tbuckley/cabot-search huggingface dataset:
Abstract LB-173: Maraviroc, a CCR5 antagonist, prevents development of hepatocellular carcinoma in a mouse model
Authors: Laura Ochoa-Callejero, Laura Pérez-Martínez, Susana Rubio-Mediavilla, José A. Oteo, Alfredo Martínez, José R. Blanco
Journal: Cancer Research (2012)

Abstract Chronic liver disease caused by infections or dietary toxins may result in liver fibrosis, cirrhosis and, eventually, hepatocellular carcinoma (HCC). The only curative treatments for patients with advanced liver disease are partial surgical resection and liver transplantation. However, organ shortage as well as an increasing organ demand call for early treatment of liver disease and prevention of fibrosis on high risk individuals. Stellate cells of the liver seem to be responsible for the fibrogenic response through the activation of an autocrine loop involving the chemokine receptor, CCR5. Since this receptor is also one of the main ports of entry for the human immunodeficiency virus (HIV), several CCR5 inhibitors are being used in the clinic to reduce viral load. We used one of these inhibitors, maraviroc (MVC), in a mouse model of diet-induced HCC to investigate whether this intervention would reduce disease progression. This diet was deficient in choline and was supplemented with ethionine in the drinking water (CDE diet). Animals receiving the CDE diet presented higher mortality, higher levels of markers for liver injury such as transaminases, alkaline phosphatase, and bilirubin, developed severe hepatic fibrosis, and were affected by numerous tumors by week 16, when compared with control mice receiving a regular diet. In addition, many cytokines, chemokines, and other matrix components including CCL2, CCL3, CCL4, CCL5, CCR5, CXCL10, IL-12, TGF-b1, or MMP9, were elevated by the CDE diet. Animals which received the CDE diet but were simultaneously treated with MVC presented significantly higher survival, less liver fibrosis, lower levels of liver injury markers and chemokines, and lower tumor burden than their counterparts receiving only the hepatotoxic diet. Animals treated with MVC on top of a normal control diet did not show any evidence of toxicity or any morphological change when compared with non-treated mice. This study suggests that MVC, a well tolerated and clinically characterized drug, may be used as a preventative treatment for HCC. Clinical studies are needed to demonstrate the efficacy of this drug, or other CCR5 inhibitors, in patients with high risk of developing HCC. 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 LB-173. doi:1538-7445.AM2012-LB-173
1220 TRIPLE COMBINATION THERAPY FOR HEPATITIS C WITH TELAPREVIR EXHIBITS GREATER EARLY ANTIVIRAL SUPPRESSION THAN WITH BOCEPREVIR REGARDLESS HIV STATUS
Authors: J.M. Benito, K. Bichoupan, C. Sanchez-Parra, A. Branch, P. Barreiro, I. Maida, A. Aguilera, N.I. Rallón, P. Labarga, J.V. Fernandez-Montero, V. Soriano, D. Dieterich
Journal: Journal of Hepatology (2013)
763 MULTIPLEXED PROTEOMIC APPROACH FOR IDENTIFICATION OF POTENTIAL SERUM BIOMARKERS IN HEPATOCELLULAR CARCINOMA PATIENTS WITH NORMAL AFP
Authors: J.E. Yeon, K.-H. Kim, J.H. Kim, K.S. Byun, S.Y. Kwon, W.H. Choe, J.Y. Bang, G.-Y. Kang, E.C. Yi, H.S. Park
Journal: Journal of Hepatology (2012)
Late-Breaking News: Morton Moves to Open John Wayne Cancer Institute
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Late-Breaking News: Morton Moves to Open John Wayne Cancer Institute Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 12, 19 June 1991, Page 827, https://doi.org/10.1093/jnci/83.12.827 Published: 19 June 1991
P297 VITAMIN E ALTERS INTESTINAL MICROBIOME THROUGH DIFFERENTIAL CHANGES IN MUCOSAL AND FECAL MICROBIOTA IN MOUSE MODEL OF NONALCOHOLIC FATTY LIVER DISEASE (NALFD)
Authors: S. Mirshahi, P. Puri, T. Pacana, K. Daita, V. Patel, H.K. Min, M. Sikaroodi, P.M. Gillevet, A.J. Sanyal
Journal: Journal of Hepatology (2014)
A1.16 Interleukin-36α activates fibroblast like synoviocytes
Authors: Verena Kästele, Olga Wagner, Anja Derer, Verena Schmitt, Georg Schett, Silke Frey, Axel J Hueber
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Interleukin-36α (IL-36α) is a member of the IL-1 family and has pro-inflammatory properties. It binds to the IL-36 receptor (IL-36R) whereby the IL-1 receptor accessory protein (IL-1RacP) is recruited to form a heterodimeric receptor. In transfected cell lines this binding activates MAP-kinases and NF-κB signalling and further induces the expression of pro-inflammatory cytokines. In rheumatoid arthritis (RA) synovium IL-36α is significantly higher expressed compared to osteoarthritis (OA) synovium. Both OA and RA synovial like fibroblasts (FLS) express IL-36R and can similarly be activated through IL-36α. <h3>Objectives</h3> To determine the role and function of IL-36α in RA, in particular the impact on FLS and how this cell activation contributes to further inflammatory responses in the pathogenesis of RA. <h3>Materials and Methods</h3> FLS of RA and OA patients were isolated and stimulated with IL-36α to analyse intracellular signal transduction by immunoblotting. To confirm signalling pathways, FLS of WT, MK2-/- and IL-36R-/- mice were cultured with IL-36α and assessed for cytokine and MMP expression. This expression pattern was additional assayed for IL-36α-activated human FLS and was performed by quantitative real time, multiplex assay and ELISA. Further, FLS were stimulated with IL-36α for one week and the effect on proliferation was detected by cell counting and cell labeling with eFluor analysed by flow cytometry. <h3>Results</h3> IL-36α signals specific via the MAP-kinase p38 that activates MK2 and HSP27 but no difference in signalling between OA and RA FLS was observed. Activated murine and human FLS showed increased expression of proinflammatory cytokines and MMPs such as IL-6, IL-8, MMP1 and MMP3. This activation was restricted to the binding of IL-36α to its receptor IL-36R due to the lack of activation in IL-36R-/- FLS. MK2-/- FLS showed a decreased activation compared to WT cells after culturing with IL-36α. Additional IL-36α-stimulated FLS showed a significantly increased proliferation compared to unstimulated controls. <h3>Conclusions</h3> We show that the activation of FLS through IL-36α is IL-36R and partially MK2 dependent and leads to pathogenic cytokine and MMP production. We conclude that FLS display a target cell for IL-36α in the synovium and this supports the interplay of IL-36α secreting plasma cells with synovial stromal cells.
Pancreatic hamartoma: a rare cause of obstructive jaundice
Authors: Hiroyuki Inoue, Masahiko Tameda, Reiko Yamada, Shunske Tano, Masaki Kasturahara, Yasuhiko Hamada, Kyosuke Tanaka, Noriyuki Horiki, Yoshiyuki Takei
Journal: Endoscopy (2014)

A 65-year-old man was referred to our hospital with obstructive jaundice. Laboratory tests showed elevated levels of alkaline phosphatase (1932 U/L; normal range 35 – 104 U/L), γ-glutamyltransferase (1030 U/L; normal value < 39 U/L), and bilirubin (3.6 mg/dL; normal value < 1.2 mg/dL). The tumor antigen CA 19-9 was also elevated (226.4 U/L; normal value < 37 U/L).
Pathophysiology of Dyspnea
Authors: Harold L. Manning, Richard M. Schwartzstein
Journal: New England Journal of Medicine (1995)

Patients with cardiopulmonary disease often have respiratory distress, which physicians refer to as dyspnea. Dyspnea is responsible for substantial disability and for millions of patient visits each year. Although dyspnea has been defined in several ways,14 we define it as "an uncomfortable sensation of breathing." This review will focus on the mechanisms of dyspnea, because a greater understanding of those mechanisms may lead to better therapy for this often troubling symptom.Problems in the Study of DyspneaDyspnea differs from other sensations in that the neural pathways underlying it are not well understood. For example, free nerve endings transmit . . .
AB0964 Assessment of periarticular tissues of the shoulder joint in patients with osteoarthritis using the tendon shoulder index
Authors: E. Kirillova, N. Shamsutdinova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Pathology of the periarticular tissues is common in dystrophic-degenerative processes in the joints. But clinically assess the severity of damage difficult. Therefore we have developed the tendon shoulder index. Tendon shoulder index gives a description of pain of shoulder tendons in their places of attachment. Tendon shoulder index is a summary indicator of pain assessment in the shoulder joint with damage of the periarticular tissues. <h3>Objectives</h3> To determine the possibility of the tendon index shoulder to assess the pathology of periarticular tissues shoulder in patients with osteoarthritis. <h3>Methods</h3> The method of evaluating tendon damage by defining shoulder pain with semiquantitative method of shoulder tendons and their attachments sites (pain: palpation of the patient indicates the presence of pain - 1 point, facial reaction - 2 points, the motor response - 3 points) with an calculation figures in points and the determination of damage intensity: low 1-5 points, average 6-10, much - more than 11 points. The study involved 20 patients with osteoarthritis complained of pain in the shoulder joint. To assess pain was used visual-analog scale (VAS) at rest, movement, and palpation. Evaluation of the shoulder joint was carried out by Constant Score. We developed the tendon shoulder index for assessment the objective status. The tendon shoulder index included an assessment of pain on a scale (0-3) during movement, causing stress the rotator cuff tendons and long head of the biceps tendon. <h3>Results</h3> The correlation noted between the tendon index shoulder and VAS at palpation (r =0,4), between the tendon index shoulder and VAS at movement (r =0,3), and between the tendon index shoulder and Constant Score (r = -0.6). <h3>Conclusions</h3> Index of tendon of shoulder joint can be used to assess the pathology of the shoulder joint periarticular tissues in patients with osteoarthritis. Using this index we can clinically asses the pathology of periarticular tissues and if necessary to correct treatment <h3>Disclosure of Interest</h3> None Declared
Abstract 4088: Cotreatment with decitabine and paclitaxel is affected by the re-expression of drug-metabolising enzymes
Authors: Laura Cosentino, Nahal Masrour, Julie Burns, Weishuo Fang, Robert Brown, Phil Burns, Klaus Pors
Journal: Cancer Research (2012)

Abstract The literature describes the role of DNA methylation in regulation of tumour suppressor genes, DNA repair genes, but not much attention has been paid to drug metabolising enzymes (DMEs). Some evidence has been reported and includes methylation of the promoter regions of CYP450 and ABC transporters. Cotreatment with decitabine (DAC) and paclitaxel (PAC) has been reported in several studies, but few of these have reported in a focused manner on the effect on DMEs. As a consequence, the major DMEs involved in the detoxification of PAC (namely ABCB1, CYP2C8 and CYP3A4) were investigated. The aldehyde dehydrogenase enzymes (ALDH1A1, ALDH2 and ALDH3A1) were also explored, as they have recently been shown to play a chemo-protective role against taxanes. Analysis of the CpG island methylation level indicated that all the above-mentioned DMEs were densely methylated and that treatment of MCF-7 cells with DAC for 24 h resulted in a decrease in methylation within the gene promoter region. Furthermore, correlation of decrease in DNA methylation with increase in mRNA level of ABCB1, CYP3A4, ALDH2 and ALDH3A1 was observed, but not for CYP2C8 and ALDH1A1. However, only the ABCB1 protein level was shown to significantly increase. Chemosensitivity of DAC combined with PAC was tested in MCF-7 cells: treatment with DAC for 24 h was followed by PAC exposure on days 4, 6 or 8. Evaluation of the cotreatment on cell survival demonstrated that the cytotoxic potential of PAC was reduced proportionally to the exposure time to DAC before PAC treatment, suggesting that ABCB1 protein confers chemo-protection on the cells. To investigate whether this resistance was applicable to other taxanes with proven efficacy against MDR-resistant cells, the preclinical agent Lx2-32c (aziditaxel) was evaluated. Lx2-32c also lost potency similar to PAC, indicating that ABCB1 is responsible for loss of activity of these two taxanes. The same experiments were also carried out in HeLa cells as they were shown to contain low level of DNA methylation of the above-mentioned DME genes including the ABCB1 gene. DAC treatment did not lead to significant reactivation at protein level and cotreatment of DAC and PAC produced a synergistic effect on cell killing. In conclusion, our data demonstrate that cotreatment of DAC and PAC can produce a synergistic effect, but that it is affected by the re-expression of DMEs. Our observations provide useful information for clinical evaluation of combination strategies comprising DAC and PAC, and chemotherapeutics in general that are affected by DMEs. 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 4088. doi:1538-7445.AM2012-4088
Memory CD4 T Cells Induce Antibody-Mediated Rejection of Renal Allografts
Authors: Victoria Gorbacheva, Ran Fan, Robert L. Fairchild, William M. Baldwin, Anna Valujskikh
Journal: Journal of the American Society of Nephrology (2016)

Despite advances in immunosuppression, antibody-mediated rejection is a serious threat to allograft survival. Alloreactive memory helper T cells can induce potent alloantibody responses and often associate with poor graft outcome. Nevertheless, the ability of memory T cells to elicit well characterized manifestations of antibody-mediated rejection has not been tested. We investigated helper functions of memory CD4 T cells in a mouse model of renal transplantation. Whereas the majority of unsensitized C57Bl/6 recipients spontaneously accepted fully MHC-mismatched A/J renal allografts, recipients containing donor-reactive memory CD4 T cells rapidly lost allograft function. Increased serum creatinine levels, high serum titers of donor-specific alloantibody, minimal T cell infiltration, and intense C4d deposition in the grafts of sensitized recipients fulfilled all diagnostic criteria for acute renal antibody-mediated rejection in humans. IFNγ neutralization did not prevent the renal allograft rejection induced by memory helper T cells, and CD8 T cell depletion at the time of transplantation or depletion of both CD4 and CD8 T cells also did not prevent the renal allograft rejection induced by memory helper T cells starting at day 4 after transplantation. However, B cell depletion inhibited alloantibody generation and significantly extended allograft survival, indicating that donor-specific alloantibodies (not T cells) were the critical effector mechanism of renal allograft rejection induced by memory CD4 T cells. Our studies provide direct evidence that recipient T cell sensitization may result in antibody-mediated rejection of renal allografts and introduce a physiologically relevant animal model with which to investigate mechanisms of antibody-mediated rejection and novel therapeutic approaches for its prevention and treatment.
INFLUENCE OF SIZE OF FAMILY UPON THE CHARACTERISTICS OF THE MENTALLY DEFICIENT
Authors: Neil A. Dayton
Journal: American Journal of Psychiatry (1935)

Dr. Neil A. Dayton calls attention to the following corrections to be made in his article: Influence of Size of Family upon the Characteristics of the Mentally Deficient, which appeared in the January, 1935, number of the Journal. Page 800, third line from bottom of page, strike out the words "or recessive"; last line, strike out the word "recessives" and substitute the word "carriers." Page 801, foot-note, line 7; strike out the word "recessives" and substitute the word "hybrid."
Over-the-scope-clipping in colonic perforation caused small-bowel fixation and pneumoperitoneum requiring surgical repair
Authors: Heinz Albrecht, Andreas Naegel, Alexander Hagel, Wolf Roesler, Thomas Foertsch, Markus Neurath, Raja Atreya, Martin Raithel
Journal: Endoscopy (2014)

Perforations during endoscopy can be treated using through-the-scope clips or the over-the-scope clip (OTSC) [1] [2] [3]. The rate of successful perforation closure using the OTSC has been reported to be approximately 89 % with an acceptable morbidity and mortality rate of 3 % [3] [4].
Intrasplenic Dissection by Pancreatic Pseudocysts
Authors: Andrew L. Warshaw, Thomas McC. Chesney, George W. Evans, Hugh F. McCarthy
Journal: New England Journal of Medicine (1972)

Four patients in whom a pancreatic pseudocyst penetrated into the spleen were seen within a six-month period. Intrasplenic pancreatic pseudocysts were associated with rupture of the spleen, splenic-artery hemorrhage, splenic-vein thrombosis, and splenic infarction. Spleen scans using 99mTc-labeled sulfur colloid and selective celiac angiography both clearly delineated the intrasplenic component of the pseudocysts. Removal of the entire pseudocyst by distal pancreatectomy and splenectomy appears to be feasible, safe, and effective treatment.
OP0075-HPR A multidisciplinary and multidimensional program for hand osteoarthritis is not effective: Results of a randomized controlled study:
Authors: M.J. Stukstette, J. Dekker, A.A. den Broeder, W. Noort van der Laan, J.W. Bijlsma, C.H. van den Ende
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Although research on the efficacy of non-pharmacological interventions is very limited and mainly based on low quality studies, international guidelines for management of hand osteoarthritis (OA) strongly recommend to treat all patients with hand OA with a combination of pharmacological and non-pharmacological interventions. The aim of this study was to examine the efficacy of a multidisciplinary, multidimensional nonpharmacological intervention in patients with hand OA. <h3>Objectives</h3> To examine the efficacy of a multidisciplinary, multidimensional non-pharmacological intervention in patients with hand OA. <h3>Methods</h3> A single blinded randomized multicenter trial was conducted. Patients were recruited at three Rheumatology outpatient clinics in the Netherlands. Included were patients with Hand OA according to the ACR classification Criteria for clinical hand OA with limitations in activities (AUSCAN function score ≥9). Patients were randomly assigned to immediate start of multidisciplinary intervention (four weekly sessions, including individual goal setting, exercises, education, and splints if considered necessary) or 30 minutes of education followed by waiting time of 3 months. Data at baseline and 3 months were collected by a research assistant who was blinded for treatment allocation. Primary outcome measures after three months were pain and limitations in activities as measured with the AUSCAN and the OARSI-20 responder criteria. Secondary outcome measures included grip strength, self-efficacy, pain coping and quality of life. (Dutch Trial Register trial number NTR1191). <h3>Results</h3> 151 patients (83% female, mean (SD) age 59.2 (7.7)) were included. After 3 months no significant and no relevant differences were observed between the treatment group (n=76) and the control group (n=75) in any of the primary and secondary outcome measures. About one third of patients were classified as responder (OARSI 20 responder criteria) (32% and 37% in the treatment group and control group, respectively). Outcome: <h3>Conclusions</h3> Patients with hand OA do not benefit from a multidimensional and multidisciplinary non-pharmacological treatment program on the short term. Future research should focus on the effectiveness of single treatment elements targeted on individual patient characteristics and needs <h3>Disclosure of Interest</h3> None Declared
STATIN USE IS ASSOCIATED WITH LOWER CIRCULATING MICRORNA 208A LEVELS IN PATIENTS WITH ATRIAL FIBRILLATION: DATA FROM THE MIRHYTHM STUDY
Authors: Suvasini Lakshmanan, Honghuang Lin, Kahraman Tanriverdi, Esa Nada, Kevin Donahue, Senthil Sivalingam, John Keaney, Emelia Benjamin, Kevin Floyd, Lawrence Rosenthal, Jane Freedman, David McManus
Journal: Journal of the American College of Cardiology (2016)
SAT0235 Predictors of flare during pregnancy in women with systemic lupus erythematosus:
Authors: M.A. Saavedra, A. Sánchez, C.V. Cruz-Reyes, U. Angeles, L.J. Jara
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Woman with systemic lupus erythematosus (SLE) have 2 to 3 times higher risk of reactivation during pregnancy. However, the predictive factors of lupus flare in pregnancy are not completely elucidated. <h3>Objectives</h3> To identify predictors of flare in pregnant women with SLE. <h3>Methods</h3> We reviewed clinical records of a cohort of pregnant women with SLE (ACR 1982, 1997) treated in our Clinic of Pregnancy and Rheumatic Diseases in a tertiary referral center for the period January 2005 to June 2011. Patients were evaluated at least once during each trimester and once postpartum. Primary endpoint was lupus flare including specific skin lesions, arthritis, hematological, neurologic, cardiopulmonary and renal manifestations. We analyzed 15 clinical and laboratory variables that potentially have predictive value for lupus flare during pregnancy, including age, duration of disease, activity of SLE before pregnancy, renal function, organ involvement, parity, drug use and immunological parameters. For analysis each pregnancy was included as an independent event and these were divided into 2 groups: those of mothers who relapsed and those who did not. Statistical analysis included descriptive statistics, chi square, Student t test, bivariate and multivariate analysis; odds ratios (OR) with confidence intervals (CI) 95% were also calculated. <h3>Results</h3> We studied 124 pregnancies in 120 women with a mean age of 26.5±5.1 years at time of pregnancy, with an mean of SLE evolution 5.2±4.1 years, 45 (36.2%) patients had lupus nephritis before pregnancy, 16 (12.9%) women had SLE activity before pregnancy, 47 (37.9%) women had at least one episode of flare during pregnancy. The significant variables associated with lupus flare during pregnancy in bivariate and multivariate analysis are shown in the table. The live birth rate was similar in both groups (80.9% vs 87%, p=0.35); on the other hand, the rate of prematurity was higher (55.3% vs 35.1%, p=0.02) with fewer weeks of gestation (34.6±3.9 vs 35.8±3.4, p=0.009) in women who relapsed. <h3>Conclusions</h3> According to the experience of our center, primiparous woman with SLE and hypocomplementemia before conception (lupus subclinical activity data) have a higher risk of relapse during pregnancy. <h3>Disclosure of Interest</h3> None Declared