tbuckley/cabot-search huggingface dataset:
Abstract 19583: Autonomous and Non-Autonomous Defects Underlie Hypertrophic Cardiomyopathy in BRAF-Mutant hiPSC-Derived Cardiomyocytes
Authors: Rebecca Josowitz, Sonia Mulero-Navarro, Christine Falce, Ninette Cohen, Erik M Ullian, Lauren A Weiss, Katherine A Rauen, Eric A Sobie, Bruce D Gelb
Journal: Circulation (2014)

Hypertrophic cardiomyopathy (HCM) is a pathological disorder predominantly due to mutations in sarcomeric components. Germline mutations in BRAF cause a developmental syndrome called cardio-facio-cutaneous syndrome (CFCS), in which 40% of patients also develop HCM. Since the role of the RAS/MAPK pathway in HCM is still unclear, we generated a human induced pluripotent stem cell model for CFCS from three patients with activating BRAF T599R or Q257R mutations. In order to examine hiPSC-derived cell-type specific phenotypes and cellular interactions underpinning HCM, we generated a method to purify cardiomyocytes and non-cardiomyocytes simultaneously by cell sorting based on SIRPα and CD90 expression. Purified BRAF-mutant SIRPα+/CD90- cells were &gt;95% cardiomyocytes, displayed cellular hypertrophy with pro-hypertrophic gene expression, and dysregulation of the RAS/MAPK pathway. BRAF-mutant cardiomyocytes also displayed intrinsic calcium handling defects, including increased calcium transient irregularity and increased stored calcium within the sarcoplasmic reticulum. In addition, purified BRAF-mutant SIRPα-/CD90+ cells, which were fibroblast-like, displayed activation of the RAS/MAPK pathway and exhibited a pro-fibrotic phenotype. Cross-culture studies revealed that BRAF-mutant fibroblast-like cells critically modulate cardiomyocyte hypertrophy through TGFβ paracrine signaling, as TGFβ inhibition prevented cardiomyocyte hypertrophy induced by BRAF-mutant fibroblast-like cells. Additionally, inhibition of RAS/MAPK signaling was capable of rescuing BRAF-mutant cardiomyocyte hypertrophy and cardiomyocyte-intrinsic calcium handling abnormalities. Thus, we show for the first time that cell autonomous and non-autonomous defects underlie RASopathy-associated HCM. As fibroblast activation has been documented previously in sarcomeric HCM, our findings suggest that cardiac fibroblasts may contribute to pathologic hypertrophy in addition to causing fibrosis in primary forms of HCM. TGFβ inhibition may be a useful therapeutic option for patients with HCM due to RASopathies or other etiologies.
Analyzing images of endobronchial ultrasonography (EBUS) using histogram to assist in the diagnosis of lung cancer
Authors: Kei Morikawa, Noriaki Kurimoto, Masamichi Mineshita, Teruomi Miyazawa
Journal: European Respiratory Journal (2012)

Background  Recently, brushing and biopsy techniques of EBUS using a Guide Sheath (EBUS-GS) is available for the diagnosis of lung cancer. Obstetrics and gynecology fields have previously reported that quantification of sonographic echogenicity with histogram were useful for the diagnoses of tissue.  Aim  To evaluate whether histogram data collected from EBUS-GS images can contribute to the diagnosis of lung cancer or not.  Methods  Fifty clear EBUS images (25 lung cancer and 25 inflammatory disease) were included in this study. The region of interest (ROI), was set within a 5mm radius from the EBUS probe with 400 pixels (20×20). Histograms were created and compared using imageJ software, with a width of the histogram: (maximum – minimum gray scale) / 256 (full gray scale) × 100 (%), height of the histogram: (maximum pixel counts), and the standard deviation of the histogram.  Results  The diagnosis yield by the width of the histogram were sensitivity of 84%, specificity of 88%, and positive predictive value of 87% when the cut-off level was 22 for lung cancer. Standard deviation of histograms also contribute to diagnosis of lung cancer, sensitivity of 80%, specificity of 88%, and positive predictive value of 87% when the cut-off level was 10.7. Height of the histogram was not useful due to low sensitivity.  Conclusion  The width and standard deviation of EBUS image histograms were useful in differentiating lung cancer from inflammatory lesion.
Abstract 2589: Combined Perfusion and Non-Invasive Coronary Angiography in Patients with Suspected Coronary Disease using 256 Row, 0.5 mm Slice Thickness Non-Helical Multi-Detector Computed Tomography
Authors: Richard T George, Albert C Lardo, Kakuya Kitagawa, Omair Yousuf, Hyuk-Jae Chang, Armin Arbab-Zadeh, Julie M Miller, David A Bluemke, Joao A Lima
Journal: Circulation (2007)

Introduction: Full volumetric cardiac imaging over a single heart beat using a 256 row multidetector computed tomography scanning system provides distinct advantages over the current generation of MDCT scanners. 256x0.5mm MDCT allows for a protocol that combines MDCT angiography (MDCTA) with rest and stress CT perfusion (CTP) imaging. The purpose of this study was to test the accuracy of combined 256x0.5mm MDCTA and CTP in patients with suspected coronary artery disease. Methods: Nineteen patients with a positive single photon emission computed tomography (SPECT) perfusion study were imaged by 256 row MDCT with 0.5mm slice thickness (12.8 cm coverage) during one heart beat in a non-helical mode. Stress CTP (120kV, 100mAs, 3 gantry rotations at 0.5 secs, 7.7mSv dose) during adenosine infusion (140μg/kg/min) was followed by rest CTP and CTA (120kV, 175mAs, 3 gantry rotations at 0.5 secs, 13.5mSv dose). Using a territory based analysis; rest and stress CTP images were visually assessed for subendocardial perfusion deficits, CTA was evaluated for stenoses ≥50%, and SPECT images were evaluated for reversible and fixed perfusion deficits. In a second analysis the gold standard for ischemia secondary to epicardial atherosclerosis was defined as a SPECT perfusion deficit in a territory supplied by a coronary artery with a stenosis ≥50%. Results: Compared to ≥50% stenosis by CTA, the sensitivity and specificity of CTP was 85% and 77% compared to 69% and 74% by SPECT. More importantly, when considering the combination of ≥50% stenosis by CTA and a corresponding perfusion deficit on SPECT as the gold standard for ischemic CAD, the sensitivity and specificity for combined CTA and CTP imaging was 78% and 90%. The area under the ROC curve for the combination of CTA and CTP was 0.84, p&lt;0.001. Conclusions: In patients with suspected coronary artery disease, 256x0.5mm MDCT enables the combination of non-invasive CT angiography and CT perfusion imaging with high accuracy and at radiation levels similar to currently used dual isotope nuclear imaging techniques.
Officials Halt NSAID Prevention Trials
Authors: Tracy Hampton
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
The long-term stability of depressive subtypes
Authors: W Coryell, G Winokur, T Shea, J D Maser, J Endicott, H S Akiskal
Journal: American Journal of Psychiatry (1994)

This study used the concept of diagnostic stability to examine the validity of three subtypes of major depression.Patients with major depressive disorder (N = 424) were assigned baseline diagnoses according to structured interviews and the Research Diagnostic Criteria. Follow-up evaluations took place at 6-month intervals over the next 5 years and annually for an additional 3 years. During this period 424, 246, 163, and 96 of the patients who had recovered from the index episode had one, two, three, and four recurrences, respectively, of major depressive disorder. The kappa statistic was used to quantify the likelihood that patients with the psychotic, agitated/retarded, or endogenous subtype of depression in a given episode would again manifest that subtype in subsequent episodes.The psychotic subtype showed the most enduring diagnostic stability across multiple subsequent episodes. Even after three intervening episodes, patients with baseline psychotic major depression were five times more likely to develop a psychotic depression than were other depressed patients. For all three subtypes, diagnostic stability was greater for contiguous episodes than for noncontiguous episodes. Psychotic, agitated/retarded, and endogenous subtypes showed significant stability after control for the bipolar/unipolar and primary/secondary distinctions. The endogenous subtype was stable among patients with primary depression but not among those with secondary depression.The psychotic subtype was the most valid of the subtypes tested from the perspective of diagnostic stability. The fact that stability across adjacent episodes exceeded stability across more distantly spaced episodes may reflect state-dependent determinants, and these are likely to vary by subtype.
407. Comparison of Transgene Expression Driven from 4 Different Retroviral Long Terminal Repeats
Authors: Sujeong Kim, Mi-Dong Kim, Seock Kang, Chang Wan Joo, Haesook An, Karim Lee, Sunyoung Kim, Seung Shin Yu
Journal: Molecular Therapy (2004)

One of the major limitations of retroviral vectors is the low level of transgene expression in the target cells. To overcome this problem, several strategies have been employed, including the replacement of 3' long terminal repeat (LTR) with other viruses' LTR, the use of different leader sequences, and insertion of RNA export elements. In this study, we tried to evaluate the effect of LTR on transgene expression. For this purpose, we constructed a series of retroviral vectors, MT, MS, MF, and MP that had the same structure except 3' LTR: murine leukemia virus (MLV) LTR for MT, myeloproliferative sarcoma virus (MPSV) LTR for MS, spleen focus-forming virus (SFFV) LTR for MF, and murine stem cell virus (MSCV) LTR for MP. The level of gene expression from these vectors was evaluated using luciferase, stem cell factor (SCF), and enhanced green fluorescence protein (eGFP) as reporters in various cells. We found that luciferase activity driven by MSCV LTR was significantly lower than that driven by other LTRs in K562 and HT1080 cells. When SCF was used as a transgene, the SCF production from the vector containing MPSV LTR was significantly lower than that from other vectors. On the contrary, in experiments using eGFP, MPSV LTR drove the highest level of fluorescence intensity in K562 cells in spite of a low percentage of eGFP expressing cells. Our results strongly indicated that the transgene expression in retroviral vectors is influenced not only by the LTR but also by the nature of the transgenes.
76. Development of Multigene Lentiviral Vectors Containing the Encephalomyocarditis Virus IRES and Foot-and-Mouth Disease Virus 2A Cleavage Factor
Authors: Kirsten K. Langfield, Troy R. Wegman, Henry J. Walker, Guy E. Griesmann, Julie A. Sauer, Sharon A. Stephan, Mark J. Federspiel
Journal: Molecular Therapy (2004)

Recombinant measles viruses have shown potent oncolytic effects against tumors in animal models. In order to test the potential of recombinant measles viruses as virotherapy agents in humans, a large quantity of high-titer purified virus is needed. The characteristics of measles virus particles add to the difficulty of scalable purification for clinical administration: large pleomorphic size (100–300 nm), enveloped, inefficient budding from the infected cell, and cytotoxicity to the producer cell. The size and pleomorphic nature of the measles virus particles prevents a final sterile filtration step, requiring aseptic processing conditions to be maintained throughout the entire production process. In support of a Phase I clinical trial using a measles virus expressing a soluble form of carcinoembryonic antigen (MV-CEA) for treatment of ovarian cancer, a process was developed to manufacture a high-titer, large-scale, clinical-grade product using current Good Manufacturing Practices.
Novel model to evaluate changes in gene expression profile of myeloma cells in vivo following interaction with human BM microenvironment
Authors: E. P. Neri, P. Tassone, M. Shammas, Y. Tai, S. Blotta, R. Prabhala, L. Catley, P. Tagliaferri, S. Venuta, K. C. Anderson, N. C. Munshi
Journal: Journal of Clinical Oncology (2006)

7613 Background: Interaction between multiple myeloma (MM) cells and the bone marrow (BM) microenvironment plays a critical role in promoting MM cell growth, survival, migration and development of drug resistance. This interaction within the bone marrow milieu is unique and its understanding is important in evaluating effects of novel agents in vitro and in vivo. We here describe a novel murine model that allows us to study the in vivo expression changes in MM cells within the human BM milieu. Methods: In our model, BM stromal and IL-6-dependent human MM cell line, INA-6, tranduced with green fluorescent protein (INA-6 GFP+ ) was injected in human fetal bone chip implanted into SCID mice. At different time points the bone chip was retrieved, cells flushed out and GFP+ MM cells were separated by flow cytometry or purified by CD138 MACS microbeads. Similar isolation process was used on INA-6 GFP+ cells cultured in vitro and used as control. Total RNA was isolated from these cells and gene expression profile analyzed using the HG-U133 array chip (Affymetrix). Results: We report that interaction between INA-6 cells and the BM microenvironment in vivo induced significant changes in expression profile; specifically, we observed up-regulation of genes implicated in cell growth; DNA transcription; chromosome structure; cell-cell signaling and adhesion. We also observed down-regulation of genes involved in apoptosis and cell death. To determine which biological pathways are modulated by interaction between MM cells and human stroma, all genes were subjected to Ingenuity Pathway Analysis. Our results indicate that the most relevant pathways modulated by the interaction between MM cells with BMSCs are involved in cell-cycle regulation, apoptosis and integrin signaling, as well as with IL-6, IGF1 and PI3K/AKT, p38-MAPK and ERK/MAPK-mediated pathways. These results are consistent with previously observed in vitro cell signaling studies. Conclusions: Taken together these results highlight the ability of BM microenvironment to modulate the gene expression profile of the MM cells in vivo. This model now provides us with an opportunity to study in vivo effects of novel agents on MM cells expression profile, to pre-clinically characterize their activity. No significant financial relationships to disclose.
Patterns of recurrence after resection surgery of lung cancer: Clinical correlations and survival
Authors: María Gabriela Cortez Montero, Raquel Dacal Quintas, Jose Abal Arca, Maria Jesus García García, Maria Teresa Alves Perez, Pedro Marcos Velazquez
Journal: European Respiratory Journal (2011)

Objectives: Analyze the patterns of recurrence and survival in lung cancer patients underwent surgery

Material and methods: Observational, retrospective cohort of lung cancer patients undergoing surgery during years 1999-2006 in CHOU-Spain. We performed a descriptive analysis of data, the continuous variables to be non-Gaussian are shown as median and categorical variables as frequencies and percentages. We determined the clinical factors associated with recurrence and survival by Kaplan-Meier curves and Cox regressions models. We used SPSS 15.0 software

Results: 168 patients underwent surgery, of whom 79.8% were men, and the median age was 67 years [35-82], 74 ex-smokers (44%) and 63 active smokers (37.5%). Most common histological type was epidermoid 88 (52.4%) followed by adenocarcinoma 48 (28.6%). The median tumor size in CM was 3.3 [0-9], and moderate degree of differentiation in 77 (45.8%). The pathological stages were: I 91 (57.6%), II 26 (16.5%), IIIA 30 (19%), IIIB 11 (6.5%). The most frequent surgical resection was lobectomy. Recurrence occurred in 78 (46%) patients, related with tumor size (p = 0.002) and pathological stage (p <0.001), no differences in the histological subtype (p = 0.232). Coughing and CNS disorders were the most prevalent symptoms of recurrence and extrathoracic involvement was in 42 cases (58.3%). The median survival in those who had recurrence was 9 months, with 95% CI [5.129 to 12.871]. Other risk factors of death were tumor size (p = 0.002) and pathological stage (p <0.001)

Conclusions: Most patients do not relapse. Recurrence was more frequent extrathoracic location. The tumor size and advanced stages determine higher risk of recurrence and mortality.
Abstract 93: Sestrin2 Mediates the LKB1-AMPK Signaling Cascade in the Ischemic Heart
Authors: Alex Morrison, Chao Tong, Jun Hee Lee, Michael Karin, Ji Li
Journal: Circulation Research (2012)

Background: AMP-activated Protein Kinase (AMPK) has emerged as a pertinent stress-activated kinase shown to have substantial cardioprotective capabilities against myocardial ischemia/reperfusion (I/R) injury. The regulation of AMPK in the ischemic and reperfused heart is critical to the development of new therapeutic strategies. We hypothesized that a novel stress-inducible protein, sestrin2, mediates AMPK activation in the ischemic heart. Methods and Results: C57BL/6 mice were subjected to left anterior descending coronary artery occlusion for different time points of ischemia and I/R in order to detect the signaling activity in the left ventricle. The kinetics of AMPK phosphorylation at Thr 172 of the α catalytic subunit appears brief and bell-shaped, peaking around 10 min (3.6-fold vs. sham, p &lt;0.01), decreasing with prolonged ischemia, and leveling off to basal levels upon reperfusion. Intriguingly, at 10 min of ischemia, there was also a robust increase in p53 accumulation compared to basal conditions. Consequently, sestrin2 a p53-inducible protein, accumulates at the peak of ischemic AMPK activation (10 min, 2.5-fold vs. sham, p &lt;0.05). Respective left ventricle lysates were immunoprecipitated with sestrin2 and the immunoblots revealed that sestrin2 forms a complex with AMPK during I/R, moreover, AMPKα2 is the predominant isoform that interact with sestrin2 as compared to AMPKα1 isoform during I/R. Interestingly, LKB1, an upstream AMPK kinase becomes significantly associated with sestrin2 (5 min), while there is a dramatic interaction between sestrin2 and p-AMPK (Thr 172 ) (10 min), suggesting the interaction of LKB1 with sestrin2 initiates the phosphorylation of AMPK in this complex. Furthermore, sestrin2 knock out hearts demonstrate impaired ischemic AMPK activation and higher sensitivity to I/R-induced injury as compared to wild type hearts ( p &lt;0.01). Conclusions: Here we show for the first time evidence of a unique mechanism that sestrin2 is a stress-induced scaffold protein that mediates the activation of AMPK in the ischemic myocardium via a time-dependent interaction with LKB1. Moreover, sestrin2 deficiency leads to blunted ischemic AMPK activation and increased sensitivity to ischemic insults.
Abstract P122: Fidelity to Motivational Interviewing and Weight Loss in Young Adults: Cellphone Intervention for You (CITY) Trial
Authors: Crystal C Tyson, Pao-Hwa Lin, Leonor C Corsino, Bryan C Batch, John A Gallis, Steven C Grambow, Jenifer Schwager, Denise Ernst, Laura P Svetkey
Journal: Circulation (2015)

Background: Weight loss interventions for obese young adults may reduce serious health complications later in life. Motivational Interviewing (MI) is part of behavioral weight loss intervention. Effective delivery of MI is variable; therefore, we assessed whether fidelity to MI was associated with change in weight and dietary pattern in overweight/obese young adults. Methods: The Cellphone Intervention for You (CITY) trial was a 24-month behavioral intervention that randomized 365 overweight/obese (BMI &gt;25 kg/m2) young adults (aged 18-35 years) to a weight loss program delivered by either mobile technology or interventionist-led personal coaching (PC) phone calls, or to a control condition. PC participants attended a series of 6-weekly group meetings immediately followed by monthly audio-recorded phone calls conducted by an interventionist trained to deliver weight loss counseling using MI. We coded the first monthly PC phone call using Motivational Interviewing Treatment Integrity Version (MITI) 3.1.1 and evaluated the impact of MITI summary scores on changes in weight and Healthy Eating Index (HEI) at 6 months. Results: Our study population was comprised of 74 participants with available audio-recordings. There were 73% (N=54) women and 49% minorities with a mean age of 29 ± 4 years and a mean BMI of 34.7 ± 7.3 kg/m2. Mean change in weight 6 months post-randomization was -3.1 ± 5.3 kg. Mean change in HEI was 3.3 ± 4.7. Mean MITI summary scores for global spirit, percent complex reflections and reflection-to-question ratio were 3.9 ± 0.8, 0.6 ± 0.3, and 0.5 ± 0.2, respectively. None were predictive of weight change 6 months post-randomization (table 1). Percent complex reflection was predictive of HEI, with a counterintuitive negative relationship (table 1). Conclusions: In our study population of overweight/obese young adults, greater fidelity to MI in the first coaching call was not associated with greater weight change or improved HEI. Additional research is needed to further explore the impact of MI on behavior.