tbuckley/cabot-search huggingface dataset:
AB0004 Erap1 Polymorphisms in Korean Patients with Behcet's Disease
Authors: E.H. Kang, S. Kim, C. Kang, Y.-M. Kang, S.W. Kang, H.J. Baek, E.Y. Lee, Y.J. Lee, E.B. Lee, Y.W. Song
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Non-synonymous <i>ERAP1</i> single nucleotide polymorphisms (SNPs), rs10050860 and rs17482078, were found to be associated with Behcet9s disease (BD) by a recessive model in Turkish patients [1]. <h3>Objectives</h3> To investigate the association between <i>ERAP1</i> SNPs and BD in Korean patients. <h3>Methods</h3> DNA samples were obtained from 391 patients who met the International Study Group criteria for BD and from 800 age- and sex-matched healthy controls. Nineteen tag-SNPs (rs27980, rs27582, rs27038, rs149481, rs149173, rs27039, rs27043, rs42398, rs10050860, rs151928, rs13170045, rs27710, rs27529, rs25866, rs26652, rs26498, rs27045, rs10062964, rs28050) in and within 1kb from <i>ERAP1</i> were selected for genotyping. <h3>Results</h3> Allele-based analysis failed to detect any significant associations between 19 SNPs and BD after correction for multiple testing. In genotype-based analysis, only an intronic variant rs27043 was associated with BD by a dominant model (for AG+GG genotypes, 85.8% in patients vs. 72.4% in controls; OR [95% CI] =2.29 [1.65-3.20], p=6.2x10<sup>–7</sup>, corrected p=1.18x10<sup>-5</sup>). This association was significant in patients with uveitis (84.4% vs. 72.4%; OR [95% CI] =2.06 [1.28-3.29], p=0.002, corrected p=0.038) as well as in patients without uveitis (85.4% vs. 72.4%, OR [95% CI] =2.23 [1.46-3.41], p=0.0001, corrected p=0.0019) compared to controls. The non-synonymous rs10050860 found to be associated with BD in a Turkish GWAS did not show any statistical significance (minor allele frequencies of 4.7% in patients and 4.9% in controls). <h3>Conclusions</h3> An intronic variant rs27043 was associated with BD notably by a dominant model in a Korean population. Efforts to impute genotypes using a reference panel from Korean/Asian HapMap data are underway to fully examine non-synonymous SNPs in strong linkage disequilibrium with rs27043 and their haplotype effects. <h3>References</h3> Kirino Y, Bertsias G, Ishigatsubo Y, et al. Genome-wide association analysis identifies new susceptibility loci for Behçet9s disease and epistasis between HLA-B*51 and ERAP1. Nat Genet 2013; 45: 202-7. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3438
Simultaneous Tc-99m MDP and Ga-67 Citrate Uptake of Benign Lymphoid Hyperplasia in the Mastoid Region
Authors: S S Sun, S C Tsai, Y C Shiau, C H Kao
Journal: Clinical Nuclear Medicine (2001)

SUN, SHUNG-SHUNG M.D.,*; TSAI, SHIH-CHUAN M.D.,†; SHIAU, YU-CHIEN M.D.‡; KAO, CHIA-HUNG M.D.* Author Information
902 IMPROVED SVR WITH SIMEPREVIR (TMC435) ASSOCIATED WITH REDUCED TIME WITH PATIENT-REPORTED FATIGUE IN TREATMENT-NAÏVE, HCV-INFECTED PATIENTS IN THE PILLAR PHASE IIB TRIAL
Authors: J. Scott, K. Rosa, M. Fu, K. Cerri, M. Peeters, M. Beumont- Mauviel, L. Gilles
Journal: Journal of Hepatology (2013)
The Steroidogenic Enzyme Cyp11a1 Is Essential for CD8+ Tc2 Conversion to Enhance Allergen-Induced Airway Hyperresponsiveness and Inflammation
Authors: Yi Jia, Joanne Domenico, Katsuyuki Takeda, Junyan Han, Meiqin Wang, Michael Armstrong, Nichole Reisdorph, Brian P. O'Connor, Joseph J. Lucas, Erwin W. Gelfand
Journal: Journal of Allergy and Clinical Immunology (2013)
Effect of dasatinib on bone metabolism in multiple myeloma
Authors: T. M. Wildes, E. Procknow, K. Weilbaecher, R. Vij
Journal: Journal of Clinical Oncology (2008)

8568 Background: Src kinases play a major role in osteoclast function. In vitro, small molecule inhibitors of Src block osteoclast formation and induce osteoclast apoptosis. Dasatinib inhibits Src and potently inhibits bone resorption in vitro and in a rat model. Markers of bone metabolism are clinically measurable. N-telopeptide (NTX) is a fragment of collagen released in osteoclast- mediated bone breakdown. Osteocalcin (OC) and bone specific alkaline phosphatase (BSAP) are produced by osteoblasts and indicate bone formation. The goal of this study was to examine whether dasatinib impacts osteoclast or osteoblast function in patients (pts) with multiple myeloma (MM). Methods: A subset of pts enrolled in a Phase II trial of dasatinib in relapsed MM participated in a correlative study of bone metabolism. Serum OC, BSAP, estradiol, testosterone and urine NTX levels were measured at baseline, and after each 28 day cycle on dasatinib. Bisphosphonates were held for the first 2 months on dasatinib. Results: Seven pts (5 male, 2 female) had studies of bone metabolism performed. Median age was 60 (range 45–65). Stages and paraproteins were: IA (2 pts), IIA (3), IIIA (2), IgA (3), IgG (4). Median number of prior therapies was 4. No pt achieved an objective paraprotein response to dasatinib. Both females were post-menopausal, with estradiol levels less <40 pg/mL. Median testosterone level in the male pts was 366 ng/dL (162–606). The mean baseline OC level was 15.6 ng/mL. The mean change in OC from baseline to cycle 1 was 0.13 ng/mL. The mean baseline BSAP was 12.9 U/L. The mean change in BSAP from baseline to cycle 1 was -2.1 U/L. The mean baseline NTX was 19.1 nmol/mmol. As several patient received bisphosphonates proximate to initiation of dasatinib, only 4 patients had urine NTX >10 nmol/mmol (mean 28.2 nmol/mmol), indicating active osteoclast function. Of these 4 patients, 3 had a decline in NTX after 1 cycle of dasatinib [Mean change -10 nmol/mmol (range +1 to -18), mean % decrease 34.4%], indicating a decrease in osteoclast function. Conclusions: In this small sample, therapy with dasatinib in pts with MM was associated with decreased osteoclast function, but no change in osteoblast function. Lack of paraprotein responses suggests that dasatinib directly inhibits osteoclasts. In vitro studies to explore this association are planned. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb
AB0053 Ikba regulatory protein is downregulated in sjögren’s syndrome salivary gland epithelial cells.
Authors: M. D’amore, S. Lisi, R. De Lucro, D. Ribatti, M. Sisto
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The transcription factor nuclear factor-κB (NF-κB) pathway has long been considered a prototypical pro-inflammatory signalling pathway, largely based on the role of NF-κB in the expression of pro-inflammatory genes including cytokines, chemokines, and adhesion molecules. The NF-κB pathway does indeed regulate pro-inflammatory cytokine production, leukocyte recruitment, or cell survival, which are important contributors to the inflammatory response during the development of autoimmune diseases. Although aberrant regulation in the NF-κB signal transduction pathway involving the inhibitory IκBa was observed in several autoimmune disorders, <i>there</i>is presently <i>no</i>publication investigating the alteration of IκBα expression in human salivary gland epithelial cells (SGEC) from SS patients. <h3>Objectives</h3> In this study we examine the expression of the NF-κB inhibitory protein termed IκBα in SGEC comparing it with SGEC from healthy controls, to test the hypothesis that an altered expression of IκBα occurs in SGEC from SS biopsies. <h3>Methods</h3> RT-PCR, Real Time-PCR, western blot, immunohistochemistry and flow cytometry were employed to examine the expression IκBα in SS biopsies in comparison with salivary gland biopsies from healthy subjects. <h3>Results</h3> Changes in the levels of IκBαin SS SGEC in comparison with healthy subjects were demonstrated, suggesting that the attenuated expression of IκBα could contribute to the deregulation of NF-κB pathways in SS. Given its key function in the fine-tuning of NF-κB signalling, it was to be expected that defects in IκBα expression or function could lead to chronic inflammation and tissue damage. In line with gene and protein analysis results, we delineated the changes in IκBα both at gene and protein expression levels, finding a clear reduction of IκBα in tissue samples from active Sjögren's syndrome patients in comparison with healthy subjects. In biopsy specimens, we found a moderate positive staining for the IκBα protein in healthy controls examined in theimmunohistochemical study, located in the cytoplasm of acini and ductal cells. Conversely, SS salivary gland biopsies elicited a weak cytoplasmic positivity for IκBα. <h3>Conclusions</h3> The analysis of IκBα expression at salivary gland epithelial cell level could be a potential new hallmark of SS progression and sustain a rationale to more deeply investigate the therapeutic potential of specific NF-κB inhibitors in SS. <h3>Disclosure of Interest</h3> None Declared
Phase I dose escalation trial of sorafenib as a single agent for adults with relapsed and refractory acute leukemias
Authors: K. W. Pratz, E. Cho, J. Karp, M. Levis, M. Zhao, M. Rudek, J. Wright, B. D. Smith
Journal: Journal of Clinical Oncology (2009)

7065 Background: Sorafenib is a multikinase inhibitor with activity against B-raf, VEGF, and FLT3. Based on preclinical activity in FLT3 mutant AML, sorafenib was studied in refractory acute leukemia. Methods: The primary objective was to determine the safety and tolerability of sorafenib in refractory acute leukemias. Secondary objectives included pharmacokinetics (PK) and pharmacodynamic (PD) effects of sorafenib on FLT3 phosphorylation. Dose escalation began at 400 mg BIDx14days per month, and proceeded through 600 mg BID x 21 days per month. Plasma concentration of sorafenib and its primary metabolite sorafenib N-oxide were measured by LC/MS//MS method. The plasma inhibitory assay was used to measure target inhibition of phosphorylated FLT3 and phosphorylated Erk. Results: Fifteen patients (13 = AML, 2 = ALL) were enrolled (ages 37–85) and treated on three dosing schedules (400 mg BID x 14 d, 400 mg BID x 21 days, 600 mg BID x 21days) of single agent sorafenib. The maximally tolerated dose was 400 mg BID x 21 days per month. Grade 3 or greater toxicities were experienced in 55% of cycles, most common grade 3 or greater toxicities being fatigue (16%) and hypokalemia (13%). No patients met criteria for complete or partial response, but 11 of 15 (73%) patients experienced stable disease as best response, with 6 showing a reduction in bone marrow blasts after only one cycle, half of who experienced a &gt;50% reduction in bone marrow blasts. Interestingly, 2 pts with FLT3-ITD mutations both showed marrow blast response (1 pt &gt;50%). Sorafenib resulted in sustained complete inhibition of FLT3 and Erk as demonstrated in all patients assessed (n = 11). Importantly, this inhibition was maintained throughout treatment cycle and 3/5 pts had FLT3 inhibitory activity 7 days post their last dose. Correlative studies suggest sorafenib N-oxide is an active metabolite. Conclusions: Sorafenib is a potent inhibitor of FLT3 with favorable PK and PD properties. Clinical activity as a single agent was limited to transient reductions in bone marrow blast counts and dose escalation was limited due to toxicities. Based on PK data in conjunction with standard curves for inhibition of FLT3 by sorafenib in plasma, the minimum FLT3 inhibitory dose of sorafenib is likely less than 400 mg BID. No significant financial relationships to disclose.
Bone Scintigraphy in Mycobacterium Avium Osteomyelitis
Authors: ROBBERT B. T. VERKOOIJEN, MARCEL P. M. STOKKEL
Journal: Clinical Nuclear Medicine (2002)

A 30-year-old woman who had a destructive Mycobacterium avium complex infection in the left inguinal fossa affecting the pubic bone underwent three-phase bone scanning to identify other possibly affected sites. Multiple skeletal lesions were seen scattered throughout the vertebral column, sternum, and pelvis. This case is presented to describe a rare extensive metastatic M. avium complex infection in an immunocompromised patient.
Case 22-1997
Authors: Michael T. Hayes, Oscar Soto, Kathryn L. Ruoff
Journal: New England Journal of Medicine (1997)

Presentation of CaseA 58-year-old right-handed woman was admitted to the hospital because of multiple cranial neuropathies.The patient had been well until two days earlier, when she began to have difficulty swallowing food while having dinner at home. During the next two or three hours, diplopia developed, with marked dysarthria to the point of losing the power of speech. She was taken to another hospital, where attempted magnetic resonance imaging (MRI) and angiographic studies could not be performed because of her inability to cooperate. Approximately 24 hours after her admission there, her condition was unimproved, and she was transferred . . .
PTH-064 Narrow Band Imaging Facilitates Detection of Inlet Patches in the Cervical Oesophagus
Authors: S Al-Mammari, U Selvarajah, J E East, A A Bailey, B Braden
Journal: Gut (2013)

<h3>Introduction</h3> Ectopic gastric mucosa in the cervical oesophagus (inlet patch) is easily missed on endoscopic examination because of its localization, usually just below the upper oesophageal sphincter. In some individuals, an inlet patch might cause symptoms such as dysphagia, globus sensation, odynophagia or coughing. We prospectively investigated whether narrow band imaging (NBI) during endoscopic inspection of the cervical oesophagus improves the visualisation of heterotopic gastric mucosa and increases the detection rate of inlet patches. <h3>Methods</h3> Subsequent upper gastrointestinal endoscopies were performed by three experienced endoscopists using videoendoscopes with NBI option (Olympus Lucera Spectrum system). Between 01/02/2010 and 01/12/2011, patients with various indications for upper gastrointestinal endoscopy were consecutively assigned to the lists of three specialists in endoscopy. One endoscopist routinely applied NBI during extubation of the endoscope (NBI) in addition to standard white light endoscopy, the second was aware of the study, but did not routinely use NBI, the third was unaware of the study and did not use NBI. The presence of an inlet patch was documented by photo imaging. <h3>Results</h3> 1407 upper endoscopies were performed. When NBI was used during extubation of the oesophagus, inlet patches were detected in 17 out of 510 endoscopies. The detection rate of inlet patches using NBI (3.3%) was significantly higher than in conventional white light endoscopy only (10/897; 1.1%; p = 0.007 ), whether the endoscopist was aware (4/382; 1.1%; p = 0.026) or unaware of the study (6/515; 1.2%; p = 0.02. ). Using NBI, the relative chance to detect an inlet patch increases about threefold (odds ratio 3.05, 95% CI 1.39–6.71). <h3>Conclusion</h3> Withdrawal of the endoscope from the cervical oesophagus using narrow band imaging increased the detection rate of inlet patches about threefold compared to standard white light endoscopy. NBI may assist in the accurate assessment of patients presenting with globus sensation, dysphagia or chronic cough, to identify rare causes such as an inlet patch that may be amenable to therapy. <h3>Disclosure of Interest</h3> None Declared.
Induced Changes in the Pattern of Pulmonary Blood Flow in the Rabbit
Authors: David E. Lehr, Martin A. Tuller, Lloyd C. Fisher, Kent Ellis, Alfred P. Fishman
Journal: Circulation Research (1963)

1. In the normal, unanesthetized rabbit, resting quietly in its normal position, catheterization of the right ventricle (and central veins) altered the distribution of blood throughout the lung in a characteristic manner. 2. Regional pulmonary vasoconstriction, rather than passive changes in vascular caliber or in the flow properties of blood, seemed to be involved. 3. The mechanism for the regional pulmonary vasoconstriction is considered in terms of a neurohumoral pathway, involving afferent pathways from the right heart, connecting channels in the upper cervical segments of the spinal cord, and release of a histamine-like substance at the neuro-vascular junctions.
A1.78 Ectopic lymphoid neogenesis in rheumatoid arthritis: a potential role for NIK expressing endothelial cells as orchestrators of tertiary lymphoid structures
Authors: A R Noort, K P M van Zoest, L G van Baarsen, N Papazian, P P Tak, T Cupedo, S W Tas
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Tertiary lymphoid structures (TLS) can be observed in rheumatoid arthritis (RA) synovial tissue, and often contain high endothelial venules (HEV) and follicular dendritic cells (FDC). Endothelial cell (EC)-specific lymphotoxin (LT)β receptor signalling is critical for lymph node and HEV formation and FDC arise from PDGFRβ<sup>+</sup> perivascular precursor cells that require lymphoid tissue inducer (LTi) cells and LTβ for their expansion. RA synovial tissue contains EC expressing NF-κB inducing kinase (NIK) which is pivotal in LTβ-induced non-canonical NF-κB signalling. Therefore, we studied the presence and relation between NIK<sup>+</sup> EC, (pre)FDC and group 3 innate lymphoid cells (ILC3) that comprise LTi cells with TLS in RA synovial tissue. <h3>Materials and Methods</h3> Microarray data were used to explore the expression levels of genes involved in NF-κB signalling in RA synovial tissue + /- TLS. Expression of NIK, PNAd, FDC-M1, RORc, and PDGFRβ was evaluated in tissues containing TLS (n = 25) and tissues without TLS (n = 15) using immunofluorescence microscopy. <h3>Results</h3> RA synovial tissues with TLS contained a significantly higher expression of non-canonical NF-κB related genes, including NIK. This was confirmed by immunohistochemistry: NIK was highly expressed in PNAd<sup>+</sup> HEV. Interestingly, we could detect small numbers of ILC3 in RA synovial tissue, which did not clearly correlate with the presence of TLS. In contrast, tissues with TLS contained significantly more perivascular PDGFRβ<sup>+</sup> cells correlating significantly with the amount of FDC. <h3>Conclusion</h3> We established a strong correlation between NIK<sup>+</sup> EC, perivascular (pre)FDC and TLS. Furthermore, we demonstrate for the first time that ILC3 are present in human RA synovial tissue, but only in very low numbers and without a clear correlation with TLS. Therefore, NIK<sup>+</sup> EC and perivascular (pre)FDC may be more important as orchestrators of TLS.
Waiting Times for Knee-Replacement Surgery in the United States and Ontario
Authors: Peter C. Coyte, James G. Wright, Gillian A. Hawker, Claire Bombardier, Robert S. Dittus, John E. Paul, Deborah A. Freund, Elsa Ho
Journal: New England Journal of Medicine (1994)

Canada, which has universal single-payer health insurance, is often criticized for waiting times for surgery that are longer than those in the United States. We compared waiting times for orthopedic consultations and knee-replacement surgery and patients' acceptance of them in the United States and in the province of Ontario, Canada.
Targeting the Basic Defect in Cystic Fibrosis
Authors: Michael J. Welsh
Journal: New England Journal of Medicine (2010)

Therapies for cystic fibrosis have been limited to alleviating clinical manifestations, and although the duration and quality of patients' lives have improved, cystic fibrosis continues to inflict major burdens and shorten lives.1 In this issue of the Journal, Accurso and colleagues2 have taken a different tack, directly targeting the defective cystic fibrosis transmembrane conductance regulator (CFTR) with a new drug that appears to be safe and to work in vivo. This research represents a milestone along the pathway of discovery leading to better preventions, treatments, and cures. It also illustrates the usefulness of genetic testing in identifying a select subgroup . . .
Fatal Fat Embolism from Steroid-Induced Fatty Liver
Authors: Rolla B. Hill
Journal: New England Journal of Medicine (1961)

SINCE the early days of cortisone therapy, occasional lipemia and lactescence of serum have been observed in patients on adrenocortical steroid or ACTH therapy. In addition, there has been an occasional indication in the literature that marked fatty metamorphosis of the liver may occur in patients receiving large doses of these hormones.1 2 3 This phenomenon has not, to my knowledge, been well studied, and the hepatomegaly and fatty liver, when present, have been considered reversible and harmless. The present communication concerns the first report of a fatal case of fat embolism from a severely fatty liver in a young girl receiving . . .
Abstract P4-02-08: STAT Signaling in Endocrine Sensitive and Resistant Breast Cancer — A Potential Target for Therapy?
Authors: R Huang, D Faratian, DJ Harrison, SP. Langdon
Journal: Cancer Research (2010)

Abstract The STAT (for signal transducer and activators of transcription) family of molecules regulate cell growth, survival, and differentiation as important integrators of cytokine and growth factor receptor signaling. STAT3 and STAT5 have been implicated in endocrine resistance in breast cancer. We aimed to identify new modifiers of endocrine sensitivity in breast cancer using functional proteomic profiling of the estrogen/tamoxifen-sensitive MCF-7 cell line and its partially sensitive (LCC1) and fully resistant (LCC9) variants. Using an unsupervised analysis of the expression of 125 paired phosphorylated and non-phosphorylated epitopes in key oncogene and tumour suppressor pathways on antibody arrays, STAT1, STAT3, and their phosphorylated epitopes were differentially expressed between endocrine resistant and parental controls. Differential expression was confirmed by qRT-PCR and western blotting. The STAT1 inhibitor EGCG inhibited cell number in endocrine insensitive and resistant LCC1/LCC9 lines, while the STAT3 inhibitors static and WP1066 were equally effective in endocrine-resistant and parental lines. Reduction in cell number was shown to be due to induction of apoptosis rather than inhibition of proliferation. The effects of the STAT inhibitors were additive, rather than synergistic, when tested in combination with tamoxifen in vitro. Finally, expression of STAT 1 and STAT3 were measured by quantitative immunofluorescence in 54 invasive breast cancers and expression levels of STAT1 and STAT3 transcript analysed in 550 breast cancers from publicly available gene expression datasets (GSE2990, GSE12093, GSE6532). High expression of STAT1, and low expression of STAT3, were associated with a worse distant metastasis free survival (DMFS; RR 1.42 and 0.46; log-rank p=0.042 and P&amp;lt;0.0001, respectively). When treatment with tamoxifen was considered, STAT1 expression was nearly predictive of DMFS (log-rank p=0.067), while STAT3 expression was predictive of DMFS (log-rank P&amp;lt;0.0001). These results suggest that STAT signaling may be important in endocrine resistance, and that STAT inhibitors, particularly STAT1 inhibitors, may be effective therapies in breast cancer even in the resistant setting. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-02-08.
P1182 RELATIONSHIP OF LEPTIN AND ADIPONECTIN LEVELS WITH EXPRESSION OF ADR1 AND ADR2, VIRAL LOAD AND INFECTING HCV-GENOTYPE IN MEXICAN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION
Authors: A.R. Rincon-Sanchez, M.A. Rios-Guerra, P. Cordero Perez, L.E. Muñoz Espinosa, M.C. Islas-Carbajal, A.M. Rivs-Estilla
Journal: Journal of Hepatology (2014)