tbuckley/cabot-search huggingface dataset:
CD14 is associated with biliary stricture formation
Authors: Kilian Friedrich, Mark Smit, Maik Brune, Thomas Giese, Christian Rupp, Andreas Wannhoff, Petra Kloeters, Yvonne Leopold, Gerald Ulrich Denk, Karl Heinz Weiss, Wolfgang Stremmel, Peter Sauer, Simon Hohenester, Peter Schirmacher, Peter Schemmer, Daniel Nils Gotthardt
Journal: Hepatology (2016)

The pathogenesis of intrahepatic biliary stricture formation in patients with primary sclerosing cholangitis (PSC) or after liver transplantation (LTx) remains elusive. CD14 receptor signaling is a key mediator of the innate immune system; its common genetic variant is associated with alcoholic liver disease. PSC and LTx cohort patients and primary biliary cirrhosis (PBC) control patients were genotyped for the CD14 ‐260C&gt;T (rs2569190) polymorphism, and genotypes were correlated with long‐term clinical outcome. Biliary tissue, bile, and whole blood of PSC patients and healthy controls were screened for markers of the innate immune system and bacterial infection. In 121 PSC patients, the CD14 ‐260C&gt;T genotype was associated with development of dominant bile duct strictures ( P = 0.02). In 365 LTx patients, TT carriers (4.1%) were protected against the formation of nonanastomotic biliary strictures versus CC/CT patients (12.6%; P = 0.01). Chemokine ligand 8 ( P = 0.04) and chemokine receptor 6 ( P = 0.004) were up‐regulated in biliary tissue of PSC patients with the TT versus the CC/CT genotype. Lipopolysaccharide whole‐blood stimulation resulted in a significant change in interleukin (IL)‐8 ( P = 0.05) and IL‐12p40 levels ( P = 0.04) in healthy control subjects carrying the TT genotype. TT PSC patients were protected against Gram‐negative bacterial biliary infection (TT: 0% vs. CC/CT: 22.5%; P = 0.02). Serum‐soluble CD14 levels correlated with the CD14 ‐260C&gt;T genotype ( P = 0.02), representing an independent risk indicator of survival in PSC patients (hazard ratio, 0.40; 95% confidence interval, 0.19‐0.86; P =0.01). Conclusions : The function of the innate immune response by CD14 is crucial during biliary infection and stricture formation. The benefits of CD14 signaling modification should be addressed in future studies. (H epatology 2016;64:843‐852)
Abstract 19172: Nanoparticle Delivery of Rosiglitazone Confers Tissue-Selective PPARgamma Activation
Authors: Maricela Ramirez, Jeyarama S Ananta narayanan, Jun Wang, Daniele Di mascolo, Yuelan Ren, Alan R Collins, Christopher J Lyon, Paolo Decuzzi, Willa A Hsueh
Journal: Circulation (2012)

Thiazolidinediones (TZDs) are potent, high-affinity PPARγ ligands widely used to promote insulin sensitivity that act, at least in part, by decreasing myeloid-mediated inflammatory processes. However, treatment with TZDs such as rosiglitazone (RSG) can promote edema, weight gain and cardiac failure, limiting their clinical utility. We hypothesized that RSG-loaded nanoparticles could reduce these side-effects by conferring tissue-selective drug delivery. To test this hypothesis we developed a methodology to engulf RSG in ~100nm polylactic-co-glycolic acid (PLGA) particles extensively used for nanoparticle based therapies. These particles are rapidly cleared from the circulation by phagocytic cells, and thus accumulate in tissues enriched in myeloid-lineage cells, such as liver, spleen and potentially atherosclerotic plaques and remodeling white adipose tissue (WAT) of obese subjects. To test the effects of RSG-loaded nanoparticles in vivo, male LDLR-/- mice (N=3-4/group) were randomly assigned to 1) high-fat diet (HFD) alone, 2) HFD supplemented with RSG (1.2g RSG/kg diet), or HFD and then retro-orbitally injected on days 1 and 2 with 100µg of nanoparticles containing 3) PLGA alone or 4) PLGA loaded with 50µg RSG (PLGA:RSG). Tissue samples were collected at day 3 post-treatment. RT-PCR analysis of PPARγ target genes found RSG, but not PLGA:RSG or PLGA, increased (P&lt;0.05) WAT expression of ABCG1 and CD36 and kidney expression of SCNN1A, which may contribute to TZD-mediated edema. RSG and PLGA:RSG, but not PLGA, induced FABP4 in spleen and increased or trended to increase (P&lt;0.01) ACO1, CD36 and FABP4 in liver. RT-PCR analysis of tissue samples obtained at day 6 post treatment also found increases or trends to increase in liver expression of CD36 and FABP4 in PLGA:RSG treated mice, indicating that RSG-inducible gene expression in whole-tissue persisted for at least 4 days post-treatment, and might persist longer in myeloid populations within this tissue. Taken together this data indicates that our PLGA nanoparticles can be used to selectively target RSG-mediated gene activation to specific tissues, and thus may represent a novel approach for targeting drug delivery to myeloid-rich tissues or sites, such as inflamed WAT or atherosclerotic plaque.
Crisis in general practice: the problem of “independent” contractor status
Authors: Naureen Bhatti, Azeem Majeed
Journal: BMJ (2016)

Roland and Everington rightly highlight the crisis in general practice and the need for greater investment.1 However, there is a third elephant in the room: continued support for “independent” contractor status.

There is inequity of current funding models, with three different contracts delivering variable and inequitable reimbursement based neither on measured workload nor on population …
Specific and Nonspecific Antitumor Immunity. II. Macrophage-Mediated Nonspecific Effector Activity Induced by BCG and Similar Agents&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: R N Germain, R M Williams, B Benacerraf
Journal: JNCI Journal of the National Cancer Institute (1975)

The recently described inhibition of DNA synthesis (IDS) assay, which measures antitumor effector (E) cell function by the quantltation of decreases in tritiated thymidine Incorporation of target tumor cells, was used to analyze the nonspecific effector activity of peritoneal ex~date cells (PEC) from mice infected intraperitoneally with BCG. These PEC could inhibit growth of and then kill all tumor target (effector to target) cells tested at E/T ratios as low as 1∶1. This activity was not due to alterations in media, nor could any activity be shown for cell-free supernatants prepared from active cells. The principal cell type mediating this effector function was the “activated” macrophage–no activity was found in lymphoid or polymorphonuclear leukocytes. Direct effector to target contact was necessary for the cytotoxic reaction. The time course of these effects and comparative 51Cr release data were reported. The removal of the adherent nonspecific effectors from PEC of mice immunized to both BeG and a specific syngeneic tumor revealed a specific cytotoxicity of the remaining lymphoid cells. These results indicated that nonspecific effector activity by “activated” macrophages Induced by BCG Infection could be a potent antitumor mechanism, at least in vitro, and the the IDS assay provided an accurate, reproducible, and quantitative method for measurement of the function of such E cells.
Apoptosis in bone marrow biopsy samples involving stromal and hematopoietic cells in 50 patients with myelodysplastic syndromes [see comments]
Authors: A Raza, S Gezer, S Mundle, XZ Gao, S Alvi, R Borok, S Rifkin, A Iftikhar, V Shetty, A Parcharidou
Journal: Blood (1995)
Suppression of Tumor Growth in Strain 2 Guinea Pigs by Xenogeneic Antitumor Antibody
Authors: Howard G. Smith, Monte S. Meltzer, Edward J. Leonard
Journal: JNCI Journal of the National Cancer Institute (1976)

Line 10 hepatoma cells were incubated with antiserum specific against line 10 cells (Ral 10) and then tested for growth in syngeneic Wright strain 2 guinea pigs. Palpable tumors appeared in only 11 of 23 animals inoculated Id with 105 RaL10-treated tumor cells, compared with an incidence of 21 of 23 for nonimmune rabbit serum (NRS)-treated cells and 23 of 23 for cells treated with syngeneic guinea pig serum. Animals inoculated with RaL10-treated tumor cells did not develop systemic tumor immunity. The long-term survival of guinea pigs receiving RaL10-treated tumor cells iv was 6 of 12 with a dose of 104 cells and 8 of 11 with 104 cells. None of the animals receiving 104 or 105 control tumor cells treated with NRS survived. RaL10 antiserum was not toxic to line 10 tumor cells in vitro, but mediated tumor-specific cytolytic reactions in the presence of fresh guinea pig serum or on the addition of peritoneal exudate cells from nonimmunized syngeneic guinea pigs.
Abstract 3073: Reorganization of metastamiRs in the evolution of metastatic aggressive high-risk neuroblastoma
Authors: Faizan Haider Khan, SatishKumar Ramraj, Sheeja Aravindan, Mohan Natarajan, Terence H. Herman, Natarajan Aravindan
Journal: Cancer Research (2015)

Abstract MetastamiRs have momentous clinical relevance and have been correlated with disease progression in many tumors. In this study, we identified neuroblastoma metastamiRs exploiting unique mouse models of favorable and high-risk metastatic human neuroblastoma. Further, we related their deregulation to the modulation of target proteins and established their association with clinical outcomes. Whole genome miRNA microarray analysis identified 74 metastamiRs across the manifold of metastatic tumors. RT-qPCR on select miRNAs validated profile expression. Results from bio-informatics across the ingenuity pathway, miRCancer, and literature data-mining endorsed the expression of these miRNAs in multiple tumor systems and showed their role in metastasis, identifying them as metastamiRs. Immunoblotting and TMA-IHC analyses revealed alterations in the expression/phosphorylation of metastamiRs’ targets, including ADAMTS-1, AKT1/2/3, ASK1, AURKβ, Birc1, Birc2, Bric5, β-CATENIN, CASP8, CD54, CDK4, CREB, CTGF, CXCR4, CYCLIN-D1, EGFR, ELK1, ESR1, CFOS, FOSB, FRA, GRB10, GSK3β, IL1α, JUND, kRAS, KRTAP1, MCP1, MEGF10, MMP2, MMP3, MMP9, MMP10, MTA2, MYB, cMYC, NF2, NOS3, P21, pP38, PTPN3, CLEAVED PARP, PKC, SDF-1β, SEMA3D, SELE, STAT3, TLR3, TNFα, TNFR1, and VEGF in aggressive cells ex vivo and in a manifold of metastatic tumors in vivo. Clinical outcome association analysis with the validated metastamiRs’ targets correlated strongly with poor overall and relapse-free survival. For the first time, these results identified a comprehensive list of neuroblastoma metastamiRs, related their deregulation to altered expression of protein targets, and established their association with poor clinical outcomes. The identified set of distinctive neuroblastoma metastamiRs could serve as potential candidates for diagnostic markers for the switch from favorable to high-risk metastatic disease. Citation Format: Faizan Haider Khan, SatishKumar Ramraj, Sheeja Aravindan, Mohan Natarajan, Terence H. Herman, Natarajan Aravindan. Reorganization of metastamiRs in the evolution of metastatic aggressive high-risk neuroblastoma. [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 3073. doi:10.1158/1538-7445.AM2015-3073
Abstract 14016: Adenoviral Gene Delivery Reprograms Cardiac Fibroblasts into Cardiomyocyte-like Cells with in vitro Contractile Activity: Implications for Clinical Cardiac Regeneration
Authors: Vivek P Singh, Maria J Chiuchiolo, Megumi Mathison, Hongran Wang, Erin L Reineke, Xueping Xu, Vivek K Patel, Narasimhaswamy S Belaguli, Stephen M Kaminsky, Ronald G Crystal, Austin Cooney, Todd K Rosengart
Journal: Circulation (2014)

Background:  A newly demonstrated capability to directly convert fibroblasts into cardiomyocyte-like cells (induced cardiomyocytes [iCMs]) has great potential for the in situ regeneration of functional myocardial tissue from cardiac scar tissue and treatment of cardiovascular disease. Whereas such transdifferentiation has previously been demonstrated using retrovirus and lentivirus vectors, the clinical utility of this cardiac regeneration strategy would be facilitated by the use of a non-integrating, short-term expression viral vector such as adenovirus. In the present study, we sought to determine whether rat cardiac fibroblasts could be converted to iCMs by adenoviral expression of Gata4 (G), Mef2c (M), and Tbx5 (T) and compare the efficiencies of two viral reprogramming strategies.   Methods and Results:  Human adenovirus serotype 5 (Ad5) or lentivirus expressing rat GMT or corresponding null viruses were transduced into cultures of rat primary cardiac fibroblasts. After 48 hours viruses were removed and the cells were allowed to transdifferentiate under normal culture conditions. Transdifferentiation was determined 2 weeks post-transduction by FACS and immunofluorescence (IF) analysis for the activation of endogenous cardiac troponin T (cTnT) and other cardiac markers, as well as detection of in vitro contractile activity. Consistent with IF expression patterns, FACS analysis demonstrated that the Ad encoding for GMT induced 7% of adult cardiac fibroblasts to express cTnT, compared with 6% cells treated with lentivirus encoding GMT, and 0.3% of cells treated with a null virus. Importantly, only AdGMT-treated cells demonstrated in vitro contractile activity, occurring 14 days after GMT administration.   Conclusion:  Adenoviral vectors encoding GMT effectively reprogram cardiac fibroblasts into cardiomyocyte-like cells possessing in vitro contractile activity. These findings represent an important milestone in the utilization of a clinically relevant, short-term expression (adenovirus) vector to generate induced cardiomyocytes.
GSK-3 Inhibition Sensitizes Acute Myeloid Leukemia Cells to 1,25D-Mediated Differentiation
Authors: Kalpana Gupta, Tammy Stefan, James Ignatz-Hoover, Stephen Moreton, Gary Parizher, Yogen Saunthararajah, David N. Wald
Journal: Cancer Research (2016)

1,25-dihydroxyvitamin D3 (1,25D), the biologically active form of vitamin D, is widely considered a promising therapy for acute myeloid leukemia (AML) based on its ability to drive differentiation of leukemic cells. However, clinical trials have been disappointing in part to dose-limiting hypercalcemia. Here we show how inhibiting glycogen synthase kinase 3 (GSK3) can improve the differentiation response of AML cells to 1,25D-mediated differentiation. GSK3 inhibition in AML cells enhanced the differentiating effects of low concentrations of 1,25D. In addition, GSK3 inhibition augmented the ability of 1,25D to induce irreversible growth inhibition and slow the progression of AML in mouse models. Mechanistic studies revealed that GSK3 inhibition led to the hyperphosphorylation of the vitamin D receptor (VDR), enabling an interaction between VDR and the coactivator, SRC-3 (NCOA3), thereby increasing transcriptional activity. We also found that activation of JNK-mediated pathways in response to GSK3 inhibition contributed to the potentiation of 1,25D-induced differentiation. Taken together, our findings offer a preclinical rationale to explore the repositioning of GSK3 inhibitors to enhance differentiation-based therapy for AML treatment. Cancer Res; 76(9); 2743-53. ©2016 AACR.
"SPECIES OF HYMENOLEPIS AS HUMAN PARASITES"
Journal: JAMA (1922)

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
Mental Health among displaced Syrians: findings from the Syria Public Health Network
Authors: Aula Abbara, Adam Coutts, Fouad M Fouad, Sharif A Ismail, Miriam Orcutt
Journal: Journal of the Royal Society of Medicine (2016)

Aula Abbara, Adam Coutts, Fouad M Fouad, Sharif A Ismail, Miriam Orcutt; the Syria Public Health Network National Heart and Lung Institute, Imperial College London, London, UK Department of Politics and International Studies, University of Cambridge, Cambridge, UK Faculty of Health Sciences, American University of Beirut, Beirut, Lebanon Department of Primary Care and Public Health, Imperial College London, London, UK Conflict and Health Research Group, King’s College London, London, UK Corresponding author: Sharif A Ismail. Email: sharif.ismail15@imperial.ac.uk
Smoking ban does not apply to prisons, Court of Appeal rules
Authors: Ingrid Torjesen
Journal: BMJ (2016)

The ban on smoking in enclosed public spaces does not apply to prisons or to other Crown premises in England and Wales, the Court of Appeal has said.

More than four in five prisoners smoke, and, although a ban on smoking in communal areas in prisons has been in force for some time, inmates are allowed to smoke in their cells. The Prison Service says that it will ultimately implement a voluntary ban, but it favours introducing this …
Meta-Analysis Evaluating the Impact of Site of Metastasis on Overall Survival in Men With Castration-Resistant Prostate Cancer
Authors: Susan Halabi, William Kevin Kelly, Hua Ma, Haojin Zhou, Nicole C. Solomon, Karim Fizazi, Catherine M. Tangen, Mark Rosenthal, Daniel P. Petrylak, Maha Hussain, Nicholas J. Vogelzang, Ian M. Thompson, Kim N. Chi, Johann de Bono, Andrew J. Armstrong, Mario A. Eisenberger, Abderrahim Fandi, Shaoyi Li, John C. Araujo, Christopher J. Logothetis, David I. Quinn, Michael J. Morris, Celestia S. Higano, Ian F. Tannock, Eric J. Small
Journal: Journal of Clinical Oncology (2016)

Reports have suggested that metastatic site is an important predictor of overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC), but these were based on a limited number of patients. We investigate the impact of site of metastases on OS of a substantial sample of men with mCRPC who received docetaxel chemotherapy in nine phase III trials.Individual patient data from 8,820 men with mCRPC enrolled onto nine phase III trials were combined. Site of metastases was categorized as lymph node (LN) only, bone with or without LN (with no visceral metastases), any lung metastases (but no liver), and any liver metastases.Most patients had bone with or without LN metastases (72.8%), followed by visceral disease (20.8%) and LN-only disease (6.4%). Men with liver metastases had the worst median OS (13.5 months). Although men with lung metastases had better median OS (19.4 months) compared with men with liver metastases, they had significantly worse median survival duration than men with nonvisceral bone metastases (21.3 months). Men with LN-only disease had a median OS of 31.6 months. The pooled hazard ratios for death in men with lung metastases compared with men with bone with or without LN metastases and in men with any liver metastases compared with men with lung metastases were 1.14 (95% CI, 1.04 to 1.25; P = .007) and 1.52 (95% CI, 1.35 to 1.73; P < .0001), respectively.Specific sites of metastases in men with mCRPC are associated with differential OS, with successive increased lethality for lung and liver metastases compared with bone and nonvisceral involvement. These data may help in treatment decisions, the design of future clinical trials, and understanding the variation in biology of different sites of metastases in men with mCRPC.
PTH-354 The association between metabolic parameters in FDG-PET/CT and pathological findings of colorectal cancer
Authors: Y Suzuki, K Okabayashi, H Hasegawa, M Tsuruta, R Seishima, Y Asada, K Sugiura, Y Tajima, J Nakadai, K Murakami, Y Kitagawa
Journal: Gut (2015)

<h3>Introduction</h3> FDG-PET/CT is a diagnostic method based on the FDG uptake reflecting the active glucose metabolism and plays an important role in cancer diagnosis. There are several metabolic parameters utilised in quantifying glucose metabolism. Of these, SUV max, metabolic tumour volume (MTV) and total legion glycolysis (TLG) are the most well known parameters. The aim of this study is to evaluate the association between tumour staging and metabolic parameters in FDG-PET/CT, such as SUV max, MTV, TLG. <h3>Method</h3> Between August 2012 and March 2014, 143 patients were retrospectively included. Our inclusion criteria was as below 1)patients who underwent FDG-PET/CT, followed by resection of colorectal cancer, 2)FDG uptake was detectable in primary tumour. Three metabolic parameters in FDG-PET/CT were measured. The individual metabolic parameters were obtained with SUV threshold of 2.5. The association between these parameters and TNM stage were compared by analysing with Mann-Whitney U test or Spearman’s rank correlation coefficient test. <h3>Results</h3> The average of SUV max, MTV, TLG was 12.8 ± 6.54 SUV, 31.4 ± 31.6ml, and 186.8 ± 220.2SUV・ml respectively. Spearman’s correlation test showed that all three parameters were positively associated with the increased number of T stage (SUV max: rs = 0.256 p = 0.002, MTV: rs = 0.498 p＜0.005, TLG: rs = 0.480 p＜0.005). And Spearman’s correlation test showed that N stage had significant positive associations with MTV and TLG (MTV: rs = 0.211 p = 0.012, TLG: rs = 0.211 p = 0.012). At M stage, there were no significant differences in any parameters with Mann-Whitney U test (SUV max: p = 0.534, MTV: p = 0.063, TLG: p = 0.070). <h3>Conclusion</h3> Not only SUV max, MTV and TLG also have a strongly positive association with TNM stage. Using these parameters, more accurate preoperative diagnosis of colorectal cancer can be realised. <h3>Disclosure of interest</h3> None Declared.
Improving Medicaid Access for Former Foster Youth
Authors: Rita Rubin
Journal: JAMA (2016)

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