tbuckley/cabot-search huggingface dataset:
SP0142 Interleukin-36: A key cytokine for innate and adaptive immune responses
Authors: C. Gabay
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> The IL-1 family of cytokines comprises 11 members, including IL-1alpha, IL-1beta, IL-18, IL-33, and three IL-36 homologues, namely IL-36alpha, IL-36beta, IL-36gamma (previously termed IL-1F6, IL-1F8, IL-1F9). IL-36 binds to IL-36R (previously termed IL-1Rrp2) leading to the recruitment of IL-1RAcP and intracellular signals similar to those induced by other IL-1 cytokines. Natural inhibitors control the biological activities of IL-1 cytokines. IL-1 receptor antagonist (IL-1Ra) is a cytokine that inhibits IL-1 activities by competitively blocking its interaction with cell surface receptors. IL-36Ra exerts the same type of inhibitory activities for IL-36. Hereditary deficiency of IL-36Ra leads to a severe form generalized pustular psoriasis, indicating that the IL-36/IL-36Ra balance is critical for the control of skin inflammation. Experimental data from animal models and human samples suggest that IL-36 is involved in the pathogenesis of psoriasis. Recently, my laboratory has shown that IL-36 exerts strong stimulatory effects on dendritic cells, leading to cytokine release and increased expression of MHC class 2 and co-stimulatory molecules. IL-36 stimulates the polarization of of naïve CD4+ T cells into interferon-gamma producing Th1 cells in vitro and in vivo. Taken together these data indicate that IL-36 stimulates both innate and adaptive immune responses that may be critical for host responses to pathogens and inflammatory conditions. <b>Take home message:</b> The family of IL-1 cytokines includes several members with different biologic functions IL-36 is a novel member of the IL-1 family of cytokines, the activity of which is controlled by IL-36Ra Several evidence suggest that IL-36 is involved skin psoriasis IL-36 exerts stimulatory activities leading to Th1 responses <h3>Disclosure of Interest</h3> None Declared
Dimerizer-Induced Proliferation of Genetically Modified Hepatocytes
Authors: Zong-Yi Li, Kevin Otto, Robert E Richard, Shaoheng Ni, Irina Kirillova, Nelson Fausto, C Anthony Blau, André Lieber
Journal: Molecular Therapy (2002)

Stable gene transfer to the liver by viral vectors is inefficient. In an attempt to stimulate expansion of retrovirally transduced hepatocytes, we employed a synthetic drug (AP20187) that can reversibly dimerize and activate fusion proteins that contain a growth factor receptor signaling domain. Signaling domains derived from receptors for interleukin-6 (gp130), hepatocyte growth factor (c-met), epithelial growth factor (EGF-R), and thrombopoietin (mpl) triggered monkey hepatocytes to enter the cell cycle. However, mitosis occurred only upon activation of the gp130 and c-met signaling domains. Primary mouse hepatocytes expressing the gp130 fusion proliferated transiently in response to AP20187. AP20187-triggered activation of gp130 also stimulated the selective (>2-fold) expansion of retrovirally transduced hepatocytes in vivo, as shown by immunohistochemical staining and quantitative proviral DNA analysis. Drug-inducible in vivo expansion of genetically modified hepatocytes may have potential applications in hepatic gene transfer or in liver repopulation by transplanted hepatocytes or their progenitors. (c)2002 Elsevier Science (USA).
A4.01 T cells are critical regulators of soft callus mineralization and normal deposition of collagen I during bone repair
Authors: A Serra, T El Khassawna, A Petersen, C Schlundt, I Könnecke, H Schell, HD Volk, A Radbruch, K Schmidt-Bleek, G Duda
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> The critical interdependency between the skeletal and immune system has been demonstrated for&nbsp;the fracture healing process. However, the current state of the art is contradictory. On one hand, lymphopenic mice display&nbsp;alleged better healing&nbsp;after injury. On the other hand, several&nbsp;studies attribute either a positive or negative role to T and B cells in bone biology, autoimmunity and fracture healing. The objective of this study is to elucidate the specific role of T and B cells in fracture repair toward early callus mineralization, bone quality, migration of osteoblast precursors and Collagen I deposition. <h3>Materials and methods</h3> Unilateral closed femoral fractures were produced in RAG1-/-, TCR βδ chain -/-, JHT -/- and&nbsp;C57BL/6 wild-type mice. Bone healing was assessed by histology, biomechanical testing and&nbsp;fluorochrome deposition. Deposition and structural properties of CollagenI were studied by second harmonic and confocal microscopy. Callus gene expression was determined by microarray analysis. Osteoblast precursors, T and B cell migration in the callus were visualised by confocal microscopy. <h3>Results</h3> Fractured bones of RAG -/- mice&nbsp;mineralized faster, but were much less capable to withstand deformation. Similarly, RAG -/- mice deposited bone quicker during the earliest phases of healing, whereas at later stages underperformed relative to controls. RAG -/- mice also failed to deposit a cross gap layer of Collagen I which correlated with diminished immigration of osteoblast precursors in the peripheral callus. The remaining network of Collagen I fibres in these mice was found to be highly disordered. Interestingly, no alteration in osteoblast precursor migration was observed when only either T or B cells were &nbsp;absent. However, Collagen I deposition was strongly impaired in T cell but not in B cell deficient mice. There, Collagen I fibres failed to organise across the gap in the peripheral callus displaying a highly disordered pattern of deposition. <h3>Conclusions</h3> Overall our data show that lack of an adaptive immune system does not lead to better, but rather deregulated and suboptimal bone healing. These features were recapitulated in mice that specifically lacked T and not B cells.
Effect of Serum Parathyroid Hormone and Bone Marrow Fibrosis on the Response to Erythropoietin in Uremia
Authors: D. Sudhaker Rao, Mei-shu Shih, Ravinder Mohini
Journal: New England Journal of Medicine (1993)

Anemia is common in patients with chronic renal insufficiency and secondary hyperparathyroidism. Erythropoietin therapy is effective, but the dose required varies greatly. One possible determinant of the efficacy of erythropoietin therapy is the extent of marrow fibrosis caused by hyperparathyroidism. We examined the relation between the erythropoietic response to erythropoietin and hyperparathyroidism in a cross-sectional study of 18 patients undergoing hemodialysis who had received erythropoietin therapy for one to three years. In 7 patients (the poor-response group) the dose of intravenous erythropoietin needed to maintain a mean (±SD) target hematocrit of 35 ±3 percent was >100 units per kilogram of body weight three times a week, and in 11 patients (the good-response group) it was ≤ 100 units per kilogram. In all patients, indexes of the adequacy of dialysis and the extent of hyperparathyroidism and aluminum toxicity were determined monthly, and bone histomorphometry was performed.
GW25-e4299 Research on pharmacological mechanisms of Qishen Granule on transcriptome RNA-seq in mini pigs with cardiac functional insufficiency and qi-deficiency and blood stasis syndrome (QDBS) induced by Ameroid constricting ring
Authors: Chuo Wenjing, Guo Shuzhen, Qiu Qi, Wang Yong, Li Chun, Lin Yang, Lian Hongjian, Feng Xuanchao, Fu Bangze, Wang Wei
Journal: Journal of the American College of Cardiology (2014)
543miR-19a replacement rescues cardiac and fin defects in zebrafish model of holt-oram syndrome
Authors: E Chiavacci, F Cremisi, E Guzzolino, A Cellerino, M Baumgart, R D'aurizio, L Pitto
Journal: Cardiovascular Research (2014)

Purpose: MicroRNAs (miRNAs) are short, single-stranded RNAs that anneal with complementary sequences in mRNAs thereby suppressing protein expression and often decreasing mRNA stability. Due to the high number of genes that are potentially targeted by one miRNA and to the relatively low number of different miRNAs coded in the genome, miRNAs are the best candidates to orchestrate gene expression in embryonic development and in response to inducing signals, by integrating distinct transcription factors pathways. Indeed, the manipulation of miRNA expression or function can have a profound impact on cellular phenotype. miRNA are critically involved in almost all the biological processes in health and disease including several cardiovascular disorders. Tbx5 is a transcription factor crucial for heart development and implicated in cardiac function. In human, TBX5 mutations are associated with Holt-Oram Syndrome (HOS), which is characterized by upper limb and congenital heart defects. In mouse model of HOS, expression profiling revealed that Tbx5 regulates hundreds of genes through complex transcriptional networks, acting both directly on gene expression and indirectly as "regulating of regulators". Our data indicate that miRNAs can be important effectors of Tbx5. The goal of our project is to better characterize the miRNAs/Tbx5 regulatory network with the aim: a) to understand the molecular roots of the complex HOS phenotype; b) to verify if it might be possible, by miRNA modulation, to restore the aberrant pathways generated by Tbx5 alteration. Methods: Using zebrafish as model systems of HOS, we characterized the miRNA profiles of wild type (WT) and Tbx5-depleted embryos by NGS. The impact of differentially expressed miRNAs on cardiac development of WT embryos and Tbx5 morphants was investigated by gain and loss of function experiments. Results: Among the identified miRNAs responsive to Tbx5 dosage we focused on miR-19a, whose expression decreases in HOS zebrafish embryos. We showed that: a) miR-19a dysregulation affects heart development; b) miR-19a modulates the expression of genes important for epicardial development and retinoic acid metabolism; c) miR-19a replacement was able to rescue cardiac and pectoral fin defects and increase the viability of Tbx5 morphants. Conclusions-Our data demonstrate that in zebrafish the modulation of a single miRNA is sufficient to reduce the defects generated by a complex syndrome like HOS, supporting enthusiasm for the continued exploration of miRNAs as a new class of drug target.
Unusual 131I Uptake in a Benign Mucinous Cystadenoma of the Ovary in a Patient With Papillary Thyroid Cancer
Authors: Zhong-Ling Qiu, Yan-Hong Xu, Hong-Jun Song, Quan-Yong Luo
Journal: Clinical Nuclear Medicine (2010)

We present a huge benign mucinous cystadenoma of the ovary, incidentally discovered by 131I whole-body scan and 131I-SPECT/CT as a false-positive 131I uptake in a patient with papillary thyroid cancer. 131I whole-body scan and 131I-SPECT/CT performed after 131I administration revealed an abnormal focus of 131I uptake in a huge mass of the pelvis. The pelvic mass was histologically confirmed to be a benign mucinous cystadenoma of ovary. The case is a classic example of false-positive findings on 131I whole-body scan for differentiated thyroid cancer.
O99 INFLAMMATORY Wnt DRIVES INTRAHEPATIC CHOLANGIOCARCINOMA GROWTH AND CAN BE THERAPEUTICALLY INHIBITED IN VIVO TO REDUCE TUMOUR BURDEN
Authors: L. Boulter, R.V. Guest, T. Kendall, R. Walker, D. Wojtacha, A.J. Robson, K. Samuel, S.J. Wigmore, O.J. Sansom, S.J. Forbes
Journal: Journal of Hepatology (2014)
Pain in the Anterior Pelvis and Postoperative Prostatectomy Findings
Authors: HANS VAN DER WALL, GEOFFREY STOREY, LOUISE EMMETT, MICHAEL MAGEE
Journal: Clinical Nuclear Medicine (1999)

A 68-year-old man came to our institution for a bone scan to evaluate pain of recent onset in the anterior aspect of the pelvis. The results of plain radiographs of the pelvis were reported as normal. His medical history included surgical resection of a carcinoma of the sigmoid colon and transurethral resection of the prostate for urinary obstructive symptoms. Metastatic disease of the pelvic bones was suspected. Extensive evaluations failed to reveal any metastatic disease or specific cause of the pelvic pain.
TRATAMIENTO ENDOSCÓPICO CON PRÓTESIS METÁLICA AUTOEXPANDIBLE DE LA ESTENOSIS EN LA ENFERMEDAD DE CROHN
Authors: X Andújar, C Loras, F Pérez Roldán, JC Espinós, P González, J Barrio, F Igea Arisqueta, M Pérez-Miranda, F González-Huix, JB Gornals, F Fernández-Bañares, M Esteve
Journal: Endoscopy (2011)

Introducción: La estenosis es una de las complicaciones más frecuentes de la enfermedad de Crohn (EC), dentro de su abordaje se incluye el tratamiento médico, endoscópico y quirúrgico. El tratamiento endoscópico de elección es la dilatación neumática y excepcionalmente se han reportado casos aislados de colocación de prótesis.
Implementing a national flexible sigmoidoscopy screening program: results of the English early pilot
Authors: Roisin Bevan, Greg Rubin, Eleni Sofianopoulou, Julietta Patnick, Colin Rees
Journal: Endoscopy (2014)

Following the results of a major UK study showing that once-only flexible sigmoidoscopy (FSIG) screening significantly reduced colorectal cancer (CRC) incidence and mortality, an FSIG screening program in England was announced in late 2010. Three "early pilot" sites were selected in 2011 in Derby, South of Tyne, and Tees to assess the practicalities of the delivery of FSIG screening.Eligible people aged 55 from selected practices in the three early pilot areas received postal invitations to participate. The South of Tyne and Derby sites employed interactive models of screening invitation, while Tees used a simple invitation. Data were collected to assess uptake, process, and outcome. A self-completion participant satisfaction questionnaire was sent to all participants 1 month after attendance.A total of 4023 55-year-olds were invited to participate. Uptake was 29 %, with 1151 people screened over a 3-month period. Screening uptake differed by method of invitation: a simple approach was significantly more successful than an interactive one (32 % vs. 27 %, P = 0.0015). Uptake decreased significantly with increasing deprivation. Adenomas were found in 111 (9.8 %) of those screened and cancer in two. The procedure was rated "very" or "fairly" acceptable by 97 % of participants. Over 90 % of respondents said they would participate in future cancer screening and a similar proportion would recommend doing so to others.Delivery of an FSIG screening program to prevent CRC is feasible and should be implemented using a simple invitation system. The national Bowel Scope program subsequently commenced at pilot sites in May 2013, with full implementation planned by 2016.
P4-11-17: Noninferiority (NI) Phase III Trials in Advanced Breast Cancer (ABC) over 12 Years.
Authors: ED Saad, MS Militao
Journal: Cancer Research (2011)

Abstract Background NI trials have gained increasing importance in oncology. The contemporary practice regarding the design features and the results of NI trials have not been formally assessed in ABC. Methods: We searched PubMed for articles reporting the efficacy results of phase III trials on systemic antineoplastic treatments for ABC published between 1/1998 and 12/2009 in 11 leading medical journals (Ann Oncol, BCRT, BJC, Cancer, CCR, EJC, JCO, JNCI, Lancet, Lancet Oncol, and NEJM). Results: We retrieved 93 reports, 12 of which (13%; 95% CI, 7% — 22%) had a NI primary hypothesis. Of note, there were no equivalence (i.e., two-sided question) studies. There was no significant trend in the proportion of NI trials in the two 6-year periods compared (17% vs 9%; P=0.36). The median (range) sample sizes for NI and superiority trials were 404 (160-1354) and 326 (118-907) patients, respectively (P=0.32). NI trials enrolled exclusively first-line patients more frequently than superiority trials (83% vs 51%; P=0.06). The primary endpoint for NI trials was response rate (RR) and progression-free survival/time to tumor progression in 8 and 4 cases, respectively. Despite their nominally higher number of patients, NI trials were more likely than superiority trials to have RR as their primary endpoints (67% vs 32%; P=0.03). The NI margin was reported in all trials, but justified by authors in only one case. Among trials with RR as primary endpoint, the NI margin was 15% in six cases and 25% in two. In trials with progression-free survival/time to tumor progression as primary endpoints, the lower limit of the confidence interval for the hazard ratio to demonstrate NI was always 0.8. Of 12 NI trials, 9 were positive (i.e., proved NI). Conclusion: NI trials represent 13% of contemporary phase III trials on ABC. Most such trials achieve their primary endpoint. At present, NI margins seem to be chosen on historical basis rather than on statistical reasoning, and such choice could bear implications on trial positivity. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-17.
Hypertension and Antihypertensive Therapy as Risk Factors for Type 2 Diabetes Mellitus
Authors: Todd W. Gress, F. Javier Nieto, Eyal Shahar, Marion R. Wofford, Frederick L. Brancati
Journal: New England Journal of Medicine (2000)

Previous research has suggested that thiazide diuretics and beta-blockers may promote the development of type 2 diabetes mellitus. However, the results of these studies have been inconsistent, and many studies have been limited by inadequate data on outcomes and by potential confounding.
Case 3-2006
Authors: Robert H. Schapiro, Michael M. Maher, Joseph Misdraji
Journal: New England Journal of Medicine (2006)

A 63-year-old woman who had recently emigrated from the Dominican Republic sought medical attention because of the recent onset of dark urine, pruritus, and epigastric pain. Imaging studies revealed a complex cystic mass in the head of the pancreas, with stenosis of the common bile duct. Stenting of the obstruction was followed by resolution of jaundice; two months later, the pancreatic mass had resolved, but new intraabdominal lymphadenopathy had appeared. A diagnostic procedure was performed.
PRE-OPERATIVE BRAIN SPECT PERFUSION IMAGING COMBINED WITH INTERNAL CAROTID BALLOON OCCLUSION IDENTIFIES PATIENTS AT HIGH RISK FOR POST-SURGICAL NEUROLOGIC DEFICITS: PREDICTIVE VALUE AND LONG-TERM FOLLOW-UP IN PATI
Authors: I. A. Weissman, V. L. Schramm, E. Seda, J. P. Gerhold, W. F. Manke
Journal: Clinical Nuclear Medicine (1996)

Weissman, I.; Schramm, V. L.; Seda, E.; Gerhold, J. P.; Manke, W. F.Editor(s): Blend, Michael; Haseman, Michael Author Information
Abstract B3: Induction of Smad4 in response to serum starvation promotes cell death through PUMA stabilization
Authors: Sun-Hye Lee, Youn-Sang Jung, Ji-Yun Chung, Ah-Young Oh, Su-Jin Lee, Bum-Joon Park
Journal: Cancer Research (2011)

Abstract Smad4 is an essential factor in TGF-β signaling and is also known as frequently mutated tumor suppressor gene in human pancreatic and colon cancer. However, considering the fact that TGF-β can contribute to cancer progression through transcriptional target genes such as Snail, MMPs, and EMT-related genes, loss of Smad4 in human cancer would be required for obtaining the TGF-β signaling independent advantage, which should be essential for cancer cell survival. Here we provide the evidence about novel role of Smad4, serum-deprivation-induced apoptosis. Elimination of serum can obviously increase the Smad4 expression and induces the cell death by p53-independent PUMA induction. Instead, Smad4 deficient cells show the resistance to serum starvation. Induced Smad4 suppresses the PAK1, which promotes the PUMA destabilization. We also found that siah-1 and pVHL are involved in PAK1 destabilization and PUMA stabilization. In fact, Smad4-expressed cancer tissues show the elevated expression of PAK1, also supprots our hypothesis that Smad4 induces PUMA-mediated cell death through PAK1 suppression. Our results strongly suggest that loss of Smad4 render the resistance to serum-deprivation-induced cell death, which is the TGF-β independent tumor suppressive role of Smad4. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B3.
Abstract 5033: Modeling Ewing's sarcoma and tolerance of EWS-FLI1 with neural crest stem cells.
Authors: Jack T. Mosher, Victor S. Chen, Elizabeth R. Lawlor
Journal: Cancer Research (2013)

Abstract Ewing's sarcoma (ES) is a highly malignant bone and soft tissue tumor that primarily affects children and young adults. These tumors are characterized by chromosomal translocations, most commonly t(11;22)(q24;q12), which generates the EWS-FLI1 fusion oncogene. Despite its oncogenic potential, the fusion protein induces cell cycle arrest or apoptosis in most non-transformed cells unless mutations in tumor suppressors such as p16 are also present. However, only a minority of patients (∼25%) have such mutations at diagnosis, suggesting other mechanisms for cellular tolerance must be present in the cell of origin. Currently, the cell of origin of these tumors is controversial, with data supporting both a mesenchymal and/or neural crest origin. To assess the potential to model ES using mouse neural crest stem cells (NCSCs) and elucidate the mechanism(s) of EWS-FLI1 tolerance, primary fetal and adult mouse NCSCs were transduced with a V5-tagged EWS-FLI1 2a eGFP construct. Both wild-type fetal and postnatal NCSCs tolerated EWS-FLI1 expression, with 40-60% of the stem cell-derived neurospheres positive for GFP. There was no difference in neurosphere forming ability between cells infected with EWS-FLI1 or an empty vector, suggesting EWS-FLI1 expression was not toxic to these cells. EWS-FLI1 expression was maintained as the stem cells self-renewed, with GFP-positive primary neurospheres giving rise to GFP-positive secondary and tertiary neurospheres but there was no difference in the frequency of GFP-positive and -negative secondary neurospheres. EWS-FLI1 expression was confirmed by quantitative PCR and the V5 tag was localized to the nucleus by immunocytochemistry, consistent with transcription factor function. EWS-FLI1-mediated gene expression analysis is currently ongoing. Interestingly, the tolerance of EWS-FLI1 was dramatically reduced in Bmi-1 deficient NCSCs. Bmi-1 is known to function cooperatively with multiple other oncogenes to mediate transformation but its role in tolerance has not been studied. In the absence of Bmi-1 only 8% of the fetal neurospheres were positive for GFP, a large decrease compared to 40% of the wild-type neurospheres. Taken together, these data are consistent with a neural crest origin for ES and demonstrate a critical role for Bmi-1-mediated tolerance to EWS-FLI1. Work is ongoing to determine whether EWS-FLI1 can transform these cells and to assess the full utility of this novel system to model ES and genetically assess important regulators of EWS-FLI1 function. Citation Format: Jack T. Mosher, Victor S. Chen, Elizabeth R. Lawlor. Modeling Ewing's sarcoma and tolerance of EWS-FLI1 with neural crest stem cells. [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 5033. doi:10.1158/1538-7445.AM2013-5033
Association of Gene Variant in IL12B Gene with Atopic Dermatitis Complicated by Eczema Herpeticum (ADEH)
Authors: P.S. Gao, N.M. Rafaels, M. Boguniewicz, L.C. Schneider, T.R. Hata, J.M. Hanifin, C. Vergara, L.A. Beck, R.A. Mathias, K.C. Barnes, D.Y. Leung
Journal: Journal of Allergy and Clinical Immunology (2012)