tbuckley/cabot-search huggingface dataset:
Natural Course of Insulin Resistance in Type I Diabetes
Authors: Hannele Yki-Järvinen, Veikko A. Koivisto
Journal: New England Journal of Medicine (1986)

To examine the natural course of insulin action in Type I diabetes, we followed 15 patients prospectively for one year after the diagnosis of diabetes and also performed a cross-sectional study of 53 additional patients who had had diabetes for 2 to 32 years. Two weeks after diagnosis, the rate of glucose uptake during hyperinsulinemia, a measure of insulin action, was 32 percent lower in the patients with diabetes than in 30 matched normal subjects (P<0.01), but it rose to normal during the subsequent three months. At three months after diagnosis, 9 of 21 patients (43 percent) were in clinical remission and did not require insulin therapy. In these patients, insulin action was 40 percent greater (P<0.002) than in the patients who continued to need insulin treatment. Fasting plasma C-peptide levels were slightly but not significantly higher in the patients who had a remission than in the other patients. In patients who had had diabetes for one year or more, insulin action was also reduced by an average of 40 percent (although there was considerable variation between patients), and it was inversely related to glycemic control and relative body weight. Thus, in patients with newly diagnosed Type I diabetes, a transient normalization of insulin action may occur after an initial reduction, along with a partial recovery of endogenous insulin secretion, and these events may contribute to the development of a clinical remission ("honeymoon" period). A majority of patients with diabetes of long duration are characterized by varying degrees of insulin resistance. (N Engl J Med 1986; 315:224–30.)
Abstract 4993: ARHI is required for induction of beclin-1/PI(3)K class III-mediated autophagy
Authors: Zhen Lu, Warren S. L. Liao, Robert C. Bast
Journal: Cancer Research (2010)

Abstract The maternally imprinted Ras-related tumor suppressor gene Aplasia Ras homolog member I (ARHI; also known as DiRAS3) is downregulated in more than 60% of ovarian cancers. We reported that re-expression of ARHI in vitro at physiologic levels induces autophagy by blocking PI(3)K-Akt signaling and inhibiting mTOR activity, and participated directly in the formation of autophagic vesicles, co-localizing with MAP-LC3-II in the vesicle membrane. Nucleation of autophagic vesicles requires the activity of multi-protein complexes that include Beclin-1 and PI(3) kinase Class III lipid kinase [PI(3)KC3]. A number of proteins have been reported to interact with Beclin-1 and positively or negatively regulate its function in autophagy. One prominent Beclin-1-interacting protein is Bcl-2, which inhibits Beclin-1-dependent autophagy. In this study, we show by indirect immunofluorescence microscopy that ARHI is colocalized with Beclin-1 at the trans-Golgi network. Further, ARHI can be co-immunoprecipitated with Beclin-1 and elimination of ARHI expression by RNA interference compromised Beclin-1-induced autophagy. Concomitant with increased ARHI-Beclin-1 interaction, there was a decreased association between Beclin-1 and its negative regulator Bcl-2. Consistent with its role in Beclin-1-mediated autophagy, knockdown of ARHI also decreased PI(3)KC3 activity, whereas overexpression of ARHI promoted GFP-FYVE co-localization with RFP-LC3. Taken together, our results suggest that ARHI is a positive and necessary regulator of Beclin-1/PI(3)KC3 complex and that ARHI regulates Beclin-1-mediated autophagy by forming a complex at the trans-Golgi network. 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 4993.
Effects of Benzo[ <i>a</i> ]pyrene Exposure on Human Hepatocellular Carcinoma Cell Angiogenesis, Metastasis, and NF- <b>κ</b> B Signaling
Authors: Qian Ba, Junyang Li, Chao Huang, Hongling Qiu, Jingquan Li, Ruiai Chu, Wei Zhang, Dong Xie, Yongning Wu, Hui Wang
Journal: Environmental Health Perspectives (2014)

BackgroundBenzo[a]pyrene (B[a]P) is a common environmental and foodborne pollutant. Although the carcinogenicity of high-dose B[a]P has been extensively reported, the effects of long-term B[a]P exposure at lower environmental doses on cancer development are less understood.ObjectivesWe investigated the impact of B[a]P on human hepatocellular carcinoma (HCC) progression at various levels of exposure and identified a potential intervention target.MethodsWe used a model based on human HCC cells exposed to various concentrations of B[a]P (i.e., 0.01, 1, or 100 nM) for 1 month to examine the effects of B[a]P on cell growth, migration, invasion, and angiogenicity. A bioluminescent murine model was established to assess tumor metastasis in vivo.ResultsChronic B[a]P exposure did not alter HCC cell growth but promoted cell migration and invasion both in vitro and in vivo. There was an negative association between B[a]P exposure and the survival of tumor-bearing mice. In addition, B[a]P-treated HCC cells recruited vascular endothelial cells and promoted tumor angiogenesis, possibly through elevating vascular endothelial growth factor secretion. Furthermore, the NF-κB pathway may be an adverse outcome pathway associated with the cumulative effects of B[a]P on HCC metastasis.ConclusionsThese findings a) indicate that B[a]P has effects on HCC progression; b) identify a possible adverse outcome pathway; and c) contribute to a better understanding of the adverse effects of chronic exposure of B[a]P to human health.CitationBa Q, Li J, Huang C, Qiu H, Li J, Chu R, Zhang W, Xie D, Wu Y, Wang H. 2015. Effects of benzo[a]pyrene exposure on human hepatocellular carcinoma cell angiogenesis, metastasis, and NF-κB signaling. Environ Health Perspect 123:246–254; http://dx.doi.org/10.1289/ehp.1408524
SAT0085 Levels of CD19+ cells and IGM as predictors of an early and maintained response to rituximab in rheumatoid arthritis patients:
Authors: C. Diaz-Torne, M.A. Ortiz, C. Geli, H. Corominas, J.M. de Llobet, I. Castellví, E. Canto, E. Perez, C. Juarez, J. Casademont, C. Diaz-Lopez, S. Vidal
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Identifying predictors of response to biological agents is important for both the individual patient and health economics. There is data about several predictors of rituximab response, like a positive anti-CCP or rheumatoid factor, a low number of preplasma cells or lymphocites or an IgG level above normal.Defining response in rituximab treated patients can be complex. If we consider to measure the response to rituximab after three months, those patients with slow response will be missed. Otherwise, if we consider to measure it after six months, those ones that respond early but relapse before six months, will be also missed. Nowadays with all the current therapeutic targets, we should expect to achieve a early and maintained response. We therefore decided to consider as responders those patients that achieved a moderate/good Eular response at three and six months. <h3>Objectives</h3> To determinate new predictors of an early and mantained response to rituximab in rheumatoid arthritis pacients. <h3>Methods</h3> Prospective study of twenty seven consecutive rheumatoid arthritis patients, that failed to anti-TNF therapy, and were treated with rituximab (2 x 1g, two weeks apart). Demographic, clinical and laboratory data was obtained. According to our response criteria, we determined the percentage of patients who achieved an Eular response at three and six months. We then compared the baseline characteristics between early and maintained response patients (E&amp;M-R) and the remaining patients (P). <h3>Results</h3> Baseline characteristics: mean age was 60.2±11.2 years, 92.6% were women, RA years of evolution were 16.2 (2-35), 96.3% were seropositive (RF and/or anti-CCP), 44.4% had a history of rheumatoid nodules, 88% had an erosive RA, previous DMARDs were 3.1±1.3, previous anti-TNF were 1.45 (1-3) and DAS28 was 5.8±0.87. When comparing the clinical characteristics of E&amp;F-R and P groups, similar DAS28 was observed. The analysis of the laboratory parameters is shown in Table. <h3>Conclusions</h3> High absolute numbers of CD19+ cells and low IgM levels at baseline were statistically associated with an early and maintained response to rituximab. These parameters could therefore be used as predictor markers of the response. <h3>Disclosure of Interest</h3> None Declared
Draft rules give Monitor power to investigate anticompetitive behaviour by commissioning groups
Authors: M. Limb
Journal: BMJ (2012)

The government has drafted new rules to police conflicts of interests and anticompetitive conduct involving the new clinical commissioning groups in England and has invited views on whether additional safeguards are needed.

A consultation published on 15 August by the Department of Health outlines the regulations and the role of the health regulator Monitor in investigating alleged breaches of conduct.1

It says that commissioners would be “specifically prohibited” from awarding a contract to a provider “where that decision is the result of an interest in the provider.”

In the event of complaints, commissioners would have to show how they managed the potential …
Sentinel Lymph Node Navigation Surgery in Paget’s Disease of the Vulva
Authors: GEN KUDO, HIROSHI TOYAMA, KIYOSHI HASEGAWA, MAKOTO KURODA, HIDEKAZU HATTORI, MASANOBU ISHIGURO, MASAKI KATO, TSUYOSHI SAWAI, KAZUTAKA EJIRI, KAZUYUKI MINAMI, YASUHIRO UDAGAWA, KAZUHIRO KATADA
Journal: Clinical Nuclear Medicine (2002)

KUDO, GEN M.D.; TOYAMA, HIROSHI M.D., Ph.D.; HASEGAWA, KIYOSHI M.D., Ph.D.; KURODA, MAKOTO M.D., Ph.D.; HATTORI, HIDEKAZU M.D.; ISHIGURO, MASANOBU R.T.; KATO, MASAKI R.T.; SAWAI, TSUYOSHI R.T.; EJIRI, KAZUTAKA R.T.; MINAMI, KAZUYUKI R.T.; UDAGAWA, YASUHIRO M.D., Ph.D.; KATADA, KAZUHIRO M.D., Ph.D. Author Information
Malignant Supraclavicular Lymph Node Visualization During Tc-99m HDP Bone Imaging
Authors: DAVID M. SCHUSTER
Journal: Clinical Nuclear Medicine (2000)

Radioactivity in the supraclavicular regions revealed on bone scans may be caused by uptake in malignant lymph nodes. Accumulation of Tc-99m HDP was noted in the right supraclavicular region on bone images of a 53-year-old man with a right lower lobe, poorly differentiated squamous cell carcinoma and extensive mediastinal adenopathy. This uptake correlated with clinically palpable fixed and enlarged lymph nodes and was also shown on computed tomographic scans. Careful correlation of a staging bone scan with the findings of physical examination and other imaging is important to avoid errors in interpretation.
Abstract LB-99: Bif-1 promotes EGFR endocytic degradation and contributes to suppression of metastatic potential in breast and colon cancers
Authors: Kristin B. Runkle, Yoshinori Takahashi, Hong-Gang Wang
Journal: Cancer Research (2011)

Abstract Bif-1, a member of the endophilin B protein family, is involved in apoptosis and autophagy induction and in regulating membrane dynamics of organelles such as the Golgi and mitochondria. While endophilin A family members are involved in the formation and fission of endocytic vesicles at the plasma membrane, recent data suggest a role for Bif-1 in promoting epidermal growth factor receptor (EGFR) endocytic degradation. Increased EGFR expression is seen in a variety of tumors including breast and colorectal cancers and has been correlated with disease progression, poor survival, poor response to therapy, and resistance to cytotoxic agents. Activation of EGFR promotes cell growth, differentiation, survival, and migration through MAPK, PI3K, STAT, and Src signaling pathways; whereas signal termination and receptor down-regulation occur primarily through clathrin-mediated endocytosis and lysosomal degradation. However, the mechanism through which Bif-1 regulates EGFR endocytic trafficking and degradation has not been thoroughly investigated. Here we report that suppression of Bif-1 expression in breast and colon cancer cells delays EGFR degradation. While Bif-1 depletion does not disrupt EGFR internalization or trafficking to the vicinity of LAMP-1 positive late endosomes/lysosomes, endosome maturation and endosome/lysosome fusion seem to be suppressed in cells lacking Bif-1. Moreover, knockdown of Bif-1 enhances breast cancer cell migration and invasion. These findings, together with previous data showing that loss of Bif-1 promotes tumorigenesis in mice and that decreased expression of Bif-1 is seen in many types of human cancers including breast and colorectal cancers, further suggest that Bif-1 functions as a tumor suppressor. In addition to its roles in apoptosis and autophagy induction, this study supports a new role for Bif-1 in regulating the late stages of EGFR lysosomal degradation and identifies Bif-1 as a suppressor of metastatic potential in breast 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 LB-99. doi:10.1158/1538-7445.AM2011-LB-99
Abstract C10: Complete genome sequencing of complex tumors and matched normals results in sensitive detection of somatic events
Authors: Sharoni Jacobs, Jonathon Baccash, Srinka Ghosh, Geoff Nilsen, Krishna Pant
Journal: Cancer Research (2011)

Abstract For a comprehensive understanding of the tumor genome, it is important to identify all somatic event types: point mutations, small insertions and deletions, copy number aberrations, translocations, inversions, gene fusions, and more. Complete genome sequencing and analysis of paired tumor and normal samples yields a comprehensive view of the mutational landscape in the tumor. An integrated pipeline for the sequencing, computational analysis and annotation of complete human cancer genomes has been developed. Sequencing is performed on Complete Genomics DNA nanoarrays using a nonsequential, unchained read technology to generate 70base-pair paired end reads. Assembly, mapping, and variation calling are performed using methods that have recently been optimized for more sensitive detection of variants of low allelic fraction, as would occur in heterogeneous and/or aneuploid tumor genomes. Algorithmic enhancements designed to accommodate non-diploid genomes result in increased call rates and higher accuracy. Higher coverage levels also help to reduce error rates and improve the sensitivity of somatic variation detection. Approaches adopted to ensure a highly accurate and sensitive representation of tumor genomes will be presented. 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 C10.
THU0480-HPR Which factors are related to fatigue in rheumatoid arthritis?
Authors: S. Nikolaus, C. Bode, E. Taal, M. van de Laar
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) complain about fatigue. However, little is still known about its causes and consequences. A fully developed theoretical model explaining the experience of fatigue in RA is lacking. <h3>Objectives</h3> Goal of this study was to systematically review studies in RA that examined factors related to fatigue and differences in fatigue between RA patients and other patient groups, to gain more insight in possible causes and consequences of fatigue in RA. <h3>Methods</h3> Four databases were searched for relevant studies; MEDLINE, Web of Science, SCOPUS and PsychInfo. All studies with RA samples about the relation between fatigue and other variables, that defined dependent and independent variables and used multivariate statistical methods, were included in the review. One hundred twenty nine studies were preliminary included. After reviewing the full-texts, we identified twenty-four studies on possible causes of fatigue, fifteen studies on possible consequences of fatigue and ten studies comparing levels of fatigue between groups. <h3>Results</h3> Studies found possible causes of fatigue in illness-related aspects (e.g. pain), physical functioning (e.g. disability), cognitive/emotional functioning (e.g. depression) and social aspects (e.g. interpersonal events). Additionally, female gender was related to more fatigue. Inflammatory activity (e.g. ESR, DAS28) showed an unclear relationship with fatigue in RA. Possible consequences for fatigue were found among illness-related aspects (e.g. morning stiffness), physical functioning (e.g. physical quality of life), cognitive/emotional aspects (e.g. psychological distress) and social aspects (e.g. work ability). Patients reported higher severity of fatigue than healthy subjects and fibromyalgia patients reported worse levels of fatigue than other patient groups. Most evidence for a relation between fatigue and other variables was found regarding pain, physical functioning and depression. Many cross-sectional and also longitudinal studies reported that these variables were associated with fatigue. <h3>Conclusions</h3> This study gave an overview about variables that are related to fatigue in RA and information about fatigue levels in RA compared to other patient groups. However, most of the included studies were cross-sectional and not all longitudinal studies controlled for baseline fatigue so that hardly conclusions about causal relationships could be drawn. Prospective longitudinal studies with adequate designs and analyses are needed to find out more about the multicausal pathways of fatigue in RA. <h3>Disclosure of Interest</h3> None Declared
AB0838 Bone Metabolism Biomarkers in Tunisian Hemodialysis Patients
Authors: M. Slouma, H. Sahli, W. Smaoui, M. Mourad, A. Hadj Salah, M. El Euch, J. Abdelmoula, F. Ben Moussa, E. Cheour
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Although bone biopsy is a golden standard in the diagnosis of chronic kidney disease mineral and bone disorders (CKD-MBD), this method is invasive and repetitive evaluation of bone status cannot be possible. <h3>Objectives</h3> The aim of this study was to clarify the issue of bone metabolic markers in regular hemodialysis (HD) patients. <h3>Methods</h3> A prospective study included 90 patients under HD therapy over a three month period. Hematological and biochemical blood samples were collected after at least 10 h of fasting just prior to the HD session. One bone formation markers: bone-specific alkaline phosphatase (BAP) and one bone resorption marker carboxy-terminal telopeptides of type 1 collagen (CTx) were selected for study. Both statistical and descriptive analyses were performed. <h3>Results</h3> Ninety patients were included: 58 male (64%) and 32 female (36%). The mean age was 53.01±14.66. The body mass index was 25.79±4.67 kg/m<sup>2</sup>. The mean age of onset of nephropathy was 48.40±15.09. It was diabetic nephropathy in 30 cases, glomerulonephritis in 34 cases, vascular nephropathy in 6 cases, amyloidosis in 1 case, polycystic in 4 cases, tubulointerstitial nephropathy in 9 cases and indeterminate nephropathy in 6 cases. The mean age of onset of HD therapy was 50.06±14.82 years. The levels of BAP and CTx showed a strongly positive correlation (r=0.56, p&lt;0.001). Moreover, both circulating BAP and CTx levels showed positive correlations with serum intact parathyroid hormone levels (r=0.63, p=0.026 and r=0.58, p=0.003 respectively). <h3>Conclusions</h3> The determination of serum intact parathyroid hormone has been used for many years as an indirect predictor of CKD-MBD. The introduction of modern biomarkers of bone metabolism offers the possibility of a direct assessment of bone metabolism. BAP is a bone formation marker, it is not influenced by either renal dysfunction or the HD procedure because it is exclusive metabolized in the liver. Thus, serum BAP concentration can provide useful information about the rate of bone remodeling in HD patients. Even if CTX is cleared by the kidney, our study showed that circulating BAP and CTx levels are strongly correlated with serum PTH levels. Therefore, in HD patients, bone metabolic markers including BAP and CTx may accurately reflect bone turnover. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6000
AB0661 Efficacy of the Use of Low Dosage and Short Term Programmed Released Prednisone in Spondyloarthritis Patients
Authors: F. Bandinelli, F. Scazzariello, E. Pimenta da Fonseca, R. De Luca, G. Piemonte, L. Benelli, F. Guidi, S. Guiducci, M.B. Santiago, M. Matucci Cerinic
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Low dose glucocorticoid administration during the night is efficacious on early morning arthritis symptoms [1,2]. Therefore, low dose treatment of prednisone might be administered in the night, during the maximal pick of IL-6 and TNFa, also in Spondyloarthritis (SpA), where steroids are usually not employed. <h3>Objectives</h3> To Investigate the clinical efficacy of low dosage of programmed released prednisone (lodotra® 5 mg –Mundipharma Pharmaceuticals-) assumed at 10 p.m, in SpA patients, evaluated with a three months follow up. <h3>Methods</h3> 50 SpA patients (19 male and 31 female, mean 55 [14 standard deviation (SD) and 27-86 interval of confidence (CI)], duration of disease mean 5,8 [7,7 SD and 1-48 CI]), all naive from previous glucocorticoids treatment (and out of 15/50 [30%] not treated with DMARDs), were treated for three months with lodotra® 5 mg administration. The results of questionnaires of BASDAI (0-10), fatigue NRS (0-10), axial pain NRS (0-10), peripheral pain NRS (0-10), morning stiffness NRS (0-10) and stiffness duration (minutes) were compared between basal (T0) and after three months therapy (T1) values with Mann Whitney non parametric test. <h3>Results</h3> After three months, the difference between activity clinical indices were all significant: BASDAI (mean T0 5,6/10 vs T1 3,2/10 p&lt;0,0001) (figure 1), fatigue NRS (mean T0 6,3/10 vs T1 3,7/10 p&lt;0,005), axial pain NRS (mean T0 5,2/10 vs T1 3,4/10 p&lt;0,05), peripheral pain (mean NRS 6,3/10 vs T1 4,2/10 p&lt;0,0005), stiffness NRS (mean T0 6,5/10 vs T1 3,8/10 p&lt;0,0005) and stiffness duration (mean T0 54,1 vs T1 14,6 minutes, p&lt;0,0001). <h3>Conclusions</h3> In naive SpA patients, low dose treatment with programmed timing morning release prednisone, may significantly reduce disease activity and reduce either stiffness or pain. <h3>References</h3> Arvidson N et al. The timing of glucocorticoid administration in rheumatoid arthritis. Annals Rheum Dis 1997;56:27–31 Cutolo M et al Efficacy of the switch to modified-release prednisone in rheumatoid arthritis patients treated with standard glucocorticoids. Clin Exp Rheumatol 2013; 31: 498-505 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1728