tbuckley/cabot-search huggingface dataset:
Marked Increase in Serum IgM during Treatment of Waldenström's Macroglobulinemia with Cladribine
Authors: Vandana M. Krishna, Robert W. Carey, Kurt J. Bloch
Journal: New England Journal of Medicine (2003)

To the Editor: We recently encountered two patients with Waldenstrom's macroglobulinemia1 who had a marked increase in the serum concentration of IgM M component during treatment with cladribine.2 Patient 1, a 78-year-old woman, reported shortness of breath and fatigue of two weeks' duration. Physical examination, a complete blood count, and serum chemical values were normal. An IgM-kappa M component was detected in serum; the total serum IgM concentration was 2580 mg per deciliter. A biopsy of a mass in the right side of the chest and right kidney revealed a B-cell lymphoma with plasma-cell differentiation. The bone marrow was also . . .
The Editors’ guide for peer review of papers submitted to Endoscopy
Authors: M. Dinis-Ribeiro, N. Vakil, T. Ponchon
Journal: Endoscopy (2012)

Peer review is fundamental to the academic process and a journal’s success depends to a large extent on the quality of its reviewers. Endoscopy is one of the leading journals worldwide in gastroenterology and endoscopy and our reviewers contribute significantly to that status.
Abstract 4193: Identification of a novel SIRT1/FEN1 interaction and their regulation by karyopherins
Authors: Daniel Feurstein, Jessica Anderson, Derek Duckett
Journal: Cancer Research (2011)

Abstract The structure-specific flap endonuclease 1 (FEN-1) is a multifunctional enzyme that participates in various activities such as DNA replication, DNA repair and apoptotic DNA fragmentation. Several mechanisms, including protein-protein interactions, sub-cellular compartmentalization and posttranslational modifications have been proposed to explain how FEN1 accomplishes these various activities. For example, the C-terminus of FEN1 has been shown to be acetylated by the histone acetyl transferase protein (HAT) p300 which is known to result in a significant reduction in the DNA binding and nuclease activities of FEN1. We now demonstrate that the NAD-dependent class III histone deacetylase SIRT1 physically interacts with FEN1 and that the opposing deacetylation by SIRT1 subsequently restores the endonuclease activity of FEN1. Moreover, clonogenicity experiments suggest that genetic knockdown of FEN1 or SIRT1 in cancer cells sensitizes those cells to irradiation treatment. This is of significance as it has been observed that increased SIRT1 levels protect mice from irradiation-induced cancer. Furthermore, we have also identified two nuclear shuttling proteins, Karyopherin α2 and Karyopherin β1 as interacting partners of both SIRT1 and FEN1. Using mass spectrometry, immunoprecipitation combined with subsequent western-blot analysis and confocal microscopy we demonstrate that, under basal conditions, a significant amount of both SIRT1 and FEN1 is located in the cytoplasm of cells. However, after induction of DNA damage by the methylating agent MMS, Karyopherin α2 and Karyopherin β1 mediate the translocation of SIRT1 and FEN1 into the nucleus in a time dependent manner. In summary we describe a novel interaction between SIRT1 and FEN1, demonstrate that acetylation/deacetylation regulates FEN1 activity and that the Karyopherins α2 and β1 mediate the nuclear import of SIRT1 and FEN1 following DNA damage. Our results suggest that inhibiting the nuclear import or activation of FEN1 or SIRT1 could represent potential anticancer strategies. 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 4193. doi:10.1158/1538-7445.AM2011-4193
Abstract 2892: Glycogen synthase kinase-3α regulates cell proliferation in pancreatic cancer cells by regulating constitutive TAK1 and NF-κB signaling
Authors: Deepali Bang, Willie Wilson, Jen Jen Yeh, Albert S. Baldwin
Journal: Cancer Research (2011)

Abstract Pancreatic ductal adenocarinoma (PDA) represents the fourth leading cause of cancer-related deaths in the United States with a 5-year patient survival rate less than 5%. The transcription factor NF-κB is constitutively active and contributes to cell survival and cancer therapy resistance in these tumors. Previous reports have linked constitutive IκB kinase (IKK) activity to canonical NF-κB signaling in human pancreatic cancer cells. However, the signaling events that drive IKK activity remain poorly understood. TGF-β activated kinase 1 (TAK1) is an established regulator of IKK activity and has been shown to be active in human cancer cell lines. Moreover, we previously reported that glycogen synthase kinase-3 (GSK-3) signals through IκB kinase (IKK) to facilitate downstream pro-survival NF-κB signaling and inhibition of GSK-3 suppressed cell proliferation in pancreatic cancer cells. Here, we investigate the status of TAK1 activity in pancreatic cancer cells and explore the potential regulation of constitutive TAK1-IKK signaling by GSK-3. We observed elevated levels of TAK1 phosphorylation and its association with TAB1 in a panel of pancreatic cancer cell lines. Genetic ablation of TAK1 in Panc-1 and MiaPaCa-2 cell lines resulted in decreased pro-survival NF-κB signaling. TAK1 was found to interact with GSK-3α in co-immunoprecipitation studies and both the genetic ablation and inhibition of GSK-3α suppressed NF-κB activity, TAK1 levels and growth of pancreatic cancer cells. We also observed reduction in the levels of TAB1 and TAB2, binding partners of TAK1, upon pharmacological inhibition of GSK-3. Additionally, pharmacological inhibition of GSK-3 significantly suppressed the levels of TAK1 and the growth of human pancreatic tumor explants in mice. Recently non-canonical or IKK- independent NF-κB signaling was also observed to be constitutively active and contributing to cell survival in pancreatic cancer cells. Preliminary data from si-RNA mediated knockdown studies suggests a positive regulation of non-canonical NF-κB signaling by GSK-3α. Overall, our data suggests that constitutive TAK1/TAB1-IKK and non-canonical NF-κB signaling in pancreatic cancer is driven by novel GSK-3α dependent mechanisms. These data provide new insight into our understanding of constitutive NF-κB regulation in pancreatic cancer and presents TAK1 as a potential new therapeutic target for this disease. Further investigation is required to understand the mechanism of GSK-3α-TAK1/TAB1 and GSK-3α-non canonical NF-κB regulation and their effect on pro-survival NF-κB signaling in pancreatic cancers. 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 2892. doi:10.1158/1538-7445.AM2011-2892
The Internet and the<i>Journal</i>
Authors: Jerome P. Kassirer, Marcia Angell
Journal: New England Journal of Medicine (1995)

The word “publishing” has taken on new meaning. For centuries, publishing required an intermediary, someone who had an editorial staff and a press — in short, a publisher. Today, anyone equipped with a computer, a modem, and a connection to the Internet can be a publisher. The consequences of this technical transformation should give pause to all of us in medicine. Direct electronic publishing of scientific studies threatens to undermine time-tested traditions that help to ensure the quality of the medical literature. The first hint that electronic publishing by medical researchers might become a reality came from the field of . . .
A2.2 Uveitis is not associated with cardiovascular disease risk factors in patients with ankylosing spondylitis
Authors: Zepa Julija, Bulina Inita, Lavrentjevs Vladimirs, Sikora Evita, Abelite Sarmite, Kadike Santa, Nikitina-Zake Liene, Lejnieks Aivars, Andersone Daina
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Ankylosing spondylitis (AS) is a chronic, autoimmune, systemic, inflammatory disease. Recently, a link has been established between autoimmune inflammatory diseases, incl. AS, and the risk of developing cardiovascular disease (CVD). Uveitis is the most frequent extraarticular location of AS - it occurs in about 25 - 40% of patients. The impact of evidence of uveitis during the course of AS still remains a challenge. Does AS with uveitis differ from AS without uveitis? The objective of this study was to detect the link between uveitis during the course of AS and the CVD risk factors in patients with AS. <h3>Materials and Methods</h3> 77 AS patients classified using the modified New York criteria were assessed clinically and 6 ml of serum was collected from each patient. Patients were divided into two groups: with and without uveitis. The following parameters were chosen as the CVD risk factors: body mass index (BMI), waist circumference (WC) and high density lipoprotein cholesterol (HDLc). Statistical analyses included a between-group comparison of age, duration of the disease, the disease activity (measured using Ankylosing Spondylitis Disease Activity Score (ASDAS) with C-reactive protein (CRP)) and values of the CVD risk factors. <h3>Results</h3> The mean age was 39.7 years (SD 10.15), disease duration 13.5 years (SD 8.44) and ASDAScrp 3.0 (SD 1.38). These parameters were not statistically significantly different between the groups. The mean value of BMI, WC and HDLc in AS group with uveitis (n = 26) were respectively 24.8 kg/cm<sup>2</sup> (SD 4.22), 91.3 cm (SD 14.23) and 1.51 mmol/l (SD 0.5). The mean value of BMI, WC and HDLc in AS group without uveitis (n = 51) were respectively 25.4 kg/cm<sup>2</sup> (SD 4.2), 93.1 cm (SD 11.67) and 1.39 mmol/l (SD 0.39). The values of the CVD risk factors were not statistically significantly different between the groups. <h3>Conclusions</h3> These results suggest that uveitis does not impact the CVD risk factors in patients with AS. Thus it can be proposed that aspects of the pathogenesis, genetics of uveitis in patients with AS do not interfere with pathways of CVD. Further investigations are needed.
Intraocular Lymphoma and Central Nervous System Lymphoma Involving the Hypothalamus
Authors: William Makis, Javier A. Novales-Diaz, Marc Hickeson
Journal: Clinical Nuclear Medicine (2010)

A 77-year-old woman presented with sudden onset of loss of vision in the left eye and bilateral eye inflammation. Biopsy of the vitreous fluid of the right eye revealed large abnormal cells suggestive of lymphoma. A staging F-18 FDG PET/CT showed intense uptake in the hypothalamus, and mild focal uptake in the subcutaneous tissues of the right lower leg, which were biopsied to reveal diffuse large B cell lymphoma. The patient was treated with high dose chemotherapy (methotrexate), and a follow-up PET/CT showed complete resolution of the hypothalamic and right leg lesions. Intraocular-central nervous system lymphoma (also known as oculocerebral lymphoma) is rare, with only 150 cases reported in the literature. This case highlights the utility of PET/CT in the staging and evaluation of response to therapy for this rare lymphoma subtype. We recommend that patients with intraocular-central nervous system lymphoma, who have a staging PET/CT should have total body acquisitions that include the head and neck, and upper and lower extremities, as these may yield unexpected sites of disease, easily accessible for biopsy.
Vascular Infiltration as an Independent Predictor of Survival for Biliary Tract Cancers
Authors: Joaquina Martinez-Galán, Julia Ruiz-Vozmediano, Lucia Castillo-Portellano, Jesús Soberino-García, Cynthia González-Rivas, Antonio Iriyogen, Pedro Ballesteros, José Antonio Ortega-Dominguez, Juan Ramón lgado De Pérez
Journal: Annals of Oncology (2013)
Abstract 803: Expression of poly(adenosine diphosphate-ribose) polymerase (PARP) and p53 in epithelial ovarian cancer
Authors: Heidi E. Godoy, Paulette Mhawech-Fauceglia, Amy Beck, Austin Miller, Shashikant Lele, Kunle Odunsi
Journal: Cancer Research (2010)

Abstract Objectives: PARP, poly(adenosine diphosphate-ribose) polymerase, is a damage sensing protein that is essential to the repair of DNA single-strand breaks. P53 acts as a “genome guardian” molecule that in response to DNA damage mediates cell cycle arrest or induces apoptosis. PARP and p53 function synergistically in repairing DNA damage and suppressing chromosomal rearrangements. The aim of this study was to determine the expression of PARP and p53 in epithelial ovarian cancer (EOC) and correlate with clinico-pathologic characteristics. Methods: PARP and p53 was examined using immuno-histochemistry applied on a tissue microarray of 189 EOC. PARP and p53 expression were examined in relation to clinco-pathologic variables, including age of diagnosis, stage, grade, histologic type, optimal debulking, progression free survival and overall survival. Progression free survival and overall survival were estimated by Kaplan-Meier method, and statistical significance was calculated by the log-rank test. Results: PARP expression was demonstrated in 61% (115/189) of specimens and 99/185 (54%) samples exhibited p53 staining. PARP positive tumors tended to have higher grade (P = 0.03) and complete response to initial treatment (P = 0.009). Patients with positive p53 staining tended to have higher stage of disease (P = 0.004) and there was a trend of patients with positive p53 and weak PARP expression to increase the likelihood of disease progression (OR 2.25 (CI 0.389-13)). The median follow-up was 40 months. However, there were no significant associations between PARP and p53 expression. There was no significant difference in disease free or overall survival for PARP or p53. Conclusion: This study indicates that PARP and p53 are upregulated in EOC with higher grade tumors and more advanced stages, respectively, and may serve as a marker of aggressive disease behavior. Additional studies are warranted to evaluate the role of PARP and p53 expression as a predictor of response to initial treatment, and to identify patients that may benefit from alternative treatments in the adjuvant setting. 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 803.
475 THE INFLUENCE OF PORTAL PRESSURE ON THE DISCORDANCE OF ABSOLUTE CD4+ COUNT AND CD4+ PERCENTAGE IN HIV/HCV COINFECTED PATIENTS
Authors: M. Mandorfer, T. Reiberger, B.A. Payer, A. Ferlitsch, F. Breitenecker, M.C. Aichelburg, A. Rieger, M. Trauner, M. Peck-Radosavljevic
Journal: Journal of Hepatology (2013)
Ethical debate: child sexual abuse: when a doctor's duty to report abuse conflicts with a duty of confidentiality to the victim (The woman who wanted to see her paediatric hospital records)
Authors: T J David
Journal: BMJ (1998)

The role of the stent graft is emerging in the management of arteriovenous dialysis access. Physicians are incorporating this device in the management of three distinct problems—vein-graft anastomotic stenosis, pseudoaneurysm formation, and cephalic arch stenosis—with varying degrees of success. Indeed, a recent randomized, controlled trial to evaluate the role of angioplasty plus stent graft <i>versus</i> angioplasty alone for the management of stenosis at the vein-graft anastomosis led to the approval of the stent graft by the Food and Drug Administration; however, several elements of the management of stenosis at the vein-graft anastomosis/cephalic arch as well as the repair of pseudoaneurysms by stent graft remain controversial. The situation is further complicated and warrants a cost-to-benefit ratio analysis when the added cost of the device is appended to the procedure. In contrast to the controversies, angioplasty-induced complete vascular rupture is one situation in which a stent graft is indicated beyond any doubt. With recent conditional Food and Drug Administration approval, it is anticipated that the use of stent grafts might increase in our patients. In this context, it is critically important that nephrologists be familiar with the current controversies and consensus that surround the use of stent grafts for dialysis access. Just as therapeutic interventions are analyzed in other disciplines within nephrology, these experts must appraise the use of this device for dialysis access. This report presents an up-to-date synopsis on the use of the stent graft that would assist renal physicians in requesting or rejecting the device for the optimal management of their patient9s vascular access dysfunction.
Abstract 228: PAK1 kinase promotes cell motility through CRK serine phosphorylation in non-small cell lung cancer cells
Authors: Fariborz (Fred) Mortazavi, Matthew Rettig
Journal: Cancer Research (2012)

Abstract The role of c-Crk (CRK) in promoting metastasis is well described but the role of CRK phosphorylation and the corresponding signaling events are not well explained. We have noticed that CRK serine 41 phosphorylation is inversely correlated with p120-catenin and E-cadherin expressions in non-small cell lung cancer (NSCLC) cells. Therefore, we investigated the role of CRK serine 41 phosphorylation in the down-regulation of p120-catenin and cell motility in NSCLC cells. We prepared A549 cell lines stably expressing phosphomimetic and phosphodeficient CRK serine 41 constructs. A549 cells expressing phosphomimetic CRK seine 41 demonstrated a more aggressive behavior in would healing assay and on the contrary, expression of phosphodeficient CRK serine 41 in A549 cells reduced cell motility. A549 cells expressing phosphomimetic CRK serine 41 had lower p120-catenin mRNA and promoter activity and vice versa. In addition, we provide evidence that PAK1 mediates CRK serine 41 phosphorylation. RNAi mediated silencing of PAK1 increased p120-catenin level and also decreased cell motility in A549 and H157 cells. These effects were abrogated in A549 cells expressing phosphomimetic CRK serine 41. In summary, our data provide evidence for the role of PAK1 in promotion of cell motility and down regulation of p120-catenin through CRK serine 41 phosphorylation in NSCLC cells. 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 228. doi:1538-7445.AM2012-228
PTU-100 Developing Swansea inflammatory bowel disease clinical severity index (SICSI)
Authors: L Alrubaiy, J Williams, H Hutchings
Journal: Gut (2012)

<h3>Introduction</h3> To assess IBD activity, many severity scales have been developed. Yet, most of them were not properly validated and did not go through robust methodology. Using different scoring systems makes it difficult to compare different trials especially when the end points are different. Because new therapies for IBD are rapidly emerging, there is a need to optimise and standardise methodology for assessing of disease activity in clinical trials. With the nationwide initiative to establish an IBD registry, a valid and easy to use activity measurement tool is needed. We believe that having a single disease activity index that is suitable for all types and presentations of IBD will make it very useful to monitor patients and assess their response to treatment. <h3>Methods</h3> Literature search was conducted using MEDLINE and Google scholar database from January 1947 to 2011 to identify the clinical severity indeces commonly used in clinical trails. Seventeen indeces were identified for both Ulcerative coltis and Crohn9s disease. We followed a clini-metric approach to develop the simple IBD clinical severity index. Common items between Ulcerative coltis and Crohn9s disease were chosen. Few items were added to cover disease specific domains. The new index was examined by gastroenterologists and methodologists in Swansea University to ensure good face and content validity. The index was tested on 50 patients with different presentations of inflammatory bowel disease. Harvey Bradshaw index and Simple clinical colitis index were used for construct validity. Responsivness was checked by repeating the test within 2-week period. <h3>Results</h3> The new index, simple IBD clinical severity index, showed good face and content validity. It covers all presentations of IBD including Crohn9s disease, ulcerative coltis and perianal disease. It has good reliability and construct validity. It is easy to use in daily practice. <h3>Conclusion</h3> Simple IBD clinical severity index is a new tool to assess the clinical activity of IBD. It is valid, reliable, user friendly and non-invasive index. Further studies are required to check how it performs on a wider range of patients. <h3>Competing interests</h3> None declared.
QUANTIFICATION OF LEFT TO RIGHT SHUNTS BY 3D ECHOCARDIOGRAPHY IN PATIENTS WITH ATRIAL SEPTUM DEFECTS COMPARED WITH INVASIVE MEASUREMENT
Authors: Terada Mai, Mahara Keitaro, Tsugu Toshimitu, Saito Mika, Tamura Harutoshi, Seki Atushi, Suzuki Makoto, Tobaru Tetuya, Tomoike Hitonobu
Journal: Journal of the American College of Cardiology (2016)
Biochemical Differentiation of Trisomic Down's Syndrome (Mongolism) from That Due to Translocation
Authors: Fred Rosner, Beale H. Ong, Richmond S. Paine, Dershananand Mahanand
Journal: New England Journal of Medicine (1965)

IN 1959 Lejeune, Gautier and Turpin1 observed that patients with Down's syndrome had 47 chromosomes instead of the usual 46. An extra small acrocentric chromosome, belonging to the No. 21 group, was present, producing "trisomy 21." Since then, other patients with mongolism have been described with only 46 chromosomes but with "translocation" of chromatin material from 1 chromosome to another. If an entire chromosome is translocated an equivalent trisomy is produced. (In translocations of human acrocentric chromosomes part of the short arms may be deleted in the process of translocation.) Thus, there are at least 2 very distinct types of . . .
NCI Survey Explores the M.D.'s Perspective on ABMT Trials
Authors: J. Mathews
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article NCI Survey Explores the M.D.'s Perspective on ABMT Trials Get access James Mathews James Mathews Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 20, 18 October 1995, Pages 1510–1511, https://doi.org/10.1093/jnci/87.20.1510 Published: 18 October 1995
SP0060 GCA and Large Vessel Involvement
Authors: E. Molloy
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Giant Cell Arteritis (GCA) is a chronic systemic granulomatous vasculitis of large and medium sized arteries. While classical manifestations of GCA are due to involvement of the carotid artery and its branches, extra cranial large vessel involvement is increasingly recognised. The diagnosis of large vessel involvement in GCA may be challenging. These patients often have a paucity of symptoms, present atypically and their temporal artery biopsies are more frequently negative. Mortality is increased in the presence of aortic and thoracic aneurysms, however much debate exists on the best imaging modality to screen for their presence and on the optimal schedule and duration of screening. Glucocorticoids remain the cornerstone of therapy in GCA. Treatment related adverse events occur in the majority and glucocorticoid resistance is not uncommon. Prospective randomised controlled trials on traditional disease modifying agents are few and in some cases have provided conflicting results. Newer biologic agents hold promise but further evidence is needed. The case to be presented demonstrates the inherent difficulties in the diagnosis and subsequent management of patients with GCA and extra cranial large vessel vasculitis. <h3>Disclosure of Interest</h3> None Declared