tbuckley/cabot-search huggingface dataset:
Abstract 9768: Cr(nMe)eka-Conjugated Micellar Formulation Improves Anticoagulation Efficacy of Bivalirudin
Authors: Zhi-Gang She, Xiangyou Liu, Venkata R Kotamraju, Erkki Ruoslahti
Journal: Circulation (2014)

Anticoagulant therapies are the primary treatment modalities for preventing and treating thrombosis. However, high rate of bleeding complications is a serious side effect of anticoagulant therapies, which compromised their applications. Bivalirudin is an oligopeptide anticoagulant that has the advantage of not causing thrombocytopenia and exhibits lower potential for bleeding risk compared to heparin. Nevertheless, hemorrhage is still the most common complication. And there is no effective antidote for bivalirudin. We report here a strategy to deliver bivalirudin specifically to the site of clotting area, and thereby reduce the bleeding risk. The site-specific delivery of bivalirudin was achieved with micellar nanocarriers which has a thrombosis-targeting peptide CR(Nme)EKA. These peptide-conjugated micellar nanocomplexes are highly dispersed and stable in aqueous solution with an average size of 30 nm. The anticoagulant activity of bivalirudin was well remained after it was incorporated into the micelles. These micellar nanocomplexes specifically accumulated in the site of clotting in mice lung thrombosis. Moreover, the micellar formulation significantly prolonged the half-life and increased the bioavailability of bivalirudin. Most importantly, this effective formulation significantly improved the anticoagulant activity of bivalirudin, when tested in both thromboplastin-induced lung thrombosis mouse model and ferric chloride (FeCl3)-induced carotid artery thrombosis mouse model. Taken together, these results demonstrate that the micellar nanocomplexes specifically target thrombi, deliver bivalirudin directly into site of clotting and exhibit improved antithrombotic activity over free bivalirudin. This strategy may improve the safety and efficacy of bivalirudin in clinical use.
Characterization of Epstein-Barr virus–infected B cells in patients with posttransplantation lymphoproliferative disease: disappearance after rituximab therapy does not predict clinical response
Authors: Jie Yang, Qian Tao, Ian W. Flinn, Paul G. Murray, Linda E. Post, Hong Ma, Steven Piantadosi, Michael A. Caligiuri, Richard F. Ambinder
Journal: Blood (2000)
Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export
Authors: Andrea Legati, Donatella Giovannini, Gaël Nicolas, Uriel López-Sánchez, Beatriz Quintáns, João R M Oliveira, Renee L Sears, Eliana Marisa Ramos, Elizabeth Spiteri, María-Jesús Sobrido, Ángel Carracedo, Cristina Castro-Fernández, Stéphanie Cubizolle, Brent L Fogel, Cyril Goizet, Joanna C Jen, Suppachok Kirdlarp, Anthony E Lang, Zosia Miedzybrodzka, Witoon Mitarnun, Martin Paucar, Henry Paulson, Jérémie Pariente, Anne-Claire Richard, Naomi S Salins, Sheila A Simpson, Pasquale Striano, Per Svenningsson, François Tison, Vivek K Unni, Olivier Vanakker, Marja W Wessels, Suppachok Wetchaphanphesat, Michele Yang, Francois Boller, Dominique Campion, Didier Hannequin, Marc Sitbon, Daniel H Geschwind, Jean-Luc Battini, Giovanni Coppola
Journal: Nature Genetics (2015)
Glucose Levels and Risk of Dementia
Authors: Jan T Kielstein
Journal: New England Journal of Medicine (2013)

BACKGROUND-Diabetes is a risk factor for dementia.It is unknown whether higher glucose levels increase the risk of dementia in people without diabetes.METHODS-We used 35,264 clinical measurements of glucose levels and 10,208 measurements of glycated hemoglobin levels from 2067 participants without dementia to examine the relationship between glucose levels and the risk of dementia.Participants were from the Adult Changes in Thought study and included 839 men and 1228 women whose mean age at baseline was 76 years; 232 participants had diabetes, and 1835 did not.We fit Cox regression models, stratified according to diabetes status and adjusted for age, sex, study cohort, educational level, level of exercise, blood pressure, and status with respect to coronary and cerebrovascular diseases, atrial fibrillation, smoking, and treatment for hypertension.RESULTS-During a median follow-up of 6.8 years, dementia developed in 524 participants (74 with diabetes and 450 without).Among participants without diabetes, higher average glucose levels within the preceding 5 years were related to an increased risk of dementia (P = 0.01); with a glucose level of 115 mg per deciliter (6.4 mmol per liter) as compared with 100 mg per deciliter (5.5 mmol per liter), the adjusted hazard ratio for dementia was 1.18 (95% confidence interval [CI], 1.04 to 1.33).Among participants with diabetes, higher average glucose levels were also related to an increased risk of dementia (P = 0.002); with a glucose level of 190 mg per deciliter (10.5 mmol per liter) as compared with 160 mg per deciliter (8.9 mmol per liter), the adjusted hazard ratio was 1.40 (95% CI, 1.12 to 1.76).CONCLUSIONS-Our results suggest that higher glucose levels may be a risk factor for dementia, even among persons without diabetes.
Book: 50 Years of Ideas in Health Care Buildings
Authors: D. Williams
Journal: BMJ (2000)

Susan Francis, Rosemary Glanville, Ann Noble, Peter Scher Nuffield Trust, £20, pp 68 ISBN 1 902089 20 0 Rating: ![Graphic][1]</img> ![Graphic][2]</img> ![Graphic][3]</img> Many of us will spend our last weeks of life in a six bedded bay of a hospital ward. Will there be a view from the window? How far will it be to the toilet and will it be occupied on arrival? Will the nurse be able to see me and I her? Suddenly, architecture matters. Read this book to discover why treatment rooms were introduced and why every bay does not have its own … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Some Applications of Organic Chemistry to Biology and Medicine.
Authors: George Barger
Journal: JAMA (1930)

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
A Surgeon and a Line of Patients
Authors: M Therese Southgate
Journal: JAMA (2005)

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
Regulation of natural killer cell-mediated cytotoxicity by recombinant human granulocyte-colony stimulating factor
Authors: Yu-Jen Chen, Hui-Fen Liao, Chih-Chia Yu
Journal: Clinical Cancer Research (2008)

AACR Centennial Conference: Translational Cancer Medicine-- July 20-23, 2008; Monterey, CA

B10 

Recombinant human granulocyte-colony stimulating factor (rhG-CSF) is the most common hematopoietic growth factor used for treatment of chemotherapy-induced neutropenia or mobilization of hematopoietic stem cells for transplantation. Natural killer (NK) cells, regulate cytotoxic response in both innate and adaptive immunity, are critical for host defense against infected cells and tumors. However, the cellular and molecular events of NK cells responding to rhG-CSF remain unclear. Toward this end, we treated human NK cells with rhG-CSF and assessed their cytotoxic function as well as proteomic characteristics. Unlike the other tested hematopoietic cytokines, rhG-CSF decreased NK cell-mediated cytotoxicity without affecting the viability of NK cells. rhG-CSF also reduced the production of nitric oxide and expression of inducible nitric oxide synthase in rhIL-2-activated NK cells. By using cytokine array, rhG-CSF reduced secretion of growth-related oncogene (GRO)-α from NK cells. Intriguingly, rhG-CSF did not affect production of various inflammatory cytokines (MCP-1, IL-6, TNF-α, GM-CSF and IL-8) which are markedly stimulated by rhGM-CSF. Proteomic analysis of rhG-CSF- and rhGM-CSF-treated NK cells by two-dimensional gel electrophoresis and mass spectrometry uncovered unique molecules possibly involving rhG-CSF effect. These proteins were classified into 6 groups according to their functions as follows: glycolysis, apoptosis, cytotoxicity, inflammation, antigen processing and presentation, and the others. We conclude that although rhG-CSF is beneficial to myelopoiesis, it may impair NK-mediated cytotoxicity accompanied by alterations in protein expression profile distinct from that of rhGM-CSF. To validate this unwanted immune shaping by rhG-CSF, further in vivo or clinical investigations are warranted.
Dermoscopy use by French private practice dermatologists: a nationwide survey
Authors: C. Moulin, N. Poulalhon, G. Duru, S. Debarbieux, S. Dalle, L. Thomas
Journal: British Journal of Dermatology (2012)

Background Dermoscopy is now recognized as an essential tool for discriminating melanoma from other pigmented lesions, as corroborated by several robust meta-analyses. Although it is considered to be widely used in European countries, no published data on this topic are available to date, unlike in Australia and the U.S.A. Objectives To describe and quantify the use and learning of dermoscopy among French private practice dermatologists. Methods A questionnaire of 19 items regarding demographic characteristics, dermoscopy use and training, and physician's judgment on dermoscopy was mailed to all French private practice dermatologists. Only questionnaires with an answer to the key item, 'Do you use dermoscopy?' were taken into account. Results Of 3179 mailed questionnaires, 1611 were returned and 1576 were analysable (49·6%). Most respondents declared using dermoscopy (94·6%), using their dermoscope several times a day (82·7%) and/or for the diagnosis of nonpigmented lesions (87·7%). Physicians learned dermoscopy mainly through books (75·8%) and/or conferences (88·6%); 12·8% reported a dedicated university degree. Dermoscopy helps to detect melanoma earlier and to perform fewer biopsies according to 86·6% and 74·6%, respectively. On multivariate analysis, female sex and age under 45 years were significantly associated with higher utilization rate of dermoscopy [odds ratio 1·89, 95% confidence interval (CI) 1·15–3·10; and 2·85, 95% CI 1·14–7·11, respectively]. Conclusions This is the first published nationwide survey of dermoscopy practice in Europe. Despite potential classification and/or selection bias, the particularly high penetration rate found in our study suggests that dermoscopy is now widely accepted by French private practice dermatologists for the routine management of both pigmented and nonpigmented lesions.
Abstract P267: Cardiorespiratory Fitness Does not Attenuate the Association Between Adiposity and Blood Lipids in Children and Adolescents: Project HeartBeat! (1991-1995)
Authors: Olakunle A Folorunso, Christina M Shay, Kai Ding, Susan B Sisson, Sheryl L Magzamen, R S Day, D M Hallman, Darwin R Labarthe
Journal: Circulation (2014)

Background: Higher levels of adiposity are associated with unfavorable blood lipid levels in pediatric populations. However, little is known about the extent to which cardiorespiratory fitness attenuates this association. Methods: Participants ages 8-16 years (n=256) with valid measures of blood lipids, cardiorespiratory fitness (CRF) and adiposity were examined from Project Heartbeat!, a longitudinal study of cardiovascular risk factors among children and adolescents. CRF was assessed by maximum oxygen uptake: VO 2max (mL/kg/min) measured during treadmill testing and adiposity was assessed by percent body fat (PBF) estimated using sex-specific formulas incorporating bioelectric impedance and six-site skinfold measures. Fasting blood lipids included total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C). Linear regression was used to quantify cross-sectional associations between CRF and adiposity with blood lipids by sex and pubertal status (Tanner stage 1 vs. 2-5). Results: When examined individually, higher PBF and lower VO 2max were associated with more favorable levels of blood lipids in pre-pubertal boys, however, the associations were not consistent across all sex/puberty groups (Table 1). In multivariate models where both VO 2max and PBF were included, PBF remained significant for all blood lipids in pre-pubertal boys but only with TC and LDL-C in pre-pubertal girls. Among pubertal participants, only TG remained significantly associated with PBF when similarly accounting for VO 2max . Conclusions: Prior to the onset of puberty, higher adiposity is independently associated with more favorable levels of TG and HDL-C in boys and TC and LDL-C in girls even after accounting for CRF. During puberty, the majority of these associations are greatly attenuated, which further highlights the complexities associated with examining correlates of blood lipids in developing children.
Gigantism, Acromegaly, and <i>GPR101</i> Mutations
Authors: Adrian F Daly, Giampaolo Trivellin, Constantine A Stratakis
Journal: New England Journal of Medicine (2015)

report a recurrent activating GPR101 mutation (p.E308D) in 11 of 248 tumor DNA samples from patients with isolated acromegaly.Of these patients, 3 carried a germline GPR101 mutation.Two of the 3 patients are being treated at our institution and were identified among 38 patients from our cohort.This might suggest a higher prevalence of germline GPR101 mutation among French patients with sporadic acromegaly.We therefore screened our entire cohort of 263 patients with gigantism or acromegaly for germline mutations in GPR101, which encodes a G-protein-coupled receptor, and in AIP, which encodes aryl hydrocarbon receptor-interacting protein (Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org).Only 3 patients (1.1%), including the 2 patients who were reported previously, had the GPR101 p.E308D mutation; all 3 of these patients had adult-onset sporadic acromegaly.This finding shows that the prevalence of this germline mutation in our large cohort is very similar to that reported by Trivellin et al.In addition, we identified in a patient with sporadic acromegaly a novel GPR101 p.D366E variant (0.4%), which was not reported in the databases of the Exome Aggregation Consortium (ExAC), 1000 Genomes Project, dbSNP, or Exome Variant Server.Germline AIP mutations were identified in 8 of 263 patients with somatotropinomas (3.0%), of whom 6 patients (75%) have gigantism. 2None of the 263 patients carried germline mutations in both GPR101 and AIP.
Plasmin inhibitor reduces T-cell lymphoid tumor growth by suppressing matrix metalloproteinase-9-dependent CD11b+/F4/80+ myeloid cell recruitment
Authors: M Ishihara, C Nishida, Y Tashiro, I Gritli, J Rosenkvist, M Koizumi, Y Okaji, R Yamamoto, H Yagita, K Okumura, M Nishikori, K Wanaka, Y Tsuda, Y Okada, H Nakauchi, B Heissig, K Hattori
Journal: Leukemia (2011)
Abstract P169: Ethnic Disparities In Short- And Long-term Prognosis After A First Cardiovascular Hospitalization
Authors: Louise Van Oeffelen, Charles Agyemang, Carla Koopman, Karien Stronks, Michiel Bots, Ilonca Vaartjes
Journal: Circulation (2014)

Introduction: Ethnic disparities in prognosis after a cardiovascular event have been reported. We investigated differences in mortality and readmission after a first hospital admission for total cardiovascular disease (CVD), AMI, CVA, peripheral arterial disease (PAD), and congestive heart failure (CHF) between several ethnic minority groups and the Dutch majority population. Methods: A nationwide prospective cohort of CVD patients hospitalized between 1998 and 2010 was constructed (N=776,574). Differences in short- and long-term mortality and readmission (0-28 days after admission and 28 days-5 years after admission respectively) between first generation ethnic minority groups (henceforth: migrants) and the Dutch majority population were calculated using multivariable Cox proportional hazard models . Results: In particular mortality after AMI and CVA was higher in migrants compared to the Dutch majority population, except for Moroccans. Short- (HR 1.36; 1.07-1.74) and long-term ( HR 1.45; 1.20-1.75) mortality after CVD was the highest in Chinese migrants. Short-term readmission rates were similar between migrants and the Dutch majority population, except after AMI where mainly lower rates were found (HR:0.37-1.26). Long-term readmission rates were also similar to the Dutch majority population, except after CHF where readmission rates were lower (HR varies between 0.67-0.95), and after AMI where readmission rates for AMI were higher (HR varies between 1.24-1.83). Conclusion: Short- and long-term mortality after CVD is higher in migrant groups than in the Dutch majority population, except after CHF. Differences in readmission rates were more similar to the Dutch majority population, with some fluctuations between sub diseases and migrant groups.
Mutations and Allelic Loss of <i>p53</i> in Primary Tumor DNA From Potentially Cured Patients With Colorectal Carcinoma
Authors: Ann Forslund, Christina Lönnroth, Marianne Andersson, Hans Brevinge, Kent Lundholm
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To compare p53 alterations in survivors and nonsurvivors after surgery for colorectal cancer. PATIENTS AND METHODS: Twenty-nine potentially cured patients with colorectal carcinoma, without recurrent disease for more than 6 years after their primary surgery, were selected to match a group of 41 colorectal cancer patients with early metastatic spread to the liver. All patients were screened for mutations in the p53 gene, exons 5 to 9, by denaturing gradient gel electrophoresis and subsequent sequencing. RESULTS: The frequency of p53 mutations was significantly different in cured patients (60%) compared with patients with early relapse (41%, P &lt; .05). A significant difference was found in the distribution of mutations, indicating that potentially cured patients had a different proportion of mutations in conserved regions of p53 (P = .02). This difference was explained by a significantly different frequency of mutations in exon 8 (40% v 15%, P = .03), which is part of the conserved region V. All mutations in region V were codon 273 mutations in cured patients, whereas three of four mutations were located in codon 273 in patients with metastatic disease. Allelic loss of p53 (loss of heterozygosity [LOH]) was demonstrated in 26% of the cured patients and in 39% of patients with metastatic disease (P = .36). The combination of mutation and LOH of p53 was the same (17%) in both groups. CONCLUSION: A large number of p53 mutations in colorectal cancer do not promote disease progression. Some mutations, particularly within conserved regions, may even counteract negative functional effects of other p53 structural alterations. A complete loss of p53 function was not related to survival or progression after curative operation of colorectal carcinoma.
Abstract 20484: Enah/Vasp-Like Protein is a Critical Component in S1P-Mediated Endothelial Lamellipodia Formation
Authors: Joseph B Mascarenhas, Ghassan Mouneimne, Carol C Gregorio, Mary E Brown, Ting Wang, Steven M Dudek, Joe G Garcia
Journal: Circulation (2014)

Ena/VASP like protein, or EVL, is an actin-binding protein that regulates cancer cell lamellipodia protrusive activity and cell motility via an actomyosin contractility-dependent mechanism. The function of EVL in human lung endothelial cell (EC) barrier regulation, especially by the endogenous bioactive lipid mediator sphingosine-1-phosphate (S1P), is largely unknown. In this current study, we demonstrated that EVL is an active component in S1P-mediated EC barrier enhancement and lamellipodia formation. Compared to other focal adhesion (FA) proteins such as paxillin, EVL protein expression is very low in human pulmonary endothelial cells (ECs). S1P (1 μM) challenge stimulates translocation of cytosolic EVL to FAs in ECs, which was attenuated by EVL knockdown (KD) by its selective siRNA. S1P also promoted significant EVL translocation to lamellipodia, further confirmed by tracking translocation of EVL-GFP fusion protein upon S1P stimulation in a time-dependent manner. In addition, S1P-mediated cortical actin filament formation is attenuated by EVL KD, further confirming the function of EVL in S1P-induced lamellipodia formation/cortical actin polymerization. S1P stimulates EVL phosphorylation by tyrosine kinase c-Abl which is attenuated by the c-Abl inhibitor, imatinib. Finally, EVL KD attenuated S1P-mediated EC barrier enhancement and paracellular gap resealing reflected by reduced transendothelial electrical resistance (TER) measurements. These findings confirm a novel role for EVL in human lung vascular barrier enhancement and cytoskeleton rearrangement by S1P.