tbuckley/cabot-search huggingface dataset:
FRI0270 Concurrent sacroiliac joint and spinal inflammation on MRI in patients with non-radiographic axial spondyloarthritis
Authors: D. van der Heijde, J. Sieper, W. Maksymowych, M.A. Brown, S. Sarkar, A.L. Pangan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The imaging arm of the ASAS axial spondyloarthritis (SpA) criteria requires the presence of sacroiliitis on MRI or radiographs. In patients (pts) with non-radiographic axial SpA (nr-axSpA), there may be inflammation along the spine in the absence of sacroiliac joint (SIJ) inflammation on MRI. <h3>Objectives</h3> To determine the concurrent existence of inflammation on MRI in the SIJ and the spine at baseline (BL) as assessed by the SPARCC scoring method in nr-axSpA pts. <h3>Methods</h3> ABILITY-1 is an ongoing multicenter, randomized, controlled trial of adalimumab vs. placebo in pts with nr-axSpA (fulfilling ASAS axial SpA criteria but not modified New York criteria for AS) who had an inadequate response, intolerance, or contraindication to NSAIDs. MRI of the SIJ and spine were performed at BL and at week 12, and were centrally read using the SPARCC method (6DVU method for the spine) by 2 independent, blinded readers. Average scores of the readers were used. The proportion of pts with SPARCC score ≥2 for either the SIJ or spine was evaluated. For the purpose of these analyses, all pts were combined, independent of randomization. <h3>Results</h3> Mean symptom duration of the study population (N=185) was 10 yrs. At BL, 48% of pts were reported by the local investigator to have past or present MRI evidence of sacroiliitis as required by the ASAS axial SpA criteria. Of pts with available BL SPARCC scores, 40% had a BL SIJ score ≥2 and 52% had a BL spine score ≥2. Of the pts with BL SPARCC SIJ score &lt;2, 49% had evidence of spinal inflammation, with a BL SPARCC spine score ≥2. Figure 1 shows the cumulative probability plot of spine scores for pts with SIJ score &lt;2 or ≥2. BL disease characteristics of pts with BL spine score &lt;2 vs. ≥2 were generally comparable except for mean age (36 vs. 40 yrs) and SIJ scores (3.2 vs. 6.5); likewise for pts with BL SIJ score &lt;2 vs. ≥2, except for gender (61% vs. 44% female). <h3>Conclusions</h3> Assessment by experienced readers shows that spinal inflammation on MRI may be observed in half of nr-axSpA pts without SIJ inflammation on MRI. MRI of both sites might be of value when evaluating for nr-axSpA. As pts in this study had long disease duration, these data need to be confirmed in pts with shorter disease duration. <h3>Disclosure of Interest</h3> D. van der Heijde Consultant for: Abbott, Amgen, AstraZeneca, BMS, Centocor, Chugai, Eli-Lilly, GSK, Merck, Novartis, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, Wyeth, J. Sieper Grant/Research support from: Abbott, Merck, Pfizer, UCB, Consultant for: Abbott, Merck, Pfizer, UCB, W. Maksymowych Grant/Research support from: Abbott, Consultant for: Abbott, M. Brown Consultant for: Abbott, S. Sarkar Shareholder of: Abbott, Employee of: Abbott, A. Pangan Shareholder of: Abbott, Employee of: Abbott
Abstract LB-275: Epithelial-mesenchymal transition rewires mechanisms upstream of PI3K-dependent growth.
Authors: Megan B. Salt, Frank McCormick
Journal: Cancer Research (2013)

Abstract Tumors that show evidence of epithelial to mesenchymal transition (EMT) have been associated with metastasis, drug resistance, and poor prognosis. EMT may alter the molecular requirements for growth and survival in different contexts, but the underlying mechanisms remain incomplete. Given the heterogeneity along the EMT spectrum between and within tumors it is important to define the requirements for growth and survival in cells with an epithelial or mesenchymal phenotype to maximize therapeutic efficacy. We have established an inducible cell line model in which a tamoxifen regulatable Twist-ER fusion protein is stably expressed in the H358 non-small cell lung cancer cell line. Upon tamoxifen addition, cells undergo EMT and provide a system in which we can compare the growth and survival requirements directly related to EMT, removing confounding factors present when comparing different cell lines. Using this system we have found that while cells require PI3K for growth before and after the transition, the mechanisms through which they can activate the signal are altered. Specifically, before EMT basal PI3K is maintained by autocrine activation of ErbB3 signaling, despite the presence of an activating Ras mutation. Loss of ErbB3 ablates proliferation in pre-EMT cells suggesting that oncogenic KRas is not sufficient to drive growth in this context. After induction of EMT ErbB3 expression is downregulated along with downstream PI3K signal, leading to a loss of cell autonomous proliferation. Restoration of PI3K signaling by either re-expression of ErbB3, activated p110, or through stimulation with various growth factors is able to restore growth in post-EMT cells. These data have implications for therapeutic targeting of different RTKs, suggesting that within a heterogeneous tumor environment, only a subset of cells may respond to such treatments. Furthering the understanding of how EMT alters signaling through specific pathways will facilitate the design of more efficacious treatment strategies to target all cells along this phenotypic spectrum. Citation Format: Megan B. Salt, Frank McCormick. Epithelial-mesenchymal transition rewires mechanisms upstream of PI3K-dependent growth. [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 LB-275. doi:10.1158/1538-7445.AM2013-LB-275
P239 METABOLIC SYNDROME AND NON-ALCOHOLIC STEATOHEPATITIS (NASH) ARE ATTENUATED BY INTERVENTION WITH CASPASE-1 INHIBITOR IN HIGH FAT DIET FED LDLR.LEIDEN MICE
Authors: P.Y. Wielinga, K. Salic, W. Liang, M. Morrison, P. Mulder, T. Kooistra, R. Kleemann
Journal: Journal of Hepatology (2014)
SAT0250 TH17 cells expressing KIR3DL2 and enriched for gut homing markers are increased in ankylosing spondylitis
Authors: A. Ridley, S. Kollnberger, I. Wong, J. Shaw, P. Bowness
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> T helper 17 (Th17) cells are a subset of pro-inflammatory CD4 T cells implicated in a number of inflammatory arthritides including the Spondyloarthritides (SpAs). Ankylosing Spondylitis (AS), the commonest spondyloarthropathy, is genetically associated with HLA-B27 (B27) and IL-23 receptor polymorphisms, however the link remains unexplained. We have previously shown KIR3DL2+CD4 T cells are expanded in the peripheral blood of individuals with AS. <h3>Objectives</h3> The aim of the study was to further characterize KIR3DL2+CD4 T cells and investigate whether activation induced expression of KIR3DL2 on CD4 T cells. <h3>Methods</h3> KIR3DL2+ CD4 T cell phenotype was investigated by flow cytometry. Production of cytokines by PMA/ionomycin stimulated-PBMCs was investigated by intracellular cytokine staining (ICS). Cytokine production by α-CD3/28-stimulated FACS-sorted KIR3DL2+ and KIR3DL2- CD4 T cells was investigated by multiplex bead analysis. Expression of KIR3DL2+ on CD4 T cells was investigated after SEB stimulation and cytokine production was investigated by ELISA. <h3>Results</h3> KIR3DL2+ CD4 T cells, increased in peripheral blood of HLA-B27+ SpA patients, were enriched for expression of Th17 phenotypic markers, IL-23R, CCR6 and IL-1R, and the gut-homing chemokine receptor, CCR9. KIR3DL2+ CD4 T cells from AS patients produced significantly more IL-17 than KIR3DL2- CD4 T cells. IL-17 levels significantly increased in the presence of the Th17 cytokines rIL-23 and IL-1. SEB activation increased the number of KIR3DL2+ cells and IL-17 production more in AS patients than controls. <h3>Conclusions</h3> KIR3DL2+ CD4 Th17 cells are expanded in patients with Spondyloarthritis. Expression of KIR3DL2 on CD4 T cells can be induced by activation. These cells constitute a significant proportion of peripheral blood CD4 T IL-23R-expressing cells and produce increased levels of IL-17, which is further increased by the presence of Th17 cytokines. Our findings would support the trial of new therapeutic strategies, such as anti-IL-17, in AS/SpA. <h3>Disclosure of Interest</h3> None Declared
An “Accessory Bone” in the Knee Area:
Authors: P K KARAK, M J KANE, RICHARD P. SPENCER, M K KARIMEDDINI, J ZIEWACZ, J A VENTO
Journal: Clinical Nuclear Medicine (1996)

Five months after knee trauma, CT showed a right femoral condylar fracture with nonunion and an “exostosis.” Radiographs showed the presence of a “bone” in the area that had metabolic activity on a bone scan. There was extensive heterotopic calcification, which mimicked a well-defined and developed bone.
Abstract LB-162: Oxidative damage disrupts telomere integrity and leads to cell senescence
Authors: Rong Tan, Luxi Sun, Ying Gao, Li Lan
Journal: Cancer Research (2015)

Abstract Cellular DNA is organized into chromosomes and capped by a unique nucleoprotein structure, the telomere. Both oxidative stress and telomere shortening/dysfunction cause aging-related degenerative pathologies and increase cancer risk. However, a direct connection between oxidative damage to telomeric DNA, comprising less than one percent of the genome, and telomere dysfunction has not been established. By fusing the KillerRed chromophore with the telomere repeat binding factor 1, TRF1, we developed a novel approach to generate localized damage to telomere DNA and to monitor the real time damage response at the single telomere level. We found that DNA damage at long telomeres in U2OS cells is not repaired efficiently compared to DNA damage in non-telomeric regions of the same length in heterochromatin. Telomeric DNA damage shortens the average length of telomeres and leads to cell senescence and cell death in U2OS, HeLa, and IMR90 cells, when DNA damage at non-telomeric regions is undetectable. Telomere-specific damage induces chromosomal aberrations, including signal-free ends and sister-chromatid fusions, distinct from the damage induced by ionizing irradiation. Taken together, our results demonstrate that oxidative damage induces telomere dysfunction and underline the importance of maintaining telomere integrity upon oxidative damage. Note: This abstract was not presented at the meeting. Citation Format: Rong Tan, Luxi Sun, Ying Gao, Li Lan. Oxidative damage disrupts telomere integrity and leads to cell senescence. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-162. doi:10.1158/1538-7445.AM2015-LB-162
Streptomycin and Friedlander's Bacillus
Authors: M. E. M. Thomas, C. P. Malley
Journal: BMJ (1951)

Thirty-five patients (88% male) with pulmonary infection caused by Mycobacterium kansasii have been reviewed. Sixty-six per cent had pre-existing lung disease, chronic bronchitis and emphysema accounting for half of the disorders. Unilateral lesions were present in 69% of patients whose chest radiographs were reviewed and 90% had cavitating disease. The development of unilateral or bilateral disease appeared to be independent of any delay in starting treatment. Five patients died while receiving treatment, but none of these deaths was due to M kansasii infection. The remaining 30 patients were successfully treated with drug regimens, all of which included rifampicin and 86% of which included ethambutol. There was 100% sputum conversion, with no relapses after a mean follow-up period of five-and-a-half years. Rifampicin and ethambutol given for a mean period of 15 months appeared to be a non-toxic, effective combination.
Abstract 2151: Activation of NF-kB and MAP kinases by TNF Family Receptors is regulated by cellular IAPs
Authors: Evgeny Varfolomeev, Tatiana Goncharov, Heather Maecker, Kerry Zobel, Laszlo Komuves, Kurt Deshayes, Domagoj Vucic
Journal: Cancer Research (2012)

Abstract Activation of NF-kB, JNK and p38 MAPK signaling pathways is innermost activity of TNF receptor protein signaling complexes that is important for proper function of the immune system. However, excessive activation of these signaling pathways may result in tumor development and progression. Therefore, elucidation of the detailed molecular mechanisms of TNF receptor signaling should gain advantage in our understanding of the tumor biology and invention of the novel anticancer therapies. The formation of TNF receptor complexes, as well structural and functional associations between different signaling molecules is regulated by ubiquitination in TRAF-dependent fashion. TNF receptors employ several proteins possessing ubiquitin E3 ligase activities including cellular Inhibitor of Apoptosis, c-IAP1 and c-IAP2 proteins. We demonstrate that c-IAPs are required for canonical NF-kB and MAPK activation by TNF receptors. By regulating the recruitment of Nemo, IKK2 and HOIP to TNFR signaling complexes c-IAPs promote induction of gene expression by TNF ligands. We also found that TNF receptors that stimulate the noncanonical NF-kB pathway trigger c-IAPs, TRAF2 and TRAF3 intracellular translocation followed by their proteasomal and lysosomal degradation. Finally, we establish that BR3-induced cytosolic depletion of TRAF3 results in noncanonical NF-κB activation. 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 2151. doi:1538-7445.AM2012-2151
Abstract 5605: Pharmacologic inhibition of EphA2 in NRAS and BRAF mutant melanomas.
Authors: Benchun Miao, Jianming Zhang, Zhenyu Ji, Ching Ni Njauw, Michael Taylor, Raj Kumar, Nathanael Gray, Hensin Tsao
Journal: Cancer Research (2013)

Abstract The Eph receptors are the largest known family of receptor tyrosine kinases (RTKs). Research studies have shown that Eph receptors and ligands may be involved in many diseases including cancer. EphA2 is a member of the Eph family of receptor tyrosine kinases and is highly expressed in many aggressive cancer types, including melanoma. Our previous studies showed that EphA2 levels are elevated in melanoma cells and EphA2 plays critical roles in melanoma cell survival, proliferation, colony formation and migration in vitro and melanoma tumor growth in vivo. Together, these data suggest that EphA2 is a critical oncogene in melanoma and a potential pharmacologic target in the treatment of metastatic disease. Herein we present early evidence that EphA2 inhibitors (ALW-II-41-27 and HG-6-64-1) are effective in inhibiting proliferation of both NRAS and BRAF mutant melanoma cell lines in vitro through suppressing a series of EphA2 downstream signaling pathways. At the same time, EphA2 inhibitors are also effective at suppressing migration and invasion of melanoma cells with a reduction in actin cytoskeleton reorganization and lamellipodia formation. Animal studies are underway to determine the effectiveness of these agents in suppressing melanoma tumor growth in vivo. These results point to EphA2 inhibition as a promising therapeutic strategy for both NRAS and BRAF mutant melanomas either singly or in combination with BRAF or MEK inhibitors currently in trial. Citation Format: Benchun Miao, Jianming Zhang, Zhenyu Ji, Ching Ni Njauw, Michael Taylor, Raj Kumar, Nathanael Gray, Hensin Tsao. Pharmacologic inhibition of EphA2 in NRAS and BRAF mutant melanomas. [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 5605. doi:10.1158/1538-7445.AM2013-5605
Problems of polypharmacy
Authors: A. Herxheimer, P. McGettigan
Journal: BMJ (2013)

The King’s Fund report discussed by Wise covers much ground, but its focus is blurred and it misses some core points.1 2 It would take years to implement the sensible changes proposed in managing multimorbidity and in prescribing in care homes. But what do the authors think should be done now?

They strangely omit the role of the patient. Patients (and …
Prevalence of Silent Gastroesophageal Reflux in Association with Recurrent Lower Respiratory Tract Infections
Authors: ELUVATHINGAL J. THOMAS, RAKESH KUMAR, J. BHARATHI DASAN, CHANDERSHEKAR BAL, SUSHIL K. KABRA, ARUN MALHOTRA
Journal: Clinical Nuclear Medicine (2003)

Purpose Gastroesophageal reflux (GER) has long been associated with pulmonary symptoms and diseases. This retrospective analysis was undertaken to determine the prevalence of GER detected by gastroesophageal scintigraphy in children with recurrent lower respiratory tract infections but none of the typical gastroesophageal symptoms of GER. Materials and Methods A total of 312 children (mean age, 2.36 years; age range, 4 months to 11 years) were evaluated. All studies were performed using Tc-99m sulfur colloid (3.7 to 7.4 MBq; 100 to 200 μCi). Results Of 312 children, 108 (34.6%) had GER on gastroesophageal scintigraphy. The children were separated into four groups, depending on their age. Group 1 (119 children, younger than 1 year), group 2 (131 children, ages 1 to 3 years), group 3 (36 children, ages 3 to 6 years), and group 4 (26 children, ages 6 to 12 years) showed silent GER with prevalences of 38.7%, 37.4%, 22.2%, and 19.2%, respectively. Because physiologic GER is common in children younger than 18 months, we also analyzed the prevalence of GER in children younger than 18 months and older than 18 months of age. The prevalences of GER in these groups were 41.7% and 24.6%, respectively. Conclusions A significant number of children with recurrent lower respiratory tract infection have scintigraphic evidence of GER. This high prevalence, even in children older than 18 months, cannot be ignored. Prospective studies including many patients are needed to establish the exact role of GER in these patients.
AB0448 Factors leading to HAQ remission after beginning biologics treatment in patients with rheumatoid arthritis
Authors: Y. Miwa, H. Furuya, R. Yanai, K. Ohtsuka, M. Sato, R. Takahashi, K. Wakabayashi, N. Yajima, T. Kasama, M. Hosaka
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> We examined the factors that led to health assessment questionnaire (HAQ) remission after beginning biologics treatment in patients with rheumatoid arthritis (RA) <h3>Methods</h3> A total of 107 RA patients were assessed prior to treatment and 30 weeks after therapy initiation. The subjects were treated as follows: infliximab, 47 patients; etanercept, 17 patients; adalimumab, 25 patients; and tocilizumab, 18 patients. The age, gender, steroid dosage, methotrexate (MTX) dosage, disease activity (DAS28) score, health-related quality of life (HRQoL) questionnaire scores (modified health assessment questionnaire (mHAQ) and Short Form (SF)-36) and depression scale scores (Japanese version of the structured interview guide for the Hamilton Depression rating scale (HAM-D) and the Self-rating Depression Scale (SDS)) were assessed before initiating biologics treatment. HAQ remission was defined as a score less than 0.5 point after 30 weeks without evaluating clinical and structural remission. <h3>Results</h3> The HAQ remission group was characterized by younger age (57.8±14.8 vs. 66.8±13.2 years, p=0.005), lower steroid dosages (3.3±3.3 vs. 5.1±3.2 mg per day, p=0.011), higher MTX dosages (8.3±4.0 vs. 6.7±3.7 mg per week, p=0.028) and lower DAS28 scores (4.7±1.3 vs. 5.3±1.4) compared with the no-HAQ-remission group before treatment. In addition, the group had lower HAQ scores (0.32±0.36 vs. 1.1±0.36, p&lt;0.001), higher SF-36 scores (all 8 categories, p&lt;0.01), lower SDS scores (39.8±9.0 vs. 43.8±10.5 points, p=0.029) and lower HAM-D scores (5.1±3.5 vs. 7.8±4.9 point, p=0.005) before treatment and high drug efficacy (p=0.044) compared with the no-HAQ-remission group. In particular, younger age (less than 70 years old, odds ratio: 0.29), lower steroid dosages (less than 5 mg prednisolone per day, odds ratio: 2.87), lower HAQ scores (less than 0.5 point, odds ratio: 52.31) and lower HAM-D scores (less than 7 points, odds ratio: 3.00) were important factors for HAQ remission. However, there was no significant difference in gender between the 2 groups. <h3>Conclusions</h3> Younger age, lower steroid dosages, higher QOL scores and lower depression scores are the important factors for HAQ remission with RA patients who undergo biologics treatment. <h3>Disclosure of Interest</h3> None Declared
Progress Reported At Skin Cancer Conference
Authors: L. B. Crossette
Journal: JNCI Journal of the National Cancer Institute (1991)

Progress Reported At Skin Cancer Conference Get access Linda Baute Crossette Linda Baute Crossette Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 11, 5 June 1991, Pages 753–754, https://doi.org/10.1093/jnci/83.11.753 Published: 05 June 1991
Vesicoureteral Reflux in a Patient with Complete Ureteral Duplication Detected on Tc-99m DTPA Renography
Authors: Ricardo B Fonseca, Paulo S Duarte, Lisa Susuki
Journal: Clinical Nuclear Medicine (2003)

FONSECA, RICARDO B. M.D.*†; DUARTE, PAULO S. M.D.*; SUSUKI, LISA M.D.† Author Information
Successful removal of a pancreatic duct stone in a patient with Whipple resection, using a short single-balloon enteroscope with a transparent hood
Authors: Kei Yane, Akio Katanuma, Manabu Osanai, Hiroyuki Maguchi, Kuniyuki Takahashi, Toshifumi Kin, Ryo Takaki, Kazuyuki Matsumoto, Katsushige Gon, Tomoaki Matsumori, Akiko Tomonari
Journal: Endoscopy (2014)

Endoscopic retrograde cholangiopancreatography (ERCP) is a challenging procedure, especially in indications involving the pancreatic duct in patients with Whipple resection [1] [2] [3]. Identification of the pancreaticojejunal anastomotic site is difficult because of the location and small size of the anastomosis, and interference from the jejunal folds. We proposed that a transparent hood would be effective for retraction of the folds to a suitable distance from the intestinal wall. Here, we report on the successful removal of a pancreatic duct stone in a patient with Whipple resection, using a prototype short, single-balloon enteroscope (SBE; working length, 152 cm; outer diameter 9.2 mm; working channel diameter 3.2 mm; SIF-Y0004-V01, Olympus Medical Systems, Tokyo, Japan) with a transparent hood.