tbuckley/cabot-search huggingface dataset:
Abstract 103: Cardiac Grk2 Blockade Augments β2-Adrenergic Receptor-Dependent Contractility and Survival Post Myocardial Infarction
Authors: Anastasios Lymperopoulos, Giuseppe Rengo, Erhe Gao, Walter J Koch
Journal: Circulation Research (2012)

ß 1 - and ß 2 -adrenergic receptors (ßARs) are G-protein coupled receptors (GPCRs) that play clearly distinct roles in cardiac physiology/pathology: cardiomyocyte contraction is readily stimulated by ß 1 AR but not ß 2 AR signaling, and ß 1 AR signaling is largely pro-apoptotic in the heart, in contrast to the cardioprotective ß 2 AR signaling. These differences might be due to assembly of different macromolecular complexes containing phosphodiesterases (PDEs), which constrain pro-contractile 3'-5'-adenosine monophosphate (cAMP) signaling. Additionally, ß 2 AR is readily phosphorylated by GPCR kinase (GRK)-2, which then recruits ß-arrestin (ßarr), a universal GPCR adapter/scaffolding molecule, to the receptor. ßarrs reduce ß 2 AR pro-contractile signaling by desensitizing the receptor and can either increase or decrease apoptosis via interactions with several downstream effectors. Herein, we sought to investigate the effect of ßarr recruitment blockade on ß 2 AR-dependent contractility and survival in vivo. To this end, we crossed ß 1 AR knockout (B1KO) mice, lacking the ß 1 AR, with M27 mice, which overexpress, specifically in cardiac myocytes, the GRK2 inhibitor GRK2ct (or ßARKct). By blocking GRK2-mediated phosphorylation, ßarr binding to ß 2 AR is prevented. We studied the offspring both under normal conditions and after surgically induced myocardial infarction (MI). Contractility was significantly augmented in M27/B1KO mice compared to control B1KO's, both in healthy mice (ejection fraction (EF): 69+1.8% vs. 57+1.7%, respectively, p&lt;0.05, n=8) and at 4 weeks post-MI (EF: 42.6+0.1% vs. 25+3.9%, respectively, p&lt;0.05, n=8). In addition, M27/B1KO mice exhibited less cardiac dilatation, increased survival and decreased cardiac apoptosis and infarct size, compared to B1KO's, at 4 weeks post-MI. At the molecular level, M27/B1KO hearts displayed significantly less membrane recruitment of PDEs, upregulation of the anti-apoptotic Bcl-2 and a more favorable inflammatory cytokine profile vs. B1KO hearts. Thus, cardiac GRK2 inhibition by GRK2ct increases both ß 2 AR-dependent contractility and survival in post-MI heart failure and could be pursued in situations where ß 2 AR agonism is beneficial, e.g. in patients awaiting cardiac transplantation.
Hyperthermia Enhances The Effect Of Magnetic Fe3O4nanoparticle Loaded With Daunorubicin On Leukemia and Drug Accumulation In Tumor In Vivo
Authors: Ran Liu, Weiwei Wu, Baoan Chen, Jian Cheng, Jun Wang, Jia Zhang, Wen Bao, Xiaoping Zhang, Dongsheng Zhang, Xuemei Wang
Journal: Blood (2013)
Activation of the Lin28/let-7 Axis by Loss of ESE3/EHF Promotes a Tumorigenic and Stem-like Phenotype in Prostate Cancer
Authors: Domenico Albino, Gianluca Civenni, Cecilia Dallavalle, Martina Roos, Hartmut Jahns, Laura Curti, Simona Rossi, Sandra Pinton, Gioacchino D'Ambrosio, Fausto Sessa, Jonathan Hall, Carlo V. Catapano, Giuseppina M. Carbone
Journal: Cancer Research (2016)

Abstract Although cancer stem-like cells (CSC) are thought to be the most tumorigenic, metastatic, and therapy-resistant cell subpopulation within human tumors, current therapies target bulk tumor cells while tending to spare CSC. In seeking to understand mechanisms needed to acquire and maintain a CSC phenotype in prostate cancer, we investigated connections between the ETS transcription factor ESE3/EHF, the Lin28/let-7 microRNA axis, and the CSC subpopulation in this malignancy. In normal cells, we found that ESE3/EHF bound and repressed promoters for the Lin28A and Lin28B genes while activating transcription and maturation of the let-7 microRNAs. In cancer cells, reduced expression of ESE3/EHF upregulated Lin28A and Lin28B and downregulated the let-7 microRNAs. Notably, we found that deregulation of the Lin28/let-7 axis with reduced production of let-7 microRNAs was critical for cell transformation and expansion of prostate CSC. Moreover, targeting Lin28A/Lin28B in cell lines and tumor xenografts mimicked the effects of ESE3/EHF and restrained tumor-initiating and self-renewal properties of prostate CSC both in vitro and in vivo. These results establish that tight control by ESE3/EHF over the Lin28/let-7 axis is a critical barrier to malignant transformation, and they also suggest new strategies to antagonize CSC in human prostate cancer for therapeutic purposes. Cancer Res; 76(12); 3629–43. ©2016 AACR.
Absolute lymphocyte count prior to rituximab therapy predicts time to progression in patients with follicular grade 1 lymphoma
Authors: D. Behl, S. N. Markovic, T. E. Witzig, J. P. Colgan, T. M. Habermann, D. J. Inwards, S. M. Ansell, I. N. Micallef, P. B. Johnston, L. F. Porrata
Journal: Journal of Clinical Oncology (2006)

7586 Background: The immunologic mechanisms of action of rituximab have been described as complement mediated lysis, vaccine like effect, antibody-dependent cellular cytotoxicity (ADCC) and the cellular microenvironment. We hypothesized that in the treatment of follicular grade 1 lymphoma (FL), the presence of a stronger host immune status prior to rituximab therapy would result in a prolonged time to progression (TTP). As a surrogate marker for immune status, we evaluated the absolute lymphocyte count (ALC) prior to rituximab treatment. Methods: Between 1996 and 2002, 1,104 consecutive FL patients were evaluated at Mayo Clinic Rochester. Of these patients, we retrospectively analyzed a group of all FL patients who received rituximab (375 mg/m 2 once a week for four weeks) alone at any time during their lymphoma treatment at the Mayo Clinic (n=79). The primary end-point was to assess the impact of ALC just prior to rituximab therapy on TTP for FL. Results: The median age of the cohort was 56.6 years (range: 25–98 years). The median follow-up was 12.5 months (range: 1–76 months). An ALC count of ≥ 890 cells/μL prior to rituximab therapy predicted a longer TTP compared with an ALC &lt; 890 cells/μl (25 months versus 8 months, respectively, p &lt; 0.0124). A higher complete response rate was observed in the ALC ≥ 890 cells/μL group compared with the ALC &lt; 890 cells/μL group [15/40 (38%) vs 5/39 (13%), p &lt; 0.035]. The groups were balanced regarding the Follicular Lymphoma International Prognostic Index (FLIPI) (p = 0.794). Multivariate analysis demonstrated ALC ≥ 890 cells/μL prior to rituximab therapy as an independent prognostic factor for TTP when compared to hemoglobin, LDH, and Ann Arbor stage. The ALC was independent of the FLIPI in multivariate analysis. Conclusions: This data supports the hypothesis that a higher lymphocyte count, as a marker of the immune status of the patient, predicts for a longer TTP following rituximab therapy. No significant financial relationships to disclose.
Coronary Heart Disease After Mediastinal Radiotherapy for Hodgkin Lymphoma: Can Risk Calculations From Historic Cohorts Be Used Today?
Authors: Dirk Vordermark, Tanja Pelz
Journal: Journal of Clinical Oncology (2016)

coronary heart disease (CHD) as a function of estimated mean heart dose (MHD) in a large cohort of 325 cases with CHD and 1,204 controls without CHD during the treatment period from 1965 to 1995. The authors must be congratulated for the comprehensive analysis of this large data set, and it is appropriate to include patients with long follow-up, given the delayed occurrence of radiotherapy-related CHD. However, applying the calculated risks of CHD for the different levels of MHD to patients treated today may be problematic. Because three-dimensional information on radiotherapy dose distribution in the patients studied was not available, the authors estimated the MHD from the two-dimensional blocked portion of the heart as documented on simulation films. This is a reasonable approach. However, other special aspects of radiotherapy as used in the historic cohort now being studied are not discussed but may limit the applicability of the findings of van Nimwegen et al to today’s patients. The details of radiotherapy technique for this cohort are described in a previous publication from the group to which the authors refer. 2 There they state that in the 1960s, patients were treated with cobalt-60 or orthovoltage therapy and that patients weretreatedwith onlyone field perdayuntil thelate 1980s. In their article, the authors simply state that all patients were treated with parallel opposed fields. If, in the majority of patients now being evaluated, anterior and posterior mediastinal radiotherapy fields were not treated in the same session, this might mean that biologically effective doses at cardiac structures were not as they are now estimated. The use of cobalt-60 or orthovoltage techniques, unlike linear accelerator photon techniques, leads to extreme overdosing in anterior portions of the heart, which is relevant for the calculation of coronary arterydoses as we showed previously. 3,4 The planning study by van Nimwegen et al showing that MHD can be estimated from two-dimensional imaging (ie, simulation films) was performed with recently treated patients and, apparently, it did not account for the overdosing observed with cobalt-60 techniques. 5 It seems possible that the biologically relevant doses to some cardiac structures may therefore have been higher than estimated in the present MHD-based approach and the risk of CHD per Gy in this series may be overestimated. Sixty-nine percent of controls and 82% of cases received radiotherapy prescription doses of 35 Gy or more to the mediastinum. Such high radiotherapy doses are no longer used in the treatment of Hodgkin lymphoma. The numbers of patients in the data set treated with currently acceptable radiotherapy doses (and associated heart doses) is rather low. Therefore, the information derivedfromthisuniquedatasetshould beusedwithsomecaution when counseling patients receiving mediastinal radiotherapy for Hodgkin lymphoma.
Abstract P375: Vitamin D Deficiency is Associated with Hypertriglyceridemic Waist Phenotype
Authors: Maithili Shenoy, Tushar Tuliani, Vikas Veeranna, Sandip Zalawadiya, Krunal H. Patel, Luis Afonso
Journal: Circulation (2012)

Introduction: Hypertriglyceridemic waist phenotype (TGW) is a clinical indicator of visceral obesity. Studies have shown that TGW predicts adverse cardiovascular outcomes. Vitamin D (Vit D) deficiency is a novel and reversible nutritional risk factor for metabolic syndrome and cardiovascular disease. This is the first study of its kind, looking at whether Vit D deficiency predicted TGW. Methods: We did a post-hoc analysis of 2301 subjects from the National Health and Nutrition Examination Survey III (1988-1994). Patients without Vit D, waist circumference (WC) and serum triglycerides (TG) measurements were excluded. TGW was defined as WC ≤85 cm and 90 cm and TG ≤1.5 mmol/l (132 mg/dl) and 2 mmol/l (177 mg/dl) in females and males respectively. Subjects were divided into equal quartiles based on serum vit D levels. Stata 11 was used to perform chi-square test for categorical variables, t-test for continuous variables and univariate and step-wise multivariate logistic and linear regression. Results: Out of 2301 subjects, 35% (798) met the definition of TGW. Patients with TGW were older (61±12 vs. 60±13 yrs, p 0.01), males (43% vs. 56%, p&lt;0.001), dyslipidemic (58% vs. 42%, p&lt;0.001), diabetic (17% vs. 10%, p&lt;0.001), hypertensive (63% vs. 51%, p&lt;0.001) and had lower serum vit D levels (22.1±8.7 vs. 23.2±9.2, p 0.008). Vit D level was negatively associated with TGW (coef -0.024, CI -0.036 to -0.013, p&lt;0.001). Patients having serum vit D level &gt;28 ng/ml (highest quartile) were significantly less likely to have TGW than patients having vit D level &lt;17 ng/ml (lowest quartile) after adjusting for age, sex, race, GFR, calcium, parathyroid hormone, hypertension, hypertension medications, hyperlipidemia, hyperlipidemia medications, diabetes, end stage renal disease and hemodialysis (OR 0.56, CI 0.42-0.75, p&lt;0.001). Conclusion: Vit D deficiency is an independent predictor of TGW. Randomized controlled trials are needed to determine whether supplementation will improve cardiovascular outcomes. Table 1. Vitamin D Quartile Q1 (&lt;17 ng/ml) reference category Odds ratio 95% CI P value Q2 (17-22) 0.84 0.65 to 1.09 0.19 Q3 (23-28) 0.63 0.48 to 0.83 0.001 Q4 (&gt;28) 0.56 0.42 to 0.75 &lt;0.001
EARLY DIAGNOSIS OF TUBERCULOSIS.
Authors: D Townsend
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
BACH2 regulates CD8+ T cell differentiation by controlling access of AP-1 factors to enhancers
Authors: Rahul Roychoudhuri, David Clever, Peng Li, Yoshiyuki Wakabayashi, Kylie M Quinn, Christopher A Klebanoff, Yun Ji, Madhusudhanan Sukumar, Robert L Eil, Zhiya Yu, Rosanne Spolski, Douglas C Palmer, Jenny H Pan, Shashank J Patel, Derek C Macallan, Giulia Fabozzi, Han-Yu Shih, Yuka Kanno, Akihiko Muto, Jun Zhu, Luca Gattinoni, John J O'Shea, Klaus Okkenhaug, Kazuhiko Igarashi, Warren J Leonard, Nicholas P Restifo
Journal: Nature Immunology (2016)
Impact Of Dysplasia On Outcome Of Patients With Acute Myeloid Leukemia and Response To Allogeneic Hematopoetic Stem Cell Transplantation
Authors: Shatha Farhan, Catherine Carroll, Danielle Pelland, Jose Carlos Velasco, Susan Wautelet, Kenneth Ruemenapp, Suseela M Janakiraman, Philip Kuriakose, Edward Peres, Nalini Janakiraman
Journal: Blood (2013)
HCP-20A CLINICAL CARE PATHWAY TO IMPROVE THE ACUTE CARE OF PATIENTS WITH GLIOMA
Authors: Natalie Riblet, Evelyn Schlosser, Jennifer Snide, Lara Ronan, Katherine Thorley, Melissa Davis, Jennifer Hong, Linda Mason, Tobi Cooney, Lanelle Jalowiec, Nancy Kennedy, Sabrina Richie, David Nalepinski, Camilo Fadul
Journal: Neuro-Oncology (2015)

BACKGROUND: Patients with glioma are at high risk for tumor and treatment related complications. Few guidelines exist to direct the management of these supportive care needs. Our prior work suggests that a standardized clinical care pathway can improve the care of patients with glioma. METHODS: We designed a quality improvement (QI) project to address the acute care needs of patients with glioma. We formed a multidisciplinary team and selected twenty best practice measures from the literature. Using a plan-do-study-act framework, we brainstormed and implemented various improvement strategies starting in October 2013. Statistical process control charts were used to assess progress. RESULTS: Retrospective data was available for 12 best practice measures. The baseline population consisted of 98 patients with gliomas. Record review suggested wide variation in performance, with compliance ranging from 30% to 100%. The team hypothesized that lack of process standardization may contribute to less-than-ideal performance. After implementing improvement strategies, we reviewed the records of 63 consecutive patients with glioma. The proportion of patients meeting criteria for 12 practice measures improved (65% pre QI-work; 76% post-QI work, p > 0.1), although not statistically significant. Unexpectedly, a higher proportion of patients were readmitted within 30 days of hospital discharge but the proportions for preventable readmissions were similar. Post-operative urinary tract infections (UTIs), venous thromboembolic complications and outpatient falls were identified as opportunities for improvement, with a significant decrease in the incidence of UTIs after interventions were established (p < 0.01). Barriers to pathway development included difficulties with transforming manual measures into electronic data sets. CONCLUSIONS: Creating evidence based clinical care pathways for addressing the acute care needs of patients with glioma is feasible and important. Data dashboards help to inform additional improvement work. There are many challenges, however, to developing sustainable systems for measuring and reporting performance outcomes over time.
Interleukin-15 receptor α on hepatic stellate cells regulates hepatic fibrogenesis in mice
Authors: Jingjing Jiao, Kohtaro Ooka, Holger Fey, Maria Isabel Fiel, Adeeb H. Rahmman, Kensuke Kojima, Yujin Hoshida, Xintong Chen, Tatiana de Paula, Diana Vetter, David Sastre, Ka Hin Lee, Youngmin A. Lee, Meena Bansal, Scott L. Friedman, Miriam Merad, Costica Aloman
Journal: Journal of Hepatology (2016)
LANDSCAPE: An FNCLCC phase II study with lapatinib (L) and capecitabine (C) in patients with brain metastases (BM) from HER2-positive (+) metastatic breast cancer (MBC) before whole-brain radiotherapy (WBR).
Authors: T. D. Bachelot, G. Romieu, M. Campone, V. Dieras, C. Cropet, H. H. Roche, M. Jimenez, E. Le Rhun, J. Pierga, A. Gonçalves, M. Leheurteur, J. Domont, M. Gutierrez, H. Cure, J. Ferrero, C. Labbe
Journal: Journal of Clinical Oncology (2011)

509 Background: With an incidence of 30%-40%, BM are common complications of HER2+ MBC. Their therapeutic management remains a challenge. As responses on central nervous system (CNS) localization have been reported with L+C combination after WBR, we sought to evaluate the clinical interest of this combination as 1st line treatment for BM in HER2+ MBC patients (pts) with the aim to avoid or to delay WBR. Methods: Eligible pts had HER2+ MBC with BM not previously treated with WBR, C or L. Pts received L1250 mg/day and C2000 mg/m2/day, days 1-14, every 21 days. The primary endpoint was a centrally assessed CNS objective response (CNS-OR) defined as a ≥50% volumetric reduction of CNS lesions in the absence of increasing steroid use, progressive neurologic symptoms, or progressive extra-CNS disease. Using a Simon's optimal two-stage design with a minimum interesting CNS-OR rate of 20%, 41 evaluable patients were needed. Secondary endpoints included: time to progression (TTP) for both CNS and extra CNS disease; time to WBR; prognostic and predictive value of circulating tumor cells (CTC) and toxicity. Results: From 04 /2009 to 08/2010, 45 pts were enrolled. Median age was 56 (range 35 to 79), 37 pts had multiple metastatic sites, PS was 0 (17 pts), 1 (25 pts) or 2 (2 pts); 36 pts had two or more BM and 42 had previously received trastuzumab. 41 pts received at least 2 cycles of study treatment. 43 pts were evaluable for efficacy endpoints, with a median follow-up of 10 months (range 2.9-16.5). The CNS-OR rate was 67% (95%CI 51-81), with a median time from inclusion to response of 1.8 month. Median TTP was 5.5 months (95% CI 3.9-5.9) and median time to WBR was 8.3 months (95% CI 5.1-11.7). At baseline, 21/42 pts had ≥ 1CTC, vs 7/39 at day 21, p<0.01 (correlation study ongoing). 20 patients (44%) experienced grade 3 or 4 treatment related toxicity, treatment was discontinued due to toxicity in 3 pts. At the time of analysis, 21 pts had received WBR and 10 pts had died. Conclusions: With a high response rate, L + C is an active treatment option and a viable alternative to immediate WBR for HER2+ MBC pts with newly diagnosed BM.
Hepcidin as a new biomarker for detecting autologous blood transfusion
Authors: Nicolas Leuenberger, Laura Barras, Raul Nicoli, Neil Robinson, Norbert Baume, Niels Lion, Stefano Barelli, Jean‐Daniel Tissot, Martial Saugy
Journal: American Journal of Hematology (2016)

Autologous blood transfusion (ABT) is an efficient way to increase sport performance. It is also the most challenging doping method to detect. At present, individual follow‐up of haematological variables via the athlete biological passport (ABP) is used to detect it. Quantification of a novel hepatic peptide called hepcidin may be a new alternative to detect ABT. In this prospective clinical trial, healthy subjects received a saline injection for the control phase, after which they donated blood that was stored and then transfused 36 days later. The impact of ABT on hepcidin as well as haematological parameters, iron metabolism, and inflammation markers was investigated. Blood transfusion had a particularly marked effect on hepcidin concentrations compared to the other biomarkers, which included haematological variables. Hepcidin concentrations increased significantly: 12 hr and 1 day after blood reinfusion, these concentrations rose by seven‐ and fourfold, respectively. No significant change was observed in the control phase. Hepcidin quantification is a cost‐effective strategy that could be used in an “ironomics” strategy to improve the detection of ABT. Am. J. Hematol. 91:467–472, 2016. © 2016 Wiley Periodicals, Inc.
Real-Life Efficacy Of Azacitidine In Myelodysplastic Syndromes According To IPSS Cytogenetic Profile
Authors: Massimo Breccia, Maria Teresa Voso, Luca Maurillo, Pasquale Niscola, Luana Fianchi, Maria Antonietta Aloe Spiriti, Francesco Buccisano, Sabrina Pelliccia, Susanna Fenu, Andrea Tendas, Roberto Latagliata, Giuliana Alimena
Journal: Blood (2013)
Innate recognition of Toxoplasma gondii in humans involves a mechanism distinct from that utilized by rodents
Authors: Alan Sher, Kevin Tosh, Dragana Jankovic
Journal: Cellular and Molecular Immunology (2016)

Toxoplasma gondii is an intracellular protozoan parasite that infects rodents as part of its natural transmission cycle and induces disease in humans, an end-stage host. As one of the natural hosts of T. gondii, the mouse has been used extensively for elucidating the cellular and molecular basis of immunity to this pathogen while relatively few studies have focused on the response of humans. In our recent work, we identified CD16+ monocytes and DC1 dendritic cells as the major myeloid cell populations that respond to T. gondii in human peripheral blood. Interestingly, these myeloid subsets represent the opposite counterparts from those triggered by the parasite in mice. Moreover, whereas the innate cytokine response to T. gondii in the mouse involves stimulation of Toll-like receptors by a soluble parasite ligand, the response of human cells instead requires phagocytosis of the live pathogen. We speculate that these marked distinctions in the pathways utilized for innate recognition of toxoplasma in mouse and man reflect the differing roles of the two hosts in the biology of this parasite.