tbuckley/cabot-search huggingface dataset:
AB0128 Total Calcium-Sensing Receptor Expression in Circulating Monocytes is Increased in Rheumatoid Arthritis Patients with Severe Coronary Artery Calcification
Authors: J. Paccou, C. Boudot, C. Renard, S. Liabeuf, S. Kamel, P. Fardellone, Z. Massy, M. Brazier, R. Mentaverri
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Human circulating monocytes express the calcium-sensing receptor (CaSR) and are involved in atherosclerosis. Vascular calcification is commonly used as a subclinical marker of atherosclerosis and has been linked to increased all-cause mortality, cardiovascular mortality and coronary events. Moreover, patients with RA are known to develop early-onset, widespread calcification in various vascular beds. We have previously assessed CaSR expression by flow cytometry in human circulating monocytes and have provided evidence that this type of approach could be useful in certain clinical situations, in which changes in CaSR expression can be expected. <h3>Objectives</h3> This study investigated the potential association between vascular calcification in rheumatoid arthritis (RA) and CaSR expression in circulating monocytes. <h3>Methods</h3> In this cross-sectional study, 50 RA patients were compared to 25 control subjects matched for age and gender. Isolation of peripheral blood mononuclear cells and flow cytometry analysis were performed to study the surface and total CaSR expression in circulating monocytes. Coronary artery calcium (CAC) and abdominal aortic calcification (AAC) scores were evaluated by computed tomography and an association between these scores and the surface and/or total CaSR expression in circulating monocytes in RA patients was investigated. <h3>Results</h3> The two groups were similar in terms of age (RA: 60.9±8.3 years, versus controls: 59.6±5.3 years) and gender (RA: 74.0% females versus 72.0% females). RA patients did not present a higher prevalence or a greater burden of CAC or AAC compared to age- and gender-matched controls. When compared with control subjects, RA patients did not exhibit greater total CaSR (101.6% ±28.8 vs. 99.9% ±22.0) or surface CaSR (104.6% ±20.4 vs. 99.9% ±13.7) expression, but total CaSR expression in circulating monocytes was significantly higher in RA patients with severe CAC (Agatston score ≥200, n=11) than in patients with mild-to-moderate CAC (1-199, n=21) (p=0.01). <h3>Conclusions</h3> This study demonstrates, for the first time, that total CaSR expression in human circulating monocytes is increased in RA patients with severe coronary artery calcification. <h3>References</h3> Paccou J, Brazier M, Mentaverri R, et al. Vascular calcification in rheumatoid arthritis: prevalence, pathophysiological aspects and potential targets. Atherosclerosis 2012;224:1418-23. Paccou J, Boudot C, Mary A, et al. Determination and modulation of total and surface calcium-sensing receptor expression in monocytes in vivo and in vitro. PLoS one 2013;8:e74800. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2377
PREDICTION OF CORONARY EVENTS BY THALLIUM-201 QUANTITATION OF JEOPARDIZED MYOCARDIUM AND CLINICAL AND EXERCISE TEST VARIABLES.
Authors: Jamshid Maddahi, Hosen Kiat, Ken Resser, Joe Areeda, Ken Van Train, Ishac Cohen, Alan Waxman, Alan Rozanski, Daniel Berman
Journal: Clinical Nuclear Medicine (1987)

Maddahi, Jamshid; Kiat, Hosen; Resser, Ken; Areeda, Joe; Train, Ken Van; Cohen, Ishac; Waxman, Alan; Rozanski, Alan; Berman, Daniel Author Information
GPR30 and HER-2 Expression in Invasive and Metastatic Breast Cancer.
Authors: H. Arias-Pulido, N. Joste, L. Lomo, N. Chaher, S. Lee, C. Verschraegen, A. Meisner, C. Martinez, E. Prossnitz, M. Royce
Journal: Cancer Research (2009)

Abstract Background: GPR30 expression, a new estrogen receptor, has been previously associated with HER-2, tumor size and metastasis in invasive breast cancer (BC) but its role in paired normal (N), invasive (I), and metastatic (M), samples is unknown. We described GPR30 and HER-2 expression in a collection of paired N/I/M samples, derived from the same individual.Materials and Methods: GPR30 and HER-2 expression was assessed by immunohistochemistry (IHC) in tissue microarrays, containing paraffin-embedded cores from 100 patients diagnosed with invasive BC. N and M samples were also available from the same patient. GPR30 expression was evaluated by an H-score (Intensity (0, negative; 1+, weak; 2+, moderate; 3+, strong) x Percentage of stained epithelial cells). HER-2 expression was evaluated per standard criteria. Log rank tests and Wald tests were employed to assess the clinical impact of these molecular targets on patient outcome based on Kaplan-Meier Product estimator and Cox Proportional Hazard Regression.Results: GPR30 was expressed in 50%, 76%, and 72% of N, I and M, respectively, samples. HER-2 (3+) was found in 14% and 18% of I and M samples, respectively. GPR30 expression in I cases correlated with expression in M cases, and HER-2 expression in I but not M cases. GPR30 expression in M cases correlated with expression in HER-2 expression in M cases. HER-2 expression in I cases correlated with expression in M samples (P&amp;lt;0.05 for all comparisons). GPR30 and HER-2 expression were not associated with grade or stage (P&amp;gt;0.05). GPR30 expression in I or M samples was not associated with either overall survival (OS) or BC-specific survival (BCSS)(P&amp;gt;0.5). HER-2 expression was marginally associated with OS in I (P=0.06; Hazard Ratios (HR): 1.91; 95%CI: 0.956, 3.83) but not in M (P=0.23) cases. HER-2 was significantly associated with BCSS in I cases (P=0.03; HR: 2.39; 95%CI: 1.07, 5.32) and marginally in M (P=0.08) cases.Discussion: A previous study suggested that GPR30 expression predicted the development of metastasis. We found high GPR30 expression in both the primary and metastatic sample but the difference was not significant. While GPR30 expression was not associated with OS or BCSS, HER-2 expression was marginally associated with OS and significantly associated with BCSS in invasive cases. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4158.
Abstract 2643: Interactions between polycyclic aromatic hydrocarbon exposure and genetic polymorphisms on benzo(a)pyrene-DNA adducts in a Polish cohort of mothers and newborns
Authors: Shoba Iyer, Wei Xiong, Deliang Tang, Wieslaw Jedrychowski, Stephen Chanock, Shuang Wang, Laura Stigter, Elzbieta Mroz, Frederica Perera
Journal: Cancer Research (2012)

Abstract Background Polycyclic aromatic hydrocarbons (PAHs) are a class of chemicals common in the environment. Major sources of PAHs include fossil fuel combustion and cigarette smoking. Certain PAHs are carcinogenic, though the degree to which genetic variation influences susceptibility to PAH exposure remains unclear. Benzo(a)pyrene (BaP) is a well-studied PAH that is classified as a probable human carcinogen. Here, we evaluated single nucleotide polymorphism (SNP) frequency in genes related to PAH metabolism and detoxification, and explored the interactions between PAH exposure and SNPs on BaP-DNA adducts, an established cancer risk marker, in umbilical cord white blood cells (WBCs). Methods Maternal and umbilical cord blood were collected at delivery from participants in a longitudinal cohort study of Polish mothers and newborns in Krakow, Poland. WBC DNA was isolated from cord blood, and genetic polymorphisms and BaP-DNA cord adducts were then measured in 503 mothers and 445 newborns. Maternal PAH exposure was measured during pregnancy with a personal air exposure monitor. For this study 7 maternal and newborn genes related to PAH metabolism, detoxification and repair were selected for SNP analyses: CYP1A1, CYP1A2, CYP1B1, GSTM3, GSTT2, NQO1 and XRCC1. SNP x PAH interactions on logarithmic (ln)-transformed BaP-DNA adduct levels were explored. Results We observed a number of significant interactions between high PAH exposure and SNPs in both mothers and newborns on BaP-DNA adducts in cord blood. For example, the interaction between a CYP1A2 SNP (rs2069514) and high PAH exposure on cord BaP-DNA adducts in newborns was significant (α=−1.34, p&amp;lt;0.01). We will present significant interaction results from analyses performed on both maternal and newborn CYP1A1, CYP1A2, GSTM3, GSTT2, NQO1 and XRCC1 SNPs. Discussion It is biologically plausible that an individual's abilities to metabolically activate and detoxify BaP and repair DNA damage play a role in susceptibility to DNA adduct formation following prenatal PAH exposure. Ultimately, this susceptibility could correlate with future risk of cancer development. Our findings of several SNP x PAH exposure interactions on cord BaP-DNA adducts support the hypothesis that genetic variability can contribute to susceptibility and potential cancer risk from prenatal PAH exposures. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2643. doi:1538-7445.AM2012-2643
Janet Helen Smellie
Authors: I. R. Affleck, J. L. Taylor
Journal: BMJ (2011)

Janet Mountford came to Merseyside when her father became professor of Latin (and later, vice chancellor) at Liverpool University. Janet’s abilities were well recognised as a medical student and, after graduating with honours, she became house physician to Professors Henry Cohen and Charles Wells at Liverpool Royal Infirmary and worked with Professor Jeffcoate at the obstetric unit at Mill Road Hospital and also …
SAT0327 Estimation of Enthesitis of Rotator Cuff Shoulder by Ultrasound in Osteoarthritis
Authors: E. Kirillova, N. Shamsutdinova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The rotator cuff consists of muscles and their tendons: subscapularis, supraspinatus, infraspinatus. The subscapularis tendon inserts in the lesser tuberosity of the humerus. The supraspinatus tendon inserts in the of the humerus. The infraspinatus tendon inserts in the posterior portion of the greater tuberosity, touching the posterior aspect of the supraspinatus tendon. Enthesitis is an inflammatory lesion of the tendon, ligament and capsular insertions into the bone. Sonography is the method of choice for studying periarticular soft tissues because it is capable of detecting both the early (oedema, thickening) and late alterations (erosions and enthesophytes). <h3>Objectives</h3> To compare ultrasonography with clinical examination in the detection of abnormality of tendon insertion in patients with osteoarthritis. <h3>Methods</h3> 60 patients with osteoarthritis underwent clinical and ultrasonographic examination of the following bilateral entheseal sites: anterior portion of the greater tuberosity, the posterior portion of the greater tuberosity and lesser tuberosity of the humerus. Clinical enthesitis was defined by the presence of at least one of the following findings: spontaneous pain, tenderness elicited by pressure, and local swelling of the enthesis. Ultrasound investigaton was performed to detect structure thickness, bony erosion, and enthesophyte (bony spur). <h3>Results</h3> Insertion abnormality detected in 58% of total count of enteses, 12% not have clinical features and detected with ultrasound investigation only. Determined a significant correlation between tenderness of tuberosities of humerus and the presence of ultrasound features. There was no significant correlation between spontaneous pain and enthesitis. No significant correlation between local swelling of the enthesis and ultrasound features was noted. <h3>Conclusions</h3> Enthesistis of rotator cuff is frequent manifestation in osteoarthritis. Ultrasound investigation exceeds clinical examination in the detection of enthesitis of the shoulder. Tenderness of tuberosities of humerus is accurate sign of enthesitis of the shoulder. <h3>Disclosure of Interest</h3> None Declared
AB0828 Effects of meldonium for chronic heart failure after miocarditis in patients with connective tissue disease
Authors: O. Mytrokhina, O. Kuryata
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> As known, miocarditis often matched the progression of chronic heart failure (CHF) in patients with connective tissue disease. Meldonium have shown miocardial cytoprotection effect, however the role of meldonium in patients with connective tissue disease remains debatable. <h3>Objectives</h3> We aimed to evaluate the effects of meldonium for CHF after miocarditis in patients with connective tissue disease. <h3>Methods</h3> 40 patients (9 M, 31 F, mean age – 37,20±4,46 years) with connective tissue disease and CHF NYHA I-III class after miocarditis were enrolled. 20 (50%) patients received the standard treatment and meldonium 500 mg/day (study group), while 20 (50%) (control group) – received only the standard treatment for 12 weeks. Echocardiographic parameters, 6 min walk test and quality-of-life scores (QoL) were performed in all patients at baseline and at the end of the study. <h3>Results</h3> Echocardiographic parameters, 6 min walk test distance and QoL scores did not differ significantly between the groups, with the exception of a more favourable emotional score in the study group (<i>P</i> =0.027). After 12 weeks of treatment with meldonium the incidence of exertion-related symptoms, including chest pain, dyspnoea, and fatigue were significantly lower in the study in comparison of control groups (P=0.05). The distance of the 6 min walk test in 30% patients have been increased in the study group by 26,47% (d&lt;0,01); in control group in 19% patients – by 9,47% (d&lt;0,01). 6 min walk test correlated to NYHA functional class (r =0,25; d&lt;0,05). <h3>Conclusions</h3> Meldonium is effective and safe for patients with CHF after miocarditis in patients with connective tissue disease. Meldonium reduces progression of CHF after miocarditis in patients with connective tissue disease. Its administration may provide benefits for the reduction of hospitalizations and mortality in its population. <h3>Disclosure of Interest</h3> None Declared
Abstract 5107: HDL and sphingosine-1-phosphate activate signal transducer and activator of transcription 3 in prostate cancer DU145 cells via ERK1/2 and S1P receptors
Authors: Yoshitaka Sekine, Kazuhiro Suzuki, Alan T. Remaley
Journal: Cancer Research (2010)

Abstract (a) Introduction and Objective: Signal transducer and activator of transcription 3 (Stat3) has been implicated in the promotion of migration, invasion and growth of prostate cancer cells. Recently, HDL, which transports the bioactive lipid sphingosine-1-phosphate (S1P), was reported to activate Stat3 in cardiomyocytes and is a known mitogen for several cell types. S1P acts by binding to several G protein-coupled receptors, namely S1P1, S1P2 and S1P3, which are expressed in prostate cancer cell lines. Androgen deprivation therapy in men with prostate cancer leads to a significant increase of HDL-C, but the effect of HDL on prostate cancer is unknown. In this study, we examined the effect of HDL and S1P on Stat3 activation in prostate cancer cells and the involvement of ERK1/2, Akt, and S1P receptors in this process in 3 prostate cancer cell lines (PC-3, LNCaP and DU145). (b) Methods: We used HDL isolated from health volunteer men. Discordial reconstituted(r) HDL containing POPC and apoA-1, (POPC/A-1)rHDL or POPC, S1P and A-1, (POPC/S1P/A-1)rHDL were prepared by the cholate dialysis method. The phosphorylations of Stat3, ERK1/2 and Akt were detected by Western blot analysis. mRNA expressions of PC cells were evaluated by quantitative real-time PCR. Cell viability, migration and invasion were determined by MTS assay, would healing assay and matrigel invasion chamber assay, respectively. (c) Results: HDL increased a dose and a time dependent Ser727 phosphorylation of Stat3, but not Tyr705 in DU145 cells but not in the other two cell lines. S1P and (POPC/S1P/A-1)rHDL also induced the phosphorylation, but not rHDL made without S1P (POPC/A-1). They also induced DU145 cells proliferation, migration, invasion and phosphorylations of ERK1/2 and Akt. PD98059, a MEK inhibitor, and pertussis toxin, a Gi inhibitor, attenuated HDL-, S1P- and (POPC/S1P/A-1)rHDL-induced Stat3 phosphorylation, whereas LY294002, a PI3K inhibitor, had no effect. Concerning S1P receptors, S1P1 expression was much lower than S1P2 and S1P3 in DU145 cells. Both JTE013, a S1P2 antagonist, and VPC23019, a S1P1/S1P3 antagonist, attenuated HDL-, S1P- and (POPC/S1P/A-1)rHDL-induced Stat3 phosphorylations and cell migrations. (d) Conclusions: HDL was shown to induce Ser727 phosphorylation of Stat3 via its S1P constituent and involved both S1P2 and S1P3 receptors in DU145 cells. Moreover, ERK1/2 activation is involved in cell activation by HDL. These results suggest that the change in HDL plasma levels by androgen deprivation therapy HDL may alter prostate cancer growth and metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5107.
Case 35-1975
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Sheldon D. Kaufman, Robert E. Scully
Journal: New England Journal of Medicine (1975)

Presentation of Case First admission. A 40-year-old woman was admitted to the hospital because of a pericardial effusion.She was well until eight days previously, when she had an attack of sharp anterior chest pain that was aggravated by respiration and was relieved by sitting up and by leaning forward. Six days before admission she entered another hospital, where fever, cardiomegaly and a pericardial friction rub were found. An electrocardiogram showed diffuse inversion of the T waves and premature ventricular contractions. An x-ray film of the chest confirmed enlargement of the heart. Aspirin, lidocaine and procainamide were administered. The . . .
Abstract 4686: Requirements of Gαi1 and Gαi3 for brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) induced PI3K/AKT and MAPK signaling as well as neuronal survival and migration
Authors: Cong Cao, Anika Toorie, Emily Latorraca, Anatoly Zhitkovich, John Marshall
Journal: Cancer Research (2011)

Abstract After the discovery of the involvement of neurotrophin receptor Trk (tropomyosin receptor kinase) in the biology of cancer, it is appreciated that inhibition of Trk activity is beneficial in the clinical oncology setting. The key intracellular mediators of activated Trk's pro-survival and pro-metastatic signals are PI3K/AKT and MAPK (mitogen-activated protein kinases) signaling, which makes it extremely important to dissect the molecular mechanism and signaling components involved in Trk regulation of those signaling. Here we focus on the two inhibitory alpha subunits of heterotrimeric guanine nucleotide-binding proteins, Gαi1 and Gαi3, in Trk signaling. Gαi proteins are couple to cell surface receptors to convey extracellular messages to their effectors. Our previous study has indicated an unexpected and critical role of Gαi proteins in mediating receptor tyrosine kinase signaling (Cao et al., Science Signaling, 2009). Here we discovered a novel function of Gαi proteins in BDNF/NGF signaling. Gαi proteins are required for Brain-Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) to transduce signals from Trk receptor to stimulate MAPK (p38, JNK and ERK) and PI3K/AKT/mTORC1 signaling. Knockout of Gαi1 and Gαi3 completely blocked BDNF and NGF induced PI3K/AKT/mTORC1 and MAPK activation in MEFs (mouse embryonic fibroblasts). Both Gαi1 and Gαi3 associated with the Grb2-associated binding protein 1 (Gab1), and were required for the interaction of Gab1 with SHP2 as well as the interactions of Grb2 with SHP2, Shc, MEKK1 and MEKK2, in response to BDNF and NGF. Loss of Gαi1 and Gαi3 impaired the phosphorylation of Gab1, SHP2 and Shc in response to BDNF and NGF. Importantly, siRNA knockdown of both Gαi1 and Gαi3 inhibited BDNF and NGF induced AKT/mTORC1 and MAPK activation in cerebellar granule neuron, and BDNF induced neuronal survival, neuronal migration and neurite outgrowth were also largely impaired in cerebellar neurons with Gαi1 and Gαi3 deficiency. Notably, in mice brain tissues (both cortex and cerebellum); double knockout of Gαi1 and Gαi3 also totally abolished BDNF induced signaling. Overall, these results showed that Gαi1 and Gαi3 lie downstream of Trk receptor, but upstream of Gab1-Shc-Grb2-Shp2, mediating MAPK and PI3K/AKT/mTORC1 signaling as well neuronal survival and migration. We discovered for the first time that Gαi1 and Gαi3 proteins are novel players in Trk signaling, we support that therapeutic options can be developed by targeting these two new players as novel anti-tumor strategy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4686. doi:10.1158/1538-7445.AM2011-4686
Abstract 1420: Microsomal prostaglandin E2 synthase 1 (mPGES-1) is expressed in neuroblastoma and may represent a novel target for therapy
Authors: Anna Kock, Agnes Rasmuson, Helena Idborg, John Inge Johnsen, Per Kogner
Journal: Cancer Research (2012)

Abstract Neuroblastoma (NB) is an embryonic tumor of the sympathetic nervous system and it is the most common extracranial tumor affecting young children. Despite a very intensive treatment regimen high-risk neuroblastoma patients still have a poor prognosis. Neuroblastoma cells are enriched in arachidonic acid, over express COX-2 and produce prostaglandin E2 (PGE2) that acts as an autocrine or paracrine survival and proliferation factor by induction of Akt signaling. Downstream of the COX enzymes, specific synthases converts PGH2 into the different prostaglandins. Microsomal prostaglandin E2 synthase-1 (mPGES-1) specifically converts PGH2 to PGE2 and is thought to primarily couple to COX-2. The aim of this study is to investigate if inhibition of mPGES-1 could represent an alternative therapeutic approach to COX- inhibition in neuroblastoma. We could detect expression of mPGES-1 in a panel of seven human neuroblastoma cell lines. Stable knock down of mPGES-1 expression using shRNA significantly reduced the clonogenic capacity and treatment with the mPGES-1 inhibitor CAY1052 inhibited neuroblastoma cell growth in vitro. By immunohistochemistry and western blot we could also detect expression of COX-1, COX-2 and mPGES-1 in tumors from the transgenic TH-MYCN mouse model of neuroblastoma. Treatment of homozygous TH-MYCN mice with 10 mg/L diclofenac for two weeks, starting at the age of four weeks, significantly reduced tumour weight compared to untreated animals. Ex vivo analysis with LC-MS/MS of tumor tissues from diclofenac treated animals revealed a significant decreased level of COX metabolites compared to control. The expression of mPGES-1was not affected by the treatment. Furthermore the number of cells staining positive for cleaved caspase-3 were higher in the treated tumors indicating induced apoptosis. In conclusion, our results show that mPGES-1 is expressed in neuroblastoma therefore mPGES-1 might represent an alternative way of reducing NB growth through specific PGE2 inhibition. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1420. doi:1538-7445.AM2012-1420
Detection of a Cerebrospinal Fluid Pseudocyst on Delayed Imaging
Authors: KEVIN K. L. CHOONG
Journal: Clinical Nuclear Medicine (1999)

Ventriculoperitoneal shunt obstruction due to a loculated abdominal cerebrospinal fluid collection is an uncommon but well-recognized complication. This report illustrates the value of delayed imaging in identifying a cerebrospinal fluid pseudocyst as the cause of shunt dysfunction.