tbuckley/cabot-search huggingface dataset:
AB0008 Blys/April Gene Expression in Synovial Fluid and Blood in Rheumatoid Arthritis: Table 1.
Authors: L.A. Mas, V. Saurit, M. Colazo, E.V. Palomino, F. Caeiro, T. Alvarellos, A. Alvarellos
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The B Lymphocyte Stimulator (BLyS) and A PRoliferation-Inducing Ligand (APRIL) signaling pathway has an important role in the selection, maturation and survival of B cells. Dysregulation of BLyS/APRIL is involved in the pathogenesis of B-cell related autoimmune diseases including Rheumatoid Arthritis (RA). Synovial fluid cells are highly activated in patients with active RA inducing lymphocyte proliferation, expression of cell surface molecules, cytokine and auto antibody secretion. <h3>Objectives</h3> The purpose of this work is to evaluate Synovial Fluid (SF) and Peripheral Blood (PB) mRNA expression of BLyS and APRIL in RA patients. <h3>Methods</h3> SF and PB were obtained and classified in two groups, Group I: active RA patients with DAS 28 score &gt;5.1 (n=11, 8F/3M, age: 56,2±20,9; range: 17-84) and Group II, control: Osteoarthritis (OA, n=20, 13F/7M, age: 69,8±9,5, range: 47-84). Levels of BLyS and APRIL expression were evaluated using Quantitative Real Time PCR (QPCR). All amplifications were carried out in duplicate and threshold cycle (C<sub>t</sub>) scores were averaged for calculations of relative expression values. The C<sub>t</sub> scores were normalized against C<sub>t</sub> scores by subtracting the corresponding β2Microglobuline (β2M) control, or ΔCt=C<sub>t,gene</sub>- C<sub>t,B2M</sub>. To test for differential gene expression between groups, a two sample t-test was performed to compare the DCt in the two groups. <h3>Results</h3> BLyS and APRIL gene expression is shown in Table 1. ΔCt is inversely proportional to the gene expression level. Analysis of PB showed no significant difference in gene expression between RA and OA. In SF, we observed a significant difference for BLyS and APRIL expression between Group I vs. Group II (p=0,002 and p=0,024 respectively). After t test, we evaluated data from $Δ $Ct analysis observing that in SF, mRNA of BLyS and APRIL in Group I was higher than those from Group II. <h3>Conclusions</h3> Gene expression of BLyS/APRIL in PB does not correlate with expression in SF. Increased BLyS and APRIL expression in active RA SF can be linked to B cell activation and maintenance in RA synovium. <h3>References</h3> Moura RA, et al. BAFF and TACI gene expression are increased in patients with untreated very early Rheumatoid Arthritis. The journal of Rheumatology 2013. La Cava A. Targeting the BLyS-APRIL signaling pathway in SLE. Clin Immunol 2013. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2971
Abstract 4956: Proteomics-based characterization of pathways involved in tamoxifen resistance in breast cancer cells
Authors: Betzabe C. Sanchez, Henrik Johansson, Janne Lehtiö, Olle Stål, Barbro K. Linderholm
Journal: Cancer Research (2010)

Abstract Background: Although the introduction of tamoxifen (tam) has contributed to the improved survival of breast cancer patients there are those that relapse despite treatment due to de novo or acquired resistance to the drug. Since the mechanisms involved in tam resistance likely involve various pathways, techniques like mass spectrometry allowing simultaneous analyses of multiple proteins are of great value. Our aim is to identify pathways involved in tam resistance by using a mass spectrometry. Material and methods: Mass spectrometry based proteomics was used to investigate the proteomic changes associated with tam exposure using a tam-responsive and resistant cell line, MCF7 and MCF7/LCC2, respectively. Cytosolic and nuclear fractions were subjected to a shotgun proteomics approach. This included immobilised pH gradient-isoelectric focusing (IPG-IEF) of trypsinized peptides followed by Maldi-TOF/TOF mass spectrometry. Advanced biostatistics was applied to narrow identified targets to those which were significantly deregulated. Results: Preliminary results indicate a clear distinction between the nuclear and cytosolic fractions in regards to proteins. Various proteins were differentially deregulated in MCF7 compared to the resistant cell line both at the basal level and following tam treatment. At basal level, glucose-6-phosphate dehydrogenase, fatty acid synthase and keratin 18 were significantly upregulated in resistant cells as compared to parental MCF7 cells. Interestingly, tam treatment in MCF7 cells induced a significant increase in expression of several proteins involved in the p53 pathway and related to Huntingtin (HTT) while downregulating other proteins related to Retinoic Acid Receptor alpha (RARA). In contrast, resistant cells showed upregulation of proteins involved with RARA without exhibiting any specific deregulated proteins related to HTT or p53. Conclusions: Basal differences in protein expression were observed between the tam-sensitive and resistant cell line. Our results indicate that there are potentially deregulated proteins in the tam-sensitive cell line involved in p53, RARA, and HTT pathways in a manner that differs from the resistant one. The expression of the identified proteins will be further characterized. Understanding of the mechanisms involved in tam resistance can potentially aid in the development of new drugs and serve as prognostic biomarkers. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 4956.
Abstract 4077: Exposure to bile acids alters intracellular expression of MnSOD in Barrett's esophagus
Authors: Russell W. Farmer, Yan Li, Charles R. St. Hill, Suzanne Schiffman, Nicholas L. Harper, Xinqin Kang, Robert C. Martin
Journal: Cancer Research (2011)

Abstract Introduction: Oxidative stress secondary to bile acid exposure has been associated with metaplastic degeneration of normal esophageal mucosa into Barrett's Esophagus cells and eventually Esophageal Adenocarcinoma. We have previously reported that the macromolecular response of BE cells to this stress is largely regulated by the expression of Manganese Superoxide Dismutase (MnSOD). As the mitochondrion plays a vital role in MnSOD activation, the purpose of this study was to determine the location and activity of MnSOD within the BE cell after exposure to oxidative stress. Methods: BE cells were cultured to 80-90% confluence in 75ml flasks. The cells were then exposed for four hours to 0.4mM concentrations of taurocholic acid (TCA) or a 0.4mM 1:1 mixture of bile salts including sodium cholate (CA), sodium deoxycholate (DCA), sodium glycocholate (GCA), and sodium taurocholate (TCA) to mimic natural biliary refluxate. Proteins were extracted and separated into mitochondrial, nuclear, and cytoplasmic fragments followed by western blot analysis. Enzymatic Activity of MnSOD was determined by silencing of other SOD molecules with potassium cyanate. Lethality testing of biliary exposure was performed with MTT assays. Results: Mitochondrial expression of MnSOD was significantly increased in the cells exposed to a mixture of bile acids vs. TCA and control. This was present on both qualitative and quantitative analyses of Western blots. Cytoplasmic expression of MnSOD was also present and conserved between treated and untreated cells. Control cells lines showed no significant change in baseline MnSOD expression. This expression was confirmed by increased MnSOD activity in the mitochondria of cells exposed to mixed bile. The lethality of mixed bile for Barrett's cells was confirmed by MTT assay, with isolated bile salts and controls having a significantly higher fraction of living cells. Conclusion: This is the first study to evaluate microcellular MnSOD expression which is increased in BE cells in response to the oxidative stress of bile exposure, specifically in the mitochondrion. Mitochondrial MnSOD activity is increased within the BE cell after exposure to bile. Further investigation is required to determine the potential correlation between bile exposure and BE to adenocarcinoma progression. 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 4077. doi:10.1158/1538-7445.AM2011-4077
P287 HEPATIC C6-CERAMIDE NANOLIPOSOMAL UPTAKE AFFECTS MCD-INDUCED NASH IN VIVO VIA ALTERATIONS IN PROLIFERATIVE, FIBROTIC AND OXIDATIVE STRESS SIGNALING PATHWAYS
Authors: F. Zanieri, S. Omenetti, D. Cavallaro, S. Galastri, S. Madiai, T.V. Luong, S.S.S. Velandy, T. Fox, M. Kester, K. Rombouts, M. Pinzani
Journal: Journal of Hepatology (2014)
Scrotal Lymphedema Mimicking Urine Leakage
Authors: Hasan Bozkurt, Erdem Sürücü, Recep Bekiş
Journal: Clinical Nuclear Medicine (2011)

Tc-99m diethylene triamine pentaacetic acid (DTPA) dynamic renal scan is widely used to evaluate urological complications after renal transplantation, especially for urine leakage. Although the most common site of urine leakage is based on urethrovesical anastomoses, it can also be seen anywhere in the abdomen, even in the scrotum. In our case, we showed scrotal lymphedema caused false-positive result for scrotal urine leakage detected by Tc-99m DTPA dynamic renal scan.
Biliary endoscopic retrograde cholangiopancreatography
Authors: S. Irani, T. Baron
Journal: Endoscopy (2012)

Direct visualization of the biliary tree by transpapillary cholangioscopy can be helpful for establishing the diagnosis of indeterminate biliary strictures by visual inspection, for obtaining biopsies, and for guiding bile duct stone therapy [2] [3] [4]. Although the first use of peroral cholangioscopy was described in the 1970 s, its widespread adoption has been limited by the cost and fragility of cholangioscopes, their technology (difficulty with irrigation, limited tip deflection, and suboptimal optics), and the need for two operators [1]. The single-operator cholangioscopy (SOC) system (SpyGlass Direct Visualization System; Boston Scientific Corp., Natick, Massachusetts, USA) was designed to overcome such limitations [5] [6]. The system features two separate irrigation channels, 4-way tip deflection for better steerability, and with the system secured to the duodenoscope handle cholangioscopy can be performed by a single operator. Thus far there are limited data demonstrating improved patient outcomes, and the advanced endoscopic skill required in these complex cases has limited both the potential for prospective data collection and replication of the initial prospective results from the initial single institution [7]. The later study by Chen et al., [1] was a large scale, multicenter, prospective, observational study of SOC procedures and was conducted to provide confirmatory evidence that direct visualization is valuable in the diagnosis of biliary disease and the treatment of choledocholithiasis.
Nonobstructive Hydronephrosis with Secondary Polycythemia
Authors: Chih-Chien Sung, Shih-Hua Lin
Journal: New England Journal of Medicine (2011)

A 34-year-old nonsmoking man was referred for evaluation of a history of polycythemia that required monthly phlebotomy. His medical history was significant for congenital nephrogenic diabetes insipidus, with a urine output of approximately 12 to 15 liters per day.
Abstract 2974: Cep57 is a novel regulator of centriole overduplication in tumor cells
Authors: Rolando A. Cuevas, Anette Duensing, Stefan Duensing
Journal: Cancer Research (2010)

Abstract Abnormal multipolar mitoses are commonly observed in human cancers where they can increase the risk for chromosome segregation errors, numerical chromosomal instability and malignant progression. The mitotic spindle poles are formed by centrosomes and tumor cells frequently show abnormal centrosomes numbers. The molecular mechanisms leading to numerical centrosome aberrations are not understood in detail. The centrosome consists of two centrioles, which normally duplicate in synchrony with the cell division cycle. We recently identified a novel mechanisms leading to abnormal centriole numbers in tumor cells in which maternal centrioles generate more than the normal one daughter at the same time (centriole multiplication). Using a siRNA library screen enriched for centrosomal proteins, we identified Cep57 as a novel protein involved in centriole multiplication. Cep57 was found to localize to centrosomes and to co-localize and functionally interact with Polo-like kinase 4 (PLK4), a master regulator of centriole duplication control. Cep57 overexpression was found to promote abnormal centrosome and centriole numbers as well as mitotic abnormalities with a significant number of cells showing multipolar metaphases as well as multipolar anaphases and telophases. Cep57 maps to chromosome 11q21, a region that is amplified in several cancer types including hematological malignancies and prostate cancer. Taken together, we identified Cep57 as regulator of centriole duplication in tumor cells and a candidate oncogene. Experiments to target the Cep57-PLK4 axis with small molecules to prevent cell division errors and malignant progression are currently under way. 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 2974.
Abstract 5489: Feasibility study of gut microbiome collection in randomly sampled women
Authors: Heather Spencer Feigelson, Kimberly Bischoff, Jacques Ravel, Mitchell H. Gail, Roberto Flores, James J. Goedert
Journal: Cancer Research (2012)

Abstract Systemic estrogen level strongly determines risk for postmenopausal breast cancer (BC). We hypothesize that differences in hormone metabolism by the gut microbiota may contribute to BC risk by modulating enterohepatic circulation of estrogens. We conducted a study to determine the feasibility of enrolling healthy postmenopausal members of Kaiser Permanente Colorado (KPCO) in a fecal microbiome study. With electronic medical records, we created a pool of potentially eligible women aged 55-69 who recently had a negative screening mammogram. We excluded those with any hormone prescription in the prior 12 months, an antibiotic prescription in the prior 6 months, or history of cancer, inflammatory bowel disease or other conditions likely to affect fecal microbiota. A packet (invitation letter, informed consent form, information pamphlet, and opt-out postcard) was sent to 250 randomly sampled women. Women who have not returned the postcard are contacted by KPCO research staff to determine interest in participating, verify eligibility, and obtain verbal informed consent. Consented participants were mailed a second packet with a self-administered risk factor questionnaire, link to an on-line diet questionnaire, collection kit for urine (to measure 15 estrogens) and stool specimens, and shipping instructions to the laboratory. Enrollees have spent an estimated 1-2 hours completing all recruitment and data collection components. To date, 60 (24%) have enrolled, 70 (28%) refused (most via the opt-out card), and the remainder are pending phone contact. As shown in the table, the enrolled women are similar to the total sample; slightly more of them are non-Hispanic white, and they are more likely to have a history of breast biopsy. These data demonstrate that we can successfully recruit an apparently representative sample of women into a microbiome study. 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 5489. doi:1538-7445.AM2012-5489
FRI0240 Usefulness of Fdg-Pet/Ct Imaging in Igg4-Related Disease
Authors: H. Ozaki, H. Dobashi, K. Susaki, T. Kameda, M. Izumikawa, Y. Takeuchi, S. Nakashima, H. Shimada, T. Matsunaga
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> IgG4-related disease (IgG4-RD) is a relatively common and clinically important disease. It is very difficult to confirm the diagnosis due to the ubiquity of its lesions, which can involve the pancreas, salivary glands, retroperitoneum, and kidney. An elevated serum IgG4 level is not diagnostic of the disease. In 2011, comprehensive diagnostic criteria for IgG4-RD were established. These criteria require histopathology to confirm the diagnosis, as well as to exclude malignancy or other similar diseases. However, the diagnostic rate is low due to difficulty in determining the site to be biopsied. <h3>Objectives</h3> FDG-PET/CT is a non-invasive imaging technique commonly used in clinical oncology. 18 F-FDG accumulation is recognized as useful for diagnosing and monitoring the response to therapy in patients with some inflammatory disorders. We investigated the utility of FDG-PET/CT to determine the diagnosis in patients suspected of having IgG4-RD. <h3>Methods</h3> We studied 36 patients with suspected IgG4-RD in our facility between Jan. 2008 and Dec. 2013. We retrospectively studied the relation of serum IgG4 levels, pattern of FDG uptake, maximum standardized uptake value (SUVmax), pathological findings, and clinical course. <h3>Results</h3> We diagnosed 27 patients with IgG4-RD or other diseases. There were nine cases in which FDG-PET/CT was the only modality indicating a disease site for biopsy. Other diagnoses included lymphoma, Castleman9s disease, and tuberculosis. There was no correlation between serum IgG4 and SUVmax, but there was a correlation between SUVmax and histopathological findings. <h3>Conclusions</h3> FDG-PET/CT is useful in selecting a biopsy site for the pathological examination of tissue that is necessary to diagnose or exclude IgG4-RD. Its regular use has the potential to improve the diagnostic rate of this entity. <h3>References</h3> Umehara H, Okazaki K, Masaki Y, et al. Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 2012 Feb;22(1):21-30. Ebbo M. Usefulness of 2-[18 F]-fluoro-2-deoxy-D-glucose Positron Emission Tomography/Computed Tomography for Staging and Evaluation of Treatment Response in IgG4-Related Disease: A Retrospective Multicenter Study. Arthritis Care Res. 2014 Jan;66(1):86-96. Nakatani K. Utility of FDG PET/CT in IgG4-related systemic disease Clin Radiol. 2012 Apr;67(4):297-305. Nguyen VX. Usefulness of PET/CT Imaging in Systemic IgG4-related Sclerosing Disease. A Report of Three Cases JOP: Journal of the Pancreas. 2011 May 6;12(3):297-305. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3036
Renal Disease in Children with the Acquired Immunodeficiency Syndrome
Authors: J Strauss, C Abitbol, G Zilleruelo, G Scott, A Paredes, S Malaga, B Montané, C Mitchell, W Parks, V Pardo
Journal: New England Journal of Medicine (1989)

Of 155 children with the acquired immunodeficiency syndrome (AIDS) whom we evaluated during a 6 1/2-year period, 12 were found to have proteinuria. Histologic studies of tissue from these 12 patients revealed a wide spectrum of renal disease: focal glomerulosclerosis in 5, mesangial hyperplasia in 5, segmental necrotizing glomerulonephritis in 1, and minimal change disease in 1. In addition, 6 had tubulointerstitial infiltrates, and 10 had glomerular dense deposits. All 10 renal specimens studied by electron microscopy contained endothelial tubuloreticular inclusions. The mean age (+/- SD) of the five patients with focal glomerulosclerosis when this condition was identified was 27 +/- 19 months. All five had severe renal failure within a year and died of other causes during the following year. The mean age of the five patients with mesangial hyperplasia was 38 +/- 31 months. Although none of them went on to have renal failure, four died within 8 +/- 7 months. Ten of the 12 patients with proteinuria died during the study period. Of the two surviving, one had mesangial hyperplasia and the other had minimal change disease. We conclude that children who acquire human immunodeficiency virus (HIV) infection during the perinatal period may have renal disease, most often focal glomerulosclerosis, as is the case in adults, or mesangial hyperplasia. Although 5 of the 12 children we studied had renal failure during the study period, none died of it. Further studies are needed to determine the correlations between clinical and pathological features and the pathophysiology of AIDS nephropathy in children.
Death and the Research Imperative
Authors: D Callahan
Journal: New England Journal of Medicine (2000)

For several years, there has been an awareness of the often harmful power of the “technological imperative” in the care of dying patients — that is, the compulsive use of technology to maintain life when palliative care would be more appropriate. There is another imperative that now deserves more attention in assessing the care of dying patients: the research imperative. It stems from the view that medicine has an almost sacred duty to combat all the known causes of death. Underlying this view is the assumption, usually tacit, that death is the principal evil of human life.At the heart . . .
Large gastric heterotopia presenting as an obstructing duodenal mass
Authors: R. Fincher, M. Donovan
Journal: Endoscopy (2011)

Gastric heterotopia is an ectopic lesion found throughout the gastrointestinal tract. The classic endoscopic appearance of gastric heterotopia is raised, salmon-red mucosal patches or clusters of nodules above normal duodenal mucosa, ranging in size from 3 mm to 10 mm [1]. Large polypoid gastric heterotopia of the duodenum, defined as being greater than 2.5 cm, is rare and clinical relevance has only been described on one other occasion [2]. We report the first published case of a large polypoid gastric heterotopia of the duodenum causing obstructive symptoms and diagnosed by endoscopy.