tbuckley/cabot-search huggingface dataset:
Signs of immune activation and local inflammation are present in the bronchial tissue of patients with untreated early rheumatoid arthritis
Authors: Gudrun Reynisdottir, Helga Olsen, Vijay Joshua, Marianne Engström, Helena Forsslund, Reza Karimi, C Magnus Sköld, Sven Nyren, Anders Eklund, Johan Grunewald, Anca I Catrina
Journal: Annals of the Rheumatic Diseases (2015)

Objectives Events in the lungs might contribute to generation of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). We investigated if signs of immune activation are present in bronchial biopsies and bronchoalveolar lavage (BAL) of patients with early-untreated RA without clinical signs of lung involvement. Methods Twenty-four patients with RA with symptom duration &lt;1 year and naïve to disease-modifying antirheumatic drugs were subjected to bronchoscopy where BAL and mucosal bronchial biopsies were retrieved. For comparison, 15 bronchial biopsies and 79 BAL samples from healthy volunteers were available. Histological examination was performed to evaluate lymphocyte infiltration, presence of immune cells (T and B cells, plasma cells, dendritic cells and macrophages) and immune activation markers. Cell composition of BAL samples was analysed by differential counting and T cell subsets by flow cytometry. Results Lymphocyte infiltration was more frequently found in ACPA-positive patients (50%) as compared with ACPA-negative patients (17%) and controls (13%). Germinal centres, B cells and plasma cells were only found in ACPA-positive patients. The frequency of T cells in bronchial biopsies of patients with ACPA-positive RA was positively associated with expression of immune activation markers. BAL samples of patients with ACPA-positive, but not ACPA-negative, RA had significantly higher relative numbers of lymphocytes and expressed higher levels of activation markers compared with controls. Conclusions Signs of immune cell accumulation and activation are present both in the bronchial tissue and in BAL of untreated patients with early RA without concomitant lung disease, strengthening the role of the lung compartment as an important player in ACPA-positive RA.
Detection of individual post translational modifications and protein interactions using in situ Proximity Ligation Assay (in situ PLA)
Authors: Erik Nystrom, Ann-Catrin Andersson, Katerina Pardali
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

LB-299 

The in situ Proximity Ligation Assay ( in situ PLA) enables visualization and detection of endogenous protein interactions and protein modifications in native, unmodified cells. Both over expression and fusion protein strategies can be avoided, making it ideal to study signaling pathways. In situ PLA requires dual antibody recognition of the target (e.g. protein complex) making the assay specific. The signals from individual targets are amplified, due to a DNA amplification process, to an extent that single molecule events can be visualized with a standard fluorescence microscope. The generic approach, using a secondary antibody system, enables in situ detection of endogenous protein complexes and post translational modifications using standard primary antibodies.    We present data visualizing the formation of individual endogenous transcription factor complexes. The formation of SMAD protein complexes in the TGF-β pathway were visualized with in situ PLA after treatment with the TGF-β ligand. The relative numbers of SMAD protein complexes were quantified before and after treatment. Cells were analyzed individually and the nuclear or cytoplasmic localization was established for each detected complex. The level of detect complexes can determine the activation status of the pathway, and in situ PLA can be used to study protein complex perturbations, in different pathways, causing diseases.    Using in situ PLA we also investigated the phosphorylation status of individual PDGF receptors in response to treatment with PDGF-BB. Single cells were analyzed and the relative numbers of phosporylated receptors were quantified. Due to the binding specificity of the primary antibodies used in assay, we detected tyrosine phosphorylated PDGFR-β. To investigate the spread of modifications within the cell population the cells were analyzed individually.
Announcement: Sarcomeric cardiomyopathies: from bedside to bench and back: to be published by end 2014
Authors: L. Carrier, J. van der Velden
Journal: Cardiovascular Research (2014)

Cardiovascular Research publishes Focus review issues devoted to a specific research topic. A Focus issue on ‘ Sarcomeric cardiomyopathies: from bedside to bench and back ’ will bring together a series of papers that highlight recent advances …
PARALYSIS IN CHILDREN DUE TO THE BITE OF WOOD-TICKS
Journal: JAMA (1921)

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
Ten year retrospective analysis of BOP (bleomycin, vincristine, predinisone)—A novel non-myelosuppressive chemotherapy regimen for treatment of non-Hodgkin’s lymphoma
Authors: A. Chan, D. Nay, W. Hopman, P. Galbraith, T. Baetz
Journal: Journal of Clinical Oncology (2006)

17560 Background: Non-Hodgkin’s Lymphoma (NHL) represents the most common hematological malignancy in North America. Patients with advanced NHL, particularly those with pancytopenia, often do not tolerate the myelosuppressive side effects of chemotherapy. BOP (Bleomycin 10 mg/m 2 IV D1, Vincristine 1.4 mg/m 2 (max 2 mg) D1 and Prednisone 100 mg PO on D1,3,5,) q weekly ± Rituximab 375 mg/m 2 IV D1 has been used as a non-myelosuppressive chemotherapy regimen for patients with advanced NHL at the Cancer Centre of Southeastern Ontario (CCSEO). Methods: This was a retrospective chart review of patients with NHL who have been treated with ≥1 cycle of BOP ± R at the CCSEO in the last 10 years. Primary endpoints included an assessment of patient demographics, clinical setting, clinical response, survival and toxicity. Results: Eighty-two patients were treated with BOP ± R (71 BOP, 11 R-BOP). The patient population was 59% male and 80% stage ≥3. The most common histology was Diffuse Large B cell Lymphoma (22%) and Follicular Lymphoma (19.5%). Eighty percent of patients had an IPI score ≥2. The median number of chemotherapy treatments prior to BOP was 2. Overall, the response rate (CR + PR) was 46.3% with a mean duration of response of 4.6 months. Median survival was 3.8 years. BOP was used successfully as a salvage regimen prior to stem cell transplant in three patients and as a first line treatment prior to myelosuppressive treatment in 19 patients. The regimen was generally well tolerated with no hematologic toxicity or infectious complication. Four patients experienced mild pulmonary toxicity. There were no deaths attributable to drug toxicity. Response rates and toxicities in the R-BOP population were not significantly different from those of BOP. Conclusions: Patients with advanced poor prognosis NHL have a favorable response rate associated with minimal toxicity to the non-myelosuppressive chemotherapy regimen BOP ± R. No significant financial relationships to disclose.
Responding to Suffering
Authors: Ronald M. Epstein, Anthony L. Back
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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 15888: Scamc-1 is a Novel Extracellular Vesicle Protein Linked to Vascular Calcification
Authors: Joshua D Hutcheson, Claudia Goettsch, Natalia Maldonado, Piero Ricchiuto, Sasha A Singh, Elena Aikawa
Journal: Circulation (2014)

Introduction:  Calcification is an excellent predictor of cardiovascular morbidity and mortality. Microcalcifications in thin fibrous caps of atherosclerotic plaques create biomechanical instability, leading to plaque rupture and subsequent myocardial infarction and stroke. We previously showed that cellular-derived extracellular vesicles (EVs) play a role in the microcalcification nucleation; however, the mechanisms remain unknown. We hypothesize that the aggregation of specialized EVs with a unique proteomic fingerprint serve as nucleating foci for microcalcifications.   Methods and Results:  Transmission electron microscopy of atherosclerotic plaques indicated aggregation of EVs within regions of disrupted collagen. Using super-resolution confocal microscopy and a near-infrared calcium tracer we observed EVs derived from human coronary artery smooth muscle cells (SMCs) cultured in osteogenic media (OM) aggregating to form microcalcifications within collagen hydrogels, a 3D model of fibrous cap. After 21 days in OM, SMCs produced an endogenous collagen matrix with entrapped microcalcifications. We collected the conditioned media from SMCs cultured in OM or control media for 21 days (enriched in non-calcifying EVs) and a collagenase digestion was performed to obtain the trapped calcifying EVs. Mass spectrometry with tandem mass tagging was used to assess the proteome of each EV population. Cluster analyses of the 621 identified proteins (> 2 unique peptides) revealed 131 proteins that increased in OM and trapped within the collagen matrix. SCaMC-1 was 3.2 fold increased in EVs from SMCs cultured in OM. A protein with homology to SCaMC-1 was recently shown to induce calcium mineralization in the Japanese pearl oyster and calcium phosphate deposition in the mitochondria of cancer cells, suggesting its role in biomineralization. We further performed immunostaining of calcified human carotid arteries that revealed a colocalization of SCaMC-1 expression and microcalcifications, while SCaMC-1 was not detected in non-calcified regions of the tissue.   Conclusions:  Here, we identify SCaMC-1, a calcium-dependent ATP transporter previously unreported in vascular calcification, that is associated with EV mineralization.
Soy-Based Infant Formula Feeding and Ultrasound-Detected Uterine Fibroids among Young African-American Women with No Prior Clinical Diagnosis of Fibroids
Authors: Kristen Upson, Quaker E. Harmon, Donna D. Baird
Journal: Environmental Health Perspectives (2015)

Early-life soy phytoestrogen exposure has been shown in Eker rats to increase uterine fibroid incidence in adulthood. Two large epidemiologic cohorts have provided some support for increased fibroid risk with infant soy formula feeding in women, but both cohorts relied on self-report of clinically diagnosed fibroids.We evaluated the relationship between infant soy formula feeding and ultrasound-detected fibroids.The Study of Environment, Lifestyle & Fibroids (SELF) is an ongoing cohort study of 1,696 African-American women ages 23-34 years with baseline ultrasound screening to detect and measure fibroids ≥ 0.5 cm in diameter. Questionnaire data on soy formula feeding during infancy was ascertained for 1,553 participants (89% based on mother's report), of whom 345 were found to have fibroids. We estimated the association between soy formula feeding and fibroid prevalence and tumor number using log-binomial regression. Among those with fibroids, we compared fibroid size between soy formula-exposed and unexposed women using multivariable linear regression.We did not observe an association between soy formula feeding and fibroid prevalence [adjusted prevalence ratio (aPR) 0.9, 95% CI: 0.7, 1.3]. Nor were exposed women with fibroids more likely to have ≥ 2 tumors than unexposed women with fibroids (aPR 1.0, 95% CI: 0.7, 1.6). However, exposed women with fibroids had significantly larger fibroids than unexposed women with fibroids. On average, soy formula feeding was associated with a 32% increase in the diameter of the largest fibroid (95% CI: 6%, 65%) and a 127% increase in total tumor volume (95% CI: 12%, 358%).Our observation that women fed soy formula as infants have larger fibroids than unexposed women provides further support for persistent effects of early life phytoestrogen exposure on the uterus.Upson K, Harmon QE, Baird DD. 2016. Soy-based infant formula feeding and ultrasound-detected uterine fibroids among young African-American women with no prior clinical diagnosis of fibroids. Environ Health Perspect 124:769-775; http://dx.doi.org/10.1289/ehp.1510082.
Cytosolic TMEM88 Promotes Invasion and Metastasis in Lung Cancer Cells by Binding DVLS
Authors: Xiupeng Zhang, Xinmiao Yu, Guiyang Jiang, Yuan Miao, Liang Wang, Yong Zhang, Yang Liu, Chuifeng Fan, Xuyong Lin, Qianze Dong, Qiang Han, Huanyu Zhao, Yong Han, Xu Han, Xuezhu Rong, Shuting Ding, Endi Wang, Enhua Wang
Journal: Cancer Research (2015)

Transmembrane protein 88 (TMEM88) is a transmembrane protein that plays a crucial role in regulating human stem cell differentiation and embryonic development. However, its expression and clinicopathologic significance in human neoplasms is unclear. In this study, the expression and subcellular localizations of TMEM88 were assessed in 214 cases of non-small cell lung cancer (NSCLC). Notably, TMEM88 was highly expressed in the cytosol of ∼60% NSCLC specimens examined. Higher expression of cytosolic TMEM88 in NSCLC correlated significantly with poor differentiation, high TNM stage, lymph node metastasis, and inferior survival. In NSCLC cells displaying membrane-localized TMEM88, we observed an inhibition of canonical Wnt signaling due to interactions of TMEM88 with the Wnt pathway factor Dishevelled (DVLS). In contrast, NSCLC cells with cytosol-localized TMEM88 lacked effects on Wnt signaling. Cytosolic interactions of TMEM88 and DVLS increased the expression of phosphorylated, active forms of p38, GSK3β (Thr390), and Snail, thereby reducing the expression of the tight junction-associated proteins ZO-1 and occludin, effects associated with enhanced invasive and metastatic cell characters. Importantly, attenuating the expression of cytosolic TMEM88 reduced metastatic prowess in xenograft models. Overall, our findings show how mislocalization of TMEM88 to the cytosol in NSCLC cells ablates its Wnt pathway regulatory properties, thereby promoting invasion and metastasis by activating the p38-GSK3β-Snail signaling pathway.
Multicenter, randomized phase II trial of GM-CSF (GM) plus ipilimumab (Ipi) versus ipi alone in metastatic melanoma: E1608.
Authors: F. Stephen Hodi, Sandra J. Lee, David F. McDermott, Uma N. M. Rao, Lisa H. Butterfield, Ahmad A. Tarhini, Philip D. Leming, Igor Puzanov, John M. Kirkwood
Journal: Journal of Clinical Oncology (2013)

CRA9007 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Saturday, June, 1, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Definitive concurrent chemoradiation (CRT) with weekly paclitaxel and carboplatin for patients (pts) with irresectable esophageal cancer: A phase II study.
Authors: E. V. Meerten, C. van Rij, M. E. Tesselaar, K. Neelis, D. Richel, M. Hulshof, A. V. Gaast
Journal: Journal of Clinical Oncology (2010)

e14508 Background: This multicenter phase II study investigated the efficacy and feasibility of a non-cisplatin based definitive CRT regimen consisting of carboplatin and paclitaxel and concurrent radiotherapy for pts with irresectable esophageal carcinoma. Methods: Patients with locally irresectable (T4N0-1M0) carcinoma of the esophagus received CRT consisting of RT (50.4 Gy in 28 fractions, 5 days/week) and concurrent paclitaxel 50 mg/m2 and carboplatin AUC = 2 on days 1, 8, 15, 22, 29 and 35. Results: From December 2003 to November 2007 52 patients: male/female 34/18, median age 63 (42-76), squamous/adeno/undifferentiated carcinoma 36/14/2, lymph node involvement yes/no 44/8 were enrolled. Forty-two pts completed CRT without delay or dose-reduction, 6 pts received less than 6 courses chemotherapy but completed radiotherapy, and 4 pts received less than 46 Gy radiotherapy and less than 6 courses of chemotherapy. Major toxicities (grade ≥ 3): neutropenia 16%, thrombocytopenia 4%, esophagitis 12%, fatigue 8%, pulmonary 2% and 2 pts died because of a fatal bleeding. Five pts needed to be hospitalized during CRT for bleeding (2 pts), pneumonia (2 pts), or esophagitis and non-neutropenic fever (1 pt). During CRT dysphagia improved in 23 pts and worsened in 7 pts. Five pts underwent surgery after CRT, 2 pts showed complete pathological response. The median overall survival was 17 months (1-49+). One-, two- and three-year overall survival was 64%, 32%, and 16%, respectively. The median disease-free survival was 9 months (8 pts local recurrence, 9 pts distant metastases, 13 pts both). The median time to local progression was 14 months. Conclusions: Radiotherapy with concurrent weekly paclitaxel and carboplatin as definitive treatment for irresectable esophageal carcinoma is a tolerable regimen, which can be given on an outpatient basis and leads to durable locoregional control and palliation in about half of the patients. No significant financial relationships to disclose.
Genomic analysis of mycosis fungoides and Sézary syndrome identifies recurrent alterations in TNFR2
Authors: Alexander Ungewickell, Aparna Bhaduri, Eon Rios, Jason Reuter, Carolyn S Lee, Angela Mah, Ashley Zehnder, Robert Ohgami, Shashikant Kulkarni, Randall Armstrong, Wen-Kai Weng, Dita Gratzinger, Mahkam Tavallaee, Alain Rook, Michael Snyder, Youn Kim, Paul A Khavari
Journal: Nature Genetics (2015)
Slow versus rapid progressors in idiopathic pulmonary fibrosis
Authors: Filipa Soares Pires, Carla Damas, Patrícia Mota, Natália Melo, Diogo Costa, José Miguel Jesus, Conceição Souto-Moura, Antόnio Morais
Journal: European Respiratory Journal (2011)

Background:  Idiopathic pulmonary fibrosis (IPF) is usually characterized by the insidious onset of dyspnea or cough, but there is a subgroup of patients who display a rapid progression to an end-stage disease. These two phenotypes, slow progressors (SP) and rapid progressors (RP) have not yet been fully characterized.   Aim:  To characterize SP and RP and identify baseline factors predicting each progression.   Methods:  A retrospective study with 81 IPF patients was performed. They were classified as SP and RP. Patients with acute exacerbations were excluded. Baseline differences in progression covariates or factors were assessed through U Mann-Whitney, Chi square or Fisher exact test. Median survival was estimated using Kaplan-Meier survival curves.   Results:  Patients were classified as SP in 55 (67.9%) and as RP in 10 (12.3%). Median survival time was 41 months in SP and 9 months in RP (Log Rank test p versus  73) and TLC (57.8  versus  72) and a higher percentage of non-smokers in RP group at time of diagnosis.   Conclusion:  The analysis of this group of IPF patients confirms two clearly separated phenotypes, SP and RP, that must be discriminated, since they seem to have different presentations and a remarkably different evolution. These results could mean distinct physiopathological pathways, which could implicate different therapeutic approaches.
Circlator: automated circularization of genome assemblies using long sequencing reads
Authors: Martin Hunt, Nishadi De Silva, Thomas D. Otto, Julian Parkhill, Jacqueline A. Keane, Simon R. Harris
Journal: Genome biology (2015)

The assembly of DNA sequence data is undergoing a renaissance thanks to emerging technologies capable of producing reads tens of kilobases long. Assembling complete bacterial and small eukaryotic genomes is now possible, but the final step of circularizing sequences remains unsolved. Here we present Circlator, the first tool to automate assembly circularization and produce accurate linear representations of circular sequences. Using Pacific Biosciences and Oxford Nanopore data, Circlator correctly circularized 26 of 27 circularizable sequences, comprising 11 chromosomes and 12 plasmids from bacteria, the apicoplast and mitochondrion of Plasmodium falciparum and a human mitochondrion. Circlator is available at http://sanger-pathogens.github.io/circlator/ .