tbuckley/cabot-search huggingface dataset:
Abstract 3492: NET as a repressor on transcriptional regulation of MT1-MMP in endothelial cells
Authors: Sun-Hee Heo, Young-Jin Choi, Hyun-Mo Ryoo, Je-Yoel Cho
Journal: Cancer Research (2011)

Abstract In mice deficient for the Ets family genes, disrupted angiogenesis and malformed vascular system inform critical role of Ets factors in vasculogenesis and angiogenesis. NET is a member of ETS transcription factors and acts as a repressor of transcription. To find role of NET in angiogenesis, angiogenesis related assay were carried out using NET specific siRNA. In addition, it was confirmed regulation of NET on transcription of angiogenesis-regulated genes. Our results showed that suppression of NET expression result in buildup of VEGF-induced tube formation. In addition, suppressed expression of NET induced expression of MT1-MMP. Induction of MT1-MMP expression by knock down of NET expression was not result direct effect of NET on transcription of MT1-MMP in endothelial cells. In endothelial cell, NET suppressed ETS-1 induced-transcriptional activity of MT1-MMP. Our results suggest that NET is a negative regulator of angiogenesis on indirect regulation of MT1-MMP and induction of tube formation by its expressional suppression. 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 3492. doi:10.1158/1538-7445.AM2011-3492
Presumed pancreatic cyst proven to be venous malformation due to intestinal malrotation
Authors: Young Na, Jong Hyun, Seung Kim, Sung Jung, Ja Koo, Hyung Yim, Sang Lee
Journal: Endoscopy (2014)

A 27-year-old man was admitted for evaluation of a 20-year history of chronic epigastric pain and weight loss of 3 kg over the preceding month. Despite several upper endoscopy examinations, no specific cause could be found. Physical examination showed mild epigastric tenderness. Laboratory findings were unremarkable apart from elevated creatinine level (3.17 mg/dL) due to focal segmental glomerulosclerosis. To investigate the cause of the abdominal pain, which became aggravated after a meal and improved with fasting, abdominal sonography was performed and showed a benign-looking 2-cm cystic lesion on the body of the pancreas ([Fig. 1 a]). Although the cyst was devoid of intraluminal Doppler signal ([Fig. 1 b]), it proved on abdominal magnetic resonance imaging (MRI) to be one of two focal venous aneurysms ([Fig. 2 a, b]). Twisting of mesenteric vessels along the mesentery was also visualized on abdominal MRI ([Fig. 2 c, d]). Thus, both the focal venous aneurysms and the persistent abdominal pain could be attributable to intestinal malrotation. The findings of a small-bowel series were also compatible with intestinal malrotation: the distal duodenum and jejunum were arranged in a corkscrew appearance on the right side of the ligament of Treitz ([Fig. 3 a]), and the cecum was also located in the right upper quadrant ([Fig. 3 b]) [1]. Surgical management was planned, and on laparotomy the small intestine was found to be arranged in a coiled fashion ([Fig. 4 a]). Ladd's band could clearly be demonstrated and was excised to resolve the intestinal malrotation ([Fig. 4 b]) [2].
THU0015 Efficacy versus Safety of Prednisone in Lupus Nephritis since 1988
Authors: M. Petri, L.S. Magder, T. Bichile
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Morbidity and damage due to prednisone use in the treatment of SLE is recognized, but prednisone has been a requisite of lupus nephritis induction regimens. We examined, by calendar years, the prednisone exposure and urine protein in lupus nephritis patients in a large single-center cohort. <h3>Methods</h3> We identified 76 SLE patients who had: 1) biopsy-proven Class III or IV lupus nephritis 2) cohort visit prior to their biopsy with elevated urine protein (dip stick of 2+ to 4+) and at least 4 cohort visits in the year following their biopsy. For each patient, the average daily prednisone dose, urine dipstick, serum cholesterol, and systolic blood pressure in the year following the biopsy were calculated. <h3>Results</h3> The average daily dose of prednisone is lower in more recent years, but the average urine protein was better. <h3>Conclusions</h3> Prednisone dose in Class III-IV lupus nephritis has been reduced in recent years, with no deleterious effect on urine protein (in fact there has been improved control of urine dipstick protein). The effect of prednisone on traditional risk factors was surprising. Patients receiving more than 20 mg/day of prednisone had a major increase in serum cholesterol. However, in those receiving 10-19 mg/d prednisone, there was a surprising decrease in both cholesterol and systolic blood pressure. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3865
THU0419 The Appropriate Age of Testing for Low BMD in Men with DXA: An Observational Study
Authors: A. Oldroyd, M. Bukhari
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> A relatively small amount of research has been carried out on male osteoporosis (OP). Thus, the appropriate age at which to test for OP via DXA scan in men is not known. Further, the t-score threshold at which to diagnose OP in men is not known - the female level of a t-score lower than -2.5 in either the hip or lumbar spine is generally defined as OP in men. <h3>Objectives</h3> To identify the most appropriate age at which to start testing for OP via DXA scan in males, assuming that male OP is defined as a t-score lower than -2.5. <h3>Methods</h3> Data of men that attended for a DXA scan at a UK district general hospital between June 2004 and October 2010 were included in the analysis. The following data was collated: age, t-scores of lumbar spine and proximal femur, and previous fragility fracture status. Analysis was carried out for each of the following lowest t-score levels in the hip or lumbar spine: -1.5, -2, -2.5, -3. For each t-score level, receiver operating characteristic (ROC) curve analysis was used to identify the lower age threshold at which to start testing for low BMD in men. The lower age threshold was identified as the age that gave 85% sensitivity that older individuals had a lower t-score. The area under the curve (AUC) was calculated for each ROC curve. <h3>Results</h3> 8,196 males were included in the analysis. The mean age of the group was 63.41 years (SD 12.70). Mean BMI was 27.37 Kg/m<sup>2</sup> (SD 3.82). The mean lowest t-score was -1.61 (SD 1.30). 999 (12.19%) of the group had previously sustained a fragility fracture. The lower age threshold for each t-score level, the associated specificity and the AUC of each ROC curve are displayed in table 1. <h3>Conclusions</h3> This study indicates that an appropriate lower age threshold at which to start testing for OP with DXA scan in males is 63 years. The study also indicates that the t-score level at which male OP is defined may significantly affect the appropriate age threshold at which to test via DXA scan. These findings can guide cost-effective DXA scanning in the male population. Further research is required to evaluate the most appropriate age range at which to test for low BMD via DXA in the male population. <h3>Disclosure of Interest</h3> None Declared
Re: Nutrition Intervention Trials in Linxian, China: Supplementation With Specific Vitamin/Mineral Combinations, Cancer Incidence, and Disease-Specific Mortality in the General Population
Authors: N. E. Day, S. A. BlNGHAM
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Re: Nutrition Intervention Trials in Linxian, China: Supplementation With Specific Vitamin/Mineral Combinations, Cancer Incidence, and Disease-Specific Mortality in the General Population Get access N. E. Day, N. E. Day Search for other works by this author on: Oxford Academic PubMed Google Scholar S. A. BlNGHAM S. A. BlNGHAM Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 21, 2 November 1994, Pages 1645–1646, https://doi.org/10.1093/jnci/86.21.1645 Published: 02 November 1994
SP0051 Activated Immune Cells Enzymatically Oxidize Membrane Lipids on Activation
Authors: V. O'donnell
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Several new families of bioactive lipids were identified that form through the enzymatic oxidation of membrane phospholipids in circulating innate immune cells and platelets. These comprise eicosanoids attached to phosphatidylethanolamine (PE) and phosphatidylcholine (PC) and are generated early following cell activation by pathophysiological agonists. They form via the coordinated action of receptors and enzymes. In this presentation, what is currently known regarding their structures, mechanisms of formation, cell biology, and signaling actions will be summarized. The lipids promote coagulation, but inhibit Toll-like receptor signailing, and modulate neutrophil antibacterial responses. Phospholipid oxidation by acutely activated immune cells is a controlled event, and a central role in regulating membrane biology and innate immune function during health and disease is proposed. Current studies are establishing their role in vascular disease and antiphospholipid syndrome. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6243
Abstract 3638: MM-302, HER2-targeted liposomal doxorubicin, does not impair cardiomyocyte function in vitro
Authors: Joseph Reynolds, Stephan Klinz, Shannon Leonard, Elena Geretti, Helen Lee, Isabelle Eckelhofer, Daniel Gaddy, Bart Hendriks, Tom Wickham
Journal: Cancer Research (2011)

Abstract In HER2+ (ErbB2+) breast cancer, the ability to combine anthracyclines, such as doxorubicin, with anti-HER2 targeted therapies is limited clinically due to potential synergistic cardiotoxicity: doxorubicin directly damages heart cells and HER2 is an important mediator of cardiac repair signaling. Herein we detail findings for MM-302, a novel HER2-targeted liposomal doxorubicin formulation. The liposomal encapsulation is designed to protect the heart from doxorubicin exposure and the HER2-targeting component mediates uptake in HER2-positive cells without blocking HER2 signaling. In order to study the potential effects of MM-302 on the heart, we performed studies using Embryonic Stem Cell (ESC)-derived cardiac cells. Total cell uptake of free doxorubicin and MM-302 into ESC-derived cardiac cells was measured using HPLC. We found that, despite expressing low levels of HER2, the ESC-derived cardiac cells do not take up MM-302, whereas doxorubicin freely enters the cells in a time and dose-dependent manner over a 3 hour time course. Subsequent to delivery, cell viability was assessed in response to free doxorubicin or MM-302 at 24 hours post 3-hour exposure. Doxorubicin resulted in cell death in a dose-dependent manner, whereas MM-302 had no effect on cardiac cell viability. To understand the mechanism underlying the cardiotoxicity associated with doxorubicin exposure, and to differentiate MM-302 from existing therapies, we measured cell functional responses in ESC-derived cardiac cells, including cell stress (phopsho-p53), DNA damage (gamma-H2AX) and apoptosis (cleaved-PARP) with high-content microscopy. We demonstrated that, while doxorubicin treatment results in DNA damage, cell stress, apoptosis, and ultimately cell death in a dose-dependent manner, MM-302 does not. Our findings demonstrate that MM-302 provides a means to deliver doxorubicin to high HER2-expressing cancer cells, while sparing exposure, accumulation, and toxicity in non-target (low HER2-expressing) cells, such as cardiomyocytes. This opens an exciting avenue for potentially introducing a novel anthracycline product for the treatment of HER2+ 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 3638. doi:10.1158/1538-7445.AM2011-3638
THU0498 Increase of CXCR3-CCR4+CCR6+CCR10- Memory T Helper Cells (TH17-LIKE) in Patients with Granulomatosis and Polyangiitis (GPA)
Authors: B. Jakiela, K. Wawrzycka, W. Szczeklik, M. Hubalewska-Mazgaj, M. Surmiak, M. Sanak, J. Musial
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Granulomatosis and polyangiitis (GPA) is a systemic vasculitis associated with anti-proteinase-3 antibodies and T-cell activation. Recruitment of memory T-cells into inflammatory sites depends on chemokine receptors and their specific patterns shape functional properties (e.g. cytokine production) of T helper-cells. <h3>Methods</h3> We analyzed subtypes of peripheral blood CD4+ memory (CD45RA-) T-cells identified by the expression of CCR7, CXCR3, CCR4, CCR6 and CCR10 chemokine receptors (multicolor flow cytometry) in GPA patients (n=20, 3 with active disease) and age matched healthy controls (n=18). <h3>Results</h3> GPA patients showed decreased percentage of CD4+ naïve cells (mean 20,8 vs. 44,4% in controls) and increased fraction of CD45RA-CCR7- effector memory cells (33,8 vs. 19,2%). A significant increase in the percentage of CXCR3+, CCR4+ and CCR6+ (but not CCR10+) CD4+ cells was also observed. When analyzing co-expression of chemokine receptors, we were able to identify 16 different subpopulations of CD4+ memory T-cells, with only CCR6+ subtypes elevated in GPA. Of note, in GPA we found significant increase in the frequency of CXCR3+CCR4-CCR6+CCR10- CD4+ cells (Th1Th17-like, 13,6 vs. 9,7% in controls) and CXCR3-CCR4+CCR6+CCR10- CD4+ cells (Th17-like, 11,2 vs. 6,4% in controls). The latter subtype was also significantly elevated in analysis limited to CD45RA- cells. Differences in CCR6+ fraction were most evident in patients with lung involvement and in those treated with low dose GCS (&lt;4 mg/d or steroid-free). However, they were not related to additional immunosuppressive treatment (e.g. AZA or MTX) or disease activity. <h3>Conclusions</h3> We show that CD4+ cells in GPA patients are switched towards effector memory phenotype, possibly as a signature of disease-related immune activation. We also found expanded CCR6+CCR10- subsets suggesting the involvement of Th1Th17-like and Th17-like cells in the pathogenesis of the disease. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3614
Case 40-1991
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, D.A. Chad, J.M. Lee
Journal: New England Journal of Medicine (1991)

Presentation of CaseA 48-year-old woman entered the hospital because of increasing weakness of the extremities and flexor muscles of the neck.The patient was well until three years earlier, when a hysterectomy was performed because of profuse vaginal bleeding; pathological examination revealed uterine leiomyomas. The hematocrit was 17 percent, and blood transfusions were administered. Several months after the operation the patient noticed weakness of the left leg, followed a few months later by weakness of the left arm manifested by difficulty in opening bottles with the left hand. The weakness of the leg and arm gradually worsened, and one . . .
A6.35 Differential B and plasma cell homing mechanisms in inflamed kidneys of NZB/W F1 mice
Authors: BF Hoyer, Q Cheng, A Taddeo, L Khodadadi, K Wu, B Rudolph, A Radbruch, RF Manz, F Hiepe
Journal: Annals of the Rheumatic Diseases (2015)

<h3></h3> NZB/W mice spontaneously develop a lupus-like disease leading to lethal immune complex-mediated nephritis. Disease manifestation is accompanied by inflammatory infiltration of the kidneys by lymphocytes. Here, we show that the immigration of B cells is mediated via CXCR5 whereas plasma cell infiltration is differently. Histology was used to analyse the distribution of lymphocyte subsets and chemokines within inflamed NZB/W kidneys, and flow cytometry was used for the qunatification of, the phenotyping and chemokine receptor expression of particular lymphocyte subsets. Our data show that kidney-infiltrating B cells accumulate within small, follicle-like structures of the kidney, whereas plasma cells and plasmablasts are scattered in conglomerates of several cells throughout the whole organ. B cells expressing the chemokine receptor CXCR5 can be found in areas of high CXCL13 concentration. In contrast plasma cells and plasmablasts express low levels of CXCR5 but high levels of CXCR3 and CXCR4, the ligands for CXCL10 and CXCL12 respecitvally known to be overexpressed in inflammatory tissue and bone marrow which might explain the different distribution pattern. Interestingly, the kidney-infiltrating B cell population contains 50% IgD/IgM+ naïve cells and also includes smaller proportions of cells exhibiting a phenotype of CD93<sup>+</sup>/CD23<sup>+</sup>/- T1/T2/3 immature B cells. These data suggest that B cells accumulate in the kidneys through homing mechanisms involving CXCR5/CXCL13 attracting primarily naïve B cells whereas plasmablast and plasma cell infiltration seems to be mediated by different mechanisms yet unclear mechanism.
Concept revision is sensitive to changes in category structure, causal history
Authors: Joanna Korman
Journal: Behavioral and Brain Sciences (2011)

Abstract Carey argues that the aspects of categorization that are diagnostic of deep conceptual structure and, by extension, narrow conceptual content, must be distinguished from those aspects that are incidental to categorization tasks. For natural kind concepts, discriminating between these two types of processes is complicated by the role of explanatory stance and the causal history of features in determining category structure.
Fingerprinting genomic heterogeneity in primary breast carcinomas and among sentinel lymph node metastases: implications for clinical management of breast cancer patients.
Authors: DL Ellsworth, RE Ellsworth, HL Patney, A Oviedo, A George, DT Croft, B Love, RM Jordan, B Deyarmin, TE Becker, JA Hooke, CD Shriver
Journal: Cancer Research (2009)

Abstract Abstract #1059 Background: Sentinel lymph node (SLN) status is a key prognostic factor for breast cancer patients. The SLN hypothesis postulates that cancer cells initially spread from the primary tumor to the first-draining (sentinel) node(s) before reaching higher echelon nodes. Although SLN biopsy is clinically useful for staging patients, little is known about the genomic heritage of cells that define the genetic makeup and clinical behavior of nodal metastases. We used allelic imbalance (AI) coupled with high-density SNP genotyping to examine the extent of genetic heterogeneity in primary tumors and relationships among metastases in sentinel and non-sentinel axillary lymph nodes in 30 patients with node positive breast cancer.&amp;#x2028; Material and Methods: Pathologically positive nodes were identified by H&amp;E/IHC, while sentinel nodes were localized by standard scintigraphic techniques. For each patient, nodal metastases and 6-15 areas from multiple paraffin blocks of the primary carcinoma were isolated by microdissection. AI was assessed by microsatellite typing at 26 chromosomal regions; genome-wide copy number variation was examined using Affymetrix GeneChip Human Mapping 500K arrays and the Genotyping Consol. The genomic heritage of sentinel and non-sentinel nodal metastases in relation to multiple areas of the primary tumor was assessed by hierarchical clustering and phylogenetic analyses.&amp;#x2028; Results: Extensive genomic heterogeneity was observed in primary tumors and among nodal metastases (0-44% in primaries, 0-36% in metastases). Overall levels of variation were significantly higher (P&amp;lt;0.01) in primary tumors (17%) than metastases (10%), but did not differ between sentinel (10.2%) and non-sentinel (10.0%) metastases. Within patients, many (but not all) metastases appeared to be descended from different areas of the primary tumor, but patterns of descent were complex. As a group, sentinel node metastases were not genomically distinct from other axillary node metastases, and there was no evidence that SLN metastases are seeded by cells that colonize the axilla early in tumorigenesis.&amp;#x2028; Discussion: Although metastases develop in a sequential manner that maintains the known capability of SLN biopsy to accurately stage the axilla, metastases appear to develop from genomically-diverse progenitor cells descended from different areas of the primary tumor. Genomic diversity in primary tumors and metastases may be an important factor in prognosis and treatment resistance in breast cancer patients. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1059.
AB0465 Clinical Efficacy of the Synthetic Anti-Rheumatic Drug, Iguratimod
Authors: K. Okamura, Y. Yonemoto, C. Okura, T. Kaneko, T. Kobayashi, K. Takagishi
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Iguratimod (IGU) is newly synthetic DMARDs and under clinical use to the rheumatoid arthritis (RA) patients from 2012 in Japan. <h3>Objectives</h3> We examined the effects of the IGU therapies for RA patients in our hospital. <h3>Methods</h3> Forty one (15 males;16 females) patients who started receiving IGU from September, 2012 to April, 2013 in our hospital, were included in this study. The age of this cohort was 68.9±10.9 years, and the disease duration was 14.7±12.7 years. Methotrexate (MTX) combination rate was 59.2%, the mean dose of MTX; 9.0±3.1 mg/week, PSL combination rate; 52.4% and the amount of PSL; 4.9±2.6 mg/day. The biological drugs were administered to seven patients. During 12 weeks prior to the initiation of the IGU therapies and 24 weeks after IGU administration, there was not any change of drugs and operation procedures. The clinical therapeutic process after the initiation of IGU were analyzed at week 0, 4, 8, 12, 16, 20 and 24 (last observation carried forward: LOCF). Wilcoxon signed-rank test were performed to assess the differences in each parameter. The logistic regression analyses were performed to investigate the parameters associated with the improvement of the disease activity with IGU treatment. <h3>Results</h3> Before IGU treatment; C-reactive protein (CRP) 1.4±1.7 mg/dl, erythrocyte sedimentation rate (ESR) 51.2±27.9 mm/h, matrix metalloproteinase-3 (MMP-3) 223.5±183.3 ng/ml, Disease activity score assessing 28-joint (DAS28) versions using ESR (4) 5.0±1.7, DAS28 versions using CRP (4) 4.1±1.7, Simplified Disease Activity Index (SDAI) 25.8±19.7 and clinical disease activity index (CDAI) 24.4±19.1. At week 24; CRP 1.1±1.9 mg/dl, ESR 44.3±28.0 mm/h, MMP-3 208.1±255.2 ng/ml, DAS28-ESR (4) 3.9±1.4, DAS28-CRP (4) 3.0±1.3, SDAI 13.0±12.7 and CDAI 11.9±2.0. The DAS28-ESR (4), DAS28-CRP (4), SDAI and CDAI significantly decreased at week 4. All parameters, with exception of MMP-3, were significantly reduced at week 24 of the IGU therapy. Twenty six cases continued the IGU therapies during 24 weeks, and 18 patients achieved the DAS28-CRP remission and 3 patients were classified into the low disease activity (LDA) of the DAS28-CRP (DAS28-CRP &lt;2.7). The DAS28-CRP (4) were significantly reduced at week 4 with (n=24) or without (n=17) the use of MTX (LOCF). In addition, at week 24, DAS28-CRP (4) of each dosage of IGU, 25 mg/day (n=13) or 50 mg/day (n=13), was significantly decreased respectively. DAS28-CRP (4) at week 0 was associated with the achievement of remission or LDA of DAS28-CRP (4) at week 24 (Odds ratio 5.509, p=0.037). <h3>Conclusions</h3> Our results suggest that IGU is clinically one of the useful synthetic DMARDs to RA patient. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4917