tbuckley/cabot-search huggingface dataset:
A1.03 Arginase I and osteoclastogenesis
Authors: JS Brunner, M Hofmann, V Saferding, H Paar, L Chen, P Cheng, G Schabbauer, S Blüml
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Osteoclasts are giant, multi-nucleated cells that derive from the monocyte-macrophage linage and are &nbsp;involved in bone turnover. They are further known as the main effector cells for development of age-related osteoporosis. While the role of Arginase I within certain myeloid lineages such as macrophages is well appreciated, its role within osteoclasts is relatively unknown. Our aim was therefore to investigate the importance of the enzyme in the context of osteoclastogenesis. <h3>Materials and methods</h3> We analysed osteoclastogenesis of C57BL/6J or BALB/c wildtype cells <i>in vitro</i> in the presence and absence of recombinant Arginase I (recARG1) and its inhibitor nor-NOHA. This was complemented via qPCR analysis of marker genes. We further investigated the potential of the enzyme to induce cell death via flow cytometry analysis of 7-AAD and Annexin V. <h3>Results</h3> In osteoclast differentiation assays, we show that Arginase I is strongly downregulated during osteoclastogenesis, suggesting involvement of this enzyme in OC differentiation. We further show that addition of recArgI completely abolishes osteoclast formation without inducing cell death. The inhibitory effect of recArgI on osteoclastogenesis was completely dependent on the enzymatic function, as no decrease in osteoclast formation could be observed during combined addition of recArgI and its specific inhibitor nor-NOHA. We further demonstrate that recArgI specifically inhibits RANKL-mediated terminal differentiation of OCs, but has no effect on MCSF dependent generation of OC precursors. In line, we could show that addition of recombinant Arginase I negatively regulated the expression of classic RANKL induced osteoclastic marker genes such as TRAP and Cathepsin K. <h3>Conclusions</h3> We propose that recArgI might be a potent inhibitor of osteoclastogenesis and could prove itself to be useful for the treatment of osteoclast driven diseases, such as osteoporosis.
Prévalence et facteurs prédictifs du recours à la chirurgie pour réséquer les polypes colorectaux ne comportant pas de cancer invasif: étude de population
Authors: F Le Roy, S Manfredi, S Hamonic, C Piette, G Bouguen, F Riou, JF Bretagne
Journal: Endoscopy (2015)

Il n'existe pas d'étude en population relative à la fréquence du recours à la chirurgie pour l'exérèse de polypes colorectaux et aux facteurs prédictifs de ce recours, notamment liés à l'endoscopiste.
The Causes and Risk of Stroke in Patients with Asymptomatic Internal-Carotid-Artery Stenosis
Authors: Domenico Inzitari, Michael Eliasziw, Peter Gates, Brenda L. Sharpe, Richard K.T. Chan, Heather E. Meldrum, Henry J.M. Barnett
Journal: New England Journal of Medicine (2000)

The causes of stroke in patients with asymptomatic carotid-artery stenosis have not been carefully studied. Information about causes might influence decisions about the use of carotid endarterectomy in such patients.
Declining Morbidity and Mortality among Patients with Advanced Human Immunodeficiency Virus Infection
Authors: Frank J. Palella, Kathleen M. Delaney, Anne C. Moorman, Mark O. Loveless, Jack Fuhrer, Glen A. Satten, Diane J. Aschman, Scott D. Holmberg
Journal: New England Journal of Medicine (1998)

National surveillance data show recent, marked reductions in morbidity and mortality associated with the acquired immunodeficiency syndrome (AIDS). To evaluate these declines, we analyzed data on 1255 patients, each of whom had at least one CD4+ count below 100 cells per cubic millimeter, who were seen at nine clinics specializing in the treatment of human immunodeficiency virus (HIV) infection in eight U.S. cities from January 1994 through June 1997.Mortality among the patients declined from 29.4 per 100 person-years in the first quarter of 1995 to 8.8 per 100 in the second quarter of 1997. There were reductions in mortality regardless of sex, race, age, and risk factors for transmission of HIV. The incidence of any of three major opportunistic infections (Pneumocystis carinii pneumonia, Mycobacterium avium complex disease, and cytomegalovirus retinitis) declined from 21.9 per 100 person-years in 1994 to 3.7 per 100 person-years by mid-1997. In a failure-rate model, increases in the intensity of antiretroviral therapy (classified as none, monotherapy, combination therapy without a protease inhibitor, and combination therapy with a protease inhibitor) were associated with stepwise reductions in morbidity and mortality. Combination antiretroviral therapy was associated with the most benefit; the inclusion of protease inhibitors in such regimens conferred additional benefit. Patients with private insurance were more often prescribed protease inhibitors and had lower mortality rates than those insured by Medicare or Medicaid.The recent declines in morbidity and mortality due to AIDS are attributable to the use of more intensive antiretroviral therapies.
Abstract 3386: Mechanisms of resistance to enzalutamide in LNCaP models.
Authors: Yohann Loriot, Alexander Wyatt, Nader Al Nakouzi, Eliana Beraldi, Paul Toren, Ka Mun Nip, Martin Gleave, Amina Zoubeidi
Journal: Cancer Research (2013)

Abstract Background MDV3100 is a potent androgen receptor (AR) antagonist with activity in castration resistant prostate cancer (CRPC); however, progression to MDV3100-resistant (MDV-R) CRPC frequently occurs with rising serum PSA levels suggesting reactivation of AR pathway. We sought to identify AR-based mechanisms of resistance. Methods We treated human CRPC LNCAP-derived xenografts with MDV3100 and assessed androgen receptor (AR) levels and localization as well as genomic alterations versus controls. We also generated by selection MDV3100-R LNCaP-derived sub-lines to study mechanisms of resistance to MDV3100. Results Serum and tumoral PSA levels were consistently increased in resistant xenogratfs as compared with sensitive xenografts along with AR nuclear localization. MDV3100 did not induce any new mutation in the DNA binding domain and any AR DNA gene amplification. AR full-length (ARfl) and AR-V7 splicing variant were both highly expressed in RNA sequencing compared to CRPC LNCaP xenografts. However, it was no enrichment of AR-V7 versus ARfl in LNCaP MDV-R xenografts. Interestingly, AR was found in the nucleus and constitutively binding to DNA on androgen response element on PSA enhancer as measured by Chromatin immunoprecipitation in MDV-R cell lines compared to CRPC cell lines. These data were translated by increase of AR responsive genes at both mRNA and protein levels. Conclusions MDV-R LNCaP cells exhibited AR overexpression without any significant genomic alterations. While MDV3100 induces both ARfl and AR-V7 levels, no enrichment of AR-V7 was detected. Immunofluorescence, CHIP and qPCR studies suggest that ARfl overexpression remains a significant mechanism of resistance to MDV3100 similar to resistance from chronic androgen depletion. Citation Format: Yohann Loriot, Alexander Wyatt, Nader Al Nakouzi, Eliana Beraldi, Paul Toren, Ka Mun Nip, Martin Gleave, Amina Zoubeidi. Mechanisms of resistance to enzalutamide in LNCaP models. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3386. doi:10.1158/1538-7445.AM2013-3386 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
P09.03 * USE OF METHYLPREDNISOLONE IN LATE EFFECTS OF RADIOTHERAPY
Authors: J. Pardo-Moreno, L. Gomez, M. Jimenez de la Pena, A. Alonso-Torres, T. Maycas-Cepeda, N. Barbero-Bordallo
Journal: Neuro-Oncology (2014)

INTRODUCTION: Radiation therapy to the brain can cause problems months or years after treatment ends. Side effects can include memory loss, movement disorders, urinary incontinence, trouble thinking, or personality changes. There is no current treatment for this late complication. and it has been proved bevacizumab, steroids, hyperbaric O2 with different results. We present three cases in which the use of methylprednisolone, as in multiple sclerosis relapses, has had a very good response in terms of clinical and radiological evaluation. Case 1: 43 year-old-woman with recurrent vestibular schwannoma received radiation therapy on the tumour site after the second surgery. Six months later she consulted for diplopia, ataxia and worsening of her facial palsy since a few days ago. The neurological exam showed a right internuclear ophtalmoplegia, vertical nistagmus with upward gaze, right limbs dysmetria and ataxia. The MRI showed high-signal intensity lesions with contrast enhancement in the radiation field (bulbopontine region, right pons and cerebellar peduncle). The diagnosis was subacute rhombencephalitis. We started five days of 1 gr of methylprednisolone. The symptomatology and the MRI changes resolved completely one month after therapy. Case 2: A 60 year-old-man with temporal glioblastoma diagnosed in 2010. He was treated with Stupp regimen followed by temozolomide. Six months later the patient was getting worse of his neurological symptons with abulia and apathy. A MRI showed worsening in brain edema with an increase in contrast enhancement, with low relative cerebral blood volume. The diagnosis was late pseudoprogression and he received a cycle of 250 mg of methylprednisolone during five days with resolution of the clinical symptoms and significant improvement in MRI brain edema. Case 3: A 33 year-old-woman diagnosed in 1993 of temporal astrocytoma grade III. It was resected and afterwards radiotherapy. In 2012 started with instability and dizziness. Examination showed slight lateropulsion and on MRI appeared a new lesion that enhanced after contrast administration at right cerebellar peduncle. It was interpreted as radionecrosis and a cycle of 1 gr of methyl-prednisolone IV per day for five days was administered. Four weeks after the the clinical picture and image were resolved. DISCUSSION: Demyelination is one of the pathological features of late effects of radiotherapy. Regarding this fact we treated all these patients as a relapsing multiple sclerosis episode with an scheme of intravenous megadosis of methyilprednisolone for five days. We obtained complete clinical and radiological response with no adverse events due to steroids. CONCLUSION: Methylprednisolone must be considered one treatment option in patients who present with clinical and or radiological suspicion of inflammatory late effects of radiotherapy. Further studies are necessary to validate this situation.
Growth rate in adolescents with obsessive-compulsive disorder
Authors: S D Hamburger, S Swedo, A Whitaker, M Davies, J L Rapoport
Journal: American Journal of Psychiatry (1989)

In an epidemiological study of 5,596 high school students, the authors identified 20 adolescents with obsessive-compulsive disorder and compared their physical size to that of adolescents of the same sex with no obsessive-compulsive symptoms. The obsessive-compulsive boys (N = 11) were shorter and weighed less than the other boys (N = 2,479) and were shorter than a subsample of normal boys (N = 33) and boys with other psychiatric diagnoses (N = 16). Regression analysis showed a flatter growth pattern through adolescence for the obsessive-compulsive boys (although within the 95% confidence limits for the other boys), suggesting a subtle neuroendocrine dysfunction in obsessive-compulsive disorder.
Abstract 915: Xenobiotic metabolizing gene variants, occupational chemical exposures, and renal cell cancer
Authors: Julia E. Heck, Yuan-Chin A. Lee, James D. McKay, Rayjean J. Hung, Sara Karami, Valerie Gaborieau, Neonila Szeszenia-Dabrowska, David G. Zaridze, Jolanta Lissowska, Peter Rudnai, Dana Mates, Lenka Foretova, Vladimir Janout, Vladimir Bencko, Wong-Ho Chow, Nathaniel Rothman, Lee E. Moore, Paul Brennan, Paolo Boffetta
Journal: Cancer Research (2010)

Abstract The countries of Central and Eastern Europe have among the highest worldwide rates of renal cell cancer. Few studies have examined whether genetic variation in xenobiotic metabolic pathway genes may modify risk for this cancer. The Central and Eastern Europe Renal Cell Cancer study was a hospital-based case-control study conducted between 1998 and 2003 across seven centers in central and eastern Europe. The study centers were in the Czech Republic (Ceske, Prague, Olomouc, Brno), Poland (Lodz), Romania (Bucharest), and Russia (Moscow). Incident cases of primary kidney cancer were recruited and underwent an in-person interview in which detailed data were collected on demographics as well as work history and occupational exposure to chemical agents. Genes (cytochrome P-450 family, N-acetyltransferases, NAD(P)H:quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH), catechol-O-methyltransferase (COMT)) were selected for the present analysis based on their putative role in xenobiotic metabolism. Genotyping (874 cases and 2396 controls) was conducted with a GoldenGate® Oligo Pool All (OPA) assay by Illumina® and the 5’ nuclease assay (Taqman, Applied Biosystems). Haplotypes were calculated using fastPhase. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression adjusted for country of residence, age, and sex. We observed an increased risk of renal cell cancer (RCC) with two NAT1 SNPs (NAT1A40T, OR=1.36, CI 1.00, 1.86; NAT1R187Q, OR=1.65, CI 1.01, 2.71) and with CYP1B1V432L (OR=1.14, CI 1.01, 1.28). The slow (NAT1*14) phenotype was associated with increased risk of RCC (OR=1.69, CI 1.00-2.86) in comparison to normal phenotype (NAT1*4, *3, *11). Among persons with NAT1*14 phenotype, occupational exposure to trichloroethylene (OR=9.94, CI 1.15, 86.1) and chlorinated solvents (OR=9.79, CI 1.13, 84.8) conferred an increased risk of RCC. Among those with the CYP1B1V432L variant, occupational exposure to trichloroethylene (OR=1.68, CI 1.21, 2.34) and chlorinated solvents (OR=1.58, CI 1.14, 2.19) also had increased risk of RCC. These results require replication, but provide evidence that the relationship between certain agents and RCC may be modified by particular variants in xenobiotic metabolism genes. 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 915.
THU0122 Safety of surgery in patients with rheumatoid arthritis treated by rituximab in routine care: Data from the french air registry:
Authors: S. Godot, J.E. Gottenberg, S. Paternotte, I. Pane, B. Combe, J. Sibilia, R.-M. Flipo, T. Schaeverbeke, P. Ravaud, E. Toussirot, F. Berenbaum, X. Mariette, D. Wendling, J. Sellam
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The risk of post-surgical complications related to the use of non anti-TNF biological agents in patients with rheumatoid arthritis (RA) remains unclear. The aim of this study was to investigate the safety of surgery in RA patients treated by rituximab (RTX) in routine care using data from the AutoImmunity and Rituximab (AIR) registry. <h3>Methods</h3> The AIR registry has been set up by the French Society of Rheumatology and includes RA patients treated with RTX. The charts of patients undergoing any surgery during the year following an infusion of RTX were reviewed in order to i)describe the frequency of postsurgical complications, ii) to compare the characteristics of patients w/o complications and iii) to identify the parameters associated with postoperative side effects in a multivariate logistic regression analysis. <h3>Results</h3> 1972 patients have been enrolled patients until August 2010. 133 patients underwent surgery during the year after an infusion of RTX for a total of 140 procedures including 94 orthopaedic surgeries (67%). Twelve complications (8.5% of procedures) occured in 9 patients (6.7%): 6 deep infections and 2 scars or superficial infections at the surgical site, 1 pulmonary infection, 1 delayed healing, 1 deep venous thrombosis and 1 death related to a septic shock. Infections at surgical site were reported for 5.7% of surgeries. The main characteristics of each group are detailed in the table. Spine surgery is associated with postoperative complications in univariate analysis (p=0.048) with 2 reported spondylodiscitis but none were proven by a biopsy. In a multivariate logistic regression analysis, no predictive factors were identified. <h3>Conclusions</h3> The occurrence of post-surgical complications in 6.7% of RA patients receiving RTX is similar with those reported with TNF alpha blockers (between 0 and 12.5%). No risk factor of complications was identified. <h3>Disclosure of Interest</h3> None Declared
The Influence of Oestrogen Receptor (ER) Status on the Pattern of Recurrence in Early Breast Cancer.
Authors: J. Mansell, W. Angerson, C. Wilson, J. Doughty
Journal: Cancer Research (2009)

Abstract IntroductionThere is an early peak in recurrence in women with early breast cancer (EBC). This may be related to underlying tumour biology or secondary to a reaction to surgery. We aim to determine if ER expression influences the pattern of recurrence.MethodsData from 3 centres in Glasgow of consecutive women with EBC diagnosed between 1995 and 2001 were examined. Recurrence was defined as invasive disease at any site. Patients were grouped as high ER (≥70% expression), low ER (&amp;lt;70% expression) and ER negative. Kaplan Meier and Time dependent Cox survival analysis was performed.Results2779 women were included with a median follow up of 5.5yrs. 1915 (68.9%) had high ER, 310 (11.2%) had low ER and 554 (19.9%) were ER negative. At 5yrs the cumulative recurrence rates were 10.4% (9.0-11.8) vs. 19.2% (14.7-23.7) vs. 30.5% (26.6-34.4) respectively. Time dependent multivariate analysis showed that low ER and ER negative were significantly stronger predictors of recurrence within 2.5yrs from diagnosis than at later intervals (p = 0.024 and p &amp;lt;0.001 respectively). The hazard ratios for recurrence within 2.5 yrs for low ER and ER negative groups were 2.23 (95% CI 1.41-3.54, p=0.001) and 3.68 (2.60-5.21, p &amp;lt;0.001). Beyond 2.5yrs the respective hazard ratios were 1.12 (0.77-1.64, p=0.558) and 1.40 (1.03-1.90, p=0.031)ConclusionsWomen with Low ER expressing and ER negative tumours are initially at a significantly increased risk of recurrence compared with women with high ER expressing tumours suggesting that underlying tumour biology contributes to the initial peak in recurrence. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6042.
PTU-195 The Population Prevalence of Gluten Sensitivity and the Diagnostic Yield in Secondary Gastrointestinal Care
Authors: I Aziz, M Hadjivassiliou, S Winfield, N Rugg, A Kelsall, L Newrick, D S Sanders
Journal: Gut (2013)

<h3>Introduction</h3> Healthcare professionals commonly encounter patients complaining of gluten sensitivity (GS) in the absence of serological and histological markers for coeliac disease (CD). This clinical entity has recently been termed non-coeliac gluten sensitivity (NCGS). The aim of this study was to determine the population prevalence of GS and to ascertain the diagnostic yield in those patients referred to secondary gastrointestinal (GI) care with gluten related symptoms. <h3>Methods</h3> A population survey was conducted during March 2012 in Sheffield, UK, comprising basic demographic information, screening for GI conditions and enquiring for GS. We also analysed diagnostic outcomes in all patients referred by GPs to a dedicated secondary care clinic (2006–2012). The referral criteria were “GI symptoms attributed to gluten ingestion.” Investigations included coeliac serology (EMA &amp; TTG), immunoglobulins, HLA DQ2/DQ8 typing, duodenal biopsies +/- gluten challenge if indicated. A diagnosis of CD was based on a positive coeliac serology, HLA typing and histological changes according to the Marsh classification. <h3>Results</h3> 1002 adults completed the population based survey (55% female, age range 16–93, mean age 39 yrs). The prevalence of GS was 13% (129/1002, female 80% [P &lt; 0.0001], age range 18–75, mean age 39yrs). The proportion of GS individuals who had seen a doctor for their symptoms was 35/129 (27%). In the absence of any known organic GI disease the prevalence of individuals fulfilling the ROME III criteria for IBS in the general population was 6%, with up to 80% being female (p &lt; 0.0001). Patients with IBS were more likely to report GS than non-IBS patients (43% vs. 10%, p &lt; 0.0001). GS individuals described a combination of intestinal &amp; extra-intestinal symptoms (Table 1). Of the GS cohort, 29% (37/129) had tried a gluten free diet (GFD) – significant factors present in those trying a GFD include longer duration of symptoms (mean 96 vs. 54 months, p = 0.013), previous doctor consultations (OR 52), diarrhoea (OR 17) and abdominal pain (OR 10.3). In secondary GI care 156 patients with GS were investigated (85% female, mean age 39yrs). A diagnosis of CD was reached in 10% with the remaining being classified as NCGS. All patients with CD were HLA positive compared to 46% of NCGS cases. <h3>Conclusion</h3> 13% of the general population self report GS. Of those investigated in the gastroenterology department only 10% have CD, with the remaining fulfilling the criteria for NCGS. The symptoms of NCGS are diverse and there is a relationship with IBS. The prevalence of a positive HLA typing in NCGS is half that of CD suggesting an alternative immune mechanism to gluten intolerance. <h3>Disclosure of Interest</h3> None Declared.