tbuckley/cabot-search huggingface dataset:
THU0327 Efficacy of Vitamin D Supplementation in the Treatment of Fibromyalgia: Randomized Controlled Trial
Authors: S. Abou-Raya, A. Abou-Raya, M. Helmii
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Fibromyalgia (FM) is a condition characterized by chronic widespread musculoskeletal pain (MSK), fatigue and muscle tenderness. In addition, many patients have mood disturbances, report fatigue, disrupted sleep, balance disorders and decreased muscle strength. Reduced vitamin D levels are implicated in the pathogenesis of diffuse musculoskeletal pain in FM patients. A possible association between chronic widespread pain of FM and vitamin D deficiency has thus been suggested. <h3>Objectives</h3> To evaluate the efficacy of vitamin D supplementation in the treatment of FM. <h3>Methods</h3> Seventy-two consecutive FM patients diagnosed according to the American College of Rheumatology (ACR) 2010 criteria for FM were randomized into 2 groups, the first group (n=36) received oral cholecalciferol 2000 IU/day and the second group (n=36) received placebo for 6 months. Outcome measures included the Fibromyalgia Impact Questionnaire (FIQ), Brief Pain Inventory (BPI), Beck Depression Inventory (BDI), Visual analogue scale for pain (VAS 0-100mm) and Survey Short Form-36 (SF-36) assessment. Vitamin D levels were measured by Liaison immunoassay (normal 30–100 ng/ml). Serum levels between 10 and 30 ng/ml were classified as vitamin D insufficiency and levels &lt;10 ng/ml as vitamin D deficiency. All measures were assessed at baseline and after 6 months. Safety and tolerability were also assessed. <h3>Results</h3> The mean 25(OH) D level at baseline was 19.9 ng/ml in patients compared to 28.5 ng/ml in controls. The overall prevalence of suboptimal and deficient 25(OH) D serum levels among patients with FM at baseline was 50/72 (69%) and 27/72 (38%), respectively. There was a statistically significant reduction in pain as shown by VAS scores in the intervention group compared to the placebo group (6.6±2.5 vs 2.9±2.7, p&lt;0.001) at 6 months. Furthermore, there was a significant improvement in physical function (SF-36 and FIQ) scores. Lower 25(OH) D levels correlated significantly with higher FIQ scores, r =0.549; p&lt;0.005). A statistically significant between-group difference was observed for depression as assessed by BDI. Optimization of vitamin D levels in FM had a positive effect on the pain perception. <h3>Conclusions</h3> Vitamin D may be an effective, cheap and useful addition to the therapeutic armamentarium for fibromyalgia. However, larger, long-term studies are required to confirm the results of the present study. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2767
AB0561 Prevalence and Clinical Manifestation of Deforming Arthropathy in Thai Patients with Systemic Lupus Erythematosus
Authors: P. Lhakum, N. Kasitanon, C. Sivasomboon, S. Wangkaew, W. Louthrenoo
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Articular manifestation in systemic lupus erythematosus (SLE) is common and can range from arthralgia to chronic erosive deforming arthropathy. <h3>Objectives</h3> This study was performed to determine the prevalence, clinical features, and serological findings in Thai SLE patients with deforming arthropathy. <h3>Methods</h3> All SLE patients seen at the Rheumatology Clinic, Chiang Mai University Hospital, between January and December 2012, were included in this study. Their medical records were reviewed, together with a review of their history and physical examination, with special attention paid to the articular system. Those patients with evidence of hand arthropathy were invited to join the study. The arthropathy was classified according to van Vugt9s classification. <h3>Results</h3> Forty of 458 SLE patients (8.7%) had deforming arthropathy. Their mean ± SD age and disease duration were 34.5±14.7 years and 8.8±7.5 years, respectively. There were erosive arthritis with 13 (2.8%) cases, Jaccoud9s arthropathy with 8 (1.7%), and mild deforming arthropathy with 19 (4.1%). Of these 40 patients, 23 (57.5%) were diagnosed rheumatoid arthritis (RA) with a mean duration of 7.5±8.9 years before the SLE diagnosis was made. Discoid rashes were significantly more common in the mild deforming arthropathy group (63.2%) than in the erosive arthritis group (7.7%) and the Jaccoud9s arthropathy group (0.0%), p&lt;0.01. Renal involvement was more common in the erosive arthritis group (69.2%) than in the Jaccoud9s arthropathy group (62.5%) and mild deforming arthropathy group (47.4%), but without statistical significance. There was no statistical significant difference in the mean accumulative number of the ACR criteria, or the disease activity determined by sum of the MEX-SLEDAI score among the three groups. Patients in the erosive arthritis group had significantly more joint deformities than those in the non-erosive ones. Rheumatoid factor (RF) and anti-CCP were present in 38.5% and 30.8% of patients, respectively, in the erosive arthritis group, and 26.3% and 26.3% of patients, respectively, in the mild deforming arthropathy group. There was no presence of RF or anti-CCP in the Jaccoud9s arthropathy group. Despite hand deformities, all group had maintained their hand functions, but with impaired grip and pinch strength. <h3>Conclusions</h3> Deforming arthropathy is not uncommon in Thai patients with SLE, and shares similar clinical features to those previously reported. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2936
Abstract 3017: Oct4B mediates hypoxia induced epithelial mesenchymal trans-differentiation of lung cancer
Authors: Yu-Ting Chou, Chi-Hsiu Chung, Chih-Hung Chung, Cheng-Wen Wu
Journal: Cancer Research (2012)

Abstract Hypoxia, a reduction of normal oxygen levels in cells or tissues, creates a variety of changes in cell metabolism, eliciting a set of genes involved in tissue development and cancer progression. Though Oct4, a homebox transcription factor, is essential for self-renewal of embryonic stem cells, little is known about the functional role of Oct4 in tumorigenesis. In this study, we discovered that hypoxia induces a short isoform of Oct4, termed as Oct4B, in lung cancer through a HIF-2α dependent pathway. Oct4B induced cell proliferation, anchorage-independent growth, and xenograft tumor formation of lung cancer cells, indicating the oncogenic potential of Oct4B. Moreover, ectopic expression of Oct4B in lung cancer cells induced epithelial mesenchymal tans-differentiation (EMT), promoting cell migration and invasion. We observed that Oct4B bound to Slug promoter upon hypoxia stimulation, promoting EMT as well as invasion of lung cancer cells. Thus, our findings provide a novel mechanism of how Oct4B mediates hypoxia signaling to encourage malignancy of lung cancer. 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 3017. doi:1538-7445.AM2012-3017
Abstract 959: Targeting renal cell carcinoma with englerin A
Authors: Carole Sourbier, Ranjala Ratnayake, Brad Scroggins, Min-Jung Lee, Sunmin Lee, Jane Trepel, John Beutler, Len Neckers, W. Marston Linehan
Journal: Cancer Research (2011)

Abstract Background: Englerin A (EA) is a natural product which has shown selective toxicity toward kidney tumor cells in the NCI60 panel. However, EA's targets and mechanism of action remain unknown. Methods: Cytotoxicity of EA toward a panel of kidney cancer cell lines was assessed in vitro by MTT and cell counting, and in vivo using a human clear cell kidney cancer xenograft mouse model. The protein kinase C family was predicted as a likely molecular target of EA using QSAR methodology. This was confirmed by PKC kinase activity assays. EA's mechanism of action was investigated using western-blot analysis, meso-scale discovery technology, and immunohistochemistry. Results: EA was cytotoxic in vitro and in vivo via induction of apoptosis. Comparison of EA's structure with other well-known compounds predicted the PKC family to be a potential drug target. Direct treatment of cell lysates with EA increased pan-PKC kinase activity, suggesting that EA directly activated at least one of the PKC isoforms. Further investigation showed that EA-dependant PKC activation inhibited the insulin pathway through inhibitory phosphorylation of Insulin Receptor Soluble 1 (IRS1) protein, and decreased phosphorylation status of Akt and GSK3beta. These data were reproduced in vivo, as phosphorylation of GSK3beta was reduced in RCC tumor treated with EA compared to tumor treated with vehicle. Conclusion: The insulin/PI3K/Akt pathway has been previously shown by us and others to be critical for the survival of renal cell carcinoma. By activating PKCs, EA indirectly induces an “insulin resistant” phenotype which appears to be selectively lethal for RCC tumor cells. Thus, EA represents a novel potential therapeutic lead for renal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 959. doi:10.1158/1538-7445.AM2011-959
Abstract 3096: ICAD deficiency in human colon cancer and predisposition to colon tumorigenesis in mice: Linkage to resistance to apoptosis and susceptibility to genomic instability
Authors: Youssef Errami, Hassan Brim, Amarjit Naura, Hogyoung Kim, Ju Jihang, Ming Xu, Jianhua Zhang, Luis Del Valle, Hamid Boulares
Journal: Cancer Research (2012)

Abstract We previously showed that DNA fragmentation factor, which comprises a caspase-3-activated DNase (CAD) and its inhibitor (ICAD), may influence the rate of cell death by generating PARP-1-activating DNA breaks. Here we tested the hypothesis that ICAD-deficient colon epithelial cells (CECs) exhibiting resistance to death stimuli may accumulate additional genetic modifications, leading to a tumorigenic phenotype. We show that ICAD deficiency is highly associated with colon malignancy in humans. Upon DNA damage caused by a low dose of irradiation, ICAD-/- cells acquire a tumorigenic phenotype. CECs derived from ICAD-/- mice showed a marked resistance to death induced by the colon carcinogen dimethylhydrazine (DMH) in vitro and in mice. Such resistance was associated with a decrease in PARP-1 activation. In an animal model of DMH-induced colon tumorigenesis, ICAD-/- mice developed significantly higher numbers of tumors with markedly larger sizes than the wild-type counterparts. Interestingly, the phenotype of the ICAD-/- mice was not associated with a significant increase in the precancerous aberrant crypt foci suggesting a link to tumor progression rather than initiation. More importantly, ICAD deficiency was associated with severe genomic instability, constituting most prominently of amplifications but with sizable deletions as compared to the wild-type counterparts affecting several cancer-related genes including RAF-1, GSN, LMO3, and Fzd6 independently of p53. Our results present a strong case for involvement of ICAD deficiency in colon carcinogenesis and show that apoptosis and genomic instability may comprise the means by which such deficiency may contribute to the process of increasing susceptibility to carcinogen-induced tumorigenesis. 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 3096. doi:1538-7445.AM2012-3096
Management of Nonulcer Dyspepsia
Authors: Robert S. Fisher, Henry P. Parkman
Journal: New England Journal of Medicine (1998)

The term "dyspepsia," derived from the Greek words dys (bad) and pepsis (digestion), refers to symptoms thought to originate in the upper gastrointestinal tract.1,2 Dyspepsia is often used to refer to upper abdominal pain or discomfort but may also encompass symptoms of early satiety, postprandial abdominal bloating or distention, nausea, and vomiting.2,3 Dyspepsia can be episodic or persistent and is often exacerbated by eating. The prevalence of dyspepsia ranges from 26 percent in the United States to 41 percent in England.4,5 Although only 20 to 25 percent of persons with dyspepsia seek medical care, the problem is . . .
Eluxadoline for Irritable Bowel Syndrome with Diarrhea
Authors: Anthony J. Lembo, Brian E. Lacy, Marc J. Zuckerman, Ron Schey, Leonard S. Dove, David A. Andrae, J. Michael Davenport, Gail McIntyre, Rocio Lopez, Lisa Turner, Paul S. Covington
Journal: New England Journal of Medicine (2016)

Effective and safe treatments are needed for patients who have irritable bowel syndrome (IBS) with diarrhea. We conducted two phase 3 trials to assess the efficacy and safety of eluxadoline, a new oral agent with mixed opioid effects (μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist), in patients with IBS with diarrhea.
PPARβ/δ directs the therapeutic potential of mesenchymal stem cells in arthritis
Authors: P Luz-Crawford, N Ipseiz, G Espinosa-Carrasco, A Caicedo, G Tejedor, K Toupet, J Loriau, C Scholtysek, C Stoll, M Khoury, D Noël, C Jorgensen, G Krönke, F Djouad
Journal: Annals of the Rheumatic Diseases (2016)

To define how peroxisome proliferator-activated receptor (PPAR) β/δ expression level in mesenchymal stem cells (MSCs) could predict and direct both their immunosuppressive and therapeutic properties. PPARβ/δ interacts with factors such as nuclear factor-kappa B (NF-κB) and regulates the expression of molecules including vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1. Since these molecules are critical for MSC function, we investigated the role of PPARβ/δ on MSC immunosuppressive properties.We either treated human MSCs (hMSCs) with the irreversible PPARβ/δ antagonist (GSK3787) or derived MSCs from mice deficient for PPARβ/δ (PPARβ/δ-/- MSCs). We used the collagen-induced arthritis (CIA) as model of immune-mediated disorder and the MSC-immune cell coculture assays.Modulation of PPARβ/δ expression in hMSCs either using GSK3787 or hMSCs from different origin reveals that MSC immunosuppressive potential is inversely correlated with Ppard expression. This was consistent with the higher capacity of PPARβ/δ-/- MSCs to inhibit both the proliferation of T lymphocytes, in vitro, and arthritic development and progression in CIA compared with PPARβ/δ+/+ MSCs. When primed with proinflammatory cytokines to exhibit an immunoregulatory phenotype, PPARβ/δ-/- MSCs expressed a higher level of mediators of MSC immunosuppression including VCAM-1, ICAM-1 and nitric oxide (NO) than PPARβ/δ+/+ MSCs. The enhanced NO2 production by PPARβ/δ-/- MSCs was due to the increased retention of NF-κB p65 subunit on the κB elements of the inducible nitric oxide synthase promoter resulting from PPARβ/δ silencing.Our study is the first to show that the inhibition or knockdown of PPARβ/δ in MSCs primes their immunoregulatory functions. Thus, the regulation of PPARβ/δ expression provides a new strategy to generate therapeutic MSCs with a stable regulatory phenotype.
L-Glyceric Aciduria
Authors: Hibbard E. Williams, Lloyd H. Smith
Journal: New England Journal of Medicine (1968)

Four patients (three of them sibs) with recurrent calcium oxalate kidney stones excreted urinary oxalic acid and also an organic acid absent from normal urine and shown to be L-glyceric acid. The enzyme defect of this newly identified inborn error of metabolism was found in leukocyte preparations to be that of D-glyceric dehydrogenase, which catalyzes interconversion of hydroxypyruvate and D-glycerate. Excessive synthesis and excretion of oxalate in this disease presumably results from the identity of D-glyceric dehydrogenase and glyoxylate reductase. L-glyceric aciduria appears to be transmitted as an autosomal trait that causes disease only when homozygous. The presence of normal serine metabolism in these patients indicates that this amino acid is predominantly synthesized by the phosphorylated rather than the nonphosphorylated pathway in man. It is suggested that primary hyperoxaluria be reclassified: Type I, glycolic aciduria (defect of 2-oxo-glutarate: glyoxylate carboligase); and Type II, L-glyceric aciduria (defect of D-glyceric dehydrogenase).
The Detection of Circulating Tumor Cells in Colorectal Cancer Using Qpcr and Its Effect on Analgesia
Authors: Josef Srovnal, Andrea Benedikova, Kamil Vyslouzil, Pavel Skalicky, David Vrana, Bohuslav Melichar, Petr Prasil, Emil Berta, Marian Hajduch
Journal: Annals of Oncology (2013)
Clinical Implications of Positive Tests for Antibodies to Human Immunodeficiency Virus Type 1 in Asymptomatic Blood Donors
Authors: Susan F. Leitman, Harvey G. Klein, Jacqueline J. Melpolder, Elizabeth J. Read, Juan I. Esteban, Eileen M. Leonard, Liana Harvath, J. Wai-Kuo Shih, Regina Nealon, John Foy, Fred Darr, Harvey J. Alter
Journal: New England Journal of Medicine (1989)

Of 693,000 volunteer blood donors in Washington, D.C., who were screened for infection with human immunodeficiency virus type 1 (HIV-1) from July 1985 through December 1988, 284 tested positive on both enzyme immunoassay and Western blot assay. To determine the clinical importance of confirmed positive test results in asymptomatic blood donors, we followed 156 donors with positive Western blot assays and 80 donors with positive enzyme immunoassays but negative or indeterminate Western blots at 6-month intervals for a mean of 28 months. As compared with Western blot-negative persons, those with positive Western blots were significantly more likely to be black, male, and first-time donors and to have a history of venereal disease, generalized lymphadenopathy on examination, CD4-cell counts lower than 0.4 x 10(9) per liter, IgG levels higher than 18 g per liter, and antibody to hepatitis B core antigen on initial evaluation. In 17 (11 percent) of the Western blot-positive donors, the disease progressed to Class IV (symptomatic disease), according to the Centers for Disease Control system. CD4 counts below 0.2 x 10(9) per liter, IgA levels above 4 g per liter, abnormal proliferative responses to tetanus toxoid, and positive viral cultures were the strongest predictors of disease progression. Among the 80 donors with repeatedly reactive assay results but either negative or indeterminate Western blot assays, there was no evidence of HIV exposure in their histories, physical examinations, or laboratory evaluations, and manifestations of HIV infection developed in none of them. We conclude that a small number of persons with HIV infection continue to donate blood, despite attempts to exclude them, but that donors who test positive on enzyme immunoassay but persistently negative or indeterminate on Western blot assay probably do not represent a risk for the transmission of HIV.
Abstract 1208: Suppressor of cytokine signaling 6 (SOCS6) is targeted to mitochondria and regulates mitochondrial morphology and function
Authors: Huan-Yu Lin, Rai-Hua Lai, Hsin-Chen Lee, Fung-Fang Wang, Jeou-Yuan Chen
Journal: Cancer Research (2010)

Abstract Mitochondria are highly motile organelles that constantly undergo fission and fusion. Impairment of mitochondrial dynamics is associated with mitochondrial dysfunction and frequently linked to the pathogenesis of neurodegenerative diseases and cancer. We have previously shown that loss-of-function of suppressor of cytokine signaling (SOCS) 6 is a frequent event in human gastric cancer and ectopic expression of SOCS6 sensitized cells to UV-induced apoptosis. In this study, we have identified SOCS6 as a novel mitochondrial protein that regulates mitochondrial dynamics. By confocal microscopy, we showed that ectopically expressed SOCS6 is predominantly localized in mitochondria, and that the carboxyl-terminal SOCS box is important for its mitochondrial localization. We further showed that localization of SOCS6 in mitochondria is accompanied with increased mitochondrial fragmentation with attenuated membrane potential, both of which can be reversed by coexpression of mitochondrial fusion proteins Mfn1 or Mfn2. Our data further suggested that SOCS6 interferes with mitochondrial dynamics by interrupting the fusion process. Firstly, SOCS6 expression severely impaired the dynamics and mobility of mitochondria in live cells as demonstrated by fluorescence recovery after photobleaching (FRAP) experiments. Secondly, SOCS6 expression significantly hampered intermitochondrial transfer and fusion in the somatic hybrid produced by PEG-induced fusion. Furthermore, elimination of the expression of endogenous SOCS6 by RNA interference technique led to elongated mitochondria, and conferred cells increased resistance to UV-induced apoptosis. Taken together, our data suggest that SOCS6 is a mitochondrial targeting protein involved in the regulation of mitochondrial dynamics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1208.
Hypothalamic tumor presenting as anorexia nervosa
Authors: G B Heron, D A Johnston
Journal: American Journal of Psychiatry (1976)

The authors describe a patient with symptoms of anorexia nervosa who was initially treated on a psychiatric ward but was later found to have a hypothalamic tumor. They recommend repeated neurological and endocrine evaluations for patients with anorexia nervosa who are unresponsive or only partially responsive to psychiatric treatment. Initially negative medical evaluations, obvious psychopathology, and even some response to treatment may all prove insufficient to rule out organic disease.