreased since the late 1990s, although not significant.
Roux-en-Y gastric bypass for diabetes (the Diabetes Surgery Study): 2-year outcomes of a 5-year, randomised, controlled trial
Authors: Sayeed Ikramuddin, Charles J Billington, Wei-Jei Lee, John P Bantle, Avis J Thomas, John E Connett, Daniel B Leslie, William B Inabnet, Robert W Jeffery, Keong Chong, Lee-Ming Chuang, Michael G Sarr, Michael D Jensen, Adrian Vella, Leaque Ahmed, Kumar Belani, Joyce L Schone, Amy E Olofson, Heather A Bainbridge, Patricia S Laqua, Qi Wang, Judith Korner
Journal: The Lancet Diabetes & Endocrinology (2015)
Abstract 128: Tyrosine 823 in the activation loop of c-Kit regulates the transforming capacity of the oncogenic mutant D816V and its sensitivity to kinase inhibitors
Authors: Shruti Agarwal, Julhash U. Kazi, Sofie Mohlin, Sven Påhlman, Lars Rönnstrand
Journal: Cancer Research (2015)

Abstract Oncogenic mutations in c-Kit have been shown to lead to ligand-independent receptor activation and contribute to transformation. A substitution of an aspartate for a valine at position 816 (D816V) is one of the most commonly found oncogenic c-Kit mutation and is found in more than 90% of cases of mastocytosis and in a subgroup of germ cell tumors, core-binding factor acute myeloid leukemia and mucosal melanomas. Previous studies have shown that the D816V mutation causes a structural change in the activation loop resulting in weaker binding of the activation loop to the juxtamembrane domain, leading to a release of the negative constraint it poses on kinase activity. Here we have investigated the role of Y823 in the activation loop of c-Kit and its role in oncogenic transformation by c-Kit/D816V. Although dispensable for the kinase activity of c-Kit/D816V, the presence of Y823 was shown to be crucial for cell proliferation and survival. Furthermore, mutation of Y823 selectively down-regulated the Ras/Erk and Akt pathways. It also led to decreased phosphorylation of STAT5 and reduced the transforming capacity of D816V/c-Kit in vitro. The sensitivity to kinase inhibitors, such as dasatinib and nilotinib, was decreased in cells expressing c-Kit/Y823F/D816V compared to cells c-Kit/D816V. Mice injected with cells expressing c-Kit/D816V/Y823F displayed significantly reduced tumor size as well as tumor weight compared to controls. Finally, microarray array analysis, comparing c-Kit/Y823F/D816V cells with cells expressing c-Kit/D816V, demonstrate that mutation of Y823 causes up-regulation of pro-apoptotic genes whereas genes of survival pathways are down-regulated. Thus, phosphorylation of Y823 is not necessary for kinase activation, but essential for the transforming ability of the c-Kit/D816V mutant. Citation Format: Shruti Agarwal, Julhash U. Kazi, Sofie Mohlin, Sven Påhlman, Lars Rönnstrand. Tyrosine 823 in the activation loop of c-Kit regulates the transforming capacity of the oncogenic mutant D816V and its sensitivity to kinase inhibitors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 128. doi:10.1158/1538-7445.AM2015-128
A novel fluorescence-based kinetic kinase assay for use with recombinant protein and cell lysates
Authors: Julie A. Vrana, Mark Surby, Xiao-Dong Qian, Min Li, C J Clark, Melissa Schults, Barbara Imperiali, Erik Schaefer
Journal: Cancer Research (2006)

87  Protein phosphorylation plays a critical role in signal transduction in normal and disease states. Recent advances in the development of specific protein kinase inhibitors illustrates the potential for a new generation of drugs to treat human cancers. We have adapted a novel fluorescent peptide substrate-based assay for the rapid, homogeneous and sensitive detection of the activity of a broad range of protein kinases. This assay platform uses the chelation-enhanced fluorophore 8-hydroxy-5-(N,N-dimethylsulfonamido)-2-methylquinoline (referred to as Sox), which is incorporated into the substrate peptide. A series of specific Ser/Thr and Tyr substrate peptides are utilized to measure a range of kinases covering all families of the kinome. Several key features of this assay include measurement of kinase activity under optimal kinetics, physiological (mM) ATP, and in real time without the use of radioactive tracer, beads, antibodies or specialized equipment. Importantly, activity increases result in a corresponding increase in fluorescence. Because the assay can be performed with a wide range of ATP concentrations it can be used to select for both ATP-competitive and ATP-non-competitive kinase inhibitors. We have applied this system for the analysis of multiple sample types including the determination of kinase activity of recombinant proteins and using crude cell lysates in a 96 or 384 well format. This technology, used in conjunction with phospho-specific antibody based profiling, provides a valuable set of tools for rapidly increasing our understanding of the kinome and the nature of signaling networks.
Estrogen Receptor Expression in 21-Gene Recurrence Score Predicts Increased Late Recurrence for Estrogen-Positive/HER2-Negative Breast Cancer
Authors: Mitch Dowsett, Ivana Sestak, Richard Buus, Elena Lopez-Knowles, Elizabeth Mallon, Anthony Howell, John F. Forbes, Aman Buzdar, Jack Cuzick
Journal: Clinical Cancer Research (2015)

Abstract Purpose: To identify the individual genes or gene modules that lead to the OncoptypeDx 21-gene recurrence score's reduced performance after 5 years and thereby identify indices of residual risk that may guide selection of patients for extended adjuvant therapy. Experimental Design: We conducted a retrospective assessment of the relationship between (i) the individual genes and gene modules of the Recurrence Score and (ii) early (0–5 years) and late (5–10 years) recurrence rates in 1,125 postmenopausal patients with primary estrogen receptor–positive breast cancer treated with anastrozole or tamoxifen in the Arimidex, Tamoxifen, Alone or Combined (ATAC) randomized clinical trial. Results: In the HER2-negative population (n = 1,009), estimates of recurrence risk were similar between years 0–5 and 5–10 for proliferation and invasion modules but markedly different for the estrogen module and genes within it (all split at the median): for low estrogen module, annual recurrence rates were similar across the two time windows (2.06% vs. 2.46%, respectively); for high estrogen module, annual rates were 1.14% versus 2.72%, respectively (Pinteraction = 0.004). Estrogen receptor transcript levels showed inverse prediction across the time windows: HR, 0.88 (0.73–1.07) and 1.19 (0.99–1.43), respectively (Pinteraction = 0.03). Similar time-, module-, and estrogen-dependent relationships were seen for distant recurrence. Conclusions: Patients with tumors with high estrogen receptor transcript levels benefit most from 5 years' endocrine therapy but show increased recurrence rates after 5 years and may benefit from extended therapy. Improved prognostic profiles may be created by considering period of treatment and follow-up time. Clin Cancer Res; 21(12); 2763–70. ©2015 AACR.
Abstract 20316: Pulse Wave Velocity During Dobutamine Stress is an Independent Predictor of MACE in Asymptomatic High Risk Middle Aged and Elderly Men
Authors: Trinity Vera, Timothy M Morgan, Jennifer H Jordan, Matthew C Whitlock, Sujethra Vasu, Craig A Hamilton, Dalane Kitzman, William C Little, W. G Hundley
Journal: Circulation (2014)

Introduction: Resting measures of pulse wave velocity have been shown to forecast future major adverse cardiovascular events (MACE), but the utility of stress induced changes in PWV to forecast events is unknown. Methods: A prospective cohort study was implemented in which 520 consecutive participants aged 55-85 years at high risk for MACE were recruited. A 1.5T MRI scanner was used to obtain PWV at baseline, low dose dobutamine (10 mcg/kg/min) and peak stress (dobutamine up to 40 mcg/kg/min and atropine up to 1.5mg administered to achieve 80% of the maximum predicted heart rate response for age). Aortic arch PWV was assessed using the velocity waveform transit time technique. Participants were followed-up at 3 month intervals by personnel who were blinded to the stress test results. Participants were stratified by gender and presence or absence of MACE. Two sample t-test was used for continuous variables while Chi-square test was used for categorical variables. Cox proportional hazards model was used to ...