tbuckley/cabot-search huggingface dataset:
Effects of deregulated Raf activation on integrin, cytokine-receptor expression and the induction of apoptosis in hematopoietic cells
Authors: C Weinstein-Oppenheimer, LS Steelman, PA Algate, WL Blalock, C Burrows, PE Hoyle, JT Lee, PW Moye, JG Shelton, R Franklin, JA McCubrey
Journal: Leukemia (2000)
THU0012 BAFF Genetic Variants in Lymphomagenesis Associated with Sjogren’s Syndrome
Authors: C. P. Mavragani, A. Nezos, A. Papageorgiou, G. E. Fragoulis, M. Koutsilieris, A. G. Tzioufas, H. M. Moutsopoulos, M. Voulgarelis
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Primary Sjogren's syndrome (pSS) is complicated by B-cell lymphoma in 5-10% of patients. Several clinical and serological features are proposed as adverse predictors for such complication and define a high risk pSS phenotype. <h3>Objectives</h3> We aimed to explore whether previously described polymorphisms of the B-cell activating factor (BAFF) as well as mutation of its receptor (BAFF-R) could be related to pSS related lymphomagenesis. <h3>Methods</h3> Five single nucleotide polymorphisms (SNPs) of the BAFF gene (rs1224141, rs12583006, rs9514828, rs1041569 and the rs9514827) and the BAFF-R mutation His159Tyr were evaluated in 111 low risk pSS patients (type II), 82 high risk/ lymphoma patients (type I) and 137 healthy controls (HC) by PCR-based assays. The classification of pSS patients into type I and II was based on the presence or absence of risk factors or lymphoma development, respectively. Genotype and haplotype analysis was performed for all variants in the pSS groups. Since the rs1041569 SNP was not in Hardy-Weinberg equilibrium in the HC group (p&lt;0.001), haplotypic analysis was performed in the remaining four out of the five SNPs tested when comparisons with HC individuals were performed. <h3>Results</h3> The high risk pSS group was characterized by higher frequency of the minor T allele of the rs9514828 BAFF polymorphism compared to HC. Compared to the low risk pSS patients but not the HC, the high risk pSS group exhibited lower frequencies of the AA genotype of the rs12583006 polymorphismas well as the TACAC and TACC haplotypes and higher frequency of the TTTC haplotype. The low risk pSS group exhibited higher frequency of the minor A allele and AA genotype of the rs12583006 variant compared to HC. Both pSS groups were characterized by increased frequency of the haplotype TATT and GTTC and decreased frequency of the TTCT when compared to HC. A significantly increased prevalence of the mutation of BAFF-R His159Tyr was observed in type I pSS patients compared to low risk type II pSS patients (p=0.035) and HC (p=0.003). Such difference was not detected between low risk type II pSS and HC (p=0.47). <h3>Conclusions</h3> Taken together, these findings suggest the implication of the host's genetic background in pSS related lymphomagenesis. The interaction of pSS related BAFF gene haplotypes together with distinct BAFF genetic variants appears to contribute to this complication. <h3>Disclosure of Interest</h3> None Declared
Abstract 1594: Significant in vivo activity of ENMD-2076, a novel inhibitor of Aurora receptor tyrosine kinases, alone and in combination with lenalidomide against plasma cell myeloma
Authors: George E. Sandusky, Matt Rodgers, ShuHong Zhang, Anthony Sinn, Karen Pollok, Sherif Farag
Journal: Cancer Research (2011)

Abstract Aurora kinases, particularly aurora A and aurora B, play a role in normal cell proliferation. Since an unusually high expression of Aurora kinases has been reported in tumor cells, they have become the target of a variety of novel anticancer drugs. One such drug, ENMD-2076, was studied in a translational research project involving a xenograft mouse model and a phase I clinical trial. The preclinical xenograft model evaluated multiple myeloma tumors in NOD/SCID mice treated with ENMD-2076, lenalidomide, and combinations of both drugs, and compared to an untreated vehicle control group. Immunohistochemistry (IHC) was used to predict the effectiveness of treatment for multiple myeloma based on caspase-3, Ki67, phospho-histone H3 (p-H3), and CD34 biomarker expression. IHC slides were quantified using both a traditional pathology hand count and an image analysis program (Image J). The Image J data closely mirrored the hand count for all four biomarkers. At the highest combined dosage, hand count data showed CD34 levels down 74.2% from the vehicle control. Ki67 and p-H3expression were down slightly, and caspase-3 was increased two fold in the combined drug treatment group. Comparing the two drugs, it was evident that the ENMD-2076 aurora kinase inhibitor had a stronger anti-angiogenic effect, while the Lenalidomide had a stronger apoptotic effect. Although the human clinical trial is still in its early stages, initial trends are consistent with results seen in this mouse model. 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 1594. doi:10.1158/1538-7445.AM2011-1594
Postmenopausal Hormone Therapy and Mortality
Authors: Francine Grodstein, Meir J. Stampfer, Graham A. Colditz, Walter C. Willett, JoAnn E. Manson, Marshall Joffe, Bernard Rosner, Charles Fuchs, Susan E. Hankinson, David J. Hunter, Charles H. Hennekens, Frank E. Speizer
Journal: New England Journal of Medicine (1997)

Postmenopausal hormone therapy has both benefits and hazards, including decreased risks of osteoporosis and cardiovascular disease and an increased risk of breast cancer.
Identification of Two Serum Components Regulating the Expression of T-Lymphocyte Function in Childhood Myasthenia Gravis
Authors: Abraham Shore, Sukanya Limatibul, Hans-Michael Dosch, Erwin W. Gelfand
Journal: New England Journal of Medicine (1979)

We studied serums and cells from nine children with myasthenia gravis to determine whether there were alterations in the distribution or function of different T-lymphocyte subpopulations. The low numbers of E-rosette-forming T lymphocytes and their failure to respond to antigen by producing normal suppressor T cells were correlated with the presence of an IgG antibody directed toward the theophylline-sensitive T-cell subset; this activity could be blocked by d-tubocurarine. Incubation of normal T lymphocytes with serum from patients rendered the cells "myasthenia-like" when assayed for E-rosettes and for antigen-induced suppressor-cell function. A second, non-IgG factor found in patients' serums had activity like that of thymic hormone and induced T-cell maturation in normal bone marrow. This factor was not inhibited by d-tubocurarine; its activity was strongest in the two patients most severely affected, and it disappeared after thymectomy in both these patients. We conclude that in childhood myasthenia gravis there may be two independent serum factors; one an IgG antibody directed at a subset of T lymphocytes, blocked by d-tubocurarine and apparently unaffected by thymectomy, and the other a thymus factor that induces T-lymphocyte maturation.
Does the Additional Prognostic Benefit of Screen Detection in Early Breast Cancer Apply to All Patients?
Authors: J. Mansell, O. Komolafe, W. Angerson, C. Wilson, J. Doughty
Journal: Cancer Research (2009)

Abstract IntroductionScreen detection may confer prognostic benefit independent of disease stage in EBC leading to suggestions that mode of presentation should be considered when deciding adjuvant therapy. We aim to determine if this additional prognostic benefit is seen in all patients.MethodsData from 3 centres in Glasgow of consecutive women aged between 50-65yrs with EBC diagnosed between 1995 and 2001 were examined. Patients were grouped by mode of presentation into screen detection and symptomatic. Breast cancer specific survival was the endpoint. Multivariate analysis including interaction between mode of presentation and pathology was performed with further subgroup analysis if the interaction was significant.Results1534 women were included with a median follow up of 5.5yrs. Mode of presentation was screening in 1007 (65.6%) women. After adjustment for pathology screen detection had no significant survival benefit: HR 0.73 (0.50-1.08, p = 0.116). Mode of presentation had an independently significant interaction with both nodal status and ER status (p = 0.003 and p = 0.01 respectively). Further analysis demonstrated that screening was an independent predictor of survival in the 1-3 node positive group (HR 0.33 (0.15-0.73), p = 0.006); the ER positive group (HR 0.53 (0.31-0.89), p = 0.017) and in the moderate NPI group only (HR 0.54 (0.31-0.94), p = 0.030).ConclusionsThese results provide evidence of a significant interaction between mode of presentation and pathology. Further research is needed before incorporating mode of presentation into decisions regarding adjuvant therapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4007.
FRI0256 Arthralgias are predictive factors of foot involvement evaluated by ultrasonography in patients with systemic sclerosis: A prospective study
Authors: G. Cuomo, R. Irace, M.E. Frongillo, L. Pirro, G. Castronuovo, G. Abignano
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Foot problems can be a major source of morbidity and disability in patients with SSc. Arthralgia is common in SSc and is poorly understood. It is usually attributed to mechanical factors resulting from fibrosis and tendon friction [1]. Musculoskeletal ultrasonography (MSUS) can identify and characterize subclinical synovial inflammation and joint damage with higher precision than X-rays [2, 3]. <h3>Objectives</h3> Our study was devoted to identify the presence and to confirm the persistence of subclinical synovial inflammation, utilizing MSUS. <h3>Methods</h3> Forty consecutive patients who had a first MSUS between January and December 2009 were included in the study. They underwent a second MSUS between January 2010 and June 2011. The mean interval between the two MSUS was 18±3,5 months (median 20, range 12-24). The study included 40 SSc patients (38 female), age ranged from 17 to 82 years (median 57); 9 (22.5%) with diffuse SSc, 18 (45%) were anticentromere antibodies positive and 13 (32,5%) anti-Scl70 antibodies positive. <h3>Results</h3> At first clinical examination 28 patients had arthralgias at metatarsophalangeal level without any symptom or sign of inflammatory arthritis, 4 patients presented calcinosis. At MSUS examination 2 patients presented osteophites, 1 patient joint effusion, no patients presented synovitis or erosions. After 1 year the patients were evaluated by the same physician. All 40 patients underwent a second MSUS. Metatarsophalangeal explored joints and tendons were evaluated for the presence of synovial fluid and synovial hypertrophy on grey scale and synovitis/tenosynovitis on power Doppler ultrasonography (PDUS) signal according to OMERACT definition criteria. MSUS identified inflammation in a high proportion of patients: tenosynovitis (in 12/40, 30%), and synovitis (in 12/40, 30%) were the most common followed by joint effusion (in 5/40, 10%). 28 (70%) patients had ultrasonography alterations, only 1 of them had not arthralgia at baseline. Arthralgia was found as predictive factor of foot involvement (HR 8; 95% CI 1.08-58.7). <h3>Conclusions</h3> This prospective study identifies arthralgia as predictor of foot MSUS alterations in patients with SSc. <h3>References</h3> Blocka KL, et al. The arthropathy of advanced progressive systemic sclerosis. A radiographic survey. Arthritis Rheum 1981;24:874-84. Farrant JM, et al. Advanced imaging in rheumatoid arthritis. Part 1: synovitis. Skeletal Radiol 2007;36:269-79. Terslev L, Torp-Pedersen S, Savnik A et al. Doppler ultrasound and magnetic resonance imaging of synovial inflammation of the hand in rheumatoid arthritis: a comparative study. Arthritis Rheum 2003;48:2434-41. <h3>Disclosure of Interest</h3> None Declared
Percutaneous Balloon Valvuloplasty Compared with Open Surgical Commissurotomy for Mitral Stenosis
Authors: Vincent P. Reyes, B. Soma Raju, Joshua Wynne, Larry W. Stephenson, Raghava Raju, Barbara S. Fromm, P. Rajagopal, Prabodh Mehta, Shailender Singh, D. Prasada Rao, P.V. Satyanarayana, Zoltan G. Turi
Journal: New England Journal of Medicine (1994)

Percutaneous balloon mitral valvuloplasty has been proposed as an alternative to open surgical commissurotomy for the treatment of rheumatic mitral-valve stenosis.
AB0539 Psychological status evaluation in spondylarthritis tunisian patients and relationship with diseases features
Authors: I. Mahmoud, L. Dridi, O. Saidane, R. Tekaya, H. Sahli, L. Abdelmoula, L. Chaabouni, R. Zouari
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The prevalence of psychological disorders is greater in patients with rheumatologic conditions than among the general population. <h3>Objectives</h3> We aim in this study to determine the frequency of depression and anxiety disorders in spondylarthritis (SA) patients and to determine predictor disease parameters. <h3>Methods</h3> We performed a cross-sectional monocentric study in 70 SA Tunisian patients. Presence of anxiety or depression disorders was evaluated by the Hospital Anxiety and Depression Scale score (HADS). A certain anxious or depression state was defined by a HADS&gt;10. Epidemiological factors of SA and different disease assessing measures were noted. For statistical analysis, we used Khi<sup>2</sup>-test for qualitative variables and Student-test for quantitative variables. A p value≤0,05 was considered significant. <h3>Results</h3> There were 65% men and 35% women. Age ranged from 16 to 74 years with an average of 40,6 years. Disease mean duration was 10,75±9 years. Mean HADS score was 15,9 and 49 patients had HADS score &gt;10 (certain depression or anxious state) corresponding to a frequency of 70%. 63% of patients had peripheral joints involvement and 65% had hips involvement. Mean Pain-VAS was 65mm and mean Tirederness-VAS was 56mm. Mean BASDAI score was 45%, mean BASFI score 44,7% and mean BASG-s score 55%. The mean BASMI score was 4,76 and the mean BASRI score 4,43. Statistical analysis showed that presence of depression or anxious state was correlated best with BASG-s (p=0,00006), followed by BASFI (p=0,001). Depression and anxiety were significally higher in female (p=0,02) and in patients with active disease (BASDAI&gt;40%) (p=0,009). Depression or anxious status was correlated with Tiredness-VAS (p=0,004) and not with Pain-VAS (p=0,171). Psychological status was independent of disease duration (p=0,959), spine mobility (BASMI) (p=0,567) and of the severity of radiologic involvement (BASRI) (p=0,237). No correlation was seen with peripheral joints involvement nor with hips involvement (respectively p=0,914 and 0,660). <h3>Conclusions</h3> Frequency of depression and anxiety disorders in SA is high. Female gender, general well- being, disease activity and functional impairment are predicting factors. <h3>Disclosure of Interest</h3> None Declared
891 REAL WORD EXPERIENCE WITH TRIPLE THERAPY FOR HCV GT1 PATIENTS IN DIFFICULT TO TREAT PATIENTS: SEVERE ADVERSE EVENTS AND HIGH RATES OF VIROLOGICAL BREAK-THROUGH
Authors: J. Petersen, K. Matschenz, K. Olah, S. Unger, T. Lorenzen, F. Kuhlendahl, A. Plettenberg, A. Stoehr, H. Wolski, K. Voelker, C. Czaja-Harder, P. Buggisch
Journal: Journal of Hepatology (2013)
Reverse vaccinology 2.0: Human immunology instructs vaccine antigen design
Authors: Rino Rappuoli, Matthew J. Bottomley, Ugo D’Oro, Oretta Finco, Ennio De Gregorio
Journal: The Journal of Experimental Medicine (2016)

Traditionally, vaccines have been developed by cultivating infectious agents and isolating the inactivated whole pathogen or some of its purified components. 20 years ago, reverse vaccinology enabled vaccine discovery and design based on information deriving from the sequence of microbial genomes rather than via the growth of pathogens. Today, the high throughput discovery of protective human antibodies, sequencing of the B cell repertoire, and the increasing structural characterization of protective antigens and epitopes provide the molecular and mechanistic understanding to drive the discovery of novel vaccines that were previously impossible. We are entering a “reverse vaccinology 2.0” era.
Abstract 149: Antisense inhibition of microRNA-21 and -221 in tumor-initiating stem-like cells modulates biological functions of pancreatic cancer including tumorigenesis, metastasis, and chemoresistance
Authors: Ivan Ischenko, Peter Camaj, Karl-Walter Jauch, Christiane J. Bruns
Journal: Cancer Research (2011)

Abstract Introduction. Our preliminary studies identified a small population of pancreatic cancer cells with stem-like properties. These cells, called Side Population (SP) cells, were able to induce fast and aggressive tumor formation in nude mice. Cultured SP were able to differentiate into daughter SP or non-SP cells and were found to be highly chemoresistant. Furthermore, performed gene expression analysis showed a significant difference in the expression of more than 1300 genes in SP cells, among which the difference in microRNA expression between SP and non-SP cells was identified as the most interesting candidate for our further studies. Methods. Pancreatic cancer stem-like cells from highly metastatic cell line L3.6pl were identified and characterized by flow cytometry using Hoechst 33342 dye staining. The gene expression was assessed by Affymetrix and the results were further confirmed by quantitative RT-PCR. The antagomir transfection was performed using microRNA-21 and -221 oligonucleotide antisense. Tumor cell apoptosis, cell cycle progression, chemoresistance, and invasion were quantitated by propidium iodide staining and Boyden chamber assay, respectively. Results. In our study, some microRNAs, including miR-21, miR-221, miR-211, and miR-30c-2 were significantly upregulated in stem-like SP from L3.6pl cells. Interestingly, in these cells both miR-21 and miR-221 were involved in the modulation of expression of more than 200 genes, including RASSF6, RAB2B, TP63, TP53INP1, TP53INP2, TET1, MAPK10, MAP2K6, CDK6, TNFRSF11B, SOCS6, STK33, and SMAD7. The administration of antagomir-21 and -221 significantly reduced the SP fracture, decreased SP cell differentiation, positively affected L3.6pl cell proliferation, invasion, and chemoresistance against gemcitabine and 5-Fluorouracil. Conclusion. Our results demonstrate the significance of both microRNA-21 and -221 in tumor-initiating capability of stem-like tumor cells in pancreatic cancer. Both microRNAs contribute to the most important biological functions of pancreatic cancer including apoptosis, metastasis, and chemoresistance, and may further serve as a potential target for pancreatic cancer therapy. 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 149. doi:10.1158/1538-7445.AM2011-149
Primary Cutaneous Histoplasmosis
Authors: Robert B. Tesh, J. D. Schneidau
Journal: New England Journal of Medicine (1966)

THE criteria suggested by several investigators1 , 2 as necessary to establish a diagnosis of primary cutaneous infection with a fungus capable of causing pulmonary mycosis are as follows: history of traumatic inoculation, with subsequent development of a chancriform lesion within three or four weeks at the point of trauma; evidence that the wound was contaminated with the causative fungus; development of lymphangitis and regional lymphadenopathy; no history or clinical or laboratory evidence of previous pulmonary or systemic mycosis; and conversion of the skin test from negative to positive and rising serologic titer (where applicable). This sequence of events, which Wilson3 calls . . .
Successful endoscopic submucosal dissection for triple sporadic nonampullary duodenal adenomas using a “push and peel off” technique
Authors: J.-W. Yun, J.-J. Park, K. Kim, H. Noh, M.-J. Kwon, S.-Y. Lee, M. Joo, B. Lee, J. Kim, Y.-T. Bak
Journal: Endoscopy (2012)

Sporadic nonampullary duodenal adenoma (SNDA) is not easy to find in symptomless patients. SNDA has low incidence and usually occurs singly [1]. Resection of duodenal neoplasm by endoscopic submucosal dissection (ESD) has been increasingly reported [2]; however, resection of triple SNDAs has not been reported before, to our knowledge. Here we describe a case of successful ESD for triple SNDAs using a unique "push and peel off" technique, which is different from conventional methods.
Polycystic Liver and Kidney Disease
Authors: H L Fred, I Siddique
Journal: New England Journal of Medicine (1995)

Figure 1. Polycystic Liver and Kidney Disease.An asymptomatic 63-year-old man was found on routine physical examination to have palpable hepatic nodules and ballotable kidneys. Contrast-enhanced abdominal computed tomography showed many hepatic masses of various sizes (arrows, Panel A), whose measured density was consistent with that of water. Both kidneys (arrows, Panel B) also contained numerous cystic masses similar to those in the liver. The patient had microscopic hematuria and a serum creatinine concentration of 1.9 mg per deciliter (168 micromoles per liter). The results of other laboratory studies, including liver-function tests, were normal. The patient had no family history . . .
Amaurosis Fugax Caused by a Branch Retinal Artery Embolus
Authors: Ilias Georgalas, Chryssanthi Koutsandrea
Journal: New England Journal of Medicine (2015)

A 77-year-old man presented to the ophthalmology clinic reporting three episodes of blurred vision in his right eye, each lasting approximately 5 minutes, during the past hour. A dilated fundus examination revealed a visible motile embolus, shown in a video.
Hematologic Responses of Patients with Sickle Cell Disease to Treatment with Hydroxyurea
Authors: Griffin P. Rodgers, George J. Dover, Constance Tom Noguchi, Alan N. Schechter, Arthur W. Nienhuis
Journal: New England Journal of Medicine (1990)

Because fetal hemoglobin contains gammaglobin chains instead of beta chains, it is not affected by the genetic defect that causes sickle cell disease. Increased levels of fetal hemoglobin decrease the tendency toward intracellular polymerization of sickle hemoglobin that characterizes this disease. Hydroxyurea is one of several cytostatic agents that have been shown to increase the production of fetal hemoglobin in some patients with sickle cell disease. We studied the effects of hydroxyurea administration in 10 hospitalized patients with sickle cell disease, each of whom was treated for three months. Seven patients responded with a 2- to 10-fold increase in fetal hemoglobin, from a mean (+/- SD) of 1.6 +/- 1.6 percent of total hemoglobin to 6.8 +/- 4.7 percent; three patients had fetal-hemoglobin levels of 10 to 15 percent of total hemoglobin. Three did not respond to treatment. Four of the patients who responded were retreated with hydroxyurea after one to four months without treatment and were found to have larger increases in fetal-hemoglobin levels. In most patients, levels were still rising at the end of the study, even after 90 days of therapy. Fetal-hemoglobin levels tended to peak at dosages of hydroxyurea that were myelosuppressive. In the patients who responded to treatment, there were significant increases in the percentage of reticulocytes and erythrocytes containing fetal hemoglobin and in the amount of fetal hemoglobin within these cells. The percentage of dense red cells decreased in the patients who responded to treatment. The tendency toward intracellular polymerization at physiologic oxygen saturation was reduced by about 33 percent in the cells containing fetal hemoglobin, whereas there was no change in the other cells. We conclude that hydroxyurea is effective in increasing the production of fetal hemoglobin, which in this study was found to be associated with a small decrease in hemolysis and an increase in hemoglobin levels despite myelosuppression. Controlled, prospective trials are necessary to establish whether these effects will lead to clinical benefit.