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Sample records for ra patients transcripts

  1. THE IMMUNOLOGICAL CHARACTERISTIC OF RA PATIENTS WITH ANAEMIA

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    A. E. Sizikov

    2014-07-01

    Full Text Available Abstract. The aim of the investigation was to study the immunological characteristics of RA patients with anaemia. Clinical and laboratory data including the percentage of the main lymphocyte subclasses, phagocyte and DTH-effector activity, serum concentration of immunoglobulins, the percentage of cells producing IFNγ and/or IL-4 and percent of monocytes producing TNF. We revealed some significant clinical, laboratory and immunological differences between RA patients and healthy donors and between patients with and without anaemia. Our data demonstrate RA anemic patients to have more severe disorders than patients without anaemia. We also revealed some significant immunological differences between RA patients and healthy donors and between patients with and without anaemia, including percent of cells producing IFNγ and/or IL-4. Our data permit to conclude that RA patients have many different immunological disturbances, more severe in anaemic patients.

  2. Productivity loss due to absenteeism and presenteeism by different instruments in patients with RA and subjects without RA

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    Braakman-Jansen, Louise Marie Antoinette; Kuper, Ina H.; van de Laar, Mart A F J; Taal, Erik

    2012-01-01

    Objectives. To explore the impact of at-work productivity loss on the total productivity cost by different instruments in patients recently diagnosed with RA and controls without RA. Methods. Cross-sectional data were collected from outpatients with RA between December 2007 and February 2008. The

  3. Pulmonary cryptococcosis in rheumatoid arthritis (RA) patients: Comparison of imaging characteristics among RA, acquired immunodeficiency syndrome, and immunocompetent patients

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    Yanagawa, Noriyo, E-mail: noriyo_yana@ybb.ne.jp [Departments of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-8-22, Honkomagome, Bunkyo-ku, Tokyo 113-8677 (Japan); Sakai, Fumikazu [Department of Diagnostic Radiology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka-shi, Saitama 350-1298 (Japan); Takemura, Tamiko [Department of Pathology, Japanese Red Cross Medical Center, 4-1-22 Hiroo, Shibuya-ku, Tokyo 150-8935 (Japan); Ishikawa, Satoru [Department of Respiratory Medicine, National Hospital Organization Chiba-East-Hospital, 673 Nitona-cho, Chuo-ku, Chiba-shi, Chiba 260-8712 (Japan); Takaki, Yasunobu [Departments of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-8-22, Honkomagome, Bunkyo-ku, Tokyo 113-8677 (Japan); Hishima, Tsunekazu [Department of Pathology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-8-22, Honkomagome, Bunkyo-ku, Tokyo 113-8677 (Japan); Kamata, Noriko [Departments of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-8-22, Honkomagome, Bunkyo-ku, Tokyo 113-8677 (Japan)

    2013-11-01

    Purpose: The imaging characteristics of cryptococcosis in rheumatoid arthritis (RA) patients were analyzed by comparing them with those of acquired immunodeficiency syndrome (AIDS) and immunocompetent patients, and the imaging findings were correlated with pathological findings. Methods: Two radiologists retrospectively compared the computed tomographic (CT) findings of 35 episodes of pulmonary cryptococcosis in 31 patients with 3 kinds of underlying states (10 RA, 12 AIDS, 13 immunocompetent), focusing on the nature, number, and distribution of lesions. The pathological findings of 18 patients (8 RA, 2 AIDS, 8 immunocompetent) were analyzed by two pathologists, and then correlated with imaging findings. Results: The frequencies of consolidation and ground glass attenuation (GGA) were significantly higher, and the frequency of peripheral distribution was significantly lower in the RA group than in the immunocompetent group. Peripheral distribution was less common and generalized distribution was more frequent in the RA group than in the AIDS group. The pathological findings of the AIDS and immunocompetent groups reflected their immune status: There was lack of a granuloma reaction in the AIDS group, and a complete granuloma reaction in the immunocompetent group, while the findings of the RA group varied, including a complete granuloma reaction, a loose granuloma reaction and a hyper-immune reaction. Cases with the last two pathologic findings were symptomatic and showed generalized or central distribution on CT. Conclusion: Cryptococcosis in the RA group showed characteristic radiological and pathological findings compared with the other 2 groups.

  4. Productivity loss due to absenteeism and presenteeism by different instruments in patients with RA and subjects without RA.

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    Braakman-Jansen, Louise M A; Taal, Erik; Kuper, Ina H; van de Laar, Mart A F J

    2012-02-01

    To explore the impact of at-work productivity loss on the total productivity cost by different instruments in patients recently diagnosed with RA and controls without RA. Cross-sectional data were collected from outpatients with RA between December 2007 and February 2008. The control group was formed by subjects without RA matched on age and gender. Absenteeism and presenteeism were estimated by the Quantity and Quality (QQ) Questionnaire, Work Productivity and Activity Impairment Questionnaire General Health V2.0 (WPAI-GH) and Health and Labor Questionnaire (HLQ) questionnaires. Differences between groups were tested by Mann-Whitney U-test. Costs were valued by the human capital approach. Data were available from 62 patients with a paid job and 61 controls. QQ- and WPAI-GH scores of presenteeism were moderately correlated (r = 0.61) while the HLQ presenteeism score correlated poorly with the other instruments (r = 0.34). The contribution of presenteeism on total productivity costs was estimated at ∼70% in the RA group. The mean costs per person per week due to presenteeism varied between €79 and €318 per week in the RA group, dependent on the instrument used. The costs due to presenteeism were about two to four times higher in the RA group compared with the control group. This study indicates that the impact of presenteeism on the total productivity costs in patients with RA is high. However, work productivity in individuals without RA was not optimal either, which implies a risk of overestimation of cost when a normal score is not taken into account. Finally, different presenteeism instruments lead to different results.

  5. Transcriptional regulation of Tal2 gene by all-trans retinoic acid (atRA) in P19 cells.

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    Kobayashi, Takanobu; Suzuki, Masayo; Morikawa, Masayuki; Kino, Katsuhito; Tanuma, Sei-ichi; Miyazawa, Hiroshi

    2015-01-01

    TAL2 is a transcription factor required in the normal development of mouse brain. In a previous study, we demonstrated that the expression of Tal2 gene is induced by the complex of all-trans retinoic acid (atRA) and retinoic acid receptor α (RARα) in mouse embryonal carcinoma P19 cells. atRA is also known to be important in inducing P19 cells to differentiate into the neural lineage. Therefore, we believe that the function of TAL2 in neural differentiation may be clarified by utilizing P19 cells. As the atRA-RARα complex induced the expression of Tal2, we focused on the regulatory region that is involved in its transcription. The atRA-RARα complex occupies a characteristic retinoic acid response element (RARE) located in the promoter of target genes. Therefore, we searched for RARE on the mouse Tal2 and found that a RARE-like element was located in the intron. We also found that a TATA-box-like element was located in the 5'-region of Tal2. Involvement between transcriptional activity and the TATA-box-like element was confirmed in the luciferase assay, and TATA-box binding protein was bound to this element upstream of Tal2 in P19 cells. atRA signaling activated the transcription through the RARE-like element, and RARα was bound to this element on Tal2 in P19 cells. In addition, the interaction between these elements on Tal2 was shown in the chromatin immunoprecipitation assay. These results suggest that the transcription of Tal2 is coordinately mediated by two distal regulatory elements.

  6. Energy efficient LoRa GPS tracker for dementia patients.

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    Hadwen, Tim; Smallbon, Vanessa; Qing Zhang; D'Souza, Matthew

    2017-07-01

    Continuous GPS tracking devices always suffer short battery life when used by caregivers to reduce the risk of wandering to dangerous areas by dementia patients. Currently the best existing tracker for dementia patients on the market only supports less than 10 hours battery life with a gigantic battery. It not only requires daily battery charging from patients/caregivers, but also becomes a very restrictive device. In this paper we inspected individual energy consumption of the components in a GPS tracker and proposed a novel energy efficient, small wristband by integrating the latest LoRa communication and GPS duty cycling technologies. We verify our prototype's communication distance and energy efficiency through extensive experiments in the real world. Our model and data show the GPS wristband is able to support up to 40 hours continuous GPS tracking with a frequent 60 seconds location update rate. Its range also spans 3km, effectively monitoring patient locations.

  7. Radiation exposure of relatives of patients treated with Ra-223 dichloride; Strahlenexposition von Angehoerigen bei Therapie mit Ra-223-Dichlorid

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    Wanke, C.; Szermerski, B.; Solle, A.; Geworski, L. [Medizinische Hochschule Hannover (Germany). Stabsstelle Strahlenschutz und Abt. Medizinische Physik; Pinkert, J. [Bayer Vital GmbH, Leverkusen (Germany); Kranert, W.T. [Frankfurt Univ. (Germany). Klinik fuer Nuklearmedizin; Andreeff, M. [Universitaetsklinikum ' ' Carl Gustav Carus' ' TU Dresden (Germany). Klinik fuer Nuklearmedizin

    2015-07-01

    Since November 2013, a radiopharmaceutical containing Ra-223 dichloride as active substance is approved in the European Union for patients with castration resistant prostate cancer with symptomatic bone metastases and no known visceral metastases. Ra-223 (T{sub 1/2} = 11.43 d) decays via a chain of 4 alpha and 2 beta decays. This therapy is presently the only application of an alpha emitter in clinical routine therapy. To show that the exposure of relatives and caregivers of patients treated with Ra-223 dichloride in an outpatient setting does not exceed a value of 1 mSv, the multicenter study ''RAPSODY'' was conducted. As Ra-223 and most of its progeny emit alpha particles, the internal exposure had to be evaluated in particular. Within this study, measurements of the radiation emitted from the patient were performed using standard dose-rate meters. Wipe-tests were taken in the patients' homes to identify significant contaminations and evaluated by liquid scintillation counting. Samples of saliva and sweat were taken and measured using gamma spectrometry. Ra-223 disintegrates to the noble gas Rn-219 and was measured in the exhaled breath from the patients using conventional Radon Monitors. Furthermore, a computational fluid dynamics simulation (CFD) was performed to assess the radioactivity in the air, which could be inhaled by persons close to the patient. Conclusions: The potential exposure of relatives and caregivers by external irradiation and incorporation of radioactivity exhaled or excreted by the patient with saliva or sweat is well below 1 mSv. No objections are seen regarding outpatient treatment. This paper summarizes contents of a poster presented at the Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging.

  8. [Risk factors for osteoporotic fractures of spine in RA patients].

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    Sun, Yu; Liu, Qiming; Zhao, Qinghua; Zhang, Jian; Li, Feng; Zhang, Ke

    2015-09-15

    To investigate the risk factors of osteoporotic fractures (OPF) in patients with RA. From February 2011 to March 2015, 244 patients with rheumatoid arthritis (RA) were treated in Department of Orthopedics, Huaibei People's Hospital, according to the occurrence of osteoporotic fractures (OPF) into the OPF group (n=31) and the non OPF group (n=213), observed two groups general information, glucocorticoid usinge, -28 joint disease activity score (DAS28), health status Questionnaire (HAQ), C-reactive protein (CRP), anti-cyclic citrullinated peptide (CCP) antibody, erythrocyte sedimentation rate (ESR), etc. OPF group the mean age and disease duration for (64.3±10.9) years and (9.0±3.3) years were significantly higher than that of non OPF group (57.4±11.2) years and (6.0±2.7) years (POPF group and non OPF group ESR, CRP, anti CCP, HAQ and DAS28 difference was not statistically significant (P>0.05); OPF group sharp score (56.0±18.4), hormone use time (785 d), and hormone cumulant (7,100 mg·d) were significantly higher than that in non OPF group [sharp score (86.1±17.1), hormone use time (191 d), and hormone cumulant (1,900 mg·d)], the difference was statistically significant (POPF femoral neck, Ward area, total femur area and thoracic spine 2-3 bone mineral density T value significantly lower than non OPF group (P<0.05). Age and osteoporosis are risk factors for the occurrence of osteoporotic fractures in patients with rheumatoid arthritis, so patients should conduct a risk assessment to guide rational drug use.

  9. Drugs or disease: evaluating salivary function in RA patients

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    Sandra Regina TORRES

    Full Text Available Abstract Oral complications of RA may include temporomandibular joint disorders, mucosa alterations and symptoms of dry mouth. The aim of this study was to evaluate the salivary gland function of subjects with rheumatoid arthritis (RA comparing it to healthy controls. Subjects with other systemic conditions known to affect salivary functions were excluded. A questionnaire was applied for the evaluation of xerostomia. Resting and chewing-stimulated salivary flow rates (SFR were obtained under standard conditions. There were 145 subjects included of the study (104 RA and 38 controls. About 66.7% of the RA subjects and 2.4% in control group presented xerostomia. The median resting SFR were 0.24 ml/min for RA subjects and 0.40 mL/min for controls (p = 0.04. The median stimulated SFR were 1.31 mL/min for RA subjects and 1.52 ml/min for controls (p = 0.33. No significant differences were found between resting and stimulated SFR of RA subjects not using xerogenic medications and controls. There was significantly higher number of subjects presenting hyposalivation in the RA group than among controls, even when subjects using xerogenic medications were eliminated from the analysis. In conclusion, hyposalivation and xerostomia were more frequent among RA subjects not using xerogenic medication than among controls, although there were no significant differences in the median SFR between groups.

  10. Follow-up study of late effects in /sup 224/Ra treated ankylosing spondylitis patients

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    Wick, R.R.; Goessner, W.

    1983-01-01

    Fifteen hundred thirty-one patients treated with /sup 224/Ra from 14 hospitals in the F.R.G. and 267 control patients with ankylosing spondylitis not treated with any form of ionizing radiation are being followed. Since 1970 three cases of malignant tumour in the skeleton have been found among /sup 224/Ra-treated patients with skeletal doses below 90 rad compared with 0.4-0.6 expected. Two of these three cases were tumours of the bone marrow. An effect of /sup 224/Ra on the haematopoietic system cannot be excluded. Also, seven cases of cataract were found among 274 /sup 224/Ra patients. The mean time since /sup 224/Ra treatment was 26 yr. The mean age at diagnosis was 66 yr. The cataract incidence was not unusual for people of this age.

  11. Specificities of anti-neutrophil autoantibodies in patients with rheumatoid arthritis (RA)

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    Brimnes, J; Halberg, P; Jacobsen, Søren

    1997-01-01

    The objective of this study was to characterize antigens recognized by neutrophil-specific autoantibodies from patients with RA. Sera from 62 RA patients were screened by indirect immunofluorescence (IIF). Positive sera were further tested by ELISAs for antibodies against various granule proteins......D from nuclei. In conclusion, anti-neutrophil autoantibodies from RA patients recognize different antigens in the cytoplasm and in the nucleus. Lactoferrin is one of the common antigens recognized, but also unknown nuclear antigens of 25-35 kD mol. wt are involved....

  12. Assessing Medication Adherence in Patients with Rheumatoid Arthritis (RA)

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    2017-03-24

    the moat useful method Jn the dnlcal aetting The Morisky Medle1tion Adherence Scale ( MMAS ) waa developed to UHH medlcebon adherence Intent 1nd hll...been v1Ud11ed in sever.I common dl1HM but not In RA There ue several v1ri1tion1 of the MMAS but we used the MMA $a8 which hll eight qu11tion1 The...than 1 minute 1IO oomplei. lh• MMAS -3 OBJECTIVES The p.n.m1ry cbjec:trve i i to dtt1rm1ne tf there 11 a conellt>on between the COR Uil, COR5, and

  13. Polymorphism analysis of IL17RA gene to the IL17RA concentration and chronicity differences in nefritis lupus NL patients

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    Mahrus Ismail

    2014-12-01

    Full Text Available Nefritis lupus (NL is autoimmune disease and one of serious complication from Systemic Eritematosus Lupus (LES. Clinical manifestation of NL was variated, there are hematuria microscopic asymptomatic until renal failure. In addition of clinical manifestation, the NL disorder degree also measured from histopathological grade. Although, the mechanism that mixed up with pathogenesis of NL was known, however the cytokine also play a role to the disease process. The cytokine that assumpted have a role to the inflammation is IL-17RA, the increase production of IL-17RA influenced to the in-flammation and NL chronicity degree. The aim of this study to analyzed the relationship between polymorphism of IL-17RA gene, blood IL-17RA con-centration with the NL disorder degree. These studies were used cross sectional with control case design. The sample were used 40 patients consist NL pa-tients and Lupus patient without nephritis as a control. The polymorphisms of IL-17RA gene were investigated by using PCR method and gene sequence analysis. The alterations of allele frequency of IL-17RA gene were analyzed by bioinformatics method. The bloods IL-17RA concentration were in-vestigated by ELISA method. The NL chronicity degrees were investigated by NL histopathological grade. The hypothesis were proofed by data normality test and homogeneity test, Chi-square and Odds ratio, Spearman correlation by using SPSS 17.0 for windows. The result of showed that there are sig-nificantly different between IL-17RA gene mutant genotype frequency of NL patient (NL with the control patient with value OR 8.48. There are sig-nificantly different between G allele of IL-17RA gene of NL patient (case with the control patient with the value OR 4.17. There are no significantly di-fferent between IL-17RA concentrations of NL patient (case with the different chronicity value. There are positive correlation with the OR value 4.17 bet-ween IL-17RA concentrations with the chronicity value

  14. Long-term clinical investigation of patients with ankylosing spondylitis treated with /sup 224/Ra

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    Schmitt, E. (Universitatsklinik Friedrichsheim, Frankfurt, West Germany); Ruckbeil, C.; Wick, R.R.

    1983-01-01

    Between 1952 and 1980 about 250 patients with ankylosing spondylitis were treated with /sup 224/Ra at the Orthopaedic University Hospital of Frankfurt/M. In 1970, 119 of them were examined and X-rayed as was another group of 40 patients in 1980. The results of those examined could be compared with a group of 40 patients treated without /sup 224/Ra. Patients with /sup 224/Ra demonstrated a long-lasting period of subjective improvement after the treatment, with reduced consumption of antirheumatoid and analgesic drugs, on the average. Blood examinations show inflammatory activities. Nevertheless, the ankylosing spondylitis proceeded. In the final stages of the disease, neither the clinical aspects nor the X-rays showed any specific changes. We observed no case of malignant bone tumor. Of the 169 examined patients, 22 had a total of 32 children after the treatment with /sup 224/Ra. Among these was a set of twins with cerebral palsy and diabetes insipidus renalis. In conclusion, /sup 224/Ra in ankylosing spondylitis is a recommended treatment without higher risk compared to the common therapy with drugs.

  15. Rheumatologists' knowledge, attitude and current management of fatigue in patients with rheumatoid arthritis (RA).

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    Repping-Wuts, H.; Riel, P.L.C.M. van; Achterberg, T. van

    2008-01-01

    To describe rheumatologists' knowledge, attitude and current management of fatigue in patients with rheumatoid arthritis (RA), a postal questionnaire was sent to all rheumatologists (N = 204) and trainees (N = 49), members of the Dutch Society of Rheumatology. The overall response rate was 44% (N =

  16. TGF-beta/atRA-induced Tregs express a selected set of microRNAs involved in the repression of transcripts related to Th17 differentiation.

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    Schiavinato, Josiane Lilian Dos Santos; Haddad, Rodrigo; Saldanha-Araujo, Felipe; Baiochi, João; Araujo, Amélia Goes; Santos Scheucher, Priscila; Covas, Dimas Tadeu; Zago, Marco Antonio; Panepucci, Rodrigo Alexandre

    2017-06-15

    Regulatory T cells (Tregs) are essential regulators of immune tolerance. atRA and TGF-β can inhibit the polarization of naïve T cells into inflammatory Th17 cells, favoring the generation of stable iTregs, however the regulatory mechanisms involved are not fully understood. In this context, the roles of individual microRNAs in Tregs are largely unexplored. Naïve T cells were immunomagnetically isolated from umbilical cord blood and activated with anti-human CD2/CD3/CD28 beads in the presence of IL-2 alone (CD4Med) or with the addition of TGF-β and atRA (CD4TGF/atRA). As compared to CD4Med, the CD4TGF/atRA condition allowed the generation of highly suppressive CD4(+)CD25(hi)CD127(-)FOXP3(hi) iTregs. Microarray profiling allowed the identification of a set of microRNAs that are exclusively expressed upon TGF-β/atRA treatment and that are predicted to target a set of transcripts concordantly downregulated. This set of predicted targets were enriched for central components of IL-6/JAK/STAT and AKT-mTOR signaling, whose inhibition is known to play important roles in the generation and function of regulatory lymphocytes. Finally, we show that mimics of exclusively expressed miRs (namely miR-1299 and miR-30a-5p) can reduce the levels of its target transcripts, IL6R and IL6ST (GP130), and increase the percentage of FoxP3(+) cells among CD4(+)CD25(+/hi) cells.

  17. Stages of change, barriers, benefits, and preferences for exercise in RA patients: a cross-sectional study.

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    Henchoz, Y; Zufferey, P; So, A

    2013-01-01

    To determine the distribution of exercise stages of change in a rheumatoid arthritis (RA) cohort, and to examine patients' perceptions of exercise benefits, barriers, and their preferences for exercise. One hundred and twenty RA patients who attended the Rheumatology Unit of a University Hospital were asked to participate in the study. Those who agreed were administered a questionnaire to determine their exercise stage of change, their perceived benefits and barriers to exercise, and their preferences for various features of exercise. Eighty-nine (74%) patients were finally included in the analyses. Their mean age was 58.4 years, mean RA duration 10.1 years, and mean disease activity score 2.8. The distribution of exercise stages of change was as follows: precontemplation (n = 30, 34%), contemplation (n = 11, 13%), preparation (n = 5, 6%), action (n = 2, 2%), and maintenance (n = 39, 45%). Compared to patients in the maintenance stage of change, precontemplators exhibited different demographic and functional characteristics and reported less exercise benefits and more barriers to exercise. Most participants preferred exercising alone (40%), at home (29%), at a moderate intensity (64%), with advice provided by a rheumatologist (34%) or a specialist in exercise and RA (34%). Walking was by far the preferred type of exercise, in both the summer (86%) and the winter (51%). Our cohort of patients with RA was essentially distributed across the precontemplation and maintenance exercise stages of change. These subgroups of patients exhibit psychological and functional differences that make their needs different in terms of exercise counselling.

  18. Transcriptional Profiling Mycobacterium tuberculosis from Patient Sputa.

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    Wildner, Leticia Muraro; Gould, Katherine A; Waddell, Simon J

    2018-01-01

    The emergence of drug resistance threatens to destroy tuberculosis control programs worldwide, with resistance to all first-line drugs and most second-line drugs detected. Drug tolerance (or phenotypic drug resistance) is also likely to be clinically relevant over the 6-month long standard treatment for drug-sensitive tuberculosis. Transcriptional profiling the response of Mycobacterium tuberculosis to antimicrobial drugs offers a novel interpretation of drug efficacy and mycobacterial drug-susceptibility that likely varies in dynamic microenvironments, such as the lung. This chapter describes the noninvasive sampling of tuberculous sputa and techniques for mRNA profiling M. tb bacilli during patient therapy to characterize real-world drug actions.

  19. Specificities of anti-neutrophil autoantibodies in patients with rheumatoid arthritis (RA)

    DEFF Research Database (Denmark)

    Brimnes, J; Halberg, P; Jacobsen, Søren

    1997-01-01

    neutrophils showed IgG reactions at 25-35 kD, in the 55-kD region, at 80 kD, and at 110 kD. Most sera reacted with more than one band. Except for the 55-kD antigen, none of the antigens appeared in lymphocytes. The most notable reactivity in subcellular fractions was with lactoferrin and with bands of 25-35 k......D from nuclei. In conclusion, anti-neutrophil autoantibodies from RA patients recognize different antigens in the cytoplasm and in the nucleus. Lactoferrin is one of the common antigens recognized, but also unknown nuclear antigens of 25-35 kD mol. wt are involved....

  20. Early vascular alterations in SLE and RA patients--a step towards understanding the associated cardiovascular risk.

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    Maria José Santos

    Full Text Available Accelerated atherosclerosis represents a major problem in both systemic lupus erythematosus (SLE and rheumatoid arthritis (RA patients, and endothelial damage is a key feature of atherogenesis. We aimed to assess early endothelial changes in SLE and RA female patients (127 SLE and 107 RA without previous CV events. Biomarkers of endothelial cell activation (intercellular adhesion molecule-1 (sICAM-1, vascular cell adhesion molecule-1 (sVCAM-1, thrombomodulin (TM, and tissue factor (TF were measured and endothelial function was assessed using peripheral artery tonometry. Reactive hyperemia index (RHI, an indicator of microvascular reactivity, and augmentation index (AIx, a measure of arterial stiffness, were obtained. In addition, traditional CV risk factors, disease activity and medication were determined. Women with SLE displayed higher sICAM-1 and TM and lower TF levels than women with RA (p = 0.001, p<0.001 and p<0.001, respectively. These differences remained significant after controlling for CV risk factors and medication. Serum levels of vascular biomarkers were increased in active disease and a moderate correlation was observed between sVCAM-1 levels and lupus disease activity (rho = 0.246 and between TF levels and RA disease activity (rho = 0.301. Although RHI was similar across the groups, AIx was higher in lupus as compared to RA (p = 0.04. Also in active SLE, a trend towards poorer vasodilation was observed (p = 0.06. In conclusion, women with SLE and RA present with distinct patterns of endothelial cell activation biomarkers not explained by differences in traditional CV risk factors. Early vascular alterations are more pronounced in SLE which is in line with the higher CV risk of these patients.

  1. Treatment with dexamethasone and monophosphoryl lipid A removes disease-associated transcriptional signatures in monocyte-derived dendritic cells from rheumatoid arthritis patients and confers tolerogenic features

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    Paulina Andrea García-González

    2016-10-01

    Full Text Available Tolerogenic dendritic cells (TolDCs are promising tools for therapy of autoimmune diseases such as rheumatoid arthritis (RA. Here we characterise monocyte-derived TolDCs from RA patients modulated with dexamethasone and activated with monophosphoryl lipid A (MPLA, referred to as MPLA-tDCs, in terms of gene expression, phenotype, cytokine profile, migratory properties and T cell-stimulatory capacity, in order to explore their suitability for cellular therapy. MPLA-tDCs derived from RA patients displayed an anti-inflammatory profile with reduced expression of costimulatory molecules and high IL-10/IL-12 ratio, but were capable of migrating towards the lymphoid chemokines CXCL12 and CCL19. These MPLA-tDCs induced hyporesponsiveness of autologous CD4+ T cells specific for synovial antigens in vitro. Global transcriptome analysis confirmed a unique transcriptional profile of MPLA-tDCs and revealed that RA-associated genes, which were upregulated in untreated DCs from RA patients, returned to expression levels of healthy donor-derived DCs after treatment with dexamethasone and MPLA. Thus, monocyte-derived DCs from RA patients have the capacity to develop tolerogenic features at transcriptional as well as at translational level, when modulated with dexamethasone and MPLA, overcoming disease-related effects. Furthermore, the ability of MPLA-tDCs to impair T cell responses to synovial antigens validates their potential as cellular treatment for RA.

  2. A Mutation in IL4RA Is Associated with the Degree of Pathology in Human TB Patients.

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    Hölscher, Christoph; Heitmann, Lisa; Owusu-Dabo, Ellis; Horstmann, Rolf D; Meyer, Christian G; Ehlers, Stefan; Thye, Thorsten

    2016-01-01

    The contribution of interleukin- (IL-) 4 receptor-alpha- (Rα-) dependent events in the pathogenesis of tuberculosis (TB) is controversial. We have recently shown IL-13 overexpression in mice to cause recrudescent Mtb replication and centrally necrotizing granulomas strongly resembling pathology of human TB. A deletion of IL-4Rα completely abrogates TB tissue pathology in these mice. To validate our results in human TB patients, we here determined the association of distinct variants of the IL4, IL13, IL4RA, IL13RA1, and IL13RA2 genes with cavity formation in a large Ghanaian cohort of HIV-negative individuals with newly diagnosed pulmonary TB. In fact, the structural variant of the IL4RA I50V, previously shown to result in enhanced signal transduction, was significantly associated with greater cavity size, and a variant of IL13RA2 was associated with disease in females. To evaluate whether the human-like TB pathology in IL-13-overexpressing mice is specifically mediated through the IL-4Rα subunit, we analyzed IL-13 transgenic mice with a genetic ablation of the IL-4Rα. In these mice, the IL-13-mediated increased susceptibility, human-like pathology of collagen deposition around centrally necrotizing granulomas, and alternative macrophage activation were abolished. Together, our genetic association study in human TB patients further supports the assumption that IL-13/IL-4Rα-dependent mechanisms are involved in mediating tissue pathology of human TB.

  3. Efficacy benefit of an NK1 receptor antagonist (NK1RA) in patients receiving carboplatin: supportive evidence with NEPA (a fixed combination of the NK1 RA, netupitant, and palonosetron) and aprepitant regimens.

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    Jordan, Karin; Gralla, Richard; Rizzi, Giada; Kashef, Kimia

    2016-11-01

    Antiemetic guideline recommendations are inconsistent as to whether a neurokinin-1 receptor antagonist (NK1 RA) should be administered with a 5-hydroxytryptamine-3 (5HT3) RA + dexamethasone (DEX) in patients receiving carboplatin. Patients receiving cisplatin routinely receive an NK1 RA-containing regimen with a resulting 14-22 % benefit in no emesis rates over a 5-HT3 RA/DEX control. Recent studies suggest a similar benefit in patients receiving carboplatin. NEPA is the first fixed antiemetic combination agent and comprises the highly selective NK1 RA, netupitant, and pharmacologically distinct 5-HT3 RA, palonosetron (PALO). This paper presents the efficacy of NEPA in the subset of patients receiving carboplatin in a phase 3 trial (NCT01376297), in the context of aprepitant (APR) data in the carboplatin setting. One hundred ninety-six patients (47 % of all study patients: n = 145 NEPA + DEX; n = 51 APR + PALO + DEX) received carboplatin in a multinational, double-blind, randomized phase 3 study. Complete response (CR: no emesis/rescue) and no significant nausea (NSN: score ≤25 on 100 mm visual analog scale) rates were calculated. Cycle 1-4 overall (0-120 h) CR rates were similar for NEPA (80, 91, 92, and 93 %) and APR (82, 88, 88, and 90 %). Overall NSN rates were also similar (NEPA 84-96 %; APR 82-90 %). Response rates for NEPA and APR regimens were similar and consistent with prior studies evaluating the contribution of adding NK1 RAs in patients receiving carboplatin. Considering such evidence, guideline groups/practitioners should consider giving a NK1 RA antiemetic triplet in patients receiving carboplatin.

  4. Ottawa Panel Evidence-Based Clinical Practice Guidelines for Patient Education in the Management of Rheumatoid Arthritis (RA)

    Science.gov (United States)

    Brosseau, Lucie; Wells, George A.; Tugwell, Peter; Egan, Mary; Dubouloz, Claire-Jehanne; Welch, Vivian A.; Trafford, Laura; Sredic, Danjiel; Pohran, Kathryn; Smoljanic, Jovana; Vukosavljevic, Ivan; De Angelis, Gino; Loew, Laurianne; McEwan, Jessica; Bell, Mary; Finestone, Hillel M.; Lineker, Sydney; King, Judy; Jelly, Wilma; Casimiro, Lynn; Haines-Wangda, Angela; Russell-Doreleyers, Marion; Laferriere, Lucie; Lambert, Kim

    2012-01-01

    Background and purpose: The objective of this article is to create guidelines for education interventions in the management of patients ([greater than] 18 years old) with rheumatoid arthritis (RA). Methods: The Ottawa Methods Group identified and synthesized evidence from comparative controlled trials using Cochrane Collaboration methods. The…

  5. Value of body mass index in the diagnosis of obesity according to DEXA in well-controlled RA patients.

    Science.gov (United States)

    Tello-Winniczuk, Nina; Vega-Morales, David; García-Hernandez, Pedro A; Esquivel-Valerio, Jorge A; Garza-Elizondo, Mario A; Arana-Guajardo, Ana C

    Rheumatoid arthritis (RA) has an indirect effect on body composition. Body mass index (BMI) is not a valid predictor of body fat in RA patients. To evaluate the accuracy of BMI in identifying obesity diagnosed according to dual energy X-ray absorptiometry (DXA) in well-controlled RA patients. An observational, cross-sectional, descriptive, analytical study. We used 3 different cutoffs for obesity as determined by DXA: >35% total fat, >40% total fat, and >35% central fat mass (central obesity). One hundred one patients were included. We found that 35% total fat corresponded to a BMI of 24kg/m2, with a sensitivity of 90% and specificity of 75% (area under the curve [AUC] 0.917); 40% total fat to a BMI of 25kg/m2, with a sensitivity of 86% and specificity of 39% (AUC 0.822); and 35% central fat mass to a BMI of 22kg/m2, with a sensitivity of 97% and specificity of 84% (AUC 0.951). Obesity according to DXA was underdiagnosed when the classic BMI cutoffs were used in well-controlled RA patients. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  6. A novel method predicting clinical response using only background clinical data in RA patients before treatment with infliximab.

    Science.gov (United States)

    Miyoshi, Fumihiko; Honne, Kyoko; Minota, Seiji; Okada, Masato; Ogawa, Noriyoshi; Mimura, Toshihide

    2016-11-01

    The aim of the present study was to generate a novel method for predicting the clinical response to infliximab (IFX), using a machine-learning algorithm with only clinical data obtained before the treatment in rheumatoid arthritis (RA) patients. We obtained 32 variables out of the clinical data on the patients from two independent hospitals. Next, we selected both clinical parameters and machine-learning algorithms and decided the candidates of prediction method. These candidates were verified by clinical variables on different patients from two other hospitals. Finally, we decided the prediction method to achieve the highest score. The combination of multilayer perceptron algorithm (neural network) and nine clinical parameters shows the best accuracy performance. This method could predict the good or moderate response to IFX with 92% accuracy. The sensitivity of this method was 96.7%, while the specificity was 75%. We have developed a novel method for predicting the clinical response using only background clinical data in RA patients before treatment with IFX. Our method for predicting the response to IFX in RA patients may have advantages over the other previous methods in several points including easy usability, cost-effectiveness and accuracy.

  7. Association of IL-1ra and adiponectin with C-peptide and remission in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Pfleger, C.; Hansen, L.; Herder, C.

    2008-01-01

    with recent-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: Serum was obtained from 256 newly diagnosed patients (122 males and 134 females, median age 9.6 years). Stimulated C-peptide, blood glucose, and A1C were determined in addition to circulating concentration of cytokines at 1, 6, and 12 months...... after diagnosis. Analyses were adjusted for sex, age, and BMI percentile. RESULTS: Anti-inflammatory IL-1ra was positively associated with C-peptide after 6 (P = 0.0009) and 12 (P = 0.009) months. The beneficial association of IL-1ra on beta-cell function was complemented by the negative association...... of IL-1 beta with C-peptide after 1 month (P = 0.009). In contrast, anti-inflammatory adiponectin was elevated in patients with poor metabolic control after 6 and 12 months (P

  8. Discontinuation of infliximab after attaining low disease activity in patients with rheumatoid arthritis: RRR (remission induction by Remicade in RA) study.

    Science.gov (United States)

    Tanaka, Y; Takeuchi, T; Mimori, T; Saito, K; Nawata, M; Kameda, H; Nojima, T; Miyasaka, N; Koike, T

    2010-07-01

    Tumour necrosis factor (TNF) inhibitors enable tight control of disease activity in patients with rheumatoid arthritis (RA). Discontinuation of TNF inhibitors after acquisition of low disease activity (LDA) is important for safety and economic reasons. To determine whether infliximab might be discontinued after achievement of LDA in patients with RA and to evaluate progression of articular destruction during the discontinuation. 114 patients with RA who had received infliximab treatment, and whose Disease Activity Score, including a 28-joint count (DAS28) was 24 weeks by infliximab treatment, the drug was discontinued and DAS28 in 102 patients was evaluated at year 1. Fifty-six patients (55%) continued to have DAS28Remicade in RA (RRR) failed: disease in 29 patients flared within 1 year and DAS28 was >3.2 at year 1 in 17 patients. Yearly progression of mTSS (DeltaTSS) remained 1 year without progression of radiological articular destruction.

  9. The performance of matrices in daily clinical practice to predict rapid radiologic progression in patients with early RA.

    Science.gov (United States)

    De Cock, D; Vanderschueren, G; Meyfroidt, S; Joly, J; Van der Elst, K; Westhovens, R; Verschueren, P

    2014-04-01

    To compare in daily clinical practice the reliability of matrices that forecast rapid radiologic progression (RRP) at year one, at year two, and over 2 years in patients with early rheumatoid arthritis (RA). Overall, 74 early RA patients with X-rays of hands and feet at baseline, year one, and year two were included. Initial DMARD combination therapy with steroids (ICTS) or DMARD monotherapy (IMT) was initiated according to patients' RA severity, based on rheumatologist opinion. The images were scored via the modified Sharp/van der Heijde (SvH) method. A total Sharp score progression of equal or higher than five per year was considered RRP. Six matrices were tested: ASPIRE CRP/ESR matrices, the BEST matrix, two SWEFOT matrices, and the ESPOIR matrix. Patients were placed in each of them yielding a RRP probability. The performance was tested by Area Under the Curve analysis reflecting the predictive value. Four patients developed RRP in year one, five in year two, and four over 2 years. With regard to face validity, the predicted probability did not correspond to the risk in reality: the one ICTS patient who developed RRP over 2 years was always found in the lowest RRP categories of all matrices. The ASPIRE CRP matrix yielded at least a moderate predicting value for the three time points. The other matrices showed moderate to no predicting value. The performance of all matrices was disappointing and it is impossible to fully rely on the existing matrices in daily clinical practice. © 2013 Published by Elsevier Inc.

  10. Large country differences in work outcomes in patients with RA - an analysis in the multinational study COMORA.

    Science.gov (United States)

    van der Zee-Neuen, Antje; Putrik, Polina; Ramiro, Sofia; Keszei, Andras P; Hmamouchi, Ihsane; Dougados, Maxime; Boonen, Annelies

    2017-09-29

    We aimed to explore whether country of residence or specific country characteristics are associated with work outcomes in rheumatoid arthritis (RA). Data from the 17 countries participating in the Comorbidities in RA (COMORA) study were used. Work outcomes were measured by the Work Productivity and Activity Impairment Questionnaire, addressing employment (yes/no), absenteeism (percentage of time; 3 categories) and presenteeism (percentage of at-work productivity restrictions; 4 categories). Contribution of country of residence, gross domestic product (GDP), Human Development Index (HDI), unemployment rate, social protection expenditures (SPE) or world region to work outcomes was investigated in adjusted (ordered) logistic regressions. The patients (n = 2395) were younger than 60 years; mean age 48 (SD 9.2) years, 1972 (84%) female and 1065 (45%) employed. Large country differences were found. Taking the country with the best work outcome as reference, Moroccan patients had the lowest odds of being employed (OR 0.2 (95% CI 0.1; 0.3) vs. Germany) and highest odds of absenteeism (OR 13.2 (3.6; 48.3) vs. Japan). Patients in Taiwan had the highest odds of presenteeism (OR 13.0 (5.5; 30.9) vs. Venezuela). All country indices except SPE were associated with work outcomes. For example, patients in low-GDP countries had lower odds of employment (OR 0.6 (0.5; 0.8)), higher odds of absenteeism (OR 2.8 (2.0; 4.1)), but lower odds of presenteeism (OR 0.5 (0.4; 0.7)) compared to higher-GDP countries. Substantial differences in work outcomes among patients with RA were observed between countries. Lower economic wealth and human development of countries were associated with worse employment and higher absenteeism, but lower presenteeism.

  11. Reduced FOXP3(+) regulatory T cells in patients with primary sclerosing cholangitis are associated with IL2RA gene polymorphisms.

    Science.gov (United States)

    Sebode, Marcial; Peiseler, Moritz; Franke, Björn; Schwinge, Dorothee; Schoknecht, Tanja; Wortmann, Frederike; Quaas, Alexander; Petersen, Britt-Sabina; Ellinghaus, Eva; Baron, Udo; Olek, Sven; Wiegard, Christiane; Weiler-Normann, Christina; Lohse, Ansgar W; Herkel, Johannes; Schramm, Christoph

    2014-05-01

    Recently, genome wide association studies in primary sclerosing cholangitis (PSC) revealed associations with gene polymorphisms that potentially could affect the function of regulatory T cells (Treg). The aim of this study was to investigate Treg in patients with PSC and to associate their numbers with relevant gene polymorphisms. Treg frequency in blood was assessed by staining for CD4(+)CD25(high)FOXP3(+)CD127(low) lymphocytes and determination of Treg-specific FOXP3 gene locus demethylation. Single nucleotide polymorphisms (SNP) in the interleukin-2 receptor alpha (IL2RA), the interleukin-2 (IL2) and interleukin-21 (IL21) gene locus were analysed. Liver biopsies taken at the time of diagnosis were stained for FOXP3 and CD3. Treg function was assessed in a CFSE-based suppression assay. The frequency of Treg in peripheral blood of PSC patients was significantly decreased. We confirmed this finding by demonstrating a reduction of non-methylated DNA in the Treg-specific demethylated FOXP3 gene region of peripheral blood cells in PSC patients. Reduced peripheral Treg numbers were significantly associated with homozygosity for the major allele of the SNP "rs10905718" in the IL2RA gene. Intrahepatic FOXP3(+) cell numbers at the time of initial diagnosis were decreased in PSC as compared to PBC. In addition to reduced numbers, the suppressive capacity of Treg isolated from PSC patients seemed to be impaired as compared to healthy controls. Our findings indicate that Treg impairment may play a role in the immune dysregulation observed in PSC. Reduced Treg numbers in patients with PSC are associated with polymorphisms in the IL2RA gene. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  12. Real life Dosages and Costs of TNFα inhibitor therapy for RA patients in Denmark

    DEFF Research Database (Denmark)

    Hostenkamp, Gisela; Sørensen, Jan; Hetland, Merete Lund

    2009-01-01

    about the true long run cost. Taking the actual medication practice into account is important for the evaluation of the costs and optimal sequencing of new and existing biological treatments. Objectives: To investigate the drug cost of TNF-inhibitors in the treatment of RA using real-life data from...... of treatment. Cost estimates based on short term observational data or on instruction leaflets from manufacturers may provide wrong cost assessments of TNF-alpha therapy. It is important to take the long term cost structure into account to arrive at unbiased treatment cost estimates.......Background: When estimating the cost of biological treatment many analyses rely on cross sectional data or standard consumption patterns indicated in the manufacturers' instruction leaflet. Unless such consumption patterns truly reflect routine clinical practice they may result in wrong assumptions...

  13. Scintigraphic, radiological and clinical results after /sup 224/Ra therapy in patients with Bechterew's disease

    Energy Technology Data Exchange (ETDEWEB)

    Redecker, S.; Crone-Muenzebrock, W.; Weh, L.; Montz, R. (Hamburg Univ. (Germany, F.R.))

    1982-04-01

    53 patients with ancylosing spondylitis (clinical stages II and III) were treated with 1 MBq Ra 224 over a period of ten weeks. In 44 patients the orthopaedic findings were improved, in 9 patients they remained unchanged. An iridocyclitis developed in 3 patients, in 1 case an uveitis could be observed 33 patients were reexamined clinically, radiologically including total body scan and by laboratory means after an average period of 7.1 years. The stiftness of the spine was slightly improved compared with the pre-therapeutical status. Radiologically the spine findings were unchanged in 7 patients, progradient in 16, and clearly deteriorated in 8 cases. Scintiscanning of the skeleton of 21 patients showed a normal activity in 6 patients, 8 patients had a slight increase of the activity, mainly in the sacroiliac region 7 patients revealed a highly increased activity in the sacro-iliac region and lumbovertebral spine. Differential blood count and electrophoresis were unchanged before and after therapy. In 60% of the cases the erythrocyte sedimentation rate was diminished compared with pretherapy findings, in 40% the rate was unchanged or increased. Subjectively 10% of the patients reported no pain symptoms, 50% felt better, 30% were unchanged and 10% felt more poorly than before.

  14. Identification of a HERV-K env surface peptide highly recognized in Rheumatoid Arthritis (RA) patients: a cross-sectional case-control study.

    Science.gov (United States)

    Mameli, G; Erre, G L; Caggiu, E; Mura, S; Cossu, D; Bo, M; Cadoni, M L; Piras, A; Mundula, N; Colombo, E; Buscetta, G; Passiu, G; Sechi, L A

    2017-07-01

    Endogenous retroviruses (HERV) are believed to be pathogenic in several autoimmune diseases. Among them, HERV-K viruses have been reported recently to be involved in the pathogenesis of rheumatoid arthritis (RA). In this study we have explored the role of humoral immune response against HERV-K as a potential pathogenetic mechanism in RA. Four different peptides from the extracellular portion of the env protein of HERV-K (env-su19-37 , env-su109-126 , env-su164-186 , env-su209-226 ) were selected by bioinformatic analysis on the basis of their putative immunogenicity. Indirect enzyme-linked immunosorbent assay (ELISA) was then carried out to quantify antibodies against those peptides on blood samples of 70 consecutive RA patients and 71 healthy controls (HC). Differences between the two groups were analysed using the Mann-Whitney test. Potential correlations between RA laboratory, clinical descriptors and immunoglobulin (Ig)G levels were explored by bivariate regression analysis. Serum autoantibodies against one of four tested peptides of HERV-K (env-su19-37 ) were significantly higher in RA than in HC (19 versus 3%, P = 0·0025). Subgroup analysis showed no association between anti-HERV-K peptide humoral response and clinical, serological and clinimetric RA disease descriptors. Serum from RA patients in our series reacted significantly against HERV-K env-su19-37 peptide in comparison to the general population suggesting a role for the HERV-K- related, secondary antigenic-driven immune response in the pathogenesis of RA. Further studies are needed to confirm these results and to explore the role of this HERV-K surface peptide as a potential therapeutic target. © 2017 British Society for Immunology.

  15. Increased CD45RA+ FoxP3(low regulatory T cells with impaired suppressive function in patients with systemic lupus erythematosus.

    Directory of Open Access Journals (Sweden)

    Xiujun Pan

    Full Text Available BACKGROUND: The role of naturally occurring regulatory T cells (Treg in the control of the development of systemic lupus erythematosus (SLE has not been well defined. Therefore, we dissect the phenotypically heterogeneous CD4(+FoxP3(+ T cells into subpopulations during the dynamic SLE development. METHODLOGY/PRINCIPAL FINDINGS: To evaluate the proliferative and suppressive capacities of different CD4(+ T cell subgroups between active SLE patients and healthy donors, we employed CD45RA and CD25 as surface markers and carboxyfluorescein diacetatesuccinimidyl ester (CFSE dilution assay. In addition, multiplex cytokines expression in active SLE patients was assessed using Luminex assay. Here, we showed a significant increase in the frequency of CD45RA(+FoxP3(low naive Treg cells (nTreg cells and CD45RA(-FoxP3(low (non-Treg cells in patients with active SLE. In active SLE patients, the increased proportions of CD45RA(+FoxP3(low nTreg cells were positively correlated with the disease based on SLE disease activity index (SLEDAI and the status of serum anti-dsDNA antibodies. We found that the surface marker combination of CD25(+CD45RA(+ can be used to defined CD45RA(+FoxP3(low nTreg cells for functional assays, wherein nTreg cells from active SLE patients demonstrated defective suppression function. A significant correlation was observed between inflammatory cytokines, such as IL-6, IL-12 and TNFα, and the frequency of nTreg cells. Furthermore, the CD45RA(+FoxP3(low nTreg cell subset increased when cultured with SLE serum compared to healthy donor serum, suggesting that the elevated inflammatory cytokines of SLE serum may promote nTreg cell proliferation/expansion. CONCLUSIONS/SIGNIFICANCE: Our results indicate that impaired numbers of functional CD45RA(+FoxP3(low naive Treg cell and CD45RA(-FoxP3(low non-suppressive T cell subsets in inflammatory conditions may contribute to SLE development. Therefore, analysis of subsets of FoxP3(+ T cells, using a

  16. Factors associated with influenza and pneumococcal vaccine uptake among rheumatoid arthritis patients in Denmark invited to participate in a pneumococcal vaccine trial (Immunovax_RA)

    DEFF Research Database (Denmark)

    Nguyen, MTT; Lindegaard, H.; Hendricks, O.

    2017-01-01

    Objective: This study investigates predictors of influenza and pneumococcal vaccine coverage among rheumatoid arthritis (RA) patients, and explores possible differences according to type of RA therapy. Method: RA patients from two clinics in the region of Southern Denmark were informed about...... the survey during scheduled follow-up visits. The questionnaire included questions concerning previous influenza and pneumococcal vaccine uptake, attitudes about vaccination, and socio-demographic factors. Factors associated with recalled vaccine uptake were assessed by multivariate logistic regression......-rheumatic drugs (bDMARDs). Self-reported uptake of vaccination against seasonal influenza ever was 59% overall; 57% among patients receiving cDMARDs and 61% in patients receiving bDMARDs. Self-reported vaccine uptake against pneumococcal diseases was only 6% overall. Older age, educational level, and information...

  17. Risk of leukaemia following intravenous treatment with {sup 224}Ra - results of a long term follow-up study of ankylosing spondylitis patients; Leukaemierisiko nach intravenoeser {sup 224}Ra-Behandlung - Ergebnisse einer Langzeitstudie an Bechterew-Patienten

    Energy Technology Data Exchange (ETDEWEB)

    Wick, R.R. [GSF - Forschungszentrum fuer Umwelt und Gesundheit Neuherberg GmbH, Oberschleissheim (Germany). Inst. fuer Strahlenbiologie; Chmelevsky, D. [GSF - Forschungszentrum fuer Umwelt und Gesundheit Neuherberg GmbH, Oberschleissheim (Germany). Inst. fuer Strahlenschutz; Goessner, W. [GSF - Forschungszentrum fuer Umwelt und Gesundheit Neuherberg GmbH, Oberschleissheim (Germany). Inst. fuer Pathologie

    1993-12-31

    In an epidemiological study of the somatic late effects risk following incorporation of a short lived {alpha}-emitter, 1473 ankylosing spondylitis patients treated with repeated intravenous injections of {sup 224}Ra in the years 1948 - 75, have been observed in the GSF. The usual therapeutic plan consisted of a total of 10 - 12 injections of 1.036 MBq (28 {mu}Ci) of {sup 224}Ra each, given at weekly intervals; this would result in an cumulative {alpha}-dose of 0.56 - 0.67 Gy to the marrow-free skeleton of a 70-kg-man (standard man). These patients have been followed together with a control group of ankylosing spondylitis patients not treated with radioactive drugs and/or X-rays. Until May 1993 (mean follow-up time 19.9 yr), 595 patients of the exposure group and 722 patients of the control group have died, causes of death have been ascertained for 578, resp. 668 patients. Among others we observed in the exposure group 10 cases of leukaemia (vs. 2.7 - 2.8 cases expected, p < 0.001) and 6 cases of leukaemia in the control group (vs. 3.3 - 3.5 exp., p = 0.14). Subclassification of the leukaemias shows a clear preference for chronic myeloid leukaemia (CML) in the exposure group (4 cases obs. vs. 0.8 cases exp., p = 0.009), whereas in the control group the observed cases of CML are within the range of expectancy. Similar observations have not been made in another group of patients, now observed by Spiess and co-workers, who have been treated at a higher dose/dose rate range. This increased incidence of leukaemias in our exposure group is in one line with results from animal experiments with bone seeking {alpha}-emitters given at low dose rates. The induction of myeloid leukaemia has been demonstrated in mice down to dose rates of only a few mGy/day also for {sup 239}Pu, an {alpha}-emitter which like {sup 224}Ra deposits preferentially on the bone surface. (orig.) [Deutsch] Im Rahmen einer epidemiologischen Studie zum somatischen Strahlenspaetschadenrisiko nach

  18. The foot: still the most important reason for walking incapacity in rheumatoid arthritis: distribution of symptomatic joints in 1,000 RA patients.

    Science.gov (United States)

    Grondal, Lollo; Tengstrand, Birgitta; Nordmark, Birgitta; Wretenberg, Per; Stark, Andre

    2008-04-01

    Our knowledge of frequency of foot involvement in rheumatoid arthritis (RA) is still often based on a study from Finland in 1956. Great changes in the treatment of RA may have led to a different situation. We investigated the distribution of joint involvement in RA patients today, with special attention given to the feet and subjective walking ability. 1,000 RA patients answered a questionnaire concerning joints affected, joint surgery, foot problems, and subjectively experienced reasons for walking incapacity. In 45% of the patients, the forefoot was involved at the start of the disease. In 17%, the hindfoot/ankle was involved at the start. Only hand symptoms were commoner. 80% of patients reported current foot problems, 86% in the forefoot and 52% in the hindfoot/ankle. Difficulty in walking due to the feet was reported by 71%. For 41% of patients, the foot was the most important part of the lower extremity causing reduced walking capacity, and for 32% it was the only part. After the hand, the foot was the most frequently symptomatic joint complex at the start of the disease, but also during active medical treatment. The foot caused walking disability in three-quarters of the cases and-4 times as often as the knee or the hip-it was the only joint to subjectively impair gait.

  19. Anti-hnRNP B1 (RA33 Autoantibodies Are Associated with the Clinical Phenotype in Russian Patients with Rheumatoid Arthritis and Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Aleksey Maslyanskiy

    2014-01-01

    Full Text Available Heterogeneous nuclear ribonucleoproteins (hnRNPs are potent autoantigenic targets in systemic autoimmune rheumatic diseases (SARD. Loss of tolerance to the RA33 complex consisting of hnRNP A2 and its alternatively spliced variants B1 and B2 has been the interest of rheumatologists. A novel ELISA for the detection of anti-hnRNP B1 autoantibodies has been developed to investigate the prevalence thereof in 397 patients with SARD, including patients with rheumatoid arthritis (RA, spondyloarthropathy (SPA, juvenile chronic arthritis, systemic lupus erythematosus (SLE, systemic sclerosis (SSc, and Sjögren’s syndrome (SS, in comparison to 174 controls. Anti-hnRNP B1 autoantibodies were significantly more prevalent in patients with SARD than controls (47/397, 11.8% versus 2/174, 1.1%; P<0.001. In particular, anti-hnRNP B1 were found more frequently in the disease cohorts than in the controls and were present in 24/165 (14.5% patients with RA, 6/58 (10.3% SPA, 11/65 (16.9% SSc, and 4/50 (8.0% SLE. In RA patients, anti-hnRNP B1 autoantibodies correlated significantly with C-reactive protein levels and erythrocyte sedimentation rate, while in patients with SSc it was associated with features of arterial wall stiffness and presence of hypertension. Anti-hnRNP B1 autoantibodies occur in SARD and seem to be correlated with distinct clinical characteristics in patients with RA and SSc.

  20. A unique drug distribution process for radium Ra 223 dichloride injection and its implication for product quality, patient privacy, and delineation of professional responsibilities.

    Science.gov (United States)

    Dansereau, Raymond N

    2014-11-01

    On May 15, 2013, Bayer Healthcare Pharmaceuticals announced that it had received marketing approval for the therapeutic radioactive medication radium Ra 223 dichloride injection (Xofigo; Ra 223). The product acquisition and distribution process for hospital-based nuclear pharmacies and nuclear medicine services is unlike any other. The product is distributed as a low-risk compounded sterile preparation through a single compounding nuclear pharmacy located in Denver, Colorado, pursuant to a prescription. This model for drug distribution and delivery to the user institution has implications for product quality, patient privacy, and delineation of professional responsibilities. © The Author(s) 2014.

  1. Successful extension of tocilizumab infusion intervals from 4 weeks to 6 or 5 weeks in 90% of RA patients with good response to 4-week intervals.

    Science.gov (United States)

    Saiki, Osamu; Uda, Hiroshi

    2017-01-01

    A period of 4 weeks (w) has been recommended as the interval between tocilizumab (TCZ) infusions for rheumatoid arthritis (RA). However, treating the patients with TCZ (8 mg/kg), we experienced that longer intervals were also effective. We conducted the study to investigate whether the intervals of TCZ infusions could extend from 4w to 5 or 6w. This was a retrospective observational study. RA patients who had shown good response to TCZ infusions at 4w intervals were enrolled, and the intervals of TCZ infusions were extended to 5w. Next, the intervals of TCZ infusion were extended to 6w for the patients who had maintained good response with 5w intervals. The patients who had maintained good response for more than two years were estimated as responders. One hundred patients were enrolled in the present study, and 62 patients maintained good response with 6w-interval infusions, and 28 patients with 5w-interval infusions, indicating that 90% of patients who had shown good response with 4w intervals could extend the intervals from 4w to 5 or 6w. The present study provides evidence that most of RA patients who showed good response to TCZ infusions at 4w could extend the intervals to 6w or 5w. This finding should be of great interest for both financial and labour reasons.

  2. Acne RA-1,2, a novel UV-selective face cream for patients with acne: Efficacy and tolerability results of a randomized, placebo-controlled clinical study.

    Science.gov (United States)

    Cestone, Enza; Michelotti, Angela; Zanoletti, Valentina; Zanardi, Andrea; Mantegazza, Raffaella; Dossena, Maurizia

    2017-06-01

    General skincare measures such as the use of moisturisers and products containing adequate photoprotection are important components of acne patients' management to complement the pharmacological regimen. Acne RA-1,2 is a novel dermato-cosmetic product which contains selective photofilters and active ingredients against the multifactorial pathophysiology of acne. To evaluate the tolerability of Acne RA-1,2 and its effect on the clinical signs of acne. This double-blind, placebo-controlled study randomized 40 adult patients with 10-25 comedones per half face to once-daily application of Acne RA-1,2 or placebo for 8 weeks. Evaluations after 4 and 8 weeks included the number of comedones, transepidermal water loss (TEWL), sebum production, and tolerability. In the Acne RA-1,2 group, there was a significant 35% decrease in the mean number of comedones from 26 at baseline to 17 at Week 8 (P<.001), a 7% significant reduction in TEWL (9.32 to 8.66 g/h/m(2) ; P<.001), and a 24% significant reduction in sebum production (154.8 to 117.6 μg/cm(2) ; P<.001). The reductions in TEWL and sebum production were significantly greater than those in the placebo group at Weeks 4 and 8 (P<0.05). There were no adverse events. Acne RA-1,2 was well tolerated and effective at reducing comedones and sebum production and improving epidermal barrier function. These results suggest that Acne RA-1,2 is useful against acne-prone facial skin, particularly as it targets sebum production, which topical pharmacological acne therapies do not address. © 2017 Wiley Periodicals, Inc.

  3. Proliferatory defect of invariant population and accumulation of non-invariant CD1d-restricted natural killer T cells in the joints of RA patients.

    Science.gov (United States)

    Gutowska-Owsiak, Danuta; Birchall, Martin A; Moots, Robert J; Christmas, Stephen E; Pazmany, Laszlo

    2014-05-01

    While numerical and functional defects of invariant NKT cells have been demonstrated in rheumatoid arthritis (RA), the detailed characterization of proliferative and secretory responses following CD1d-mediated presentation is lacking; the presence of non-invariant populations has never been assessed in human autoimmunity. We have evaluated both invariant and non-invariant populations in the blood and synovial fluid from patients to assess feasibility of NKT cell-directed manipulations in RA. NKT cell populations were quantified by anti-CD4/anti-Vα24 staining and/or CD1d tetramers. Proliferation was measured in cultures of mononuclear cells following stimulations with αGalCer and cytokine secretion determined by multi-bead assay. We have confirmed a proliferative defect of iNKT cells in both peripheral blood and synovial fluid from RA patients, but no changes in baseline frequencies. Moreover, we have detected an enlargement of non-invariant cell pool in synovial fluid samples. In addition, we noted an evident Th2 shift following exposure to αGalCer and pronounced IL-6 secretion. While RA patients suffer from defective proliferative responses of invariant NKT cells, non-invariant cells accumulate at the site of inflammation. While stimulation with αGalCer results in reduced TNF-α and increased suppressive IL-10, abundantly produced IL-6 could potentially contribute to the induction of Th17 cells in the joints.

  4. [Clinical features of atypical refractory anemia (RA)].

    Science.gov (United States)

    Matsuda, A; Jinnai, I; Kusumoto, S; Shiramatsu, F; Bessho, M; Saito, M; Hirashima, K

    1991-08-01

    Twenty-three patients with bicytopenia or pancytopenia were retrospectively studied. The patients with underlying disorders, blast count of more than 5% on bone marrow (BM) aspirate, blast count of more than 1% on peripheral blood or ringed sideroblast count of more than 15% on BM aspirate were excluded. According to Yoshida's criteria, 23 patients were classified into 6 subtypes [AA (aplastic anemia)1: typical AA, AA2: atypical AA, MDS (myelodysplastic syndrome)3: typical RA (refractory anemia, MDS4-6: atypical RA], and AA1 7 cases; AA2 2 cases; MDS3 5 cases; MDS4 1 case; MDS5 2 cases; MDS6 6 cases. To clarify the clinical features of atypical RA group (MDS4-6), we investigated ferrokinetics, RBC life span, karyotype, serum Epo (erythropoietin) concentration, response to therapy and prognosis. Results were as follows: 1) all three RA patients who were younger than 30 years old were included in atypical RA group, 2) in ferrokinetics study PID (plasma iron disappearance time) values of MDS4 and MDS6 patients ranged between those of AA1 and those of MDS3 patients (5 of 7 patients), 3) two cases who developed leukemia belonged to typical RA group, 4) patients with atypical RA showed response to therapy and their prognosis were better than those with typical RA. These observations suggest that atypical RA have different clinical features from typical RA.

  5. Expression of Biomarkers CXCR4, IL11-RA, TFF1, MLF1P in Advanced Breast Cancer Patients with Bone Metastatic: a Diagnostic Study

    Directory of Open Access Journals (Sweden)

    Cosphiadi Irawan

    2017-02-01

    Full Text Available Aim: to analyze expression of biomarkers CXCR4, IL11-RA, TFF1 and MLF1P, and clinicopathology in advanced breast cancer patients with bone metastatic. Methods: this is a cross-sectional study. Analysis was done against a total of 92 breast cancer patients, including 46 bone metastatic patients and 46 non-bone metastatic patients. Immunohistochemistry and microarray analysis was performed in 81 formalin fixed paraffin embedded (FFPE samples from 81 patients were used. Data were collected through medical records, immunohistochemistry (IHC, and microarray with nanoString nCounterTM. Results: this article is part one of a two stage reporting research results. In part one we got the results of the IHC analysis, IL11-RA with cut-off ≥103.5 showed OR 3.803 (95 % confidence interval [CI], 1.375-10.581, p=0.010, MLF1P with cut-off ≥83.0 OR 2.784 (95% CI, 1.009-7.681, p=0.048, and ER+ OR 7.640 (95 % CI, 2.599-22.459, p<0.000, were associated with bone metastastic incidences in advanced breast cancer, and were statistically significantly different. A combination of IL-11RA, MLF1P and ER+, showed an accuracy of approaching 80% to discriminate between bone metastatic and non bone metastatic in advanced breast cancer patients. Conclusion: IL11-RA, MLF1P, and ER+ were the determinants that were associated with increasing bone metastasis incidence.

  6. Chôra

    DEFF Research Database (Denmark)

    Isar, Nicoletta

    2009-01-01

    , for whom "il y a khôra" (there is chôra), Sallis keeps the definite article (the chôra) as an index of certain differentiation in chôra. This article takes as a point of departure Sallis' thesis regarding the manifestation of the chôra, grounded in the manner in which the chôra is apprehended, that is......, as in a dream. Sallis' interpretation opens up the possibility for a new reading of the dialogue, and offers a tool to examine phenomena occurred in the aftermath of the Platonic cosmogony. One of the most fascinating episodes of the afterlife of the Platonic chôra is the Byzantine chôra, presented...

  7. PADI4 and HLA-DRB1 are genetic risks for radiographic progression in RA patients, independent of ACPA status: results from the IORRA cohort study.

    Directory of Open Access Journals (Sweden)

    Taku Suzuki

    Full Text Available INTRODUCTION: Rheumatoid arthritis (RA is a systemic, chronic inflammatory disease influenced by both genetic and environmental factors, leading to joint destruction and functional impairment. Recently, a large-scaled GWAS meta-analysis using more than 37,000 Japanese samples were conducted and 13 RA susceptibility loci were identified. However, it is not clear whether these loci have significant impact on joint destruction or not. This is the first study focused on the 13 loci to investigate independent genetic risk factors for radiographic progression in the first five years from onset of RA. METHODS: Sharp/van der Heijde score of hands at 5-year disease duration, which represents joint damage, were measured retrospectively and used as an outcome variable in 865 Japanese RA patients. Genetic factors regarded as putative risk factors were RA-susceptible polymorphisms identified by the Japanese GWAS meta-analysis, including HLA-DRB1 (shared epitope, SE, rs2240340 (PADI4, rs2230926 (TNFAIP3, rs3093024 (CCR6, rs11900673 (B3GNT2, rs2867461 (ANXA3, rs657075 (CSF2, rs12529514 (CD83, rs2233434 (NFKBIE, rs10821944 (ARID5B, rs3781913 (PDE2A-ARAP1, rs2841277 (PLD4 and rs2847297 (PTPN2. These putative genetic risk factors were assessed by a stepwise multiple regression analysis adjusted for possible non-genetic risk factors: autoantibody positivity (anti-citrullinated peptide antibody [ACPA] and rheumatoid factor, history of smoking, gender and age at disease onset. RESULTS: The number of SE alleles (P = 0.002 and risk alleles of peptidyl arginine deiminase type IV gene (PADI4, P = 0.04 had significant impact on progressive joint destruction, as well as following non-genetic factors: ACPA positive (P = 0.0006, female sex (P = 0.006 and younger age of onset (P = 0.02. CONCLUSIONS: In the present study, we found that PADI4 risk allele and HLA-DRB1 shared epitope are independent genetic risks for radiographic progression in Japanese

  8. Are RA patients from a non-endemic HCV population screened for HCV? A cross-sectional analysis of three different settings.

    Science.gov (United States)

    Skinner-Taylor, Cassandra Michelle; Erhard-Ramírez, Alejandro; Garza-Elizondo, Mario Alberto; Esquivel-Valerio, Jorge Antonio; Abud-Mendoza, Carlos; Martínez-Martínez, Marco Ulises; Vega-Morales, David; Arana-Guajardo, Ana

    In Mexico, other risk factors are associated with hepatitis C virus (HCV): prior heroin users, living alone, widower, and northern region residence. Rheumatoid arthritis (RA) patients are considered immunosuppressed and HCV testing is recommended before treatment. The aim of the study was to describe the characteristics of HCV testing in RA patients in three different medical care settings in a non-endemic area. A retrospective observational study was performed using medical records from 960 RA patients describing the indications for HCV testing. The test was performed in 28.6% and the HCV overall frequency was 0.36%. Population characteristics were not associated with an increased risk of HCV infection; therefore, anti-HCV positivity was low. The main reason for testing was before starting biological agents. Due to the low pre-test probability, testing for HCV infection should be personalized; i.e., according to disease prevalence in a particular geographical location and the individual risk factors. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  9. Breaking communication barriers for RA patients of South Asian origin: the use of a bilingual educational audio CD and linguistically appropriate peer support and education.

    Science.gov (United States)

    Kumar, Kanta; John, Holly; Gordhan, Chandrika; Situnayake, Deva; Raza, Karim; Bacon, Paul A

    2011-03-01

    People from the Indian subcontinent represent one of the largest ethnic groups in the UK. Patient education resources are required to address language barriers, poor literacy and (potentially discordant) cultural beliefs. We have investigated a novel strategy to meet this need. Rheumatoid arthritis (RA) patients of South Asian origin who prefer to communicate in a South Asian language were invited to a face-to-face interaction with a trained patient volunteer to provide linguistically appropriate peer support and education, and given a bilingual educational audio CD. Qualitative methods were used to assess this approach; three focus groups were held and 15 patients participated in total. Four important themes were identified: (1) The need for information about RA; all patients agreed that this was vital to learn how to live with their chronic disease. (2) Currently available approaches to education; particular concerns related to a lack of time in clinic, language barriers, difficulties in communicating via interpreters and that most written information was available only in English. (3) Support provided by a trained patient volunteer; patients appreciated that they were listened to, and were motivated by the volunteers' positive attitude. (4) The usefulness of the audio CD; patients appreciated that information was presented in a language they could understand, via a convenient medium and which offered a helpful perspective on their illness. This approach is a successful way of delivering information and encouraged patients from a difficult-to-reach community to become more involved in their disease management. Copyright © 2010 John Wiley & Sons, Ltd.

  10. Patient-reported outcomes from a phase 3 study of baricitinib versus placebo or adalimumab in rheumatoid arthritis: secondary analyses from the RA-BEAM study

    Science.gov (United States)

    Keystone, Edward C; Taylor, Peter C; Tanaka, Yoshiya; Gaich, Carol; DeLozier, Amy M; Dudek, Anna; Zamora, Jorge Velasco; Cobos, Jose Arturo Covarrubias; Rooney, Terence; de Bono, Stephanie; Arora, Vipin; Linetzky, Bruno; Weinblatt, Michael E

    2017-01-01

    Background To assess the effect of baricitinib on patient-reported outcomes (PROs) in patients with active rheumatoid arthritis and an inadequate response to methotrexate (MTX). Methods In this double-blind phase 3 study, patients were randomised 3:3:2 to placebo (n=488), baricitinib 4 mg once daily (n=487), or adalimumab 40 mg biweekly (n=330) with background MTX. PROs included the SF-36, EuroQol 5-D (EQ-5D) index scores and visual analogue scale, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient’s Global Assessment of Disease Activity (PtGA), patient’s assessment of pain and Work Productivity and Activity Impairment Questionnaire-Rheumatoid Arthritis (WPAI-RA), and measures collected in electronic patient daily diaries: duration and severity of morning joint stiffness (MJS), Worst Ttiredness and Worst Joint Pain. The primary study endpoint was at week 12. Treatment comparisons were assessed with logistic regression for categorical measures or analysis of covariance for continuous variables. Results Compared with placebo and adalimumab, baricitinib showed statistically significant improvements (p≤0.05) in HAQ-DI, PtGA, pain, FACIT-F, SF-36 physical component score, EQ-5D index scores and WPAI-RA daily activity at week 12. Improvements were maintained for measures assessed to week 52. Statistically significant improvement in patient diary measures (MJS duration and severity), worst tiredness and worst joint pain were observed for baricitinib versus placebo and adalimumab at week 12 (p≤0.05). Conclusions Baricitinib provided significantly greater improvement in most PROs compared with placebo and adalimumab, including physical function MJS, pain, fatigue and quality of life. Improvement was maintained to the end of the study (week 52). Trial registration NCT01710358. PMID:28798049

  11. Factors that influence fatigue status in patients with severe rheumatoid arthritis (RA) and good disease outcome following 6 months of TNF inhibitor therapy: a comparative analysis.

    LENUS (Irish Health Repository)

    Minnock, Patricia

    2015-11-01

    The objective of the present study is to determine the factors associated with persistent fatigue in patients with severe rheumatoid arthritis (RA) and good disease response to 6 months of tumour necrosis factor inhibitor therapy. Eligible patients with either persistent (PF) or no fatigue (NF) were compared. Using validated questionnaires and bivariate analysis, this cross-sectional survey explored if clinical characteristics, pain, self-efficacy, sleep and mood\\/depression differed between groups. Patients with PF (PF; NF) (n = 28; 28) reported significantly more overall pain (11.3 ± 9.4 (0-33); 6.9 ± 8.9 (0-33)), more recent and current pain intensity (41.4 ± 26.6 (0-80) 24.4 ± 26.6 (0-100) and depression (11.8 ± 7.5 (1-35); 8.2 ± 6.6 (0-26)), than the NF group. There was no significant difference between groups in self-efficacy and both groups experienced poor sleep quality (Pittsburgh Sleep Quality Index >5). Despite having good disease response, the PF group had significantly higher rheumatoid factor incidence, disease activity score-28, early morning stiffness duration and lower incidence of ever-failing disease-modifying anti-rheumatic drugs than the NF group. These findings enhance the fatigue literature in patients with RA prescribed tumour necrosis factor (TNF) inhibition therapy, identifying the potentially modifiable factors of pain and depression, previously demonstrated to be strongly associated with fatigue in non-biologic populations. In addition, this study highlights the association between persistent fatigue and an on-going state of low disease activity. This infers that more judicious disease management could minimise the symptom burden of pain and depression and consequentially fatigue.

  12. Expression of a pathogen-response program in peripheral blood cells defines a subgroup of rheumatoid arthritis patients

    NARCIS (Netherlands)

    van der Pouw Kraan, T. C. T. M.; van Baarsen, L. G. M.; Wijbrandts, C. A.; Voskuyl, A. E.; Rustenburg, F.; Baggen, J. M.; Dijkmans, B. A. C.; Tak, P. P.; Verweij, C. L.

    2008-01-01

    Rheumatoid arthritis (RA) is a heterogeneous disease with unknown etiology. Here we aimed to distinguish RA subtypes based on peripheral blood (PB) gene expression profiles in comparison with a pathogen-response transcriptional program. PB was obtained from 35 RA patients and 15 healthy individuals.

  13. Measuring the radium quartet (228Ra, 226Ra, 224Ra, 223Ra) in seawater samples using gamma spectrometry.

    Science.gov (United States)

    van Beek, P; Souhaut, M; Reyss, J-L

    2010-07-01

    Radium isotopes are widely used in marine studies (eg. to trace water masses, to quantify mixing processes or to study submarine groundwater discharge). While 228Ra and 226Ra are usually measured using gamma spectrometry, short-lived Ra isotopes (224Ra and 223Ra) are usually measured using a Radium Delayed Coincidence Counter (RaDeCC). Here we show that the four radium isotopes can be analyzed using gamma spectrometry. We report 226Ra, 228Ra, 224Ra, 223Ra activities measured using low-background gamma spectrometry in standard samples, in water samples collected in the vicinity of our laboratory (La Palme and Vaccarès lagoons, France) but also in seawater samples collected in the plume of the Amazon river, off French Guyana (AMANDES project). The 223Ra and 224Ra activities determined in these samples using gamma spectrometry were compared to the activities determined using RaDeCC. Activities determined using the two techniques are in good agreement. Uncertainties associated with the 224Ra activities are similar for the two techniques. RaDeCC is more sensitive for the detection of low 223Ra activities. Gamma spectrometry thus constitutes an alternate method for the determination of short-lived Ra isotopes. 2009 Elsevier Ltd. All rights reserved.

  14. Impact of a magnetic resonance imaging-guided treat-to-target strategy on disease activity and progression in patients with rheumatoid arthritis (the IMAGINE-RA trial)

    DEFF Research Database (Denmark)

    Møller-Bisgaard, Signe; Hørslev-Petersen, Kim; Ejbjerg, Bo Jannik

    2015-01-01

    . This demonstrates that additional methods for prognostication and monitoring of the disease activity are needed. Bone marrow edema (BME) detected by magnetic resonance imaging (MRI) has proved to be an independent predictor of subsequent radiographic progression. Guiding the treatment based on the presence....../absence of BME may therefore be clinically beneficial. We present the design of a randomized controlled trial (RCT) aiming to evaluate whether an MRI-guided treatment strategy compared to a conventional treatment strategy in anti-CCP-positive erosive RA is better to prevent progression of erosive joint damage...... swollen joints and treatment with synthetic disease-modifying antirheumatic drugs (DMARDs) will be included. Patients will be randomized to either a treatment strategy based on conventional laboratory and clinical examinations (control group) or a treatment strategy based on conventional laboratory...

  15. Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of ASP2408, a Potent Selective T-Cell Costimulation Modulator After Single and Multiple Ascending Doses in Healthy Volunteers and RA Patients.

    Science.gov (United States)

    Zhu, Tong; Keirns, James; Howieson, Corrie; Kaibara, Atsunori; Goldwater, Ronald; Kivitz, Alan J; Chindalore, Vishala; Cohen, Stanley; Santos, Vicki; Akinlade, Bolanle; Kernstock, Robert; Delgado-Herrera, Leticia; Blahunka, Paul C; Karrer, Erik E; Garg, Jay P; Samberg, Nancy; Zeiher, Bernhardt G

    2016-09-01

    ASP2408 is a next-generation anti-cytotoxic T lymphocyte antigen-4 fusion protein engineered for improved CD86 binding affinity as a treatment for rheumatoid arthritis (RA). In 72 healthy subjects (n = 6/treatment), ASP2408 was administered as single ascending doses intravenously at 0.003 to 10.0 mg/kg or subcutaneously at 0.3 to 3.0 mg/kg. It showed decreased clearance and prolonged half-life with increasing doses, consistent with target-mediated disposition. The apparent bioavailability was 36.3%-56.7% across single subcutaneous doses. Sixteen RA patients (n = 8/treatment) on stable methotrexate received 3 × 3.0 mg/kg subcutaneously every 4 weeks or every 2 weeks. Similar to single-dose treatment, ASP2408 concentrations peaked 2 to 3 days postdose, with a median t1/2 of approximately 8 days. Using CD86 receptor occupancy (RO) as a mechanistic biomarker, ASP2408 demonstrated dose-dependent binding to its target. ASP2408 3.0 mg/kg subcutaneously every 4 weeks and every 2 weeks led to a mean %CD86 RO ≥ 74.7% and ≥ 81.5%, respectively, within each dosing interval. ASP2408 was well tolerated across studies with no evidence of dose-limiting toxicity or clinically significant changes in clinical laboratory test results, vital signs, or 12-lead electrocardiograms. ASP2408 elicited antidrug antibodies in the majority of patients, but with no clinical sequelae. © 2016, The American College of Clinical Pharmacology.

  16. Serum of patients with active rheumatoid arthritis inhibits differentiation of osteochondrogenic precursor cells.

    Science.gov (United States)

    Pathak, Janak L; Verschueren, Patrick; Lems, Willem F; Bravenboer, Nathalie; Klein-Nulend, Jenneke; Bakker, Astrid D; Luyten, Frank P

    2016-05-01

    Delayed fracture healing is frequently experienced in patients with systemic inflammation such as during rheumatoid arthritis (RA). The reasons for this are diverse, but could also be caused by inflammatory cytokines and/or growth factors in serum from patients with active disease. We hypothesized that serum from patients with active RA contains circulating inflammatory factors that inhibit differentiation of osteochondrogenic precursors. Serum was obtained from 15 patients with active RA (active RA-sera) and from the same patients in clinical remission 1 year later (remission RA-sera; controls). The effect of active RA-sera on osteochondrogenic differentiation of chondrogenic ATDC5 cells and primary human periosteum-derived progenitor cells (HPDC) was determined in micromass culture. In ATDC5 cells, active RA-sera reduced Ki67 transcription levels by 40% and cartilage matrix accumulation by 14% at day 14, and Alp transcription levels by 16%, and matrix mineralization by 17% at day 21 compared with remission RA-sera. In HPDCs, active RA-sera inhibited metabolic activity by 8%, SOX9 transcription levels by 14%, and cartilage matrix accumulation by 7% at day 7 compared with remission RA-sera. In conclusion, sera from patients with active RA negatively affect differentiation of osteochondrogenic precursors, and as a consequence may contribute to delayed fracture healing in these patients.

  17. The role of inflammation, the autonomic nervous system and classical cardiovascular disease risk factors on subendocardial viability ratio in patients with RA: a cross-sectional and longitudinal study.

    Science.gov (United States)

    Sandoo, Aamer; Protogerou, Athanassios D; Hodson, James; Smith, Jacqueline P; Zampeli, Evi; Sfikakis, Petros P; Kitas, George D

    2012-11-28

    Evidence indicates that rheumatoid arthritis (RA) patients have increased susceptibility to myocardial ischaemia that contributes to myocardial infarction. The subendocardial viability ratio (SEVR) can be measured using pulse wave analysis and reflects myocardial oxygen supply and demand. The objective of the present study was to examine specific predictors of SEVR in RA patients, with a specific focus on inflammation and classical cardiovascular disease (CVD) risk factors. Two patient cohorts were included in the study; a primary cohort consisting of 220 RA patients and a validation cohort of 127 RA patients. All patients underwent assessment of SEVR using pulse wave analysis. Thirty-one patients from the primary cohort who were about to start anti-inflammatory treatment were prospectively examined for SEVR at pretreatment baseline and 2 weeks, 3 months and 1 year following treatment. Systemic markers of disease activity and classical CVD risk factors were assessed in all patients. The SEVR (mean ± standard deviation) for RA in the primary cohort was 148 ± 27 and in the validation cohort was 142 ± 25. Regression analyses revealed that all parameters of RA disease activity were associated with SEVR, along with gender, blood pressure and heart rate. These findings were the same in the validation cohort. Analysis of longitudinal data showed that C-reactive protein (P < 0.001), erythrocyte sedimentation rate (P < 0.005), Disease Activity Score in 28 joints (P < 0.001), mean blood pressure (P < 0.005) and augmentation index (P < 0.001) were significantly reduced after commencing anti-TNFα treatment. Increasing C-reactive protein was found to be associated with a reduction in SEVR (P = 0.02) and an increase in augmentation index (P = 0.001). The present findings reveal that the SEVR is associated with markers of disease activity as well as highly prevalent classical CVD risk factors in RA, such as high blood pressure and diabetes. Further prospective studies are

  18. QUEST-RA: quantitative clinical assessment of patients with rheumatoid arthritis seen in standard rheumatology care in 15 countries

    DEFF Research Database (Denmark)

    Sokka, Tuulikki; Kautiainen, Hannu; Toloza, Sergio

    2007-01-01

    clinical assessment and a patient self-report questionnaire, which was translated into each language. Data on demographic, disease and treatment-related variables were collected and analysed using descriptive statistics. Variation in disease activity on DAS28 (disease activity score on 28-joint count...

  19. Determining the Lowest Optimally Effective Methotrexate Dose for Individual RA Patients Using Their Dose Response Relation in a Tight Control Treatment Approach.

    Directory of Open Access Journals (Sweden)

    Sandhya C Nair

    Full Text Available To determine the optimal methotrexate dose in individual patients and to explore whether this optimal dose and the level of disease activity at that dose could be predicted.Data from CAMERA II trial comparing MTX and MTX with 10 mg of prednisone both in a tight control treatment strategy in early RA was used. For each patient a curve for disease activity over time was fitted and the MTX dose after which further step-up did not result in relevant improvement in disease activity anymore was determined the 'lowest optimally effective MTX dose (LOED'. The association of demographic and clinical characteristics at baseline with this LOED and with the level of disease activity reached at LOED was studied.In 204 (100 MTX and 104 MTX with prednisone out of 236 patients LOED could be defined. 10 mg/wk was the most prevalent LOED in patients treated with MTX and prednisone and 10 mg/wk, 20 mg/wk and 30 mg/wk in the MTX strategy. Although the specific LOED could not reliably be predicted, higher baseline disease activity, height and lower weight were associated with higher LOEDs (i.e at least 15 mg/wk. A score was presented to decide on a starting dose of 10 mg/wk or (at least 15 mg/wk. The level of disease activity at LOED could not be reliably predicted.A starting dose of 10 mg/wk might be a good choice for most patients and is frequently already the optimal dose. However, a subgroup of patient can be determined who would require higher MTX doses.

  20. Identification of a CTL4/Neu1 fusion transcript in a sialidosis patient.

    Science.gov (United States)

    Uhl, Johannes; Penzel, Roland; Sergi, Consolato; Kopitz, Jürgen; Otto, Herwart F; Cantz, Michael

    2002-06-19

    The deficiency of the lysosomal neuraminidase (NEU1; sialidase) causes the storage disorder sialidosis with symptoms ranging from eye abnormalities and neurological disturbances to skeletal malformations, mental retardation and early death. Sialidosis patients encompassing a wide spectrum of clinical symptoms were screened for mutations in neu1. We identified the same homozygous interstitial deletion (11 kb) in two patients causing the fusion of exon 10 of CTL4 (New Gene 22; NG22) with the 3'-UTR of neu1. In one patient we found the resulting CTL4/Neu1 fusion transcript, in the other we detected an alternatively spliced CTL4 transcript (retention of intron 9).

  1. ra-nollenergibyggnader

    OpenAIRE

    Allard, Ingrid

    2011-01-01

    Det nya EU-direktivet EPBD2, Energy Performance of Buildings Directive (recast), som antogs 2010, specificerar att alla nya byggnader ska vara så kallade nära-nollenergibyggnader år 2021. En nära-nollenergibyggnad definieras som en byggnad med mycket hög energiprestanda, som till mycket hög grad förses med förnybar energi. Hur detta ska tolkas och var kravnivån ska sättas för energianvändningen är upp till varje land att besluta. I Sverige pågår just nu en debatt om detta och Energimyndighete...

  2. The association of fatigue, comorbidity burden, disease activity, disability and gross domestic product in patients with rheumatiod arthritis. Results from 34 countries participating in the Quest-RA programme

    NARCIS (Netherlands)

    Grøn, K.L.; Ørnbjerg, L.M.; Hetland, M.L.; Aslam, F.; Khan, N.A.; Jacobs, J.W.G.; Henrohn, D.; Rasker, Hans J.; Kauppi, M.J.; Lang, H.C.; Mota, L.M.H.; Aggarwal, A.; Yamanaka, H.; Badsha, H.; Gossec, L.; Cutolo, M.; Ferraccioli, G.; Gremese, E.; Bong Lee, E.; Inanc, N.; Direskeneli, H.; Taylor, Peter; Huisman, Marieke; Alten, R.; Pohl, C.; Oyoo, O.; Stropuviene, S.; Drosos, A.A.; Kerzberg, E.; Ancuta, C.; Mofti, A.; Bergman, M.; Detert, J.; Selim, Z.I.; Abda, E.A.; Rexhepi, B.; Sokka, T.

    2014-01-01

    OBJECTIVES: The aim is to assess the prevalence of comorbidities and to further analyse to which degree fatigue can be explained by comorbidity burden, disease activity, disability and gross domestic product (GDP) in patients with rheumatoid arthritis (RA).METHODS: Nine thousands eight hundred

  3. Transcript expression in endometrial cancers from Black and White patients.

    Science.gov (United States)

    Maxwell, G Larry; Allard, Jay; Gadisetti, Chandramouli V R; Litzi, Tracy; Casablanca, Yovanni; Chandran, Uma; Darcy, Kathleen M; Levine, Douglas A; Berchuck, Andrew; Hamilton, Chad A; Conrads, Thomas P; Risinger, John I

    2013-07-01

    Previous studies suggest that differences in molecular features of endometrial cancers between racial groups may contribute to the poorer survival in Blacks. The objective of this investigation was to determine whether gene expression among endometrial cancers is different between Blacks and Whites. Fresh frozen tumors from 25 Black patients were matched by stage, grade, and histology to endometrial cancer specimens from 25 White patients. Each case was macrodissected to produce specimens possessing a minimum of 75% cancer cellularity. A subset of 10 matched pairs was also prepared using laser microdissection (LMD) to produce specimens possessing a minimum of 95% cancer cells. Total RNA isolated from each sample was analyzed using the Affymetrix Human Genome U133 Plus 2.0 arrays. Data were analyzed using principal component analysis and binary class comparison analyses. Unsupervised analysis of the 50 endometrial cancers failed to identify global gene expression profiles unique to Black or White patients. In a subset analysis of 10 matched pairs from Blacks and Whites prepared using LMD and macrodissection, unsupervised analysis did not reveal a unique gene expression profile associated with race in either set, but associations were identified that relate to sample preparation technique, histology and stage. Our microarray data revealed no global gene expression differences and identified few individual gene differences between endometrial cancers from Blacks and Whites. More comprehensive methods of transcriptome analysis could uncover RNAs that may underpin the disparity of outcome or prevalence of endometrial cancers in Blacks and Whites. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Patient mutation in AIRE disrupts P-TEFb binding and target gene transcription.

    Science.gov (United States)

    Žumer, Kristina; Plemenitaš, Ana; Saksela, Kalle; Peterlin, B Matija

    2011-10-01

    Autoimmune regulator (AIRE) is a transcription factor that induces the expression of a large subset of otherwise strictly tissue restricted antigens in medullary thymic epithelial cells, thereby enabling their presentation to developing T cells for negative selection. Mutations in AIRE lead to autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a rare monogenetic disease. Although it has been reported that AIRE interacts with proteins involved in nuclear transport, DNA-damage response, chromatin remodeling, transcription and pre-mRNA-splicing, the precise mechanism of AIRE-induced tissue restricted antigen expression has remained elusive. In this study, we investigated an APECED patient mutation that causes the loss of the extreme C-terminus of AIRE and found that this mutant protein is transcriptionaly inactive. When tethered heterologously to DNA, this domain could stimulate transcription and splicing by itself. Moreover, the loss of this C-terminus disrupted interactions with the positive transcription elongation factor b (P-TEFb). Via P-TEFb, AIRE increased levels of RNA polymerase II on and enhanced pre-mRNA splicing of heterologous and endogenous target genes. Indeed, the inhibition of CDK9, the kinase subunit of P-TEFb, inhibited AIRE-induced pre-mRNA splicing of these genes. Thus, AIRE requires P-TEFb to activate transcription elongation and co-transcriptional processing of target genes.

  5. Patient mutation in AIRE disrupts P-TEFb binding and target gene transcription

    Science.gov (United States)

    Plemenitaš, Ana; Saksela, Kalle; Peterlin, B. Matija

    2011-01-01

    Autoimmune regulator (AIRE) is a transcription factor that induces the expression of a large subset of otherwise strictly tissue restricted antigens in medullary thymic epithelial cells, thereby enabling their presentation to developing T cells for negative selection. Mutations in AIRE lead to autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a rare monogenetic disease. Although it has been reported that AIRE interacts with proteins involved in nuclear transport, DNA-damage response, chromatin remodeling, transcription and pre-mRNA-splicing, the precise mechanism of AIRE-induced tissue restricted antigen expression has remained elusive. In this study, we investigated an APECED patient mutation that causes the loss of the extreme C-terminus of AIRE and found that this mutant protein is transcriptionaly inactive. When tethered heterologously to DNA, this domain could stimulate transcription and splicing by itself. Moreover, the loss of this C-terminus disrupted interactions with the positive transcription elongation factor b (P-TEFb). Via P-TEFb, AIRE increased levels of RNA polymerase II on and enhanced pre-mRNA splicing of heterologous and endogenous target genes. Indeed, the inhibition of CDK9, the kinase subunit of P-TEFb, inhibited AIRE-induced pre-mRNA splicing of these genes. Thus, AIRE requires P-TEFb to activate transcription elongation and co-transcriptional processing of target genes. PMID:21724609

  6. Expression of Lectin-Like Transcript 1, the Ligand for CD161, in Rheumatoid Arthritis.

    Directory of Open Access Journals (Sweden)

    Paulina Chalan

    Full Text Available Precursor Th17 lineage cells expressing CD161 are implicated in Rheumatoid Arthritis (RA pathogenesis. CD4+CD161+ T-cells accumulate in RA joints and may acquire a non classical Th1 phenotype. The endogenous ligand for CD161 is lectin-like transcript 1 (LLT1. CD161/LLT1 ligation may co-stimulate T-cell IFN-γ production. We investigated the presence and identity of LLT1-expressing cells in RA synovial fluid (SF and synovial tissue (ST. We also assessed levels of soluble LLT1 (sLLT1 in different phases of RA development.Paired samples of peripheral blood mononuclear cells (MC and SFMC (n = 14, digested ST cells (n = 4 and ST paraffin sections (n = 6 from late-stage RA were analyzed for LLT1 expression by flow cytometry and immunohistochemistry. sLLT1 was measured using a sandwich ELISA. Sera and SF from late-stage RA (n = 26, recently diagnosed RA patients (n = 39, seropositive arthralgia patients (SAP, n = 31, spondyloarthropathy patients (SpA, n = 26 and healthy controls (HC, n = 31 were assayed.In RA SF, LLT1 was expressed by a small proportion of monocytes. In RA ST, LLT1-expressing cells were detected in the lining, sublining layer and in areas with infiltrates. The LLT1 staining pattern overlapped with the CD68 staining pattern. FACS analysis of digested ST confirmed LLT1 expression by CD68+ cells. Elevated systemic sLLT1 was found in all patient groups.In RA joints, LLT1 is expressed by cells of the monocyte/macrophage lineage. Serum levels of sLLT1 were increased in all patient groups (patients with early- and late-stage RA, seropositive arthralgia and spondyloarthropathy when compared to healthy subjects.

  7. Identification of moaA3 gene in patient isolates of Mycobacterium tuberculosis in Kerala, which is absent in M. tuberculosis H37Rv and H37Ra

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    Radhakrishnan Indulakshmi

    2005-10-01

    Full Text Available Abstract Background Tuberculosis is endemic to developing countries like India. Though the whole genome sequences of the type strain M. tuberculosis H37Rv and the clinical strain M. tuberculosis CDC1551 are available, the clinical isolates from India have not been studied extensively at the genome level. This study was carried out in order to have a better understanding of isolates from Kerala, a state in southern India. Results A PCR based strategy was followed making use of the deletion region primers to understand the genome level differences between the type strain H37Rv and the clinical isolates of M. tuberculosis from Kerala. PCR analysis of patient isolates using RD1 region primers revealed the amplification of a 386 bp region, in addition to the expected 652 bp amplicon. Southern hybridization of genomic DNA with the 386 bp amplicon confirmed the presence of this new region in a majority of the patient isolates from Kerala. Sequence comparison of this amplicon showed close homology with the moaA3 gene of M. bovis. In M. bovis this gene is present in the RvD5 region, an IS6110 mediated deletion that is absent in M. tuberculosis H37Rv. Conclusion This study demonstrates the presence of moaA3 gene, that is absent in M. tuberculosis H37Rv and H37Ra, in a large number of local isolates. Whether the moaA3 gene provides any specific advantage to the field isolates of the pathogen is unclear. Field strains from Kerala have fewer IS6110 sequences and therefore are likely to have fewer IS6110 dependent rearrangements. But as deletions and insertions account for much of the genomic diversity of M. tuberculosis, the mechanisms of formation of sequence polymorphisms in the local isolates should be further examined. These results suggest that studies should focus on strains from endemic areas to understand the complexities of this pathogen.

  8. Evaluation of Real-World Experience with Tofacitinib Compared with Adalimumab, Etanercept, and Abatacept in RA Patients with 1 Previous Biologic DMARD: Data from a U.S. Administrative Claims Database.

    Science.gov (United States)

    Harnett, James; Gerber, Robert; Gruben, David; Koenig, Andrew S; Chen, Connie

    2016-12-01

    Real-world data comparing tofacitinib with biologic disease-modifying antirheumatic drugs (bDMARDs) are limited. To compare characteristics, treatment patterns, and costs of patients with rheumatoid arthritis (RA) receiving tofacitinib versus the most common bDMARDs (adalimumab [ADA], etanercept [ETN], and abatacept [ABA]) following a single bDMARD in a U.S. administrative claims database. This study was a retrospective cohort analysis of patients aged ≥ 18 years with an RA diagnosis (ICD-9-CM codes 714.0x-714.4x; 714.81) and 1 previous bDMARD filling ≥ 1 tofacitinib or bDMARD claim in the Truven MarketScan Commercial and Medicare Supplemental claims databases (November 1, 2012-October 31, 2014). Monotherapy was defined as absence of conventional synthetic DMARDs within 90 days post-index. Persistence was evaluated using a 60-day gap. Adherence was assessed using proportion of days covered (PDC). RA-related total, pharmacy, and medical costs were evaluated in the 12-month pre- and post-index periods. Treatment patterns and costs were adjusted using linear models including a common set of clinically relevant variables of interest (e.g., previous RA treatments), which were assessed separately using t-tests and chi-squared tests. Overall, 392 patients initiated tofacitinib; 178 patients initiated ADA; 118 patients initiated ETN; and 191 patients initiated ABA. Tofacitinib patients were older versus ADA patients (P = 0.0153) and had a lower proportion of Medicare supplemental patients versus ABA patients (P = 0.0095). Twelve-month pre-index bDMARD use was greater in tofacitinib patients (77.6%) versus bDMARD cohorts (47.6%-59.6%). Tofacitinib patients had greater 12-month pre-index RA-related total costs versus bDMARD cohorts (all P 0.10) proportion of patients were persistent with tofacitinib (42.6%) versus ADA (37.6%), ETN (42.4%), and ABA (43.5%). Mean PDC was 0.55 for tofacitinib versus 0.57 (ADA), 0.59 (ETN), and 0.44 (ABA; P = 0.0003). Adjusted analyses

  9. Gene expression analysis in RA: towards personalized medicine

    Science.gov (United States)

    Burska, A N; Roget, K; Blits, M; Soto Gomez, L; van de Loo, F; Hazelwood, L D; Verweij, C L; Rowe, A; Goulielmos, G N; van Baarsen, L G M; Ponchel, F

    2014-01-01

    Gene expression has recently been at the forefront of advance in personalized medicine, notably in the field of cancer and transplantation, providing a rational for a similar approach in rheumatoid arthritis (RA). RA is a prototypic inflammatory autoimmune disease with a poorly understood etiopathogenesis. Inflammation is the main feature of RA; however, many biological processes are involved at different stages of the disease. Gene expression signatures offer management tools to meet the current needs for personalization of RA patient's care. This review analyses currently available information with respect to RA diagnostic, prognostic and prediction of response to therapy with a view to highlight the abundance of data, whose comparison is often inconclusive due to the mixed use of material source, experimental methodologies and analysis tools, reinforcing the need for harmonization if gene expression signatures are to become a useful clinical tool in personalized medicine for RA patients. PMID:24589910

  10. Remission induction by Raising the dose of Remicade in RA (RRRR study: Rationale and study protocol for a randomized controlled trial comparing for sustained clinical remission after discontinuation of infliximab in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Koji Oba

    2017-12-01

    Full Text Available Infliximab, an inhibitor of TNF-α, is one of the most widely used biological disease-modifying antirheumatic drugs. Recent studies indicated that baseline serum TNF-α could be considered as a key indicator for optimal dosing of infliximab for RA treatment to achieve the clinical response and its sustained remission. The Remission induction by Raising the dose of Remicade in RA (RRRR study is an open-label, parallel group, multicenter randomized controlled trial to compare the proportions of clinical remission based on the simplified disease activity index (SDAI after 1 year of treatment and its sustained remission rate after another 1 year between the investigational treatment strategy (for which the dose of infliximab was chosen based on the baseline serum TNF and the standard strategy of 3 mg/kg per 8 weeks of infliximab administration in infliximab-naïve patients with RA showing an inadequate response to MTX. The primary endpoint is the proportion of patients who kept discontinuation of infliximab 1 year after discontinued infliximab at the time of 54 weeks after the first administration of infliximab. The secondary endpoints are the proportion of clinical remission based on SDAI and changes in SDAI from baseline at each time point, other clinical parameters, quality of life measures and adverse events. Target sample size of randomized patients is 400 patients in total. The main results of the RRRR study are expected to be published at the end of 2017.

  11. Low prevalence of transcriptionally active human papilloma virus in Indian patients with HNSCC and leukoplakia.

    Science.gov (United States)

    Bhosale, Priyanka G; Pandey, Manishkumar; Desai, Rajiv S; Patil, Asawari; Kane, Shubhada; Prabhash, Kumar; Mahimkar, Manoj B

    2016-11-01

    In the present study, we comprehensively analyzed the prevalence of transcriptionally active human papilloma virus (HPV) in tissue samples of Indian patients with leukoplakia, predominantly hyperplastic lesions and head and neck squamous cell carcinoma (HNSCC). In addition, saliva samples from patients with HNSCC were screened for HPV detection. P16 overexpression was analyzed by immunohistochemistry. Tissue samples of leukoplakia (n = 121) and HNSCC (n = 427) and saliva from patients with HNSCC (n = 215) were tested for HPV using nested polymerase chain reaction. Positive samples were sequenced for subtyping. The presence of HPV E6/E7 mRNA was confirmed by RNA in situ hybridization. P16 expression and HPV DNA were not detected in any of the leukoplakia specimens. Of the 427 HNSCC tumors, 9 showed p16 overexpression and 7/427 cases were positive for HPV16 DNA, in saliva or tissue. E6/E7 mRNA positivity was observed in 8 HNSCC samples, primarily from patients with no habit of tobacco consumption. The prevalence of high-risk HPV was restricted to oropharynx and larynx, with very little concordance between p16 overexpression and HPV positivity. All patients with HPV-positive saliva samples had transcriptionally active HPV present in their tumors. The presence of HPV DNA does not necessarily reflect transcriptionally active virus in tumors; hence, it is important to consider this fact while categorizing HPV-associated tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Responder and nonresponder patients exhibit different peripheral transcriptional signatures during major depressive episode

    Science.gov (United States)

    Belzeaux, R; Bergon, A; Jeanjean, V; Loriod, B; Formisano-Tréziny, C; Verrier, L; Loundou, A; Baumstarck-Barrau, K; Boyer, L; Gall, V; Gabert, J; Nguyen, C; Azorin, J-M; Naudin, J; Ibrahim, E C

    2012-01-01

    To date, it remains impossible to guarantee that short-term treatment given to a patient suffering from a major depressive episode (MDE) will improve long-term efficacy. Objective biological measurements and biomarkers that could help in predicting the clinical evolution of MDE are still warranted. To better understand the reason nearly half of MDE patients respond poorly to current antidepressive treatments, we examined the gene expression profile of peripheral blood samples collected from 16 severe MDE patients and 13 matched controls. Using a naturalistic and longitudinal design, we ascertained mRNA and microRNA (miRNA) expression at baseline, 2 and 8 weeks later. On a genome-wide scale, we detected transcripts with roles in various biological processes as significantly dysregulated between MDE patients and controls, notably those involved in nucleotide binding and chromatin assembly. We also established putative interactions between dysregulated mRNAs and miRNAs that may contribute to MDE physiopathology. We selected a set of mRNA candidates for quantitative reverse transcriptase PCR (RT-qPCR) to validate that the transcriptional signatures observed in responders is different from nonresponders. Furthermore, we identified a combination of four mRNAs (PPT1, TNF, IL1B and HIST1H1E) that could be predictive of treatment response. Altogether, these results highlight the importance of studies investigating the tight relationship between peripheral transcriptional changes and the dynamic clinical progression of MDE patients to provide biomarkers of MDE evolution and prognosis. PMID:23149449

  13. SMN transcript levels in leukocytes of SMA patients determined by absolute real-time PCR

    Science.gov (United States)

    Tiziano, Francesco Danilo; Pinto, Anna Maria; Fiori, Stefania; Lomastro, Rosa; Messina, Sonia; Bruno, Claudio; Pini, Antonella; Pane, Marika; D'Amico, Adele; Ghezzo, Alessandro; Bertini, Enrico; Mercuri, Eugenio; Neri, Giovanni; Brahe, Christina

    2010-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by homozygous mutations of the SMN1 gene. Three forms of SMA are recognized (type I–III) on the basis of clinical severity. All patients have at least one or more (usually 2–4) copies of a highly homologous gene (SMN2), which produces insufficient levels of functional SMN protein, because of alternative splicing of exon 7. Recently, evidence has been provided that SMN2 expression can be enhanced by pharmacological treatment. However, no reliable biomarkers are available to test the molecular efficacy of the treatments. At present, the only potential biomarker is the dosage of SMN products in peripheral blood. However, the demonstration that SMN full-length (SMN-fl) transcript levels are reduced in leukocytes of patients compared with controls remains elusive (except for type I). We have developed a novel assay based on absolute real-time PCR, which allows the quantification of SMN1-fl/SMN2-fl transcripts. For the first time, we have shown that SMN-fl levels are reduced in leukocytes of type II–III patients compared with controls. We also found that transcript levels are related to clinical severity as in type III patients SMN2-fl levels are significantly higher compared with type II and directly correlated with functional ability in type II patients and with age of onset in type III patients. Moreover, in haploidentical siblings with discordant phenotype, the less severely affected individuals showed significantly higher transcript levels. Our study shows that SMN2-fl dosage in leukocytes can be considered a reliable biomarker and can provide the rationale for SMN dosage in clinical trials. PMID:19603064

  14. Imbalances in T Cell-Related Transcription Factors Among Patients with Hashimoto’s Thyroiditis

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    Vahid Safdari

    2017-06-01

    Full Text Available Objectives: Imbalances in effector T cell functioning have been associated with a number of autoimmune diseases, including Hashimoto’s thyroiditis (HT. Differentiation of effector T helper (Th 1, Th2, Th17 and regulatory T cell (Treg lymphocytes is regulated by transcription factors, including Th1-specific T box (T-bet, GATA binding protein-3 (GATA3, retinoid-related orphan receptor (ROR-α and forkhead box P3 (FOXP3. This study aimed to investigate Th1/Th2, Th1/Treg, Th2/Treg and Th17/Treg balances at the level of these transcription factors. Methods: This study took place between October 2015 and August 2016. Peripheral blood mononuclear cells were collected from a control group of 40 healthy women recruited from the Zahedan University of Medical Sciences, Zahedan, Iran, and a patient group of 40 women with HT referred to the Hazrat Ali Asghar Hospital, Zahedan. Total ribonucleic acid extraction was performed and the gene expression of transcription factors was quantitated using a real-time polymerase chain reaction technique. Results: Expression of T-bet and GATA3 was significantly elevated, while FOXP3 expression was significantly diminished among HT patients in comparison with the controls (P = 0.03, 0.01 and 0.05, respectively. Expression of RORα was higher among HT patients, although this difference was not significant (P = 0.15. Expression of T-bet/FOXP3, GATA3/FOXP3 and RORα/FOXP3 ratios were increased among HT patients in comparison with the controls (P <0.02, <0.01 and <0.01, respectively. Conclusion: These results indicate that HT patients have imbalances in Th1/Treg, Th2/Treg and Th17/Treg lymphocytes at the level of the transcription factors, deviating towards Th1, Th2 and Th17 cells. Correction of these imbalances may therefore be therapeutic.

  15. IL-1Ra: its role in rheumatoid arthritis

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    M. Cutolo

    2011-09-01

    Full Text Available Interleukin-1 (IL-1 is one of the pivotal cytokines in initiating and driving the processes of rheumatoid arthritis (RA, and the body’s natural response, IL-1 receptor antagonist (IL-1Ra, has been shown conclusively to block its effects. IL-1 mediate several clinical symptoms of the inflammatory reaction (i.e. fever, pain, sleep disturbances. IL-1 is considered a key mediator in RA joint damage because of its greater capacity (greater than TNF of increasing matrix degradation by inducing the production of MMPs and PGE2 in synovial cells, as well by its role as mediator of bone and cartilage destruction. In addition, IL-1 decreases the repair process by suppressing matrix synthesis and shows a strong synergism with TNF in inducing many inflammatory genes at both local and systemic level. The induced endogenous production of IL-1Ra, in presence of the RA synovitis, is too low to contrast the high affinity of IL-1 for the cell receptors. Therefore, IL-1Ra presence should result in very effective prevention of IL-1 signal transduction particularly in the inflammatory site. In laboratory and animal studies inhibition of IL-1 by either antibodies to IL-1 or IL-1Ra proved beneficial to the outcome. IL-1Ra is a member of the IL-1 superfamily. The effects of different DMARDs on IL-1Ra levels in RA patients support the important role that selected anticytokine treatments might exert in the pathophysiology of the disease. However, since anti TNFα therapy it is not effective in all RA patients, nor does it fully control the arthritic process in affected joints of good responders and complete TNF suppression should be avoided, the combined treatment with intermediate doses of TNF and IL-1 blockers, reaching synergistic suppression of arthritis, seems warranted in RA.

  16. TARGETED INFORMATION ON METHOTREXATE AND LIFTING ALCOHOL RESTRICTIONS IN PATIENTS WITH RA AND PSA IS SAFE AND REDUCES PATIENTS' NEGATIVE BELIEFS

    DEFF Research Database (Denmark)

    Larsen, Janni Lisander; Nordin, Henrik

    as a cytotoxic agent. Thus patients often associate the drug to cancer treatment and thereby resent the treatment. However, the doses used in the treatment of arthritis of restrictions on alcohol...... restrictions asking patients to adhere to national Danish guidelines (5). Objectives To investigate the effects of altered information strategy and the safety of increased alcohol limits for patients with Rheumatoid Arthritis and Psoriatic Arthritis. Methods Patients in a single outpatient clinic receiving MTX...... for Rheumatoid Arthritis or Psoriatic Arthritis were interviewed by postal delivered questionnaire for their beliefs regarding MTX and their alcohol consumption (6). Informed consent was obtained. The patients were on stable treatment for at least 6 months prior to answering the questionnaire. Liver enzyme...

  17. Does Regular Use of a Complementary Medicine of Olea Europe and Ficus carica Have Adverse Effects on Lipid Profile and Fasting Blood Glucose of Rheumatoid Arthritis (RA) Patients Under Treatment with DMARD Regimens Containing Methotrexate?

    Science.gov (United States)

    Bahadori, Shahnaz; Ahmadzadeh, Arman; Shams Ardekani, Mohammad Reza; Kamalinejad, Mohammad; Keshavarz, Mansoor; Salamzadeh, Jamshid

    2016-01-01

    Rheumatoid arthritis (RA) patients are vulnerable to cardiovascular morbidity and mortality in which atherosclerosis plays a major role. In this study, the lipid profile and fasting blood sugar (FBS) of RA patients receiving a complementary medicine of olive and fig, as add-on therapy for routine disease-modifying antirheumatic drugs (DMARDs) regimen containing low dose methotrexate (MTX), were studied. A randomized controlled clinical trial was designed. Adult RA patients were randomly allocated in two groups receiving routine DMARDs regimen (control group) and routine DMARDs regimen plus the herbal supplementary formulation of olive oil, fig and olive fruits (intervention group). Patients were followed every 4 weeks for total study period of 16 weeks. In addition to demographic and medical history of the patients, the total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), the atherogenic index of plasma (AIP) defined as log(TG/HDL-C), and the fasting blood sugar (FBS) were determined and recorded. 56 patients (control = 27 and intervention = 29), with mean ± sd age of 50.9 ± 12.3 years completed the study. Average MTX dose received by intervention and control groups were 24.30 ± 18.39 and 17.61 ± 15.53 mg/week, respectively (p = 0.11). Repeated measures analysis of variance (ANOVA) revealed that differences between lipid profile indicators and FBS in the two study groups were not statistically significant (P>0.05). No additional substantial adverse reaction was seen in the study groups. Our findings are more reassuring for patients and their doctors to trust on the safety of the investigated complementary preparation to be used as add-on therapy to manage rheumatoid arthritis.

  18. Radium Ra 223 dichloride in castration-resistant prostate cancer.

    Science.gov (United States)

    Joung, J Y; Ha, Y S; Kim, I Y

    2013-08-01

    Radium Ra 223 dichloride (Xofigo®, formerly Alpharadin) is one of the representative α-particle-emitting isotopes that delivers radiation with a higher biological effect to a more localized area. Preclinical studies in mouse, rat and canine models have demonstrated that radium Ra 223 dichloride has a definite skeletal affinity and antitumor effect with a relatively low toxicity on bone marrow. More recently, in a large randomized phase III trial (ALSYMPCA), patients with bone metastasis and castration-resistant prostate cancer (CRPC) received six cycles of 50 kBq/kg of radium Ra 223 dichloride in 4-week intervals. In these men, radium Ra 223 dichloride improved the median overall survival by 3.6 months when compared to the placebo group. Collectively, these results suggest that radium Ra 223 dichloride is a promising candidate for managing bone metastases in patients with CRPC. Copyright 2013 Prous Science, S.A.U. or its licensors. All rights reserved.

  19. The association of fatigue, comorbidity burden, disease activity, disability and gross domestic product in patients with rheumatoid arthritis. Results from 34 countries participating in the Quest-RA program

    DEFF Research Database (Denmark)

    Grøn, Kathrine Lederballe; Ornbjerg, Lykke Midtbøll; Hetland, Merete Lund

    2014-01-01

    OBJECTIVES: The aim is to assess the prevalence of comorbidities and to further analyse to which degree fatigue can be explained by comorbidity burden, disease activity, disability and gross domestic product (GDP) in patients with rheumatoid arthritis (RA). METHODS: Nine thousands eight hundred...... seventy-four patients from 34 countries, 16 with high GDP (>24.000 US dollars [USD] per capita) and 18 low-GDP countries (visual analogue scale...... [VAS] [10=worst]), disease activity in 28 joints (DAS28), and physical disability (Health Assessment Questionnaire score [HAQ]) were assessed. Univariate and multivariate linear regression analyses were performed to assess the association between fatigue and comorbidities, disease activity, disability...

  20. Activating transcription factor 3 is not up-regulated in hypospadias patients in Japan

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    Toshiaki Takahashi

    2013-01-01

    Full Text Available Background: The aetiology of hypospadias is largely uncharacterized. Some of the researchers have advocated that activating transcription factor 3 (ATF3, an oestrogen-responsive transcription factor, is up-regulated in patients with hypospadias. The purpose is to evaluate the universality of this fact; we studied the expression of ATF3 protein in prepuce tissue obtained from hypospadias and phimosis patients living in metropolitan Tokyo. Materials and Methods: Prepuce tissue was obtained from outer foreskin at the time of surgery, quickly prepared for paraffin-embedded sectioning and stained immunohistochemically for ATF3. Two researchers blindly evaluated immunoreactivity and scored it semi-quantitatively as nil = 0, weak = 1, or strong = 2, to give a final staining intensity score (SIS. Subjects were 18 hypospadias patients and 17 phimosis patients (as controls who had surgery between January, 2009 and March, 2010. Results: All subjects lived in metropolitan Tokyo, Japan. Mean ages at surgery were 2.9 ± 1.0 and 3.9 ± 2.4 years, respectively (P > 0.05. SIS was not statistically different between hypospadias patients (1.4 ± 0.5 and controls (1.5 ± 0.5, (P > 0.05. Conclusions: Our data suggest that ATF3 is not highly associated with hypospadias in metropolitan Tokyo. Differences in ethnicity might have influenced our results.

  1. Induced myelomonocytic differentiation in leukemia cells is accompanied by noncanonical transcription factor expression.

    Science.gov (United States)

    Jensen, Holly A; Yourish, Harmony B; Bunaciu, Rodica P; Varner, Jeffrey D; Yen, Andrew

    2015-01-01

    Transcription factors that drive non-neoplastic myelomonocytic differentiation are well characterized but have not been systematically analyzed in the leukemic context. We investigated widely used, patient-derived myeloid leukemia cell lines with proclivity for differentiation into granulocytes by retinoic acid (RA) and/or monocytes by 1,25-dihyrdroxyvitamin D3 (D3). Using K562 (FAB M1), HL60 (FAB M2), RA-resistant HL60 sublines, NB4 (FAB M3), and U937 (FAB M5), we correlated nuclear transcription factor expression to immunophenotype, G1/G0 cell cycle arrest and functional inducible oxidative metabolism. We found that myelomonocytic transcription factors are aberrantly expressed in these cell lines. Monocytic-lineage factor EGR1 was not induced by D3 (the monocytic inducer) but instead by RA (the granulocytic inducer) in lineage bipotent myeloblastic HL60. In promyelocytic NB4 cells, EGR1 levels were increased by D3, while Gfi-1 expression (which promotes the granulocytic lineage) was upregulated during D3-induced monocytic differentiation in HL60, and by RA treatment in monocytic U937 cells. Furthermore, RARα and VDR expression were not strongly correlated to differentiation. In response to different differentiation inducers, U937 exhibited the most distinct transcription factor expression profile, while similarly mature NB4 and HL60 were better coupled. Overall, the differentiation induction agents RA and D3 elicited cell-specific responses across these common FAB M1-M5 cell lines.

  2. Radium isotope ((223)Ra, (224)Ra, (226)Ra and (228)Ra) distribution near Brazil's largest port, Paranaguá Bay, Brazil.

    Science.gov (United States)

    Dias, Thais H; de Oliveira, Joselene; Sanders, Christian J; Carvalho, Franciane; Sanders, Luciana M; Machado, Eunice C; Sá, Fabian

    2016-10-15

    This work investigates the (223)Ra, (224)Ra, (226)Ra and (228)Ra isotope distribution in river, estuarine waters and sediments of the Paranaguá Estuarine Complex (PEC). The stratification of the Ra isotopes along water columns indicate differing natural sources. In sediments, the radium isotope activities was inversely proportional to the particle size. The highest concentrations of (223)Ra, (224)Ra, (226)Ra and (228)Ra in the water column were found in the bottom more saline waters and towards the inner of the estuary. These relatively high concentrations towards the bottom of the estuary may be attributed to the influence of tidally driven groundwater source and desorption from particles at the maximum turbidity zone. The apparent river water ages from the radium isotope ratios, (223)Ra/(224)Ra and (223)Ra/(228)Ra, indicate that the principal rivers that flow into the estuary have residence times from between 6 and 11days. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Association between Acne and Serum Pro-inflammatory Cytokines (IL-1α, IL-1β, IL-1Ra, IL-6, IL-8, IL-12 and RANTES) in Mustard Gas-Exposed Patients: Sardasht-Iran Cohort Study.

    Science.gov (United States)

    Askari, Nayere; Ghazanfari, Tooba; Yaraee, Roya; Vaez Mahdavi, Mohammad Reza; Soroush, Mohammad-Reza; Mohammad Hassan, Zuhair; Khodashenas, Zohre; Shams, Jalaleddin; Faghihzadeh, Soghrat

    2017-02-01

    Acne vulgaris is a very common chronic inflammatory disorder, yet its pathogenesis is not clearly understood. As part of the SICS, this study was conducted to evaluate the association between the incidence of acne vulgaris in SM-exposed subjects (20 years after the exposure) and serum levels of proinflammatory cytokines (IL-1α, IL-1β, IL-1Ra, IL-6, IL-8, IL-12 and RANTES) in an attempt to better understand the pathogenesis of long-term skin disorders of these individuals. Serum concentrations of cytokines (IL-1α, IL-1β, IL-1Ra, IL-6, IL-8, IL-12 and RANTES) were measured using sandwich ELISA technique. The median of serum levels of IL-1β, IL-8 and RANTES were significantly higher in the exposed patients with acne than those without acne (P = 0.05, 0.03 and 0.001 respectively). There was no significant difference in serum levels of IL-1α, IL-1Ra and IL-6 between the exposed subgroups. We found a positive association between serum levels of pro-inflammatory cytokines (IL-1β, IL-8, IL-12 and RANTES) and acne among SM-exposed population.

  4. Erythroid-specific transcriptional changes in PBMCs from pulmonary hypertension patients.

    Directory of Open Access Journals (Sweden)

    Chris Cheadle

    Full Text Available Gene expression profiling of peripheral blood mononuclear cells (PBMCs is a powerful tool for the identification of surrogate markers involved in disease processes. The hypothesis tested in this study was that chronic exposure of PBMCs to a hypertensive environment in remodeled pulmonary vessels would be reflected by specific transcriptional changes in these cells.The transcript profiles of PBMCs from 30 idiopathic pulmonary arterial hypertension patients (IPAH, 19 patients with systemic sclerosis without pulmonary hypertension (SSc, 42 scleroderma-associated pulmonary arterial hypertensio patients (SSc-PAH, and 8 patients with SSc complicated by interstitial lung disease and pulmonary hypertension (SSc-PH-ILD were compared to the gene expression profiles of PBMCs from 41 healthy individuals. Multiple gene expression signatures were identified which could distinguish various disease groups from controls. One of these signatures, specific for erythrocyte maturation, is enriched specifically in patients with PH. This association was validated in multiple published datasets. The erythropoiesis signature was strongly correlated with hemodynamic measures of increasing disease severity in IPAH patients. No significant correlation of the same type was noted for SSc-PAH patients, this despite a clear signature enrichment within this group overall. These findings suggest an association of the erythropoiesis signature in PBMCs from patients with PH with a variable presentation among different subtypes of disease.In PH, the expansion of immature red blood cell precursors may constitute a response to the increasingly hypoxic conditions prevalent in this syndrome. A correlation of this erythrocyte signature with more severe hypertension cases may provide an important biomarker of disease progression.

  5. Understanding Rheumatoid Arthritis (RA): Research

    Science.gov (United States)

    ... this page please turn JavaScript on. Feature: Understanding Rheumatoid Arthritis (RA) Research Past Issues / Summer 2014 Table of ... a project plan to address relevant challenges for rheumatoid arthritis. Read Part 1 on Lupus in MedlinePlus magazine, ...

  6. Association of HLA antigens and BCR-ABL transcripts in leukemia patients with the Philadelphia chromosome

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    Daiana Landenberger de Carvalho

    2012-01-01

    Full Text Available OBJECTIVE: This study aimed to verify the association between human leukocyte antigens and the bcr-abl fusion protein resulting from t(9;22(q34;q11 in chronic leukemia myeloid and acute lymphoblastic leukemia patients. METHODS: Forty-seven bcr-abl positive individuals were evaluated. Typing was performed bymicrolymphocytotoxicity and molecular biological methods (human leukocyte antigens Class I and Class II. A control group was obtained from the data of potential bone marrow donors registered in the Brazilian Bone Marrow Donor Registry (REDOME. RESULTS: Positive associations with HLA-A25 and HLA-B18 were found for the b2a2 transcript, as well as a tendency towards a positive association with HLA-B40 and a negative association with HLA-A68. The b3a2 transcript showed positive associations with HLA-B40 and HLA-DRB1*3. CONCLUSION: The negative association between human leukocyte antigens and the BCR-ABL transcript suggests that binding and presentation of peptides derived from the chimeric protein are effective to increase a cytotoxic T lymphocyte response appropriate for the destruction of leukemic cells.

  7. EXPRESSION OF NEGATIVE TRANSCRIPTION REGULATORS IN PERIPHERAL BLOOD MONONUCLEARS IN PATIENTS WITH BRONCHIAL ASTHMA

    Directory of Open Access Journals (Sweden)

    V. V. Lim

    2016-01-01

    Full Text Available Sixty patients with allergic bronchial asthma (ABA and forty-one, with non-allergic bronchial asthma (NABA, as well as 23 healthy controls were under study. Expression of the SOCS5 mRNA from mononuclear blood cells was analyzed by RT-PCR. In patients with bronchial asthma, (ABA and NABA we determined a significant increase of mRNA expression levels for a SOCS5 negative transcription regulator in peripheral blood mononuclears, in comparison with control group. Thus, an increase of SOCS5-expression, and of the SOCS3 mRNA expression in patients with BA may be associated with protective anti-inflammatory response.

  8. Reduced transcription of TCOF1 in adult cells of Treacher Collins syndrome patients

    Directory of Open Access Journals (Sweden)

    Camargo Anamaria A

    2009-12-01

    Full Text Available Abstract Background Treacher Collins syndrome (TCS is an autosomal dominant craniofacial disorder caused by frameshift deletions or duplications in the TCOF1 gene. These mutations cause premature termination codons, which are predicted to lead to mRNA degradation by nonsense mediated mRNA decay (NMD. Haploinsufficiency of the gene product (treacle during embryonic development is the proposed molecular mechanism underlying TCS. However, it is still unknown if TCOF1 expression levels are decreased in post-embryonic human cells. Methods We have estimated TCOF1 transcript levels through real time PCR in mRNA obtained from leucocytes and mesenchymal cells of TCS patients (n = 23 and controls (n = 18. Mutational screening and analysis of NMD were performed by direct sequencing of gDNA and cDNA, respectively. Results All the 23 patients had typical clinical features of the syndrome and pathogenic mutations were detected in 19 of them. We demonstrated that the expression level of TCOF1 is 18-31% lower in patients than in controls (p , even if we exclude the patients in whom we did not detect the pathogenic mutation. We also observed that the mutant allele is usually less abundant than the wild type one in mesenchymal cells. Conclusions This is the first study to report decreased expression levels of TCOF1 in TCS adult human cells, but it is still unknown if this finding is associated to any phenotype in adulthood. In addition, as we demonstrated that alleles harboring the pathogenic mutations have lower expression, we herein corroborate the current hypothesis of NMD of the mutant transcript as the explanation for diminished levels of TCOF1 expression. Further, considering that TCOF1 deficiency in adult cells could be associated to pathologic clinical findings, it will be important to verify if TCS patients have an impairment in adult stem cell properties, as this can reduce the efficiency of plastic surgery results during rehabilitation of these

  9. Determination of Ra-224 and Ra-226 in drinking waters

    Science.gov (United States)

    Semenishchev, V. S.; Betenekov, N. D.; Tomashova, L. A.; Voronina, A. V.

    2017-09-01

    Activity of 224Ra and 226Ra were determined in some types of natural drinking water. An improved method of radiochemical analysis of radium was developed. The method included radium preconcentration by the granulated titanium dioxide and further thin alpha source preparation by radium sorption onto a thin-layer manganese dioxide disk based on cellulose triacetate (MnO2-CTA). It was shown that time of radium sorption on MnO2-CTA should be 1 day; sorption degree of 75 % was achieved. Longer sorption resulted in sorption degree of 85 % but the quality of alpha spectrum was lower due to radium diffusion into the MnO2 film. 22 samples of commercially available mineral waters, 4 samples from springs and 4 samples from wells near Yekaterinburg city were analyzed. The results demonstrated that mineral waters contain more 226Ra (0.4-125 mBq L-1) than fresh underground water (0.5-29 mBq L-1); no samples were found with 226Ra activity exceeding maximum allowable level (490 mBq L-1). Activities of 224Ra in fresh waters were found to be 0.5 to 20 mBq L-1 that was also less than the maximum allowable level.

  10. Phenotypic and transcriptional fidelity of patient-derived colon cancer xenografts in immune-deficient mice.

    Directory of Open Access Journals (Sweden)

    Jeffrey Chou

    Full Text Available Xenografts of human colorectal cancer (CRC in immune-deficient mice have great potential for accelerating the study of tumor biology and therapy. We evaluated xenografts established in NOD/scid/IL2Rγ-null mice from the primary or metastatic tumors of 27 patients with CRC to estimate their capacity for expanding tumor cells for in vitro studies and to assess how faithfully they recapitulated the transcriptional profile of their parental tumors. RNA-seq analysis of parental human CRC tumors and their derivative xenografts demonstrated that reproducible transcriptional changes characterize the human tumor to murine xenograft transition. In most but not all cases, the human stroma, vasculature, and hematopoietic elements were systematically replaced by murine analogues while the carcinoma component persisted. Once established as xenografts, human CRC cells that could be propagated by serial transplantation remained transcriptionally stable. Three histologically atypical xenografts, established from patients with peritoneal metastases, contained abundant human stromal elements and blood vessels in addition to human tumor cells. The transcriptomes of these mixed tumor/stromal xenografts did not closely resemble those of their parental tumors, and attempts to propagate such xenografts by serial transplantation were unsuccessful. Stable expression of numerous genes previously identified as high priority targets for immunotherapy was observed in most xenograft lineages. Aberrant expression in CRC cells of human genes that are normally only expressed in hematopoietic cells was also observed. Our results suggest that human CRC cells expanded in murine xenografts have great utility for studies of tumor immunobiology and targeted therapies such as immunotherapy but also identify potential limitations.

  11. Activation of Epithelial Signal Transducer and Activator of Transcription 1 by Interleukin 28 Controls Mucosal Healing in Mice With Colitis and Is Increased in Mucosa of Patients With Inflammatory Bowel Disease.

    Science.gov (United States)

    Chiriac, Mircea T; Buchen, Barbara; Wandersee, Alexandra; Hundorfean, Gheorghe; Günther, Claudia; Bourjau, Yvonne; Doyle, Sean E; Frey, Benjamin; Ekici, Arif B; Büttner, Christian; Weigmann, Benno; Atreya, Raja; Wirtz, Stefan; Becker, Christoph; Siebler, Jürgen; Neurath, Markus F

    2017-07-01

    We investigated the roles of interleukin 28A (also called IL28A or interferon λ2) in intestinal epithelial cell (IEC) activation, studying its effects in mouse models of inflammatory bowel diseases (IBD) and intestinal mucosal healing. Colitis was induced in C57BL/6JCrl mice (controls), mice with IEC-specific disruption of Stat1 (Stat1IEC-KO), mice with disruption of the interferon λ receptor 1 gene (Il28ra-/-), and mice with disruption of the interferon regulatory factor 3 gene (Irf3-/-), with or without disruption of Irf7 (Irf7-/-). We used high-resolution mini-endoscopy and in vivo imaging methods to assess colitis progression. We used 3-dimensional small intestine and colon organoids, along with RNA-Seq and gene ontology methods, to characterize the effects of IL28 on primary IECs. We studied the effects of IL28 on the human intestinal cancer cell line Caco-2 in a wound-healing assay, and in mice colon wounds. Colonic biopsies and resected tissue from patients with IBD (n = 62) and patients without colon inflammation (controls, n = 23) were analyzed by quantitative polymerase chain rection to measure expression of IL28A, IL28RA, and other related cytokines; biopsy samples were also analyzed by immunofluorescence to identify sources of IL28 production. IECs were isolated from patient tissues and incubated with IL28; signal transducer and activator of transcription 1 (STAT1) phosphorylation was measured by immunoblots and confocal imaging. Lamina propria cells in colon tissues of patients with IBD, and mice with colitis, had increased expression of IL28 compared with controls; levels of IL28R were increased in the colonic epithelium of patients with IBD and mice with colitis. Administration of IL28 induced phosphorylation of STAT1 in primary human and mouse IECs, increasing with dose. Il28ra-/-, Irf3-/-, Irf3-/-Irf7-/-, as well as Stat1IEC-KO mice, developed more severe colitis after administration of dextran sulfate sodium than control mice, with reduced

  12. Avaliação da expressão de interleucina 1 beta (IL-1β e antagonista do receptor de interleucina 1 (IL-1Ra em pacientes com hanseníase Evaluation of the expression of interleukin 1 beta(IL-1β and interleukin 1 receptor antagonist (IL-1Ra in leprosy patients

    Directory of Open Access Journals (Sweden)

    Rosane Dias Costa

    2008-01-01

    Full Text Available A hanseníase é uma doença infectocontagiosa espectral que acompanha-se por uma série de eventos imunológicos desencadeados pela resposta do hospedeiro frente ao agente etiológico, o Mycobacterium leprae. Evidências sugerem que a indução e manutenção da resposta imune/inflamatória na hanseníase estão vinculadas a interações de múltiplas células e fatores solúveis, particularmente através da ação de citocinas. Nesse estudo, foram mensurados níveis de IL-1β e IL-1Ra de 37 casos novos de hanseníase acompanhados ao longo do tratamento e 30 controles sadios pelo teste ELISA. A coleta de sangue periférico foi realizada em quatro tempos para os casos de hanseníase (pré-tratamento com PQT, 2ª dose, 6ª dose e pós-PQT e em único momento para os controles. Na comparação dos níveis das moléculas de casos no pré-PQT e controles, houve diferença estatisticamente significativa somente para IL-1β. Nossos resultados sugerem a participação dessa citocina no processo imune/inflamatório.Leprosy is an infectious and contagious spectral disease accompanied by a series of immunological events triggered by the host's response to the etiologic agent, Mycobacterium leprae. Evidence suggests that the induction and maintenance of the immune/inflammatory response in leprosy are linked to multiple cell interactions and soluble factors, mainly through the action of cytokines. The ELISA test was used to measure the levels of IL-1β and IL-1Ra in 37 new leprosy patients followed-up during treatment and 30 healthy controls. Peripheral blood was collected four times during the treatment of leprosy patients (MDT pretreatment, 2nd dose, 6th dose and post-MDT, and only once from the controls. The comparison of molecular levels in pre-MDT patients and controls showed a statistically significant difference for IL-1β. The results suggest the participation of this cytokine in the genesis of the immune/inflammatory process.

  13. The association of fatigue, comorbidity burden, disease activity, disability and gross domestic product in patients with rheumatoid arthritis. Results from 34 countries participating in the Quest-RA program

    DEFF Research Database (Denmark)

    Grøn, Kathrine Lederballe; Ørnbjerg, Lykke Midtbøll; Hetland, Merete Lund

    2014-01-01

    OBJECTIVES: The aim is to assess the prevalence of comorbidities and to further analyse to which degree fatigue can be explained by comorbidity burden, disease activity, disability and gross domestic product (GDP) in patients with rheumatoid arthritis (RA). METHODS: Nine thousands eight hundred...... [VAS] [10=worst]), disease activity in 28 joints (DAS28), and physical disability (Health Assessment Questionnaire score [HAQ]) were assessed. Univariate and multivariate linear regression analyses were performed to assess the association between fatigue and comorbidities, disease activity, disability...... and GDP. RESULTS: Overall, patients reported a median of 2 comorbid conditions of which hypertension (31.5%), osteoporosis (17.6%), osteoarthritis (15.5%) and hyperlipidaemia (14.2%) were the most prevalent. The majority of comorbidities were more common in high-GDP countries. The median fatigue score...

  14. Early recognition improves prognosis in elderly onset RA. .

    Science.gov (United States)

    Negoescu, Andra; Ostör, Andrew J K

    2014-01-01

    Although commonly diagnosed in the third to fifth decades of life, the incidence and prevalence of RA continue to increase up to the ninth decade. Age at onset is particularly relevant as the presentation may differ in elderly onset RA (EORA) compared with young onset RA (YORA). Patients with EORA frequently report a more acute presentation, especially if positive for rheumatoid factor (RF). Fever, fatigue and weight loss appear to be more common in EORA. Although small joints are most frequently involved in the RA population overall, there is common involvement of large joints in EORA and these proximal symptoms may mimic polymyalgia rheumatica (PMR). In YORA, approximately 80% of patients are seropositive for RF however a lower frequency has been reported in EORA. Anti-CCP antibodies have been detected in over 70% of patients with RA and are highly specific for RA. The value of anti-CCP antibodies is even higher in patients with an atypical presentation (e.g. PMR-like symptoms), or those who are RF negative. X-rays of the hands and feet should always be performed in patients with a suspected inflammatory arthritis. Baseline joint erosions are present in a similar proportion in patients with YORA and EORA. In the elderly, the differential diagnosis of RA is extensive as many conditions present in a similar way e.g. PMR, osteoarthritis, polyarticular gout, pseudogout and malignancy. Anti-CCP antibodies are very useful for identifying EORA patients with a polymyalgic onset. Ultrasonography or MRI can also be helpful in differentiating PMR from EORA.

  15. EXTRACTS FROM THE TEZKIRE OF BUGRA (TRANSCRIPTION – SOME NOTES ON DIALECTOLOGY – TRANSLATION BUĞRA TEZKİRESİ’NDEN PARÇALAR (TRANSKRİPSİYON – DİL ÖZELLİKLERİ ÜZERİNE BAZI AÇIKLAMALAR – TERCÜME

    Directory of Open Access Journals (Sweden)

    Mehmet Turgut BERBERCAN

    2011-12-01

    Full Text Available In this work, extracts from the tazkira of Bughra, a typical text ofthe term Post-Classical Chagatay written in Arabic script is analysedfrom a philological perspective for Turkish language researches. At firstin the work, the text is divided into lines and each line is numerated inorder to analyse the dialectology of the text properly. In this form,transcription from the Arabic script to Latin script is prepared.Additionally, various determinations are made on some grammarelements and dialectology of the text and also the text is translated intoTurkey Turkish. Bu çalışmada, tipik Klasik Dönem Sonrası Çağatayca özelliklerigösteren Arap harfli Buğra Tezkiresi’nden Parçalar, Türk dili araştırmalarıaçısından filolojik bir bakış açısıyla incelenmiştir. Öncelikle çalışmada,metnin dil özelliklerinin uygun bir şekilde incelenmesi amacıyla metinsatırlara bölünmüş ve her satır numaralandırılmış; bu düzen içindemetnin, Arap harflerinden Latin harflerine transkripsiyonuhazırlanmıştır. İlâveten, metinde geçen bazı gramer unsurları ve dilözellikleri üzerine çeşitli tespitler yapılmış ve ayrıca metin TürkiyeTürkçesine tercüme edilmiştir.

  16. Lightcurve of NEA 1993 RA

    Science.gov (United States)

    Vaduvescu, Ovidiu; Aznar Macias, Amadeo

    2018-01-01

    The near-Earth asteroid (NEA) 1993 RA was observed with the 2.5-m Isaac Newton Telescope (INT) in full Moon conditions for 8h total during three successive nights (2017 Oct 3-6). The composite lightcurve could be fit by a 3-order period P = 5.64 ± 0.01 h with amplitude of 0.13 mag; other solutions are possible.

  17. Early Development of Hyperparathyroidism Due to Loss of PTH Transcriptional Repression in Patients With HNF1beta Mutations?

    NARCIS (Netherlands)

    Ferre, S.; Bongers, E.M.H.F.; Sonneveld, R.; Cornelissen, E.A.M.; Vlag, J. van der; Boekel, G.A.J van; Wetzels, J.F.M.; Hoenderop, J.G.J.; Bindels, R.J.M.; Nijenhuis, T.

    2013-01-01

    Context: Heterozygous mutations or deletions of the transcription factor hepatocyte nuclear factor 1beta (HNF1beta) result in a heterogeneous syndrome characterized by renal cysts and diabetes, together with a variety of other extrarenal and renal manifestations. Interestingly, in several patients

  18. Evaluation of Lama5 as a candidate for the mouse ragged (Ra) mutation

    DEFF Research Database (Denmark)

    Durkin, M E; Albrechtsen, R; Chambers, D M

    1998-01-01

    The laminin alpha5 chain is a component of the basement membranes of many developing and adult tissues. The mouse laminin alpha5 chain gene (Lama5) has been mapped close to the locus of the semidominant ragged (Ra) mutation on distal chromosome 2. The cause of the Ra mutation, which is usually...... lethal in the homozygous state, has not been determined. We have investigated whether a defect in Lama5 is responsible for the ragged mutation, using the RaJ strain. No differences in the level of the laminin alpha5 chain transcript were found in placental RNA from homozygous RaJ mutant embryos compared....... These results exclude Lama5 as a candidate gene for the Ra mutation....

  19. NPM and BRG1 Mediate Transcriptional Resistance to Retinoic Acid in Acute Promyelocytic Leukemia.

    Science.gov (United States)

    Nichol, Jessica N; Galbraith, Matthew D; Kleinman, Claudia L; Espinosa, Joaquín M; Miller, Wilson H

    2016-03-29

    Perturbation in the transcriptional control of genes driving differentiation is an established paradigm whereby oncogenic fusion proteins promote leukemia. From a retinoic acid (RA)-sensitive acute promyelocytic leukemia (APL) cell line, we derived an RA-resistant clone characterized by a block in transcription initiation, despite maintaining wild-type PML/RARA expression. We uncovered an aberrant interaction among PML/RARA, nucleophosmin (NPM), and topoisomerase II beta (TOP2B). Surprisingly, RA stimulation in these cells results in enhanced chromatin association of the nucleosome remodeler BRG1. Inhibition of NPM or TOP2B abrogated BRG1 recruitment. Furthermore, NPM inhibition and targeting BRG1 restored differentiation when combined with RA. Here, we demonstrate a role for NPM and BRG1 in obstructing RA differentiation and implicate chromatin remodeling in mediating therapeutic resistance in malignancies. NPM mutations are the most common genetic change in patients with acute leukemia (AML); therefore, our model may be applicable to other more common leukemias driven by NPM. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Identification of Differentially Expressed K-Ras Transcript Variants in Patients With Leiomyoma.

    Science.gov (United States)

    Zolfaghari, Nooshin; Shahbazi, Shirin; Torfeh, Mahnaz; Khorasani, Maryam; Hashemi, Mehrdad; Mahdian, Reza

    2017-10-01

    Molecular studies have demonstrated a wide range of gene expression variations in uterine leiomyoma. The rat sarcoma virus/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase (RAS/RAF/MAPK) is the crucial cellular pathway in transmitting external signals into nucleus. Deregulation of this pathway contributes to excessive cell proliferation and tumorigenesis. The present study aims to investigate the expression profile of the K-Ras transcripts in tissue samples from patients with leiomyoma. The patients were leiomyoma cases who had no mutation in mediator complex subunit 12 ( MED12) gene. A quantitative approach has been applied to determine the difference in the expression of the 2 main K-Ras messenger RNA (mRNA) variants. The comparison between gene expression levels in leiomyoma and normal myometrium group was performed using relative expression software tool. The expression of K-Ras4B gene was upregulated in leiomyoma group ( P = .016), suggesting the involvement of K-Ras4B in the disease pathogenesis. Pairwise comparison of the K-Ras4B expression between each leiomyoma tissue and its matched adjacent normal myometrium revealed gene upregulation in 68% of the cases. The expression of K-Ras4A mRNA was relatively upregulated in leiomyoma group ( P = .030). In addition, the mean expression of K-Ras4A gene in leiomyoma tissues relative to normal samples was 4.475 (95% confidence interval: 0.10-20.42; standard error: 0.53-12.67). In total, 58% of the cases showed more than 2-fold increase in K-Ras4A gene expression. Our results demonstrated increased expression of both K-Ras mRNA splicing variants in leiomyoma tissue. However, the ultimate result of KRAS expression on leiomyoma development depends on the overall KRAS isoform balance and, consequently, on activated signaling pathways.

  1. Compilation of Spectroscopic Data of Radium (Ra I and Ra II)

    NARCIS (Netherlands)

    Dammalapati, U.; Jungmann, K.; Willmann, L.

    2016-01-01

    Energy levels, wavelengths, lifetimes, and hyperfine structure constants for the isotopes of the first and second spectra of radium, Ra I and Ra II, have been compiled. Wavelengths and wavenumbers are tabulated for 226Ra and for other Ra isotopes. Isotope shifts and hyperfine structure constants of

  2. Determining the lowest optimally effective methotrexate dose for individual RA patients using their dose response relation in a tight control treatment approach

    NARCIS (Netherlands)

    Nair, Sandhya C.; Jacobs, Johannes W G|info:eu-repo/dai/nl/075134373; Bakker, Marije F.|info:eu-repo/dai/nl/304812498; Jahangier, Z. Nazira; Bijlsma, Johannes W J|info:eu-repo/dai/nl/069357536; Van Laar, Jacobs M.; Lafeber, Floris P J G|info:eu-repo/dai/nl/073410071; Welsing, Paco M J|info:eu-repo/dai/nl/288401921

    2016-01-01

    Objective: To determine the optimal methotrexate dose in individual patients and to explore whether this optimal dose and the level of disease activity at that dose could be predicted. Methods: Data from CAMERA II trial comparing MTX and MTX with 10 mg of prednisone both in a tight control treatment

  3. Compilation of spectroscopic data of Radium (Ra I and Ra II)

    CERN Document Server

    Dammalapati, U; Willmann, L

    2016-01-01

    Energy levels, wavelengths, lifetimes and hyperfine structure constants for the isotopes of the first and second spectra of radium, Ra I and Ra II have been compiled. Wavelengths and wave numbers are tabulated for 226Ra and for other Ra isotopes. Isotope shifts and hyperfine structure constants of even and odd-A isotopes of neutral radium atom and singly ionized radium are included. Experimental lifetimes of the states for both neutral and ionic Ra are also added, where available. The information is beneficial for present and future experiments aimed at different physics motivations using neutral Ra and singly ionized Ra.

  4. Tocilizumab: a novel humanized anti-interleukin 6 (IL-6) receptor antibody for the treatment of patients with non-RA systemic, inflammatory rheumatic diseases.

    Science.gov (United States)

    Alten, Rieke; Maleitzke, Tazio

    2013-06-01

    Tocilizumab is a highly effective therapeutic agent for the treatment of rheumatoid arthritis and systemic juvenile idiopathic arthritis. Furthermore, a large amount of case study data reveals that tocilizumab can be an effective therapy for not only rheumatoid arthritis but also for other mostly rare inflammatory rheumatic diseases. By blocking the interleukin-6 pathway tocilizumab can be a useful therapeutic alternative when conventional treatment fails. It is successful in treating diseases such as the adult-onset Still's disease, amyloidosis, giant cell arteritis, multiple myeloma, polymyalgia rheumatica, relapsing polychondritis, remitting seronegative symmetrical synovitis with pitting edema-syndrome, systemic lupus erythematosus, systemic sclerosis, and Takayasu arteritis. Studies underway are now recruiting patients to acquire further data on treating patients with non-rheumatic arthritis, inflammatory diseases. This review focuses on tocilizumab as a promising agent for treating rare and orphan diseases in rheumatology for which no satisfactory treatment is yet available.

  5. Effect of radium-223 dichloride (Ra-223) on hospitalisation: An analysis from the phase 3 randomised Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) trial.

    Science.gov (United States)

    Parker, Christopher; Zhan, Lin; Cislo, Paul; Reuning-Scherer, Jonathan; Vogelzang, Nicholas J; Nilsson, Sten; Sartor, Oliver; O'Sullivan, Joe M; Coleman, Robert E

    2017-01-01

    Symptomatic skeletal events (SSEs) commonly occur in patients with bone metastases, often leading to hospitalisations and decreased quality-of-life. In the ALSYMPCA trial, radium-223 significantly improved overall survival (hazard ratio 0.70, 95% confidence interval [CI] 0.58-0.83, P radium-223 (218/589; 37.0%) versus placebo patients (133/292; 45.5%) had at least one hospitalisation event (P = 0.016). However, mean number of hospitalisation events per patient was similar (radium-223 0.69 versus placebo 0.79, P = 0.226), likely due to the significantly longer follow-up time for radium-223 (7.82 months versus 6.92 months for placebo; P radium-223 (4.44 versus 6.68, respectively, P = 0.004). The reduction in hospitalisation days with radium-223 was observed both before first SSE (2.35 days versus 3.36 days, respectively) and after SSE (7.74 days versus 9.19 days, respectively). Our data suggest that this reduced hospital days along with the survival benefit and reduction in time to SSEs with radium-223 treatment may contribute to improvements in health-related quality-of-life in patients with castration-resistant prostate cancer with symptomatic bone metastases (ALSYMPCA ClinicalTrials.gov number, NCT00699751.). Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Compilation of spectroscopic data of Radium (Ra I and Ra II)

    OpenAIRE

    Dammalapati, U.; Jungmann, K.; Willmann, L.

    2016-01-01

    Energy levels, wavelengths, lifetimes and hyperfine structure constants for the isotopes of the first and second spectra of radium, Ra I and Ra II have been compiled. Wavelengths and wave numbers are tabulated for 226Ra and for other Ra isotopes. Isotope shifts and hyperfine structure constants of even and odd-A isotopes of neutral radium atom and singly ionized radium are included. Experimental lifetimes of the states for both neutral and ionic Ra are also added, where available. The informa...

  7. Carbamylation/citrullination of IgG Fc in bronchiectasis, established RA with bronchiectasis and RA smokers: a potential risk factor for disease

    Directory of Open Access Journals (Sweden)

    David Hutchinson

    2017-09-01

    Full Text Available Bronchiectasis (BR and smoking are risk factors for rheumatoid arthritis (RA development. The mechanisms by which smoking and BR trigger RA are unknown, but are associated with concurrent rheumatoid factor (RF and anti-cyclic citrullinated peptide antibody (anti-CCP positivity. Anti-carbamylated protein antibodies (anti-CarP have also been observed in BR patients and can be induced by smoking. Given that RF only has one antigen, immunoglobulin G (IgG we have suggested that post-translational modifications to the Fc region of the heavy chain of IgG (IgGH are a potential explanation for the clustering of the RA-associated autoantibodies in RA. Protein analysis was undertaken on 22 individuals. Four of the individuals had a diagnosis of BR at the time of protein analysis and subsequently developed RA up to 18 months following blood sampling. Four smoking RA patients and 4 patients with both BR and RA and 10 healthy controls were also studied. We identified modified arginines (Arg frequently in the variable region and CH3 domains of IgG in patients and control subjects alike, but only observed carbamylated Lys and/or citrullinated Arg modifications in the RF binding site of the IgG CH2 domain of 5/12 (41.7% patients investigated (1 BR, 2 RA and 2 BRRA, but in no control subjects (0/10, 0% p=0.02. This is the first report of citrullination and carbamylation at the RF binding site of IgG in RA. These results point towards the concept of a universal antigen in RA, an antigen that is post-translationally modified at the Fc region of IgGH.

  8. Are Fusion Transcripts in Relapsed/Metastatic Head and Neck Cancer Patients Predictive of Response to Anti-EGFR Therapies?

    Directory of Open Access Journals (Sweden)

    Paolo Bossi

    2017-01-01

    Full Text Available Prediction of benefit from combined chemotherapy and the antiepidermal growth factor receptor cetuximab is a not yet solved question in head and neck squamous cell carcinoma (HNSCC. In a selected series of 14 long progression-free survival (PFS and 26 short PFS patients by whole gene and microRNA expression analysis, we developed a model potentially predictive of cetuximab sensitivity. To better decipher the “omics” profile of our patients, we detected transcript fusions by RNA-seq through a Pan-Cancer panel targeting 1385 cancer genes. Twenty-seven different fusion transcripts, involving mRNA and long noncoding RNA (lncRNA, were identified. The majority of fusions (81% were intrachromosomal, and 24 patients (60% harbor at least one of them. The presence/absence of fusions and the presence of more than one fusion were not related to outcome, while the lncRNA-containing fusions resulted enriched in long PFS patients (P=0.0027. The CD274-PDCD1LG2 fusion was present in 7/14 short PFS patients harboring fusions and was absent in long PFS patients (P=0.0188. Among the short PFS patients, those harboring this fusion had the worst outcome (P=0.0172 and increased K-RAS activation (P=0.00147. The associations between HNSCC patient’s outcome following cetuximab treatment and lncRNA-containing fusions or the CD274-PDCD1LG2 fusion deserve validation in prospective clinical trials.

  9. LCA versus RA - an introduction

    DEFF Research Database (Denmark)

    Olsen, Stig Irving

    2000-01-01

    Risk Assessment (RA) of chemicals is an environmental management tool used to assess the risk of specific chemicals, which are harmful to man or the environment under certain circumstances of use or in certain environmental recipients. Life Cycle Assessment (LCA) or environmental assessment...... of products is another environmental management tool that gains more and more ground, and which is often thought of as universal due to its basic holistic philosophy. As the environmental impacts of one product can only be seen in relation to the impacts of other products providing the same functions, LCA...... is a comparative tool. The primary purpose of this article is to identify harmonies, discrepancies and relations between the two tools, exemplified by the risk assessment principles of the European Commission (EC) as stated in 'Technical Guidance Document' (EC, 1996) and the LCA method 'EDIP' (Environmental Design...

  10. Repetitive element transcripts are elevated in the brain of C9orf72 ALS/FTLD patients.

    Science.gov (United States)

    Prudencio, Mercedes; Gonzales, Patrick K; Cook, Casey N; Gendron, Tania F; Daughrity, Lillian M; Song, Yuping; Ebbert, Mark T W; van Blitterswijk, Marka; Zhang, Yong-Jie; Jansen-West, Karen; Baker, Matthew C; DeTure, Michael; Rademakers, Rosa; Boylan, Kevin B; Dickson, Dennis W; Petrucelli, Leonard; Link, Christopher D

    2017-09-01

    Significant transcriptome alterations are detected in the brain of patients with amyotrophic lateral sclerosis (ALS), including carriers of the C9orf72 repeat expansion and C9orf72-negative sporadic cases. Recently, the expression of repetitive element transcripts has been associated with toxicity and, while increased repetitive element expression has been observed in several neurodegenerative diseases, little is known about their contribution to ALS. To assess whether aberrant expression of repetitive element sequences are observed in ALS, we analysed RNA sequencing data from C9orf72-positive and sporadic ALS cases, as well as healthy controls. Transcripts from multiple classes and subclasses of repetitive elements (LINEs, endogenous retroviruses, DNA transposons, simple repeats, etc.) were significantly increased in the frontal cortex of C9orf72 ALS patients. A large collection of patient samples, representing both C9orf72 positive and negative ALS, ALS/FTLD, and FTLD cases, was used to validate the levels of several repetitive element transcripts. These analyses confirmed that repetitive element expression was significantly increased in C9orf72-positive compared to C9orf72-negative or control cases. While previous studies suggest an important link between TDP-43 and repetitive element biology, our data indicate that TDP-43 pathology alone is insufficient to account for the observed changes in repetitive elements in ALS/FTLD. Instead, we found that repetitive element expression positively correlated with RNA polymerase II activity in postmortem brain, and pharmacologic modulation of RNA polymerase II activity altered repetitive element expression in vitro. We conclude that increased RNA polymerase II activity in ALS/FTLD may lead to increased repetitive element transcript expression, a novel pathological feature of ALS/FTLD. © The Author 2017. Published by Oxford University Press.

  11. Novel clinical associations with specific C9ORF72 transcripts in patients with repeat expansions in C9ORF72.

    Science.gov (United States)

    van Blitterswijk, Marka; Gendron, Tania F; Baker, Matthew C; DeJesus-Hernandez, Mariely; Finch, NiCole A; Brown, Patricia H; Daughrity, Lillian M; Murray, Melissa E; Heckman, Michael G; Jiang, Jie; Lagier-Tourenne, Clotilde; Edbauer, Dieter; Cleveland, Don W; Josephs, Keith A; Parisi, Joseph E; Knopman, David S; Petersen, Ronald C; Petrucelli, Leonard; Boeve, Bradley F; Graff-Radford, Neill R; Boylan, Kevin B; Dickson, Dennis W; Rademakers, Rosa

    2015-12-01

    The loss of chromosome 9 open reading frame 72 (C9ORF72) expression, associated with C9ORF72 repeat expansions, has not been examined systematically. Three C9ORF72 transcript variants have been described thus far; the GGGGCC repeat is located between two non-coding exons (exon 1a and exon 1b) in the promoter region of transcript variant 2 (NM_018325.4) or in the first intron of variant 1 (NM_145005.6) and variant 3 (NM_001256054.2). We studied C9ORF72 expression in expansion carriers (n = 56) for whom cerebellum and/or frontal cortex was available. Using quantitative real-time PCR and digital molecular barcoding techniques, we assessed total C9ORF72 transcripts, variant 1, variant 2, variant 3, and intron containing transcripts [upstream of the expansion (intron 1a) and downstream of the expansion (intron 1b)]; the latter were correlated with levels of poly(GP) and poly(GA) proteins aberrantly translated from the expansion as measured by immunoassay (n = 50). We detected a decrease in expansion carriers as compared to controls for total C9ORF72 transcripts, variant 1, and variant 2: the strongest association was observed for variant 2 (quantitative real-time PCR cerebellum: median 43 %, p = 1.26e-06, and frontal cortex: median 58 %, p = 1.11e-05; digital molecular barcoding cerebellum: median 31 %, p = 5.23e-10, and frontal cortex: median 53 %, p = 5.07e-10). Importantly, we revealed that variant 1 levels greater than the 25th percentile conferred a survival advantage [digital molecular barcoding cerebellum: hazard ratio (HR) 0.31, p = 0.003, and frontal cortex: HR 0.23, p = 0.0001]. When focusing on intron containing transcripts, analysis of the frontal cortex revealed an increase of potentially truncated transcripts in expansion carriers as compared to controls [digital molecular barcoding frontal cortex (intron 1a): median 272 %, p = 0.003], with the highest levels in patients pathologically diagnosed with frontotemporal lobar degeneration

  12. Correlation of p210 BCR-ABL transcript variants with clinical, parameters and disease outcome in 45 chronic myeloid leukemia patients.

    Science.gov (United States)

    Al-Achkar, Walid; Moassass, Faten; Youssef, Nagham; Wafa, Abdulsamad

    2016-01-01

    The aim of this study was to search the BCR/ABL 1 fusion gene in 45 chronic myeloid leukemia (CML) Syrian patients using nested reverse transcription polymerase chain reaction (RT-PCR) and compare our results with those of conventional cytogenetics and molecular cytogenetics methods. 45 bone marrow or peripheral blood samples from untreated CML patients in chronic phase (CP) were obtained at diagnosis, and analyzed by nested RT-PCR, conventional cytogenetics and molecular cyto-genetics methods. 45 patients examined were positive for some type of BCR/ABL1 fusion gene rearrangement. Out of 45 studied CML patients, 23 (51.1%) expressed b3a2 fusion transcript, 21 (46.7%) b2a2 transcript, and 1 (2.2%) a rare b2a3 transcript. No patient co-expressed both b3a2/b2a2 types. The distribution BCR-ABL1 transcript types found in Syria were similar to that of Indian Far-Eastern, African or European populations and the M-BCR rearrangement types were not dependent on white blood count (WBC), platelet count, hemoglobin level or gender of the patients. Overall, we could show that patients with b3a2 rearrangements were younger than patients with b2a2 transcripts, thus our young patients may have a worse prognosis.

  13. Validation of aspirin response-related transcripts in patients with coronary artery disease and preliminary investigation on CMTM5 function.

    Science.gov (United States)

    Zhang, J W; Liu, T F; Chen, X H; Liang, W Y; Feng, X R; Wang, L; Fu, Sidney W; McCaffrey, Timothy A; Liu, M L

    2017-08-15

    Aspirin is widely used in the prevention of cardiovascular diseases, but the antiplatelet responses vary from one patient to another. To validate aspirin response related transcripts and illustrate their roles in predicting cardiovascular events, we have quantified the relative expression of 14 transcripts previously identified as related to high on-aspirin platelet reactivity (HAPR) in 223 patients with coronary artery disease (CAD) on regular aspirin treatment. All patients were followed up regularly for cardiovascular events (CVE). The mean age of our enrolled population was 75.80±8.57years. HAPR patients showed no significant differences in terms of co-morbidities and combined drugs. Besides, the relative expression of HLA-DQA1 was significantly lower in low on-aspirin platelet reactivity (LAPR) patients, when compared with HAPR and high normal (HN) group (p=0.028). What's more, the number of arteries involved, HAPR status and the relative expression of CLU, CMTM5 and SPARC were independent risk factors for CVE during follow up (p<0.05). In addition, overexpression of CMTM5 attenuated endothelial cells (ECs) migration and proliferation, with significantly decreased phosphorylated-Akt levels, while its inhibition promoted these processes in vitro (p<0.05).Our study provides evidence that circulating transcripts might be potential biomarkers in predicting cardiovascular events. CMTM5 might exert anti-atherosclerotic effects via suppressing migration and proliferation in the vessel wall. Nevertheless, larger-scale and long-term studies are still needed. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Determination of 226Ra and 224Ra in drinking waters by liquid scintillation counting.

    Science.gov (United States)

    Manjón, G; Vioque, I; Moreno, H; García-Tenorio, R; García-León, M

    1997-04-01

    A method for the determination of Ra-isotopes in water samples has been developed. Ra is coprecipitated with Ba as sulphate. The precipitate is then dissolved with EDTA and counted with a liquid scintillation system after mixing with a scintillation cocktail. The study of the temporal evolution of the separated activity gives the isotopic composition of the sample, i.e. the 224Ra and 226Ra contribution to the total activity. The method has been applied to some Spanish drinking waters.

  15. Expression of Caspase-1 Gene Transcript Variant mRNA in Peripheral Blood Mononuclear Cells of Patients with Primary Gout in Different TCM Syndromes

    Directory of Open Access Journals (Sweden)

    Wan-Tai Dang

    2015-01-01

    Full Text Available A large number of studies have shown that cysteinyl aspartate specific protease-1 (CASP1 played an important role in the inflammatory response of primary gout, but the decreased expression of different CASP1 transcript variant could inhibit the activation of IL-1β. Our study mainly analyzed the expression level and function of CASP1 gene transcript variant mRNA in peripheral blood mononuclear cells of patients with gout in different TCM syndromes. The expression of CASP1 gene transcript variant and IL-1β mRNA in PBMCs were detected in patients with PG [acute phase (AP: 44 cases; nonacute phase (NAP: 52 cases] and healthy controls (HC: 30 cases by reverse transcription-polymerase chain reaction and/or real-time quantitative polymerase chain reaction. The expressions of plasma IL-1β in patients with PG and HC were detected by enzyme-linked immunosorbent assay. Dysregulated expression of the CASP1 gene and its transcript variant, plasma proinflammatory cytokines in all patients with primary gout in different TCM syndromes, correlation analysis showed that there was negative correlation between the expression of CASP1-gamma gene transcript variant mRNA and IL-1β protein in APPG group. The study suggested that CASP1 gene and its transcript variant may play a critical role in the inflammatory response of patients with PG in different phases and TCM syndromes.

  16. Inherent transcriptional signatures of NK cells are associated with response to IFNα + rivabirin therapy in patients with Hepatitis C Virus.

    Science.gov (United States)

    Ascierto, Maria Libera; Bozzano, Federica; Bedognetti, Davide; Marras, Francesco; Schechterly, Cathy; Matsuura, Kentaro; Picciotto, Antonino; Marenco, Simona; Zhao, Yingdong; DeGiorgi, Valeria; Sommariva, Michele; Moretta, Lorenzo; Wang, Ena; Alter, Harvey J; Marincola, Francesco M; De Maria, Andrea

    2015-03-01

    Differences in the expression of Natural Killer cell receptors have been reported to reflect divergent clinical courses in patients with chronic infections or tumors. However, extensive molecular characterization at the transcriptional level to support this view is lacking. The aim of this work was to characterize baseline differences in purified NK cell transcriptional activity stratified by response to treatment with PEG-IFNα/RBV in patients chronically infected with HCV. To this end we here studied by flow cytometer and gene expression profile, phenotypic and transcriptional characteristics of purified NK cells in patients chronically infected with HCV genotype-1 virus who were subsequently treated with PEG-IFNα/RBV. Results were further correlated with divergent clinical response obtained after treatment. The pre-treatment transcriptional patterns of purified NK cells from patients subsequently undergoing a sustained virologic response (SVR) clearly segregated from those of non-responder (NR) patients. A set of 476 transcripts, including molecules involved in RNA processing, ubiquitination pathways as well as HLA class II signalling were differently expressed among divergent patients. In addition, treatment outcome was associated with differences in surface expression of NKp30 and NKG2D. A complex relationship was observed that suggested for extensive post-transcriptional editing. Only a small number of the NK cell transcripts identified were correlated with chronic HCV infection/replication indicating that inherent transcriptional activity prevails over environment effects such as viral infection. Collectively, inherent/genetic modulation of NK cell transcription is involved in setting the path to divergent treatment outcomes and could become useful to therapeutic advantage.

  17. Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients

    DEFF Research Database (Denmark)

    Urup, Thomas; Staunstrup, Line Maersk; Michaelsen, Signe Regner

    2017-01-01

    expression profiling of formalin-fixed paraffin-embedded tumor tissue was performed using RNA-sequencing.Results: By comparing pretreatment samples of responders with those of non-responders no significant difference was observed. In a paired comparison analysis of pre- and posttreatment samples of non...... distinct gene expression changes while responding tumors adaptively respond or progress by means of the same transcriptional changes. In conclusion, we hypothesize that the identified gene expression changes of responding tumors are associated to bevacizumab response or resistance mechanisms....

  18. Quantitative analysis of interferon alpha receptor subunit 1 and suppressor of cytokine signaling 1 gene transcription in blood cells of patients with chronic hepatitis C.

    Science.gov (United States)

    Sedeño-Monge, Virginia; Santos-López, Gerardo; Rocha-Gracia, Rosa C; Meléndez-Mena, Daniel; Ramírez-Mata, Alberto; Vallejo-Ruiz, Verónica; Reyes-Leyva, Julio

    2010-09-18

    Interferon (IFN)-α receptor 1 (ifnar1) and suppressor of cytokine signaling 1 (socs1) transcription levels were quantified in peripheral blood mononuclear cells (PBMC) of 59 patients infected with hepatitis C virus (HCV) and 17 non-infected individuals. Samples were obtained from patients infected with HCV that were either untreated or treated with IFN-α2 plus ribavirin for 1 year and divided into responders and non-responders based on viral load reduction 6 months after treatment. Ifnar1 and socs1 transcription was quantified by real-time RT-PCR, and the fold difference (2(⁻ΔΔCT)) with respect to hprt housekeeping gene was calculated. Ifnar1 transcription increased significantly in HCV-infected patients either untreated (3.26 ± 0.31), responders (3.1 ± 0.23) and non-responders (2.18 ± 0.23) with respect to non-infected individuals (1 ± 0.34; P = 0.005). Ifnar1 transcription increased significantly (P = 0.003) in patients infected with HCV genotypes 1a (4.74 ± 0.25) and 1b (2.81 ± 0.25) but not in 1a1b (1.58 ± 0.21). No association was found of Ifnar1 transcription with disease progress, initial viral load or other clinical factors. With respect to socs1 transcription, values were similar for non-infected individuals (1 ± 0.28) and untreated patients (0.99 ± 0.41) but increased in responders (2.81 ± 0.17) and non-responder patients (1.67 ± 0.41). Difference between responder and non-responder patients was not statistically significant. Socs1 transcription increased in patients infected with HCV genotypes 1a and 1b (2.87 ± 0.45 and 2.22 ± 0.17, respectively) but not in 1a1b (1.28 ± 0.40). Socs1 transcript was absent in three patients infected with HCV genotype 1b. A weak correlation between ifnar1 and socs1 transcription was found, when Spearman's correlation coefficient was calculated. Our results suggest that HCV infection may up-regulate ifnar1 transcription. HCV genotypes differ in their capacity to affect ifnar1 and socs1 transcription, as

  19. Quantitative analysis of interferon alpha receptor subunit 1 and suppressor of cytokine signaling 1 gene transcription in blood cells of patients with chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    Sedeño-Monge Virginia

    2010-09-01

    Full Text Available Abstract Background Interferon (IFN-α receptor 1 (ifnar1 and suppressor of cytokine signaling 1 (socs1 transcription levels were quantified in peripheral blood mononuclear cells (PBMC of 59 patients infected with hepatitis C virus (HCV and 17 non-infected individuals. Samples were obtained from patients infected with HCV that were either untreated or treated with IFN-α2 plus ribavirin for 1 year and divided into responders and non-responders based on viral load reduction 6 months after treatment. Ifnar1 and socs1 transcription was quantified by real-time RT-PCR, and the fold difference (2-ΔΔCT with respect to hprt housekeeping gene was calculated. Results Ifnar1 transcription increased significantly in HCV-infected patients either untreated (3.26 ± 0.31, responders (3.1 ± 0.23 and non-responders (2.18 ± 0.23 with respect to non-infected individuals (1 ± 0.34; P = 0.005. Ifnar1 transcription increased significantly (P = 0.003 in patients infected with HCV genotypes 1a (4.74 ± 0.25 and 1b (2.81 ± 0.25 but not in 1a1b (1.58 ± 0.21. No association was found of Ifnar1 transcription with disease progress, initial viral load or other clinical factors. With respect to socs1 transcription, values were similar for non-infected individuals (1 ± 0.28 and untreated patients (0.99 ± 0.41 but increased in responders (2.81 ± 0.17 and non-responder patients (1.67 ± 0.41. Difference between responder and non-responder patients was not statistically significant. Socs1 transcription increased in patients infected with HCV genotypes 1a and 1b (2.87 ± 0.45 and 2.22 ± 0.17, respectively but not in 1a1b (1.28 ± 0.40. Socs1 transcript was absent in three patients infected with HCV genotype 1b. A weak correlation between ifnar1 and socs1 transcription was found, when Spearman's correlation coefficient was calculated. Conclusion Our results suggest that HCV infection may up-regulate ifnar1 transcription. HCV genotypes differ in their capacity to affect

  20. RA-RAR-β counteracts myelin-dependent inhibition of neurite outgrowth via Lingo-1 repression.

    Science.gov (United States)

    Puttagunta, Radhika; Schmandke, André; Floriddia, Elisa; Gaub, Perrine; Fomin, Natalie; Ghyselinck, Norbert B; Di Giovanni, Simone

    2011-06-27

    After an acute central nervous system injury, axonal regeneration is limited as the result of a lack of neuronal intrinsic competence and the presence of extrinsic inhibitory signals. The injury fragments the myelin neuronal insulating layer, releasing extrinsic inhibitory molecules to signal through the neuronal membrane-bound Nogo receptor (NgR) complex. In this paper, we show that a neuronal transcriptional pathway can interfere with extrinsic inhibitory myelin-dependent signaling, thereby promoting neurite outgrowth. Specifically, retinoic acid (RA), acting through the RA receptor β (RAR-β), inhibited myelin-activated NgR signaling through the transcriptional repression of the NgR complex member Lingo-1. We show that suppression of Lingo-1 was required for RA-RAR-β to counteract extrinsic inhibition of neurite outgrowth. Furthermore, we confirm in vivo that RA treatment after a dorsal column overhemisection injury inhibited Lingo-1 expression, specifically through RAR-β. Our findings identify a novel link between RA-RAR-β-dependent proaxonal outgrowth and inhibitory NgR complex-dependent signaling, potentially allowing for the development of molecular strategies to enhance axonal regeneration after a central nervous system injury.

  1. Treatment of ankylosing spondylitis with [{sup 224}Ra]-Radiumchloride; Therapie der Spondylitis ankylosans mit [{sup 224}Ra]-Radiumchlorid

    Energy Technology Data Exchange (ETDEWEB)

    Reiners, C. [Klinik und Poliklinik fuer Nuklearmedizin der Univ. Wuerzburg (Germany); Braun, J. [Rheumazentrum Ruhrgebiet Herne (Germany)

    2001-07-01

    Ankylosing spondylitis (AS) is a chronic disease which in 30-50% of the patients leads to considerable episodes of pain, a remarkable reduction of quality of life and disablement. For treatment mostly nonsteroidal antiphlogistic drugs are used which are able to reduce pain in approximately 80% of the patients only. Those drugs however, have to be withdrawn in approximately 30% of the patients due to its known toxicity (mainly in the gastrointestinal tract). Basis medication (DMARDs) is helpful in a minority of AS patients only. Recently [{sup 224}Ra]-Radiumchloride, which has been used previously between 1955 and 1990, has been made available again for treatment of AS. Whereas biokinetics, radiation exposure and the risk-profile of [{sup 224}Ra]-Radiumchloride are documented well by experimental and clinical data, most of the historical studies about the efficacy of this radiopharmaceutical do not fulfill the requirements of modern therapy studies. Therefore as many patients as possible should be recruited for a prospective long-time Phase IV study. A close and well-coordinated cooperation between rheumatologists and nuclear medicine physicians is needed, when [{sup 224}Ra]-Radiumchloride is used for treatment of AS. (orig.) [German] Die meist chronisch, oft auch in Schueben verlaufende Spondylitis ankylosans (AS) fuehrt bei 30-50% der Patienten zu betraechtlichen Schmerzen und einer nicht selten erheblichen Einschraenkung der Lebensqualitaet und Behinderung. Die am haeufigsten zur Therapie verwendeten nichtsteroidalen Antiphlogistika koennen nur bei etwa 80% der Patienten die Schmerzen lindern. Allerdings muessen diese Medikamente bei 20-30% der AS-Patienten wegen ihrer bekannten Toxizitaet - vor allem im Gastrointestinaltrakt - abgesetzt werden. Basistherapeutika (DMARDs) helfen bei der AS nur sehr begrenzt. Mit [{sup 224}Ra]-Radiumchlorid steht seit kurzem ein bereits in den Jahren 1945-1990 fuer die Behandlung der AS verwendetes Radiopharmakon wieder zur

  2. Developing a Construct to Evaluate Flares in Rheumatoid Arthritis: A Conceptual Report of the OMERACT RA Flare Definition Working Group

    DEFF Research Database (Denmark)

    Alten, Rieke; Choy, Ernest H; Christensen, Robin

    2011-01-01

    is intended to enhance patient-HCP communication. This article describes the conceptual framework being used by the OMERACT RA Flare Definition Working Group in developing a standardized method for description and measurement of "flare in RA" to guide individual patient treatment.......Rheumatoid arthritis (RA) patients and healthcare professionals (HCP) recognize that episodic worsening disease activity, often described as a "flare," is a common feature of RA that can contribute to impaired function and disability. However, there is no standard definition to enable measurement...... of its intensity and impact. The conceptual framework of the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA Flare Definition Working Group includes an anchoring statement, developed at OMERACT 9 in 2008: "flare in RA" is defined as worsening of signs and symptoms of sufficient intensity...

  3. Defective transcription-coupled repair of oxidative base damage in Cockayne syndrome patients from XP group G.

    Science.gov (United States)

    Cooper, P K; Nouspikel, T; Clarkson, S G; Leadon, S A

    1997-02-14

    In normal human cells, damage due to ultraviolet light is preferentially removed from active genes by nucleotide excision repair (NER) in a transcription-coupled repair (TCR) process that requires the gene products defective in Cockayne syndrome (CS). Oxidative damage, including thymine glycols, is shown to be removed by TCR in cells from normal individuals and from xeroderma pigmentosum (XP)-A, XP-F, and XP-G patients who have NER defects but not from XP-G patients who have severe CS. Thus, TCR of oxidative damage requires an XPG function distinct from its NER endonuclease activity. These results raise the possibility that defective TCR of oxidative damage contributes to the developmental defects associated with CS.

  4. ICMPv6 RA Flooding Vulnerability Research

    National Research Council Canada - National Science Library

    Linas Jočys

    2016-01-01

    .... It is know that ICMPv6 is technologically vulnerable. One of those vulnerabilities is the ICMPv6 RA flooding vulnerability, which can lead to systems in Local Area Network slow down or full stop...

  5. Understanding Rheumatoid Arthritis (RA): Treatment and Causes

    Science.gov (United States)

    ... this page please turn JavaScript on. Feature: Understanding Rheumatoid Arthritis (RA) Treatment and Causes Past Issues / Summer 2014 Table of Contents How Is Rheumatoid Arthritis Treated? Doctors have many ways to treat this ...

  6. RA Construction KC, LLC Information Sheet

    Science.gov (United States)

    RA Construction KC, LLC (the Company) is located in Gladstone, Missouri. The settlement involves renovation activities conducted at a property constructed prior to 1978, located in Kansas City, Missouri.

  7. Outcome prediction by the transcript level of BCR-ABL at 3 months in patients with chronic myeloid leukemia treated with imatinib--a single institution historical experience.

    Science.gov (United States)

    Yin, Xiu-Feng; Ma, Qiu-Ling; Mu, Qi-Tian; Shao, Li; Wang, Sha-Sha; Meng, Hai-Tao; Xu, Wei-Lai; Wang, Yun-Gui; Chen, Zhi-Mei; Chen, Fei-Fei; Jin, Jie

    2014-10-01

    The BCR-ABL transcript level (≤ 10%) at 3 months after tyrosine kinase inhibitors can predict long term outcome in the patients with chronic myeloid leukemia in chronic phase (CML-CP). However, the significance of transcript level was still not determined in different risk groups of patients. A total of 299 patients with CML-CP were enrolled and stratified according to prior interferon-α (IFN) treatment, age, and interval time between diagnosis and imatinib treatment to investigate the prediction value of BCR-ABL transcript level for overall survival (OS), event-free survival (EFS), progression-free survival (PFS). Univariate and multivariate analysis proved that BCR-ABL transcript level at 3 months were associated with the treatment outcome. However, in the patients with prior IFN treatment, younger age, and longer interval between diagnosis and IM treatment, the predictive value of transcript value remain obscure in terms of EFS, PFS and OS, respectively, as well as cumulative incidence of PCyR, CCR, MMR and CMR. In conclusion, the transcript level of BCR-ABL at 3 months could serve as a predictive parameter, but should be used with caution. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Napadi na računarske sisteme

    OpenAIRE

    Vuletić V. Dejan

    2012-01-01

    Računarski sistemi su kritični segment ljudskog društva u 21. veku. Ekonomski sektor, odbrana, bezbednost, energetika, telekomunikacije, industrijska proizvodnja, finansije i druge vitalne infrastrukture zavise od računarskih sistema koje rade u lokalnim, nacionalnim ili globalnim razmerama. Poseban problem jeste što se zbog ubrzanog razvoja informaciono-komunikacione tehnologije i nezaustavljivog rasta njene primene u svim sferama ljudskog društva uvećava njegova ranjivost ...

  9. Article sur barrage de Téra

    African Journals Online (AJOL)

    ENI DOSSO

    Situé dans le Liptako nigérien, en zone de socle, où les ressources en eau souterraines sont limitées, le département de Téra et, en particulier, son chef lieu, la ville de Téra, est confrontée à un problème aigu d'approvisionnement en eau potable des populations. Aussi, comme solution à ce manque d'eau qui bloque.

  10. Verjetnostni model računanja:

    OpenAIRE

    Žerovnik, Janez

    1989-01-01

    In article a survey of a probabilistic model of computation is given. Some classes of probabilistic algorithms are defined. Preliminary sections give definition of classical (deterministic) model of computation and introduction to the theory of time complexity of computation. V preglednem članku predstavimo verjetnostni model računanja in podamo definicijo nekaterih razredov časovne zahtevnosti verjetnostnih algoritmov. V začetnih razdelkih vpeljemo klasični (deterministični) model računan...

  11. Influence of BCR-ABL Transcript Type on Outcome in Patients With Chronic-Phase Chronic Myeloid Leukemia Treated With Imatinib.

    Science.gov (United States)

    Pagnano, Katia Borgia Barbosa; Miranda, Eliana Cristina; Delamain, Márcia Torresan; Duarte, Gislaine Oliveira; de Paula, Erich Vinicius; Lorand-Metze, Irene; de Souza, Carmino Antonio

    2017-11-01

    The prognostic significance of breakpoint cluster region gene-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL1) transcripts in chronic myeloid leukemia (CML) is still controversial. All consecutive CML patients in chronic phase treated with imatinib in a single center were analyzed (n = 170). BCR-ABL1 transcript was evaluated using multiplex reverse transcription polymerase chain reaction. Exclusively patients with BCR-ABL transcripts e13a2 and/or e14a2 were included in this analysis. Patients with e14a2 transcripts presented higher rates of optimal molecular responses at 3 months and higher rates of complete cytogenetic response (CCR) at 6 months. E13a2, e14a2, and e14a2 with e13a2 (e14a2+e13a2) groups presented similar rates of 5-year event-free, progression-free, and overall survival. There was a superior 10-year overall survival in patients with transcripts e13a2 compared with e14a2 (alone or coexpressed with e13a2; 93% vs. 73%; P = .03), although the 5-year overall survival was 96% vs. 88%, respectively (P = not significant). In a multivariate analysis, high/intermediate Sokal score and e14a3/e14a3+e14a2 were independent factors for poor overall survival (hazard risk [HR], 4.63; P = .023 for Sokal score and HR, 10.6; P = .041 for BCR-ABL transcript). Patients with BCR-ABL transcripts e14a2 transcripts have higher rates of CCR at 6 months and higher rates of optimal molecular response at 3 months compared with e13a2 or with both transcripts, but no difference in 5-year overall, progression-free, and event-free survival. There was a superior 10-year overall survival among patients with transcripts e13a2 compared with e14a2 (alone or coexpressed with e13a2). Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Bacteria in the adventitia of cardiovascular disease patients with and without rheumatoid arthritis.

    Science.gov (United States)

    Curran, Samuel A; Hollan, Ivana; Erridge, Clett; Lappin, David F; Murray, Colin A; Sturfelt, Gunnar; Mikkelsen, Knut; Førre, Oystein T; Almdahl, Sven M; Fagerhol, Magne K; Goodyear, Carl S; Riggio, Marcello P

    2014-01-01

    The incidence of atherosclerosis is significantly increased in rheumatoid arthritis (RA). Infection is one factor that may be involved in the pathogenesis of both diseases. The cause of RA and atherosclerosis is unknown, and infection is one of the factors that may be involved in the pathogenesis of both diseases. The aims of this study were to identify bacteria in the aortic adventitia of patients with cardiovascular disease (CVD) in the presence and absence of RA, and to determine the effect of identified candidate pathogens on Toll-like receptor (TLR)-dependent signalling and the proinflammatory response. The aortic adventitia of 11 CVD patients with RA (RA+CVD) and 11 CVD patients without RA (CVD) were collected during coronary artery bypass graft surgery. Bacteria were detected in four samples from CVD patients and three samples from RA+CVD patients and identified by 16S rRNA gene sequencing. Methylobacterium oryzae was identified in all three RA+CVD samples, representing 44.1% of the bacterial flora. The effect of M. oryzae on TLR-dependent signalling was determined by transfection of HEK-293 cells. Although mild TLR2 signalling was observed, TLR4 was insensitive to M. oryzae. Human primary macrophages were infected with M. oryzae, and a TLDA qPCR array targeting 90 genes involved in inflammation and immune regulation was used to profile the transcriptional response. A significant proinflammatory response was observed, with many of the up-regulated genes encoding proinflammatory cytokines (IL-1α, IL-1β, IL-6, TNF-α) and chemokines (CCR7, IL-8). The aortic adventitia of CVD patients contains a wide range of bacterial species, and the bacterial flora is significantly less diverse in RA+CVD than CVD patients. M. oryzae may stimulate an proinflammatory response that may aggravate and perpetuate the pathological processes underlying atherosclerosis in RA patients.

  13. Bacteria in the adventitia of cardiovascular disease patients with and without rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Samuel A Curran

    Full Text Available The incidence of atherosclerosis is significantly increased in rheumatoid arthritis (RA. Infection is one factor that may be involved in the pathogenesis of both diseases. The cause of RA and atherosclerosis is unknown, and infection is one of the factors that may be involved in the pathogenesis of both diseases. The aims of this study were to identify bacteria in the aortic adventitia of patients with cardiovascular disease (CVD in the presence and absence of RA, and to determine the effect of identified candidate pathogens on Toll-like receptor (TLR-dependent signalling and the proinflammatory response. The aortic adventitia of 11 CVD patients with RA (RA+CVD and 11 CVD patients without RA (CVD were collected during coronary artery bypass graft surgery. Bacteria were detected in four samples from CVD patients and three samples from RA+CVD patients and identified by 16S rRNA gene sequencing. Methylobacterium oryzae was identified in all three RA+CVD samples, representing 44.1% of the bacterial flora. The effect of M. oryzae on TLR-dependent signalling was determined by transfection of HEK-293 cells. Although mild TLR2 signalling was observed, TLR4 was insensitive to M. oryzae. Human primary macrophages were infected with M. oryzae, and a TLDA qPCR array targeting 90 genes involved in inflammation and immune regulation was used to profile the transcriptional response. A significant proinflammatory response was observed, with many of the up-regulated genes encoding proinflammatory cytokines (IL-1α, IL-1β, IL-6, TNF-α and chemokines (CCR7, IL-8. The aortic adventitia of CVD patients contains a wide range of bacterial species, and the bacterial flora is significantly less diverse in RA+CVD than CVD patients. M. oryzae may stimulate an proinflammatory response that may aggravate and perpetuate the pathological processes underlying atherosclerosis in RA patients.

  14. The BCR-ABL1 transcript type influences response and outcome in Philadelphia chromosome-positive chronic myeloid leukemia patients treated frontline with imatinib.

    Science.gov (United States)

    Castagnetti, Fausto; Gugliotta, Gabriele; Breccia, Massimo; Iurlo, Alessandra; Levato, Luciano; Albano, Francesco; Vigneri, Paolo; Abruzzese, Elisabetta; Rossi, Giuseppe; Rupoli, Serena; Cavazzini, Francesco; Martino, Bruno; Orlandi, Ester; Pregno, Patrizia; Annunziata, Mario; Usala, Emilio; Tiribelli, Mario; Sica, Simona; Bonifacio, Massimiliano; Fava, Carmen; Gherlinzoni, Filippo; Bocchia, Monica; Soverini, Simona; Bochicchio, Maria Teresa; Cavo, Michele; Giovanni, Martinelli; Saglio, Giuseppe; Pane, Fabrizio; Baccarani, Michele; Rosti, Gianantonio

    2017-08-01

    The most frequent BCR-ABL1 fusion transcripts in chronic myeloid leukemia (CML) are the e13a2 (b2a2) and the e14a2 (b3a2) ones. In the imatinib era few studies addressing the prognostic significance of the BCR-ABL1 transcript type in early chronic phase CML have been published. Overall, these studies suggest that in e14a2 patients the response to imatinib is faster and deeper. To evaluate if the BCR-ABL1 transcript type (e13a2 compared to e14a2) affect the response to imatinib and the clinical outcome in newly diagnosed adult CML patients, 559 patients enrolled in 3 prospective studies (NCT00514488, NCT00510926, observational study CML/023) were analyzed. A qualitative PCR was performed at baseline: 52% patients had a e14a2 transcript, 37% a e13a2 transcript, 11% co-expressed both transcripts and 1% had other rare transcripts. The median follow-up was 76 months (95% of the patients had at least a 5-year observation). The complete cytogenetic response rates were comparable in e14a2 and e13a2 patients. The median time to MR3.0 (6 and 12 months) and MR4.0 (41 and 61 months) was significantly shorter for e14a2 patients compared to e13a2 patients, with a higher cumulative probability of MR3.0 (88% and 83%, P < .001) and MR4.0 (67% and 52%, P = .001). The 7-year overall survival (90% and 83%, P = .017), progression-free survival (89% and 81%, P = .005) and failure-free survival (71% and 54%, P < .001) were significantly better in patients with e14a2 transcript. In conclusion, patients with e13a2 transcript had a slower molecular response with inferior response rates to imatinib and a poorer long-term outcome. © 2017 Wiley Periodicals, Inc.

  15. Over-Expression of POU Class 1 Homeobox 1 Transcription Factor (Pit-1) Predicts Poor Prognosis for Breast Cancer Patients.

    Science.gov (United States)

    Gao, Zhongcheng; Xue, Kecheng; Zhang, Lianfang; Wei, Meng

    2016-10-31

    The POU class 1 homeobox 1 transcription factor (POU1F1, also known as Pit-1) was reported to be associated with tumor progression and metastasis. The purpose of this study was to evaluate the prognostic value of Pit-1 in breast cancer patients. The relative expression levels of Pit-1 in breast cancer patients were detected by quantitative real-time PCR (qRT-PCR). Chi-square analysis was used to analyze the association between Pit-1 expression and clinical features. The Kaplan-Meier method was used to estimate the overall survival of the patients and Cox regression analysis was used to analyze the prognostic value of Pit-1. Increased expression of Pit-1 was detected in the tumor tissues compared with the normal tissues (1.086 vs. 0.541) and the abnormal expression was associated with tumor size, clinical stage, tumor grade, and lymph node metastasis (PPit-1 was significantly associated with poor overall survival of the patients (P=0.001) and Cox regression analysis indicated that Pit-1 might be a prognostic factor for breast cancer prognosis (HR=1.955, 95% CI=1.295-3.035, P=0.003). Pit-1 may be a potential prognostic biomarker for breast cancer patients and it is associated with tumor progression.

  16. IL-1 receptor antagonism and muscle gene expression in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Berchtold, L. A.; Larsen, C. M.; Vaag, A.

    2009-01-01

    Background. We have previously reported that systemic blockade of IL-1 beta in patients with type 2 diabetes with anakinra (a recombinant human interleukin-1-receptor antagonist, IL-1Ra), lowered glycated hemoglobin improved beta-cell function and reduced circulating levels of IL-6 and CRP (7......). To investigate the effects of IL-1Ra in insulin-sensitive tissue, gene expression levels in skeletal muscle from type 2 diabetic patients treated with IL-1Ra were analysed. Methods. Gene expression profiles in vastus lateralis muscle biopsies from five obese patients (BMI>27) were determined before and after 13......RT-PCR, were significantly altered when comparing the number of transcripts before and after treatment for each individual. Conclusion. Treatment with IL-1Ra did not significantly affect gene expression levels in skeletal muscle in this limited and selected sample of obese patients with type 2 diabetes. Larger...

  17. Transcriptional profiling of Plasmodium falciparum parasites from patients with severe malaria identifies distinct low vs. high parasitemic clusters.

    Science.gov (United States)

    Milner, Danny A; Pochet, Nathalie; Krupka, Malkie; Williams, Chris; Seydel, Karl; Taylor, Terrie E; Van de Peer, Yves; Regev, Aviv; Wirth, Dyann; Daily, Johanna P; Mesirov, Jill P

    2012-01-01

    In the past decade, estimates of malaria infections have dropped from 500 million to 225 million per year; likewise, mortality rates have dropped from 3 million to 791,000 per year. However, approximately 90% of these deaths continue to occur in sub-Saharan Africa, and 85% involve children less than 5 years of age. Malaria mortality in children generally results from one or more of the following clinical syndromes: severe anemia, acidosis, and cerebral malaria. Although much is known about the clinical and pathological manifestations of CM, insights into the biology of the malaria parasite, specifically transcription during this manifestation of severe infection, are lacking. We collected peripheral blood from children meeting the clinical case definition of cerebral malaria from a cohort in Malawi, examined the patients for the presence or absence of malaria retinopathy, and performed whole genome transcriptional profiling for Plasmodium falciparum using a custom designed Affymetrix array. We identified two distinct physiological states that showed highly significant association with the level of parasitemia. We compared both groups of Malawi expression profiles with our previously acquired ex vivo expression profiles of parasites derived from infected patients with mild disease; a large collection of in vitro Plasmodium falciparum life cycle gene expression profiles; and an extensively annotated compendium of expression data from Saccharomyces cerevisiae. The high parasitemia patient group demonstrated a unique biology with elevated expression of Hrd1, a member of endoplasmic reticulum-associated protein degradation system. The presence of a unique high parasitemia state may be indicative of the parasite biology of the clinically recognized hyperparasitemic severe disease syndrome.

  18. Transcriptional profiling of Plasmodium falciparum parasites from patients with severe malaria identifies distinct low vs. high parasitemic clusters.

    Directory of Open Access Journals (Sweden)

    Danny A Milner

    Full Text Available In the past decade, estimates of malaria infections have dropped from 500 million to 225 million per year; likewise, mortality rates have dropped from 3 million to 791,000 per year. However, approximately 90% of these deaths continue to occur in sub-Saharan Africa, and 85% involve children less than 5 years of age. Malaria mortality in children generally results from one or more of the following clinical syndromes: severe anemia, acidosis, and cerebral malaria. Although much is known about the clinical and pathological manifestations of CM, insights into the biology of the malaria parasite, specifically transcription during this manifestation of severe infection, are lacking.We collected peripheral blood from children meeting the clinical case definition of cerebral malaria from a cohort in Malawi, examined the patients for the presence or absence of malaria retinopathy, and performed whole genome transcriptional profiling for Plasmodium falciparum using a custom designed Affymetrix array. We identified two distinct physiological states that showed highly significant association with the level of parasitemia. We compared both groups of Malawi expression profiles with our previously acquired ex vivo expression profiles of parasites derived from infected patients with mild disease; a large collection of in vitro Plasmodium falciparum life cycle gene expression profiles; and an extensively annotated compendium of expression data from Saccharomyces cerevisiae. The high parasitemia patient group demonstrated a unique biology with elevated expression of Hrd1, a member of endoplasmic reticulum-associated protein degradation system.The presence of a unique high parasitemia state may be indicative of the parasite biology of the clinically recognized hyperparasitemic severe disease syndrome.

  19. Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database

    DEFF Research Database (Denmark)

    Sokka, T; Kautiainen, H; Pincus, T

    2009-01-01

    OBJECTIVE: To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. METHODS: The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) cohort includes clinical and que...

  20. SF Treg cells transcribing high levels of Bcl-2 and microRNA-21 demonstrate limited apoptosis in RA

    NARCIS (Netherlands)

    van der Geest, Kornelis S. M.; Smigielska, Katarzyna; Park, Ji-Ah; Abdulahad, Wayel H.; Kim, Hye-Won; Kroesen, Bart-Jan; van den Berg, Anke; Boots, Annemieke M. H.; Lee, Eun-Bong; Brouwer, Elisabeth

    Objective. The aim of this study was to investigate the turnover of Treg cells in the SF of RA patients. Methods. Treg cells were enumerated in peripheral blood and SF of RA patients and analysed by flow cytometry for expression of the proliferation marker Ki-67 and binding of the apoptosis marker

  1. The Potential Role of Th9 Cell Related Cytokine and Transcription Factors in Patients with Hepatic Alveolar Echinococcosis

    Directory of Open Access Journals (Sweden)

    Tuerhongjiang Tuxun

    2015-01-01

    Full Text Available Human alveolar echinococcosis (AE is a lethal parasitic infectious disease which may lead to liver failure if left untreated. It is caused by the larval stage of the fox tapeworm Echinococcus multilocularis and usually develops a substantial infiltrative occupation in solid organs. During the infection, T helper subsets are known to play crucial role in crosstalk between the parasite and human host. Th9 cells, a new member of CD4+ T cell family which is characterized by its specific cytokine IL-9 and transcription factors PU.1 and IRF-4, have been known recently to have a critical role in allergic diseases, and cancers as well as the parasitic infection. To assess the potential role of Th9 cells during the infection, the mRNA levels of IL-9, PU.1, and IRF-4 both in peripheral blood mononuclear cells and in liver tissues were, respectively, detected by using real-time PCR. The plasma concentration levels of IL-9 were detected by using enzyme linked immunosorbent assay (ELISA. Th9 related cytokine IL-9 and transcription factors PU.1 and IRF-4 mRNA levels elevated both in PBMCs, and in hepatic lesion and paralesion tissues in AE patients. This may facilitate the infiltrative growth of the parasite and its persistence in human host.

  2. Decreased expression of methylene tetrahydrofolate reductase (MTHFR) gene in patients with rheumatoid arthritis.

    Science.gov (United States)

    Remuzgo-Martínez, Sara; Genre, Fernanda; López-Mejías, Raquel; Ubilla, Begoña; Mijares, Veronica; Pina, Trinitario; Corrales, Alfonso; Blanco, Ricardo; Martín, Javier; Llorca, Javier; González-Gay, Miguel Á

    2016-01-01

    Impairment of methylene tetrahydrofolate reductase (MTHFR), a key enzyme in the folate metabolism, results in an elevated plasma level of homocysteine, considered an independent risk factor for cardiovascular (CV) disease. Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased risk of CV death. Polymorphisms in the MTHFR gene increase the frequency of CV disease in RA. The aim of this study was to determine the expression of MTHFR gene in patients with RA, with and without ischaemic heart disease (IHD). Relative expression of MTHFR gene and beta-actin and GAPDH as housekeeping genes was quantified by quantitative real-time polymerase chain reaction. It was analysed by the comparative Ct (threshold cycle) method in peripheral blood from 26 Spanish patients with RA (12 with IHD and 14 without IHD) and 10 healthy controls. MTHFR expression level in RA patients was also assessed according to disease activity, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies status. MTHFR expression was significantly reduced in patients with RA compared to controls (fold change = 0.85, p=0.029). It was especially true for RA patients with IHD (fold change= 0.79, p=0.021). However, no statistically significant relationship between MTHFR expression level in patients with RA and DAS28 CRP, DAS28 ESR, RF and anti-CCP status was observed. Patients with RA, in particular those with IHD, show a decreased expression of the MTHFR gene. This may support a potential implication of the transcriptional regulation of MTHFR in the pathogenesis of RA.

  3. Gastric Cancer Transcription Factors in Patient Reported Outcomes (GCTF-PRO) – Draft proposal

    OpenAIRE

    Lee, Sonia

    2015-01-01

    The GCTF-PRO seeks to examine the extent gastric cancer patients are tapping into new information particularly outside of conventional healthcare disclosures. Its significance is in assessing dimensions of QOL paradigms that frame statistical power using predictive methods. It seeks to embed evidence-based theories (perceptual and cognitive) to awareness levels in an attempt to bridge the biotechnological advances with prognostic/ diagnostic-related patient satisfactions. At present, it may c...

  4. Association of variants in IL2RA with progression of joint destruction in rheumatoid arthritis.

    Science.gov (United States)

    Knevel, R; de Rooy, D P C; Zhernakova, A; Gröndal, G; Krabben, A; Steinsson, K; Wijmenga, C; Cavet, G; Toes, R E M; Huizinga, T W J; Gregersen, P K; van der Helm-van Mil, A H M

    2013-07-01

    Heritability studies have suggested an important role of genetic predisposition in the progression of joint destruction in rheumatoid arthritis (RA); the heritability is estimated at 45-58%. Several single-nucleotide polymorphisms (SNPs) have been identified as being associated with RA susceptibility. Our objective was to study the association of several of these loci with progression of joint destruction. We studied 1,750 RA patients in 4 independent data sets with 4,732 radiographs scored using the modified Sharp/van der Heijde method. Thirteen susceptibility SNPs that were not previously associated with joint destruction were tested in 596 Dutch RA patients. Subsequently, significant SNPs were studied in data sets of RA patients from North America and Iceland. Data were summarized in inverse-weighted variance meta-analyses. Further, the association with circulating protein levels was studied and the associated region was fine-mapped. In stage 1, 3 loci (AFF3, IL2RA, and BLK) were significantly associated with the rate of joint destruction and were further analyzed in the additional data sets. In the combined meta-analyses, the minor (C) allele of IL2RA (rs2104286) was associated with less progression of joint destruction (P = 7.2 × 10(-4) ). Furthermore, the IL2RA (rs2104286) protective genotype was associated with lower (0.85-fold [95% confidence interval 0.77-0.93], P = 1.4 × 10(-3) ) circulating levels of soluble interleukin-2 receptor α (sIL-2Rα). Additionally, lower sIL-2Rα levels were associated with a lower rate of joint destruction (P = 3.4 × 10(-3) ). The association of IL2RA with the rate of joint destruction was further localized to a 40-kb region encompassing the IL2RA intron 1 and the 5' region of IL2RA and RBM17. The present genetic and serologic data suggest that inherited altered genetic constitution at the IL2RA locus may predispose to a less destructive course of RA. Copyright © 2013 by the American College of Rheumatology.

  5. Copy number analysis of 413 isolated talipes equinovarus patients suggests role for transcriptional regulators of early limb development.

    Science.gov (United States)

    Alvarado, David M; Buchan, Jillian G; Frick, Steven L; Herzenberg, John E; Dobbs, Matthew B; Gurnett, Christina A

    2013-04-01

    Talipes equinovarus is one of the most common congenital musculoskeletal anomalies and has a worldwide incidence of 1 in 1000 births. A genetic predisposition to talipes equinovarus is evidenced by the high concordance rate in twin studies and the increased risk to first-degree relatives. Despite the frequency of isolated talipes equinovarus and the strong evidence of a genetic basis for the disorder, few causative genes have been identified. To identify rare and/or recurrent copy number variants, we performed a genome-wide screen for deletions and duplications in 413 isolated talipes equinovarus patients using the Affymetrix 6.0 array. Segregation analysis within families and gene expression in mouse E12.5 limb buds were used to determine the significance of copy number variants. We identified 74 rare, gene-containing copy number variants that were present in talipes equinovarus probands and not present in 759 controls or in the Database of Genomic Variants. The overall frequency of copy number variants was similar between talipes equinovarus patients compared with controls. Twelve rare copy number variants segregate with talipes equinovarus in multiplex pedigrees, and contain the developmentally expressed transcription factors and transcriptional regulators PITX1, TBX4, HOXC13, UTX, CHD (chromodomain protein)1, and RIPPLY2. Although our results do not support a major role for recurrent copy number variations in the etiology of isolated talipes equinovarus, they do suggest a role for genes involved in early embryonic patterning in some families that can now be tested with large-scale sequencing methods.

  6. A Transcriptional Signature of Fatigue Derived from Patients with Primary Sjögren's Syndrome.

    Directory of Open Access Journals (Sweden)

    Katherine James

    Full Text Available Fatigue is a debilitating condition with a significant impact on patients' quality of life. Fatigue is frequently reported by patients suffering from primary Sjögren's Syndrome (pSS, a chronic autoimmune condition characterised by dryness of the eyes and the mouth. However, although fatigue is common in pSS, it does not manifest in all sufferers, providing an excellent model with which to explore the potential underpinning biological mechanisms.Whole blood samples from 133 fully-phenotyped pSS patients stratified for the presence of fatigue, collected by the UK primary Sjögren's Syndrome Registry, were used for whole genome microarray. The resulting data were analysed both on a gene by gene basis and using pre-defined groups of genes. Finally, gene set enrichment analysis (GSEA was used as a feature selection technique for input into a support vector machine (SVM classifier. Classification was assessed using area under curve (AUC of receiver operator characteristic and standard error of Wilcoxon statistic, SE(W.Although no genes were individually found to be associated with fatigue, 19 metabolic pathways were enriched in the high fatigue patient group using GSEA. Analysis revealed that these enrichments arose from the presence of a subset of 55 genes. A radial kernel SVM classifier with this subset of genes as input displayed significantly improved performance over classifiers using all pathway genes as input. The classifiers had AUCs of 0.866 (SE(W 0.002 and 0.525 (SE(W 0.006, respectively.Systematic analysis of gene expression data from pSS patients discordant for fatigue identified 55 genes which are predictive of fatigue level using SVM classification. This list represents the first step in understanding the underlying pathophysiological mechanisms of fatigue in patients with pSS.

  7. A Transcriptional Signature of Fatigue Derived from Patients with Primary Sjögren's Syndrome.

    Science.gov (United States)

    James, Katherine; Al-Ali, Shereen; Tarn, Jessica; Cockell, Simon J; Gillespie, Colin S; Hindmarsh, Victoria; Locke, James; Mitchell, Sheryl; Lendrem, Dennis; Bowman, Simon; Price, Elizabeth; Pease, Colin T; Emery, Paul; Lanyon, Peter; Hunter, John A; Gupta, Monica; Bombardieri, Michele; Sutcliffe, Nurhan; Pitzalis, Costantino; McLaren, John; Cooper, Annie; Regan, Marian; Giles, Ian; Isenberg, David; Saravanan, Vadivelu; Coady, David; Dasgupta, Bhaskar; McHugh, Neil; Young-Min, Steven; Moots, Robert; Gendi, Nagui; Akil, Mohammed; Griffiths, Bridget; Wipat, Anil; Newton, Julia; Jones, David E; Isaacs, John; Hallinan, Jennifer; Ng, Wan-Fai

    2015-01-01

    Fatigue is a debilitating condition with a significant impact on patients' quality of life. Fatigue is frequently reported by patients suffering from primary Sjögren's Syndrome (pSS), a chronic autoimmune condition characterised by dryness of the eyes and the mouth. However, although fatigue is common in pSS, it does not manifest in all sufferers, providing an excellent model with which to explore the potential underpinning biological mechanisms. Whole blood samples from 133 fully-phenotyped pSS patients stratified for the presence of fatigue, collected by the UK primary Sjögren's Syndrome Registry, were used for whole genome microarray. The resulting data were analysed both on a gene by gene basis and using pre-defined groups of genes. Finally, gene set enrichment analysis (GSEA) was used as a feature selection technique for input into a support vector machine (SVM) classifier. Classification was assessed using area under curve (AUC) of receiver operator characteristic and standard error of Wilcoxon statistic, SE(W). Although no genes were individually found to be associated with fatigue, 19 metabolic pathways were enriched in the high fatigue patient group using GSEA. Analysis revealed that these enrichments arose from the presence of a subset of 55 genes. A radial kernel SVM classifier with this subset of genes as input displayed significantly improved performance over classifiers using all pathway genes as input. The classifiers had AUCs of 0.866 (SE(W) 0.002) and 0.525 (SE(W) 0.006), respectively. Systematic analysis of gene expression data from pSS patients discordant for fatigue identified 55 genes which are predictive of fatigue level using SVM classification. This list represents the first step in understanding the underlying pathophysiological mechanisms of fatigue in patients with pSS.

  8. Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients

    DEFF Research Database (Denmark)

    Urup, Thomas; Staunstrup, Line Maersk; Michaelsen, Signe Regner

    2017-01-01

    and resistance to bevacizumab combination therapy.Methods: Recurrent glioblastoma patients who had biomarker-accessible tumor tissue surgically removed both before bevacizumab treatment and at time of progression were included. Patients were grouped into responders (n = 7) and non-responders (n = 14). Gene...... expression profiling of formalin-fixed paraffin-embedded tumor tissue was performed using RNA-sequencing.Results: By comparing pretreatment samples of responders with those of non-responders no significant difference was observed. In a paired comparison analysis of pre- and posttreatment samples of non...

  9. A Transcriptional Signature of Fatigue Derived from Patients with Primary Sjögren’s Syndrome

    Science.gov (United States)

    James, Katherine; Al-Ali, Shereen; Tarn, Jessica; Cockell, Simon J.; Gillespie, Colin S.; Hindmarsh, Victoria; Locke, James; Mitchell, Sheryl; Lendrem, Dennis; Bowman, Simon; Price, Elizabeth; Pease, Colin T.; Emery, Paul; Lanyon, Peter; Hunter, John A.; Gupta, Monica; Bombardieri, Michele; Sutcliffe, Nurhan; Pitzalis, Costantino; McLaren, John; Cooper, Annie; Regan, Marian; Giles, Ian; Isenberg, David; Saravanan, Vadivelu; Coady, David; Dasgupta, Bhaskar; McHugh, Neil; Young-Min, Steven; Moots, Robert; Gendi, Nagui; Akil, Mohammed; Griffiths, Bridget; Wipat, Anil; Newton, Julia; Jones, David E.; Isaacs, John; Hallinan, Jennifer; Ng, Wan-Fai

    2015-01-01

    Background Fatigue is a debilitating condition with a significant impact on patients’ quality of life. Fatigue is frequently reported by patients suffering from primary Sjögren’s Syndrome (pSS), a chronic autoimmune condition characterised by dryness of the eyes and the mouth. However, although fatigue is common in pSS, it does not manifest in all sufferers, providing an excellent model with which to explore the potential underpinning biological mechanisms. Methods Whole blood samples from 133 fully-phenotyped pSS patients stratified for the presence of fatigue, collected by the UK primary Sjögren’s Syndrome Registry, were used for whole genome microarray. The resulting data were analysed both on a gene by gene basis and using pre-defined groups of genes. Finally, gene set enrichment analysis (GSEA) was used as a feature selection technique for input into a support vector machine (SVM) classifier. Classification was assessed using area under curve (AUC) of receiver operator characteristic and standard error of Wilcoxon statistic, SE(W). Results Although no genes were individually found to be associated with fatigue, 19 metabolic pathways were enriched in the high fatigue patient group using GSEA. Analysis revealed that these enrichments arose from the presence of a subset of 55 genes. A radial kernel SVM classifier with this subset of genes as input displayed significantly improved performance over classifiers using all pathway genes as input. The classifiers had AUCs of 0.866 (SE(W) 0.002) and 0.525 (SE(W) 0.006), respectively. Conclusions Systematic analysis of gene expression data from pSS patients discordant for fatigue identified 55 genes which are predictive of fatigue level using SVM classification. This list represents the first step in understanding the underlying pathophysiological mechanisms of fatigue in patients with pSS. PMID:26694930

  10. 228Ra, 226Ra, 224Ra and 223Ra in potential sources and sinks of land-derived material in the German Bight of the North Sea: implications for the use of radium as a tracer

    NARCIS (Netherlands)

    Schmidt, C.; Hanfland, C.; Regnier, P.; Van Cappellen, P.; Schlüter, M.; Knauthe, U.; Stimac, I.; Geibert, W.

    2011-01-01

    Activities of the naturally occurring radium nuclides 228Ra, 226Ra, 224Ra and 223Ra were determined in waters of the open German Bight and adjacent nearshore areas in the North Sea, in order to explore the potential use of radium isotopes as natural tracers of land–ocean interaction in an

  11. Statistical thermodynamics of transcription profiles in normal development and tumorigeneses in cohorts of patients.

    Science.gov (United States)

    Remacle, F; Levine, R D

    2015-12-01

    Experimental biology is providing the distribution of numerous different biological molecules inside cells and in body fluids of patients. Statistical methods of analysis have very successfully examined these rather large databases. We seek to use a thermodynamic analysis to provide a physical understanding and quantitative characterization of human cancers and other pathologies within a molecule-centered approach. The key technical development is the introduction of a Lagrangian. By imposing constraints the minimal value of the Lagrangian defines a thermodynamically stable state of the cellular system. The minimization also allows using experimental data measured at a number of different conditions to evaluate the steady-state distribution of biomolecules such as messenger RNAs. Thereby the number of effectively accessible quantum states of biomolecules is determined from the experimentally measured expression levels. With the increased resolution provided by the minimization of the Lagrangian one can differentiate between normal and diseased patients and further between disease subtypes. Each such refinement corresponds to imposing an additional constraint of biological origin. The constraints are the unbalanced ongoing biological processes in the system. MicroRNA expression level data for control and diseased lung cancer patients are analyzed as an example.

  12. Analysis of mRNA transcripts in chronic myeloid leukemia patients

    Directory of Open Access Journals (Sweden)

    Meissner Rosely de V.

    1999-01-01

    Full Text Available The nature of BCR/ABL hybrid mRNA was analyzed by RT-PCR in cells from 33 patients (22 males, 11 females with chronic myeloid leukemia (CML. b3a2 mRNA was found in 14 cases, whereas 13 patients had b2a2 mRNA and six had both kinds of mRNA, with a predominance of the b3a2 type. The type of mRNA present showed no significant correlation with age, hemoglobin level, number of leukocytes and platelets, percentage of blasts or basophils or the presence of splenomegaly at diagnosis. There was also no correlation with sex or duration of the chronic phase. When these results were combined with those reported by other groups, a significant association (P = 0.029 was observed for mRNA type vs. sex, with a predominance of men in the groups expressing b2a2 (2.68:1 and b3a2 (1.33:1. We conclude that the classification of patients according to mRNA type does not homogenize the clinical and hematological data within groups, where variance is large, nor does it allow a differentiation between groups.

  13. GLI1 Transcription Factor Affects Tumor Aggressiveness in Patients With Papillary Thyroid Cancers.

    Science.gov (United States)

    Lee, Jandee; Jeong, Seonhyang; Lee, Cho Rok; Ku, Cheol Ryong; Kang, Sang-Wook; Jeong, Jong Ju; Nam, Kee-Hyun; Shin, Dong Yeob; Chung, Woong Youn; Lee, Eun Jig; Jo, Young Suk

    2015-06-01

    A significant proportion of patients with papillary thyroid cancer (PTC) present with extrathyroidal extension (ETE) and lymph node metastasis (LNM). However, the molecular mechanism of tumor invasiveness in PTC remains to be elucidated. The aim of this study is to understand the role of Hedgehog (Hh) signaling in tumor aggressiveness in patients with PTC. Subjects were patients who underwent thyroidectomy from 2012 to 2013 in a single institution. Frozen or paraffin-embedded tumor tissues with contralateral-matched normal thyroid tissues were collected. Hh signaling activity was analyzed by quantitative RT-PCR (qRT-PCR) and immunohistochemical (IHC) staining. Datasets from Gene Expression Omnibus (GEO) (National Center for Biotechnology Information) were subjected to Gene Set Enrichment Analysis (GSEA). BRAFT1799A and telomerase reverse transcriptase promoter mutation C228T were analyzed by direct sequencing. Among 137 patients with PTC, glioma-associated oncogene homolog 1 (GLI1) group III (patients in whom the ratio of GLI1 messenger ribonucleic acid (mRNA) level in tumor tissue to GLI1 mRNA level in matched normal tissue was in the upper third of the subject population) had elevated risk for ETE (odds ratio [OR] 4.381, 95% confidence interval [CI] 1.414-13.569, P = 0.01) and LNM (OR 5.627, 95% CI 1.674-18.913, P = 0.005). Glioma-associated oncogene homolog 2 (GLI2) group III also had elevated risk for ETE (OR 4.152, 95% CI 1.292-13.342, P = 0.017) and LNM (OR 3.924, 95% CI 1.097-14.042, P = 0.036). GSEA suggested that higher GLI1 expression is associated with expression of the KEGG gene set related to axon guidance (P = 0.031, false discovery rate < 0.05), as verified by qRT-PCR and IHC staining in our subjects.GLI1 and GLI2 expressions were clearly related to aggressive clinicopathological features and aberrant activation of GLI1 involved in the axon guidance pathway. These results may contribute to development of new prognostic markers

  14. ICMPv6 RA Flooding Vulnerability Research

    Directory of Open Access Journals (Sweden)

    Linas Jočys

    2016-06-01

    Full Text Available ICMPv6 is the newest version of internet control message protocol, whose main purpose is to send error message indicating packet processing failure. It is know that ICMPv6 is technologically vulnerable. One of those vulnerabilities is the ICMPv6 RA flooding vulnerability, which can lead to systems in Local Area Network slow down or full stop. This paper will discuss Windows (XP, 7, 8.1 and Linux Ubuntu 14 operating systems resistance to RA flooding attack research and countermeasures to minimize this vulnerability.

  15. SMN transcript levels in leukocytes of SMA patients determined by absolute real-time PCR

    OpenAIRE

    Tiziano, Francesco Danilo; Pinto, Anna Maria; Fiori, Stefania; Lomastro, Rosa; Messina, Sonia; Bruno, Claudio; Pini, Antonella; Pane, Marika; D'Amico, Adele; Ghezzo, Alessandro; Bertini, Enrico; Mercuri, Eugenio; Neri, Giovanni; Brahe, Christina

    2009-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by homozygous mutations of the SMN1 gene. Three forms of SMA are recognized (type I–III) on the basis of clinical severity. All patients have at least one or more (usually 2–4) copies of a highly homologous gene (SMN2), which produces insufficient levels of functional SMN protein, because of alternative splicing of exon 7. Recently, evidence has been provided that SMN2 expression can be enhanced by pharmacol...

  16. Transcription profile analysis of vastus lateralis muscle from patients with chronic fatigue syndrome.

    Science.gov (United States)

    Pietrangelo, T; Mancinelli, R; Toniolo, L; Montanari, G; Vecchiet, J; Fanò, G; Fulle, S

    2009-01-01

    Chronic fatigue syndrome (CFS) is a disabling condition characterized by unexplained chronic fatigue that impairs normal activities. Many body systems are affected and etiology has not yet been identified. In addition to immunological and psychological aspects, skeletal muscle symptoms are prominent in CFS patients. In an effort to establish which pathways might be involved in the onset and development of muscle symptoms, we used global transcriptome analysis to identify genes that were differentially expressed in the vastus lateralis muscle of female and male CFS patients. We found that the expression of genes that play key roles in mitochondrial function and oxidative balance, including superoxide dismutase 2, were altered, as were genes involved in energy production, muscular trophism and fiber phenotype determination. Importantly, the expression of a gene encoding a component of the nicotinic cholinergic receptor binding site was reduced, suggesting impaired neuromuscular transmission. We argue that these major biological processes could be involved in and/or responsible for the muscle symptoms of CFS.

  17. Early administration of IL-6RA does not prevent radiation-induced lung injury in mice

    Directory of Open Access Journals (Sweden)

    Inoue Takehiro

    2010-04-01

    Full Text Available Abstract Background Radiation pneumonia and subsequent radiation lung fibrosis are major dose-limiting complications for patients undergoing thoracic radiotherapy. Interleukin-6 (IL-6 is a pleiotropic cytokine and plays important roles in the regulation of immune response and inflammation. The purpose of this study was to investigate whether anti-IL-6 monoclonal receptor antibody (IL-6RA could ameliorate radiation-induced lung injury in mice. Methods BALB/cAnNCrj mice having received thoracic irradiation of 21 Gy were injected intraperitoneally with IL-6RA (MR16-1 or control rat IgG twice, immediately and seven days after irradiation. Enzyme-linked immunosorbent assay was used to examine the plasma level of IL-6 and serum amyloid A (SAA. Lung injury was assessed by histological staining with haematoxylin and eosin or Azan, measuring lung weight, and hydroxyproline. Results The mice treated with IL-6RA did not survive significantly longer than the rat IgG control. We observed marked up-regulation of IL-6 in mice treated with IL-6RA 150 days after irradiation, whereas IL-6RA temporarily suppressed early radiation-induced increase in the IL-6 release level. Histopathologic assessment showed no differences in lung section or lung weight between mice treated with IL-6RA and control. Conclusions Our findings suggest that early treatment with IL-6RA after irradiation alone does not protect against radiation-induced lung injury.

  18. Evaluation of T Regulatory Lymphocytes Transcription Factors in HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) Patients.

    Science.gov (United States)

    Ghezeldasht, Sanaz Ahmadi; Sadeghian, Hamed; Azarpazhooh, Mahmoud Reza; Shamsian, Seyyed Ali Akbar; Rafatpanah, Houshang; Mahmoodi, Mahmood; Rezaee, Seyyed Abdolrahim

    2017-08-01

    HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an aggressive neurological disease. The CD4+CD25+ T cell population plays pivotal roles in the maintenance of immunological tolerance and prevention of such autoimmune diseases. In the current study, proviral load (PVL), factor forkhead box p3 (Foxp3), and glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) gene expression and regulatory T cells (Tregs) counts of 21 HAM/TSP patients and 16 HTLV-1 healthy carriers (ACs) were measured using real-time PCR, TaqMan method, and flow cytometry. The demographic, history of disease, and severity of myelopathy were assessed by a checklist and the Osame motor disability score (OMDS). The mean OMDS for HAM/TSP was 4.82 ± 2.37 which had no significant correlation with Treg count or the expression of Foxp3, GITR, and PVL. The CD4+CD25+ cell counts had no significant differences between HAM/TSP and ACs. Findings revealed a higher PVL in HAM/TSPs (313.36 copies/104) compared to ACs (144.93 copies/104, p = 0.035). The Foxp3 and GITR mRNA levels were lower in HAM/TSP patients (11.78 and 13.80, respectively) than those in healthy carriers (18.44 and 21.00, p = 0.041 and 0.03, respectively). There was a significant correlation between Treg frequency and Foxp3 gene expression (R = 0.67, p = 0.006) and GITR and Foxp3 (R = 0.84, p = 0.042) in HAM/TSP patients. Furthermore, the transcription factors have strong correlations with CD4+CD25+ T cell frequencies. These findings suggest that HTLV-1 infection can modify the expression of main functional transcription factors, FOXP3 and GITR, which may lead to immune response deterioration of Tregs and consequently HAM/TSP manifestation.

  19. A novel BCR-ABL transcript e2a2 in a chronic myelogenous leukaemia patient with a duplicated Ph-chromosome and monosomy 7.

    Science.gov (United States)

    Leibundgut, E O; Jotterand, M; Rigamonti, V; Parlier, V; Mühlematter, D; Tobler, A; Solenthaler, M

    1999-09-01

    A novel BCR-ABL transcript was detected by multiplex RT-PCR in a patient with Philadelphia chromosome (Ph) positive chronic myelogenous leukaemia (CML) in accelerated phase. Sequencing of the aberrant transcript revealed an in-frame e2a2 fusion that included a 9 basepairs insertion. Cytogenetic analysis showed t(9;22), an additional Ph chromosome and monosomy 7. The clinical course was dismal: therapy was poorly tolerated, and the patient died in blast crisis 10 months after diagnosis. These data support the association of additional Ph and monosomy 7 with poor prognosis and suggest that the novel e2a2 BCR-ABL transcript may be related to an aggressive clinical course.

  20. Intragenic deletions affecting two alternative transcripts of the IMMP2L gene in patients with Tourette syndrome

    Science.gov (United States)

    Bertelsen, Birgitte; Melchior, Linea; Jensen, Lars R; Groth, Camilla; Glenthøj, Birte; Rizzo, Renata; Debes, Nanette Mol; Skov, Liselotte; Brøndum-Nielsen, Karen; Paschou, Peristera; Silahtaroglu, Asli; Tümer, Zeynep

    2014-01-01

    Tourette syndrome is a neurodevelopmental disorder characterized by multiple motor and vocal tics, and the disorder is often accompanied by comorbidities such as attention-deficit hyperactivity-disorder and obsessive compulsive disorder. Tourette syndrome has a complex etiology, but the underlying environmental and genetic factors are largely unknown. IMMP2L (inner mitochondrial membrane peptidase, subunit 2) located on chromosome 7q31 is one of the genes suggested as a susceptibility factor in disease pathogenesis. Through screening of a Danish cohort comprising 188 unrelated Tourette syndrome patients for copy number variations, we identified seven patients with intragenic IMMP2L deletions (3.7%), and this frequency was significantly higher (P=0.0447) compared with a Danish control cohort (0.9%). Four of the seven deletions identified did not include any known exons of IMMP2L, but were within intron 3. These deletions were found to affect a shorter IMMP2L mRNA species with two alternative 5′-exons (one including the ATG start codon). We showed that both transcripts (long and short) were expressed in several brain regions, with a particularly high expression in cerebellum and hippocampus. The current findings give further evidence for the role of IMMP2L as a susceptibility factor in Tourette syndrome and suggest that intronic changes in disease susceptibility genes should be investigated further for presence of alternatively spliced exons. PMID:24549057

  1. Stabilization of circulating thyroglobulin mRNA transcripts in patients treated for differentiated thyroid carcinoma

    DEFF Research Database (Denmark)

    Feddersen, Søren; Bastholt, Lars; Pedersen, Susanne Møller

    2017-01-01

    BACKGROUND: The clinical utility of serum thyroglobulin (TG) in the follow-up of patients with differentiated thyroid carcinoma (DTC) may be compromised by the presence of endogenous anti-thyroglobulin antibodies (TGAb). To prevent interference by TGAb several groups have developed real-time PCR...... (RT-PCR) based assays for quantification of blood TG mRNA levels. For accurate quantification of TG mRNA in blood preanalytical factors must be recognized and controlled. In this study we evaluate the effect of different blood RNA stabilizing systems - the Tempus(T) (M) Blood RNA system...... hours, and RNA yield, integrity and purity was determined. TG, GAPDH and ACTB mRNA levels were quantified by semi-quantitative RT-PCR. RESULTS: The RNA yield was significantly higher for blood collected in Tempus tubes compared to PAXgene tubes following storage for 72 hours at room temperature (p = 0...

  2. Patients' perceptions of fatigue in rheumatoid arthritis: overwhelming, uncontrollable, ignored.

    Science.gov (United States)

    Hewlett, Sarah; Cockshott, Zoë; Byron, Margaret; Kitchen, Karen; Tipler, Sue; Pope, Denise; Hehir, Maggie

    2005-10-15

    Fatigue is commonly reported by patients with rheumatoid arthritis (RA) but is rarely a treatment target. The aim of this study was to explore the concept of fatigue as experienced by patients with RA. Fifteen patients with RA and fatigue (> or =7 on a 10-cm visual analog scale) were individually interviewed and asked about the description, cause, consequence, and management of fatigue. Transcripts were systematically analyzed by 2 researchers independently, relevant phrases were coded, and earlier transcripts were checked for the emerging codes. A random sample of analyses were independently reviewed. A total of 191 codes arising from the data were grouped into 46 categories and overarching themes. Vivid descriptions reflect 2 types of fatigue: severe weariness and dramatic overwhelming fatigue. RA fatigue is different from normal tiredness because it is extreme, often not earned, and unresolving. Participants described physical, cognitive, and emotional components and attributed fatigue to inflammation, working the joints harder, and unrefreshing sleep. Participants described far-reaching effects on physical activities, emotions, relationships, and social and family roles. Participants used self-management strategies but with limited success. Most did not discuss fatigue with clinicians but when they did, they felt it was dismissed. Participants held negative views on the management of fatigue. The data show that RA fatigue is important, intrusive, and overwhelming, and patients struggle to manage it alone. These data on the complexity of fatigue experiences will help clinicians design measures, interventions, and self-managment guidance.

  3. A rotating target for Ra production

    NARCIS (Netherlands)

    Sohani, M.; Wilschut, H. W.

    2012-01-01

    A target wheel with pyrolytic graphite targets is designed and constructed at the TRI mu P facility to boost the production rate of Ra isotopes. Simulation, design properties and production results are discussed. (C) 2012 Elsevier B.V. All rights reserved.

  4. Chôra : Creation and Pathology

    DEFF Research Database (Denmark)

    Isar, Nicoletta

    2009-01-01

    Plato's dialogue the Timaeus describes not only the making of the cosmos (order), but also the condition of what is not order, neither for the human body nor for the universe. What is disorder in cosmogonic terms it is disease for the human body. Timaeus applies to the concept chôra in discussing...

  5. Nuclear structure of Ra at high spin

    Indian Academy of Sciences (India)

    However, nuclear structure at high spin and excitation energies (∼ 6 MeV) would require a coupling of excited 1p–1h with 208Pb core. The coupling between single- particle orbitals and collective vibrations of core complicates the simple shell model picture. With increasing neutron number, Ra isotopes show an abrupt ...

  6. Rapid Method for Ra-226 and Ra-228 in Water Samples

    Energy Technology Data Exchange (ETDEWEB)

    Maxwell, Sherrod, L. III

    2006-02-10

    The measurement of radium isotopes in natural waters is important for oceanographic studies and for public health reasons. Ra-226 (1620 year half-life) is one of the most toxic of the long-lived alpha emitters present in the environment due to its long life and its tendency to concentrate in bones, which increases the internal radiation dose of individuals. The analysis of radium-226 and radium-228 in natural waters can be tedious and time-consuming. Different sample preparation methods are often required to prepare Ra-226 and Ra-228 for separate analyses. A rapid method has been developed at the Savannah River Environmental Laboratory that effectively separates both Ra-226 and Ra-228 (via Ac-228) for assay. This method uses MnO{sub 2} Resin from Eichrom Technologies (Darien, IL, USA) to preconcentrate Ra-226 and Ra-228 rapidly from water samples, along with Ba-133 tracer. DGA Resin{reg_sign} (Eichrom) and Ln-Resin{reg_sign} (Eichrom) are employed in tandem to prepare Ra-226 for assay by alpha spectrometry and to determine Ra-228 via the measurement of Ac-228 by gas proportional counting. After preconcentration, the manganese dioxide is dissolved from the resin and passed through stacked Ln-Resin-DGA Resin cartridges that remove uranium and thorium interferences and retain Ac-228 on DGA Resin. The eluate that passed through this column is evaporated, redissolved in a lower acidity and passed through Ln-Resin again to further remove interferences before performing a barium sulfate microprecipitation. The Ac-228 is stripped from the resin, collected using cerium fluoride microprecipitation and counted by gas proportional counting. By using vacuum box cartridge technology with rapid flow rates, sample preparation time is minimized.

  7. IL-1Ra (recombinant human IL-1 receptor antagonist in the treatment of rheumatoid arthritis: the efficacy

    Directory of Open Access Journals (Sweden)

    L. Cozzi

    2011-09-01

    Full Text Available Interleukin 1 receptor antagonist (IL-1Ra is a naturally occurring IL-1 inhibitor, acting as a “receptor antagonist”, which blocks IL-1 mediated signal transduction. In 1990 IL-1Ra was cloned and later on, a large numbers of studies led to disclosure of the crucial importance of the imbalance between IL-1 and IL-1Ra in the pathogenesis of rheumatoid arthritis (RA. In 1991, almost 8 years after the initial isolation of IL-1, recombinant IL-1Ra (IL-1ra, Kineret was introduced in clinical trials involving patients with RA. Between 2001 and 2002 IL-1ra was approved by the US Food and Drug Administration and by the European Agency for the Evaluation of the Medicinal Products and in 2003 it was registered in Italy, too. In RA recombinant IL-1ra has been evaluated in 5 randomized, placebo-controlled clinical trials involving more than 2900 patients. Two of the trials involved the use of IL-1ra as monotherapy versus placebo and two trials in combination with methotrexate (MTX; the last trial explored the use of a fixed 100 mg/day IL-1ra dosage in a RA patient population including a wide array of co-morbid conditions as well as concomitant medications. The studies confirmed both the efficacy and the safety of IL-1ra in patients with active and severe RA. 43% of patients receiving 150 mg/day IL-1ra achieved a 20% response according to the American College of Rheumatology criteria (ACR20, compared to 27% in the placebo group. In the MTX combination therapy study, 42% of the patients receiving 1 mg/Kg/day of IL-1ra achieved an ACR20, 24% an ACR50 and 10% an ACR70. In each study, significant improvements in the Health Assessment Questionnaire scores (HAQ were observed. There were rapid gains in the number of days at work or domestic activity in the treated patients, and the increases in productivity were dose related. At early 24 weeks, there was significant reduction of both the score for progression of joint space narrowing (JSN and the Total modified

  8. Longitudinal peripheral blood transcriptional analysis of a patient with severe Ebola virus disease.

    Science.gov (United States)

    Kash, John C; Walters, Kathie-Anne; Kindrachuk, Jason; Baxter, David; Scherler, Kelsey; Janosko, Krisztina B; Adams, Rick D; Herbert, Andrew S; James, Rebekah M; Stonier, Spencer W; Memoli, Matthew J; Dye, John M; Davey, Richard T; Chertow, Daniel S; Taubenberger, Jeffery K

    2017-04-12

    The 2013-2015 outbreak of Ebola virus disease in Guinea, Liberia, and Sierra Leone was unprecedented in the number of documented cases, but there have been few published reports on immune responses in clinical cases and their relationships with the course of illness and severity of Ebola virus disease. Symptoms of Ebola virus disease can include severe headache, myalgia, asthenia, fever, fatigue, diarrhea, vomiting, abdominal pain, and hemorrhage. Although experimental treatments are in development, there are no current U.S. Food and Drug Administration-approved vaccines or therapies. We report a detailed study of host gene expression as measured by microarray in daily peripheral blood samples collected from a patient with severe Ebola virus disease. This individual was provided with supportive care without experimental therapies at the National Institutes of Health Clinical Center from before onset of critical illness to recovery. Pearson analysis of daily gene expression signatures revealed marked gene expression changes in peripheral blood leukocytes that correlated with changes in serum and peripheral blood leukocytes, viral load, antibody responses, coagulopathy, multiple organ dysfunction, and then recovery. This study revealed marked shifts in immune and antiviral responses that preceded changes in medical condition, indicating that clearance of replicating Ebola virus from peripheral blood leukocytes is likely important for systemic viral clearance. Copyright © 2017, American Association for the Advancement of Science.

  9. Velocity of early BCR-ABL transcript elimination as an optimized predictor of outcome in chronic myeloid leukemia (CML) patients in chronic phase on treatment with imatinib.

    Science.gov (United States)

    Hanfstein, B; Shlyakhto, V; Lauseker, M; Hehlmann, R; Saussele, S; Dietz, C; Erben, P; Fabarius, A; Proetel, U; Schnittger, S; Krause, S W; Schubert, J; Einsele, H; Hänel, M; Dengler, J; Falge, C; Kanz, L; Neubauer, A; Kneba, M; Stegelmann, F; Pfreundschuh, M; Waller, C F; Spiekermann, K; Baerlocher, G M; Pfirrmann, M; Hasford, J; Hofmann, W-K; Hochhaus, A; Müller, M C

    2014-10-01

    Early assessment of response at 3 months of tyrosine kinase inhibitor treatment has become an important tool to predict favorable outcome. We sought to investigate the impact of relative changes of BCR-ABL transcript levels within the initial 3 months of therapy. In order to achieve accurate data for high BCR-ABL levels at diagnosis, beta glucuronidase (GUS) was used as a reference gene. Within the German CML-Study IV, samples of 408 imatinib-treated patients were available in a single laboratory for both times, diagnosis and 3 months on treatment. In total, 301 of these were treatment-naïve at sample collection. (i) with regard to absolute transcript levels at diagnosis, no predictive cutoff could be identified; (ii) at 3 months, an individual reduction of BCR-ABL transcripts to the 0.35-fold of baseline level (0.46-log reduction, that is, roughly half-log) separated best (high risk: 16% of patients, 5-year overall survival (OS) 83% vs 98%, hazard ratio (HR) 6.3, P=0.001); (iii) at 3 months, a 6% BCR-ABL(IS) cutoff derived from BCR-ABL/GUS yielded a good and sensitive discrimination (high risk: 22% of patients, 5-year OS 85% vs 98%, HR 6.1, P=0.002). Patients at risk of disease progression can be identified precisely by the lack of a half-log reduction of BCR-ABL transcripts at 3 months.

  10. Retinoic acid signaling and mouse embryonic stem cell differentiation: Cross talk between genomic and non-genomic effects of RA.

    Science.gov (United States)

    Rochette-Egly, Cécile

    2015-01-01

    Retinoic acid (RA), the active derivative of vitamin A, a fat-soluble vitamin, plays key roles in cell growth and differentiation by activating nuclear receptors, RARs (α, β and γ), which are ligand dependent regulators of transcription. The past years highlighted several novelties in the field that increased the complexity of RA effects. Indeed, in addition to its classical genomic effects, RA also has extranuclear and non-transcriptional effects. RA induces the rapid and transient activation of kinase cascades, which are integrated in the nucleus via the phosphorylation of RARs at a conserved serine residue located in the N-terminal domain and their coregulators. In order to investigate the relevance of RARs' phosphorylation in cell differentiation, mouse embryonic stem (mES) cells were used as a model. When treated with RA, these pluripotent cells give rise to neuronal cells. Cells invalidated for each RAR were generated as well as stable rescue lines expressing RARs mutated in phosphor acceptor sites. Such a strategy revealed that RA-induced neuronal differentiation involves the RARγ2 subtype and requires RARγ2 phosphorylation. Moreover, in gene expression profiling experiments, the phosphorylated form of RARγ2 was found to regulate a small subset of genes through binding a novel RA response element consisting of two direct repeats with a 7 base pair spacer. These new findings suggest an important role for RAR phosphorylation during cell differentiation, and pave the way for further investigations with other cell types and during embryonic development. This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Contrasting genetic association of IL2RA with SLE and ANCA – associated vasculitis

    Directory of Open Access Journals (Sweden)

    Todd John A

    2009-03-01

    Full Text Available Abstract Background Autoimmune diseases are complex and have genetic and environmental susceptibility factors. The objective was to test the genetic association of systemic lupus erythematosus (SLE and anti-neutrophil cytoplasmic antibody (ANCA – associated systemic vasculitis (AAV with SNPs in the IL2RA region and to correlate genotype with serum levels of IL-2RA. Methods Using a cohort of over 700 AAV patients, two SLE case-control studies and an SLE trio collection (totalling over 1000 SLE patients, and a TaqMan genotyping approach, we tested 3 SNPs in the IL2RA locus, rs11594656, rs2104286 & rs41295061, each with a prior association with autoimmune disease; rs11594656 and rs41295061 with type 1 diabetes (T1D and rs2104286 with multiple sclerosis (MS and T1D. Results We show that SLE is associated with rs11594656 (P = 3.87 × 10-7 and there is some evidence of association of rs41295061 with AAV (P = 0.0122, which both have prior association with T1D. rs2104286, an MS and T1D – associated SNP in the IL2RA locus, is not associated with either SLE or AAV. Conclusion We have confirmed a previous suggestion that the IL2RA locus is associated with SLE and showed some evidence of association with AAV. Soluble IL-2RA concentrations correlate with rs11594656 genotype in quiescent disease in both AAV and SLE. Differential association of autoimmune diseases and SNPs within the IL2RA locus suggests that the IL2RA pathway may prove to play differing, as yet undefined, roles in each disease.

  12. Removal of 226Ra and 228Ra from TENORM sludge waste using surfactants solutions.

    Science.gov (United States)

    Attallah, M F; Hamed, Mostafa M; El Afifi, E M; Aly, H F

    2015-01-01

    The feasibility of using surfactants as extracting agent for the removal of radium species from TENORM sludge produced from petroleum industry is evaluated. In this investigation cationic and nonionic surfactants were used as extracting agents for the removal of radium radionuclides from the sludge waste. Two surfactants namely cetyltrimethylammonium bromide (CTAB) and Triton X-100 (TX100) were investigated as the extracting agents. Different parameters affecting the removal of both (226)Ra and (228)Ra by the two surfactants as well as their admixture were studied by the batch technique. These parameters include effect of shaking time, surfactants concentration and temperature as well as the effect of surfactants admixture. It was found that, higher solution temperature improves the removal efficiency of radium species. Combined extraction of nonionic and cationic surfactants produces synergistic effect in removal both (226)Ra and (228)Ra, where the removals reached 84% and 80% for (226)Ra and (228)Ra, respectively, were obtained using surfactants admixture. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Microchip, reverse transcription-polymerase chain reaction and culture methods to detect enterovirus infection in pediatric patients.

    Science.gov (United States)

    Tsao, Lon-Yen; Lin, Chi-Yung; Yu, Ya-Yan; Wang, Bao-Tyan

    2006-02-01

    Enterovirus infection usually presents with mild and self-limited illness in children. However, Enterovirus type 71 can be characterized by neurotropism and may cause severe illness or even sudden death. Early detection of the virus will allow a physician to provide intensive or aggressive intervention. The purpose of the present study was to compare sensitivity of two innovative laboratory methods, that is, the DR.EV microchip method (DR. Chip Biotechnology, Shin-Tsu, Taiwan) and the reverse transcription-polymerase chain reaction (RT-PCR) method following conventional virus culture in detecting enterovirus infection in pediatric patients with herpangina or hand-foot-mouth disease. A total of 87 children (age range: 1-8 years) were enrolled because of typical clinical findings of herpangina and hand-foot-mouth disease. Two hundred children selected after a careful clinical history review and physical examinations, were included as controls. All of these children had at least throat swab and rectal swab specimens taken and tested for evidence of enterovirus infection by microchip, RT-PCR and virus culture methods. In addition, 21 patients also had cerebrospinal fluid (CSF) specimens taken to test for possible central nervous system involvement. The test results obtained from the 200 healthy kindergarten children were all negative for enteroviral infection by these three methods. Among the 87 test patients, the positive rates for throat swab, rectal swab and CSF by DR.EV chip, RT-PCR and virus culture were 71%, 68%, and 45% (throat swab); 66%, 61%, and 33% (rectal swab); and 52%, 29%, and 5% (CSF), respectively. There was no significant difference in the positive rates between the DR.EV chip and the RT-PCR methods (P > 0.1) on all types of specimens. However, statistically significant differences in positive rates were noted between the DR.EV chip and the conventional virus culture methods on all types of specimens (P < 0.001). Sensitivity of the microchip, RT

  14. Subtle mutations in the SMN1 gene in Chinese patients with SMA: p.Arg288Met mutation causing SMN1 transcript exclusion of exon7

    Directory of Open Access Journals (Sweden)

    Yu-jin Qu

    2012-09-01

    Full Text Available Abstract Background Proximal spinal muscular atrophy (SMA is a common neuromuscular disorder resulting in death during childhood. Around 81 ~ 95% of SMA cases are a result of homozygous deletions of survival motor neuron gene 1 (SMN1 gene or gene conversions from SMN1 to SMN2. Less than 5% of cases showed rare subtle mutations in SMN1. Our aim was to identify subtle mutations in Chinese SMA patients carrying a single SMN1 copy. Methods We examined 14 patients from 13 unrelated families. Multiplex ligation-dependent probe amplification analysis was carried out to determine the copy numbers of SMN1 and SMN2. Reverse transcription polymerase chain reaction (RT-PCR and clone sequencing were used to detect subtle mutations in SMN1. SMN transcript levels were determined using quantitative RT-PCR. Results Six subtle mutations (p.Ser8LysfsX23, p.Glu134Lys, p.Leu228X, p.Ser230Leu, p.Tyr277Cys, and p.Arg288Met were identified in 12 patients. The p.Tyr277Cys mutation has not been reported previously. The p.Ser8LysfsX23, p.Leu228X, and p.Tyr277Cys mutations have only been reported in Chinese SMA patients and the first two mutations seem to be the common ones. Levels of full length SMN1 (fl-SMN1 transcripts were very low in patients carrying p.Ser8LysfsX23, p.Leu228X or p.Arg288Met compared with healthy carriers. In patients carrying p.Glu134Lys or p.Ser230Leu, levels of fl-SMN1 transcripts were reduced but not significant. The SMN1 transcript almost skipped exon 7 entirely in patients with the p.Arg288Met mutation. Conclusions Our study reveals a distinct spectrum of subtle mutations in SMN1 of Chinese SMA patients from that of other ethnicities. The p.Arg288Met missense mutation possibly influences the correct splicing of exon 7 in SMN1. Mutation analysis of the SMN1 gene in Chinese patients may contribute to the identification of potential ethnic differences and enrich the SMN1 subtle mutation database.

  15. Subtle mutations in the SMN1 gene in Chinese patients with SMA: p.Arg288Met mutation causing SMN1 transcript exclusion of exon7.

    Science.gov (United States)

    Yu-Jin, Qu; Juan, Du; Er-zhen, Li; Jin-li, Bai; Yu-wei, Jin; Hong, Wang; Fang, Song

    2012-09-20

    Proximal spinal muscular atrophy (SMA) is a common neuromuscular disorder resulting in death during childhood. Around 81~95% of SMA cases are a result of homozygous deletions of survival motor neuron gene 1 (SMN1) gene or gene conversions from SMN1 to SMN2. Less than 5% of cases showed rare subtle mutations in SMN1. Our aim was to identify subtle mutations in Chinese SMA patients carrying a single SMN1 copy. We examined 14 patients from 13 unrelated families. Multiplex ligation-dependent probe amplification analysis was carried out to determine the copy numbers of SMN1 and SMN2. Reverse transcription polymerase chain reaction (RT-PCR) and clone sequencing were used to detect subtle mutations in SMN1. SMN transcript levels were determined using quantitative RT-PCR. Six subtle mutations (p.Ser8LysfsX23, p.Glu134Lys, p.Leu228X, p.Ser230Leu, p.Tyr277Cys, and p.Arg288Met) were identified in 12 patients. The p.Tyr277Cys mutation has not been reported previously. The p.Ser8LysfsX23, p.Leu228X, and p.Tyr277Cys mutations have only been reported in Chinese SMA patients and the first two mutations seem to be the common ones. Levels of full length SMN1 (fl-SMN1) transcripts were very low in patients carrying p.Ser8LysfsX23, p.Leu228X or p.Arg288Met compared with healthy carriers. In patients carrying p.Glu134Lys or p.Ser230Leu, levels of fl-SMN1 transcripts were reduced but not significant. The SMN1 transcript almost skipped exon 7 entirely in patients with the p.Arg288Met mutation. Our study reveals a distinct spectrum of subtle mutations in SMN1 of Chinese SMA patients from that of other ethnicities. The p.Arg288Met missense mutation possibly influences the correct splicing of exon 7 in SMN1. Mutation analysis of the SMN1 gene in Chinese patients may contribute to the identification of potential ethnic differences and enrich the SMN1 subtle mutation database.

  16. Competition of IL-1 and IL-1ra determines lymphocyte response to delayed stimulation with PHA.

    Science.gov (United States)

    Dabrowski, M P; Stankiewicz, W; Płusa, T; Chciałowski, A; Szmigielski, S

    2001-06-01

    Human peripheral blood mononuclear cells (PBMC) left in microcultures for 24h without mitogen do not respond to subsequent stimulation with PHA. They regain reactivity if the native culture medium is absorbed with other party lymphocytes or partially replaced with the medium from a PHA-stimulated culture. The observations suggest that, during the incubation, some inhibitory agent had accumulated in the culture medium. The study was performed to determine the nature of the observed phenomenon in respect of the possible role of monocytes and their products IL-1 and IL-1 receptor antagonist (IL-1ra), and to test for immunodiagnostic purposes the significance of quantifying the lymphocyte response to delayed stimulation with PHA in patients suffering from inflammatory prosesses. Lymphocyte response to delayed stimulation with PHA, calculated as the lymphocyte-monokine interaction (LM) index, was determined in the microcultures of PBMC isolated from the blood of healthy donors or of patients with acute tonsilitis. The values of LM indices were compared with the ratios of IL-1ra/IL-1beta concentration estimated by enzyme-linked immunosorbent assay method in the culture supernatants. The influences of exogenous IL-1beta, IL-1ra, anti-IL1ra antibodies and antibiotic cefaclor on the monokine concentrations and on the values of LM index were tested. The results show that the level of lymphocyte response to delayed stimulation with PHA (LM index) is inversely proportional to the ratio of IL-1ra/IL-1beta concentration in the culture. The low LM values at high IL-1ra/IL-1beta ratios in PBMC cultures from healthy donors, reversed proportions found in patients' PBMC (acute tonsilitis), and the cefaclor-induced reduction of LM value with correlated increase of the IL-1ra/IL-1beta ratio suggest that the LM assay may prove to be useful for immunodiagnostic purposes.

  17. Factors affecting {sup 223}Ra therapy: clinical experience after 532 cycles from a single institution

    Energy Technology Data Exchange (ETDEWEB)

    Etchebehere, Elba C. [The University of Texas MD Anderson Cancer Center, Department of Nuclear Medicine, Houston, TX (United States); Campinas State University (Unicamp), Department of Nuclear Medicine, Campinas (Brazil); Milton, Denai R. [The University of Texas MD Anderson Cancer Center, Department of Biostatistics, Houston, TX (United States); Araujo, John C. [The University of Texas MD Anderson Cancer Center, Department of Genitourinary Medical Oncology, Houston, TX (United States); Swanston, Nancy M.; Macapinlac, Homer A.; Rohren, Eric M. [The University of Texas MD Anderson Cancer Center, Department of Nuclear Medicine, Houston, TX (United States)

    2016-01-15

    The aim of this study was to identify baseline features that predict outcome in {sup 223}Ra therapy. We retrospectively reviewed 110 patients with metastatic castration-resistant prostate cancer treated with {sup 223}Ra. End points were overall survival (OS), progression-free survival (PFS), bone event-free survival (BeFS), and bone marrow failure (BMF). The following parameters were evaluated prior to the first {sup 223}Ra cycle: serum levels of hemoglobin (Hb), prostate-specific antigen (PSA), alkaline phosphatase (ALP), Eastern Cooperative Oncology Group (ECOG) status, pain score, use of chemotherapy, and external beam radiation therapy (EBRT). During/after {sup 223}Ra we evaluated: the total number of radium cycles (Ra{sub Tot}), the PSA doubling time (PSA{sub DT}), and the use of chemotherapy, EBRT, abiraterone, and enzalutamide. A significant reduction of ALP (p < 0.001) and pain score (p = 0.041) occurred throughout the {sup 223} Ra cycles. The risk of progression was associated with declining ECOG status [hazard ratio (HR) = 3.79; p < 0.001] and decrease in PSA{sub DT} (HR = 8.22; p < 0.001). Ra{sub Tot}, ALP, initial ECOG status, initial pain score, and use of abiraterone were associated with OS (p ≤ 0.008), PFS (p ≤ 0.003), and BeFS (p ≤ 0.020). Ra{sub Tot}, ALP, initial ECOG status, and initial pain score were significantly associated with BMF (p ≤ 0.001) as well as Hb (p < 0.001) and EBRT (p = 0.009). On multivariable analysis, only Ra{sub Tot} and abiraterone remained significantly associated with OS (p < 0.001; p = 0.033, respectively), PFS (p < 0.001; p = 0.041, respectively), and BeFS (p < 0.001; p = 0.019, respectively). Additionally, Ra{sub Tot} (p = 0.027) and EBRT (p = 0.013) remained significantly associated with BMF. Concomitant use of abiraterone and {sup 223}Ra seems to have a beneficial effect, while the EBRT may increase the risk of BMF. (orig.)

  18. MRI comes of age in RA clinical trials

    DEFF Research Database (Denmark)

    Peterfy, Charles; Østergaard, Mikkel; Conaghan, Philip G

    2013-01-01

    The success of modern rheumatoid arthritis (RA) therapies and treatment strategies has led to extended placebo phases being unethical in RA randomised controlled trials (RCTs). Modern trials therefore increasingly involve active comparator designs, and this together with some technical issues has...... in support of claims of inhibition of progression of structural damage in RA trials....

  19. Automated measurement of {sup 224}Ra and {sup 226}Ra in water

    Energy Technology Data Exchange (ETDEWEB)

    Dimova, N. [Department of Oceanography, Environmental Radioactivity Measurement Facility, Florida State University, Tallahassee, FL 32306 (United States); Burnett, W.C. [Department of Oceanography, Environmental Radioactivity Measurement Facility, Florida State University, Tallahassee, FL 32306 (United States)]. E-mail: wburnett@mailer.fsu.edu; Horwitz, E.P. [PG Research Foundation, 8205 S. Cass Avenue, Suite III, Darien, IL 60561 (United States); Lane-Smith, D. [Durridge Co., Inc., 7 Railroad Avenue, Suite D, Bedford, MA 01730 (United States)

    2007-04-15

    We present a new simple approach for automated, non-destructive measurement of the alpha-emitting radium isotopes ({sup 223}Ra, {sup 224}Ra, and {sup 226}Ra) in water based on the emanation of their respective radon daughters ({sup 219}Rn, {sup 220}Rn, and {sup 222}Rn). The method combines the high adsorption uptake of MnO{sub 2} Resin for radium (K {sub d}=2.4x10{sup 4} ml/g) over a wide pH range with the simplicity of the activity registration using a commercial radon-in-air analyzer (RAD7, DURRIDGE Company, Inc). Radium is first adsorbed onto the MnO{sub 2} Resin by passing a water sample through the resin packed in a gas-tight glass cartridge. The same cartridge is then connected to the radon analyzer via a simple tubing system to circulate air through the resin and a drying system. The efficiency of the proposed system is determined by running standards prepared in the same manner. Our results indicate that the efficiency for {sup 226}Ra is >22% if both {sup 218}Po and {sup 214}Po counts are collected. This is comparable with typical efficiencies for alpha spectrometry but with much less sample preparation. We estimate that an MDA of 0.8 pCi/L for {sup 226}Ra may be obtained with this new approach using a 1 L water sample and less than 4 h of counting.

  20. Transcriptional Signatures Related to Glucose and Lipid Metabolism Predict Treatment Response to the Tumor Necrosis Factor Antagonist Infliximab in Patients with Treatment-Resistant Depression

    Science.gov (United States)

    Mehta, Divya; Raison, Charles L.; Woolwine, Bobbi J.; Haroon, Ebrahim; Binder, Elisabeth B.; Miller, Andrew H.; Felger, Jennifer C.

    2013-01-01

    The tumor necrosis factor (TNF) antagonist infliximab was recently found to reduce depressive symptoms in patients with increased baseline inflammation as reflected by a plasma C-reactive protein concentration >5mg/L. To further explore predictors and targets of response to infliximab, differential gene expression was examined in peripheral blood mononuclear cells from infliximab responders (n=13) versus non-responders (n=14) compared to placebo at baseline and 6hr, 24hr, and 2 weeks after the first infliximab infusion. Treatment response was defined as 50% reduction in depressive symptoms at any point during the 12-week trial. One-hundred-forty-eight gene transcripts were significantly associated (1.2 fold, adjusted p≤0.01) with response to infliximab and were distinct from placebo responders. Transcripts predictive of infliximab response were associated with gluconeogenesis and cholesterol transport, and were enriched in a network regulated by hepatocyte nuclear factor (HNF)4-alpha, a transcription factor involved in gluconeogenesis and cholesterol and lipid homeostasis. Of the 148 transcripts differentially expressed at baseline, 48% were significantly regulated over time in infliximab responders, including genes related to gluconeogenesis and the HNF4-alpha network, indicating that these predictive genes were responsive to infliximab. Responders also demonstrated inhibition of genes related to apoptosis through TNF signaling at 6hr and 24hr after infusion. Transcripts down-regulated in responders 2 weeks after infliximab were related to innate immune signaling and nuclear factor-kappa B. Thus, baseline transcriptional signatures reflective of alterations in glucose and lipid metabolism predicted antidepressant response to infliximab, and infliximab response involved regulation of metabolic genes and inhibition of genes related to innate immune activation. PMID:23624296

  1. Immunomodulation of RA Patients’ PBMC with a Multiepitope Peptide Derived from Citrullinated Autoantigens

    Directory of Open Access Journals (Sweden)

    Smadar Gertel

    2017-01-01

    Full Text Available Citrullinated peptides are used for measuring anticitrullinated protein antibodies (ACPA in rheumatoid arthritis (RA. Accumulation of citrullinated proteins in the inflamed synovium suggests that they may be good targets for inducing peripheral tolerance. In view of the multiplicity of citrullinated autoantigens described as ACPA targets, we generated a multiepitope citrullinated peptide (Cit-ME from the sequences of major citrullinated autoantigens: filaggrin, β-fibrinogen, vimentin, and collagen type II. We assessed the ability of Cit-ME or the citrullinated β60-74 fibrinogen peptide (β60-74-Fib-Cit which bears immunodominant citrullinated epitopes (i to modify cytokine gene expression and (ii to modulate Treg and Th17 subsets in PBMC derived from newly diagnosed untreated RA patients. RA patient’s PBMC incubated with Cit-ME or β60-74-Fib-Cit, showed upregulation of TGF-β expression (16% and 8%, resp., and increased CD4+Foxp3+ Treg (22% and 19%, resp.. Both peptides were shown to downregulate the TNF-α and IL-1β expression; in addition, Cit-ME reduced CD3+IL17+ T cells. We showed that citrullinated peptides can modulate the expression of anti- and proinflammatory cytokines in PBMC from RA patients as well as the proportions of Treg and Th17 cells. These results indicate that citrullinated peptides could be active in vivo and therefore might be used as immunoregulatory agents in RA patients.

  2. Document management system "Raštvedyba"

    OpenAIRE

    Fokina, Julija

    2007-01-01

    SUMMARY Document management system “Raštvedyba” Modern people really very rarely think about how important is the electic power nowdays. We understand it’s importance only when we don’t have it because of emergency or something like that. This way we have the evening with “candle”, without radio and television, all home appliences don’t work at all. Although energetic specialists apply the best disaster facilities to avoid the emergency situations, sometimes it doesnt help and people ...

  3. Ra-226 bioaccumulation and growth indices in fish.

    Science.gov (United States)

    Shi, Xiaopei; Smith, Richard; Seymour, Colin; Mothersill, Carmel

    2017-06-01

    To determine the accumulated activity of Ra-226 in fathead minnows fed with environmentally relevant levels of Ra-226 for 5 months in water at 20 °C, and to evaluate the influence of this level of Ra-226 on the growth of fathead minnows. Fathead minnows were fed with fish food containing 10-10,000 mBq/g Ra-226 for 5 months. At the end of the experiment, the fish were sacrificed, flash frozen in liquid nitrogen and kept at -20 °C. Longitudinal sections of 40 μm thickness were cut at the middle of the fish body using a cryostat. The activity of Ra-226 in each section was determined using autoradiography with a nuclear track detector CR-39. According to the weight and the width of the fish, the activity of Ra-226 in the whole fish body could be estimated. In addition, the length and the weight of the fish were measured and the condition factor was calculated to evaluate the growth and fitness of the fish. There is a positive but non-linear relationship between the accumulated activity of Ra-226 in fish body and the concentration of Ra-226 in fish food. The highest activity of Ra-226 accumulated in fish body was found from fish fed with 10,000 mBq/g Ra-226 food. This was calculated as 256.4 ± 49.1 mBq/g, p fish fed with food containing lower concentration of Ra-226 (up to 1000 mBq/g), the bioaccumulation of Ra-226 in the body saturated. The Ra-226 concentration factor (CF) for fish was inversely proportional to the Ra-226 activity in food, and the highest CF value was 2.489, obtained from the lowest dietary Ra-226 activity (10 mBq/g). In addition, condition factors (K) of fish in all Ra-226-treated groups were significantly lower than those of the controls. The results show that the bioaccumulation of Ra-226 in fish is not simply related to the dietary Ra-226 activity, and has a saturation value when the dietary activity is low. In addition, the environmental level of Ra-226 in the fish food has a small adverse effect on the growth and fitness of fathead

  4. Epigenomic study identifies a novel mesenchyme homeobox2-GLI1 transcription axis involved in cancer drug resistance, overall survival and therapy prognosis in lung cancer patients

    Science.gov (United States)

    Armas-López, Leonel; Piña-Sánchez, Patricia; Arrieta, Oscar; de Alba, Enrique Guzman; Ortiz-Quintero, Blanca; Santillán-Doherty, Patricio; Christiani, David C.; Zúñiga, Joaquín; Ávila-Moreno, Federico

    2017-01-01

    Several homeobox-related gene (HOX) transcription factors such as mesenchyme HOX-2 (MEOX2) have previously been associated with cancer drug resistance, malignant progression and/or clinical prognostic responses in lung cancer patients; however, the mechanisms involved in these responses have yet to be elucidated. Here, an epigenomic strategy was implemented to identify novel MEOX2 gene promoter transcription targets and propose a new molecular mechanism underlying lung cancer drug resistance and poor clinical prognosis. Chromatin immunoprecipitation (ChIP) assays derived from non-small cell lung carcinomas (NSCLC) hybridized on gene promoter tiling arrays and bioinformatics analyses were performed, and quantitative, functional and clinical validation were also carried out. We statistically identified a common profile consisting of 78 gene promoter targets, including Hedgehog-GLI1 gene promoter sequences (FDR≤0.1 and FDR≤0.2). The GLI-1 gene promoter region from −2,192 to −109 was occupied by MEOX2, accompanied by transcriptionally active RNA Pol II and was epigenetically linked to the active histones H3K27Ac and H3K4me3; these associations were quantitatively validated. Moreover, siRNA genetic silencing assays identified a MEOX2-GLI1 axis involved in cellular cytotoxic resistance to cisplatinum in a dose-dependent manner, as well as cellular migration and proliferation. Finally, Kaplan-Maier survival analyses identified significant MEOX2-dependent GLI-1 protein expression associated with clinical progression and poorer overall survival using an independent cohort of NSCLC patients undergoing platinum-based oncological therapy with both epidermal growth factor receptor (EGFR)-non-mutated and EGFR-mutated status. In conclusion, this is the first study to investigate epigenome-wide MEOX2-transcription factor occupation identifying a novel overexpressed MEOX2-GLI1 axis and its clinical association with platinum-based cancer drug resistance and EGFR

  5. Comparative transcriptional profiling-based identification of raphanusanin-inducible genes

    Directory of Open Access Journals (Sweden)

    Hasegawa Koji

    2010-06-01

    Full Text Available Abstract Background Raphanusanin (Ra is a light-induced growth inhibitor involved in the inhibition of hypocotyl growth in response to unilateral blue-light illumination in radish seedlings. Knowledge of the roles of Ra still remains elusive. To understand the roles of Ra and its functional coupling to light signalling, we constructed the Ra-induced gene library using the Suppression Subtractive Hybridisation (SSH technique and present a comparative investigation of gene regulation in radish seedlings in response to short-term Ra and blue-light exposure. Results The predicted gene ontology (GO term revealed that 55% of the clones in the Ra-induced gene library were associated with genes involved in common defence mechanisms, including thirty four genes homologous to Arabidopsis genes implicated in R-gene-triggered resistance in the programmed cell death (PCD pathway. Overall, the library was enriched with transporters, hydrolases, protein kinases, and signal transducers. The transcriptome analysis revealed that, among the fifty genes from various functional categories selected from 88 independent genes of the Ra-induced library, 44 genes were up-regulated and 4 were down-regulated. The comparative analysis showed that, among the transcriptional profiles of 33 highly Ra-inducible genes, 25 ESTs were commonly regulated by different intensities and duration of blue-light irradiation. The transcriptional profiles, coupled with the transcriptional regulation of early blue light, have provided the functional roles of many genes expected to be involved in the light-mediated defence mechanism. Conclusions This study is the first comprehensive survey of transcriptional regulation in response to Ra. The results described herein suggest a link between Ra and cellular defence and light signalling, and thereby contribute to further our understanding of how Ra is involved in light-mediated mechanisms of plant defence.

  6. Arthritic and non-arthritic synovial fluids modulate IL10 and IL1RA gene expression in differentially activated primary human monocytes.

    Science.gov (United States)

    Lopa, S; Leijs, M J C; Moretti, M; Lubberts, E; van Osch, G J V M; Bastiaansen-Jenniskens, Y M

    2015-11-01

    Synovitis with an increased presence of macrophages is observed in osteoarthritis (OA) and rheumatoid arthritis (RA). Given the important role of macrophages in arthritis, we investigated the influence of OA and RA synovial fluid (SF) on primary human monocytes (Mo), their lineage precursors. Adherent monocytes without any stimulation (Mo(-)) or stimulated with IFN-γ and TNF-α (Mo(IFN-γ/TNF-α)) or IL-4 (Mo(IL-4)) were exposed to SF from 6 donors without any known joint disease (SF-Ctrl), 10 OA donors (SF-OA), and 10 RA donors (SF-RA). The transcriptional expression of IL6, IL1B, TNFA, IL10, CCL18, CD206, and IL1RA was analyzed. Mo(-) exposed to SF-RA had a lower expression of IL10 and a higher expression of IL1RA than when exposed to SF-Ctrl. Mo(IL-4) exposed to SF-RA had a lower expression of IL10 and CCL18 than when exposed to SF-Ctrl and Mo(IFN-γ/TNF-α) were not affected by SF-RA. Mo exposed to SF-OA also expressed less IL10, but only upon stimulation with IL-4, and expressed more IL1RA than when exposed to SF-Ctrl in any condition. A lower expression of IL10 may be regarded as a response to less inflammatory conditions since IL10 expression is higher in response to IFN-γ/TNF-α stimulation, probably as a feedback mechanism. Therefore, the lower expression of IL10 and the higher expression of IL1RA in Mo exposed to arthritic than to non-arthritic SF suggest that arthritic SF is mainly reducing the inflammatory responses in Mo. This may mimic the response of monocytes/macrophages recruited to the joint, where feedback mechanisms counteract pro-inflammatory processes. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  7. Tivantinib (ARQ 197), a selective inhibitor of MET, in patients with microphthalmia transcription factor-associated tumors: results of a multicenter phase 2 trial.

    Science.gov (United States)

    Wagner, Andrew J; Goldberg, John M; Dubois, Steven G; Choy, Edwin; Rosen, Lee; Pappo, Alberto; Geller, James; Judson, Ian; Hogg, David; Senzer, Neil; Davis, Ian J; Chai, Feng; Waghorne, Carol; Schwartz, Brian; Demetri, George D

    2012-12-01

    Microphthalmia transcription factor (MITF)-associated (MiT) tumors are a family of rare malignancies, including alveolar soft part sarcoma (ASPS), clear cell sarcoma (CCS), and translocation-associated renal cell carcinoma (tRCC) that have dysregulated expression of oncogenic MITF family proteins. The MET receptor tyrosine kinase gene is transcriptionally activated by MITF family proteins, making MET a potential therapeutic target for MiT tumors. This study assessed the activity of tivantinib (ARQ 197), a selective MET inhibitor, in patients with MiT-associated tumors. This multicenter, single-arm, phase 2 trial enrolled patients with advanced MiT tumors. Patients initially received tivantinib 120 mg orally twice daily, then 360 mg twice daily per protocol amendment. The primary endpoint was overall response rate. Secondary endpoints included safety, progression-free survival, pharmacokinetics, and correlative studies. A total of 47 patients (median age, 25 years; range, 11-73 years) with ASPS (n = 27), CCS (n = 11), tRCC (n = 6), or other tumor types (n = 3) were enrolled. Common grade 3/4 drug-related adverse events included anemia (4%) and neutropenia (4%). Three patients (6.4%) experienced 4 treatment-related serious adverse events (grade 3 febrile neutropenia, thrombocytopenia, and deep vein thrombosis, and grade 4 thrombocytopenia). Best response was partial response in 1 CCS patient (2%) and stable disease in 28 patients (60%). Median progression-free survival was 3.6 months (overall), 5.5 months (ASPS), and 1.9 months (CCS and tRCC). Baseline MET expression was strongly or focally positive in tumor samples from 14 of 19 patients (74%). Tivantinib was safe and tolerable in patients with MiT tumors, but antitumor activity was modest. Copyright © 2012 American Cancer Society.

  8. Multiplexed automated digital quantification of fusion transcripts: comparative study with fluorescent in-situ hybridization (FISH) technique in acute leukemia patients.

    Science.gov (United States)

    Akhter, Ariz; Mughal, Muhammad Kashif; Elyamany, Ghaleb; Sinclair, Gary; Azma, Raja Zahratul; Masir, Noraidah; Shuib, Salwati; Rashid-Kolvear, Fariborz; Shabani-Rad, Meer-Taher; Stewart, Douglas Allan; Mansoor, Adnan

    2016-09-15

    The World Health Organization (WHO) classification system defines recurrent chromosomal translocations as the sole diagnostic and prognostic criteria for acute leukemia (AL). These fusion transcripts are pivotal in the pathogenesis of AL. Clinical laboratories universally employ conventional karyotype/FISH to detect these chromosomal translocations, which is complex, labour intensive and lacks multiplexing capacity. Hence, it is imperative to explore and evaluate some newer automated, cost-efficient multiplexed technologies to accommodate the expanding genetic landscape in AL. "nCounter® Leukemia fusion gene expression assay" by NanoString was employed to detect various fusion transcripts in a large set samples (n = 94) utilizing RNA from formalin fixed paraffin embedded (FFPE) diagnostic bone marrow biopsy specimens. This series included AL patients with various recurrent translocations (n = 49), normal karyotype (n = 19), or complex karyotype (n = 21), as well as normal bone marrow samples (n = 5). Fusion gene expression data were compared with results obtained by conventional karyotype and FISH technology to determine sensitivity/specificity, as well as positive /negative predictive values. Junction probes for PML/RARA; RUNX1-RUNX1T1; BCR/ABL1 showed 100 % sensitivity/specificity. A high degree of correlation was noted for MLL/AF4 (85 sensitivity/100 specificity) and TCF3-PBX1 (75 % sensitivity/100 % specificity) probes. CBFB-MYH11 fusion probes showed moderate sensitivity (57 %) but high specificity (100 %). ETV6/RUNX1 displayed discordance between fusion transcript assay and FISH results as well as rare non-specific binding in AL samples with normal or complex cytogenetics. Our study presents preliminary data with high correlation between fusion transcript detection by a throughput automated multiplexed platform, compared to conventional karyotype/FISH technique for detection of chromosomal translocations in AL patients. Our

  9. Raúl Pepe Verano Montesinos

    OpenAIRE

    José Luis Luque

    2013-01-01

    El 31 de enero de 2005 falleció en Lima el doctor Raúl Verano. Nacido el 12 de julio de 1940 en Cajatambo, realizó sus estudios superiores en la Universidad Nacional Mayor de San Marcos, graduándose en 1971 de bachiller en Educación y en 1972 obtuvo el grado de bachiller en Biología con la tesis Foraminíferos del litoral del departamento de Lima; optando la profesión de Biólogo en 1973. Empezó sus actividades docentes en 1965 como Ayudante de Prácticas en las cá- tedras de zoología y desde 19...

  10. Pregnancy in Rađevina customs

    Directory of Open Access Journals (Sweden)

    Petrović-Savić Mirjana

    2012-01-01

    Full Text Available The paper discusses the representation of pregnancy in the customs and beliefs of a region in Serbia known as Rađevina. The research was aimed at recording and preserving the customs and lexis regarding pregnancy in this part of Serbia. We obtained the lexis through topic guided conversations with the informants. The article is divided into several sections: on pregnancy before pregnancy, prohibitions during pregnancy and consequences if they are not observed, revealing the baby's gender, conclusion and glossary. Rađevina used to have a system of regulations that the pregnant woman had to adhere to. Special attention was paid to the behavior of the pregnant woman herself. It was in larger part regulated by means of numerous prohibitions and limitations. Most of those prohibitions were based on the assumption of a magical relation of the future mother and the fetus in her womb. It is interesting to note that some prohibitions were observed before pregnancy itself, during the wedding ritual. In this period, the community tended to facilitate the bride's conception of a fair, healthy male child. During pregnancy itself the pregnant woman used certain objects to protect herself from evil and negative influences of her surroundings. The largest number of prohibitions during pregnancy were implemented so that a healthy, but also fair child should be born. Apart from that, the prohibitions were intended to influence the child's longevity. The section on pregnancy before pregnancy lists the techniques applied in the wedding ritual which influenced the bride's fertility with imitative magic. We also shed some light on the traditional revealing of the future child's gender, and the paper is ends with a glossary.

  11. Transcription activity of MMP-2 and MMP-9 metalloproteinase genes and their tissue inhibitor (TIMP-2 in acute coronary syndrome patients

    Directory of Open Access Journals (Sweden)

    J Dabek

    2013-01-01

    Full Text Available Background: Acute coronary syndromes (ACS are a consequence of coronary vessel atherosclerosis and they are a leading cause of death in industrialized countries. One of the ACS causative factors is the deranged ratio equilibrium of the matrix metalloproteinase/tissue inhibitor of metalloproteinases (MMPs/TIMPs. Aims: Assessment of transcriptional activity of metalloproteinase genes using Human Genome-U133A oligonucleotide microarrays and selection of candidate genes differentiating ACS patients from healthy subjects and finally, QRT-PCR (quantitative real time polymerase chain reaction confirmation of the results. Settings and Design: The study involved 67 ACS patients, admitted on a consecutive basis, to the Cardiology Clinic as well as 24 healthy subjects (control. Materials and Methods: Ribonucleic acid isolated from peripheral blood mononuclear cells was analyzed by QRT-PCR. Transcriptional activity of the analyzed gene was assessed with TaqMan gene expression assays. Statistical Analysis: U Mann-Whitney test was used to compare the results. Results: Homogeneity of the investigated group was assessed through hierarchical clusterization whereas the nine genes differentiating ACS patients from healthy persons were selected using the Bland-Altman technique. Among these genes three (platelet derived growth factor D, NUAK family SNF1-like kinase 1 and peroxisomal biogenesis factor 1 showed decreased transcriptional activity whereas the remaining six genes (MMP-2 and MMP-9, CDK5RAP3, transmembrane BAX inhibitor motif containing 1, adenylate cyclase-associated protein 1 and TIMP-2 were increased. MMP-2, MMP-9 and TIMP-2 were further characterized by QRT-PCR. Conclusions: The obtained results permit to conclude that the increased expression of MMP-2 and MMP-9 metalloproteinases and their tissue inhibitor (TIMP-2 is responsible for disturbed equilibrium of the metalloproteinase/tissue inhibitors system and as a consequence, for destabilization of

  12. The genetics of rheumatoid arthritis: risk and protection in different stages of the evolution of RA

    Science.gov (United States)

    Yarwood, Annie; Huizinga, Tom W. J.

    2016-01-01

    There is now a general consensus that RA has a spectrum of disease stages that can begin many years before the onset of clinical symptoms. It is widely thought that understanding the complex interplay between genetics and environment, and their role in pathogenesis, is essential in gaining further insight into the mechanisms that drive disease development and progression. More than 100 genetic susceptibility loci have now been identified for RA through studies that have focused on patients with established RA compared with healthy controls. Studying the early preclinical phases of disease will provide valuable insights into the biological events that precede disease and could potentially identify biomarkers to predict disease onset and future therapeutic targets. In this review we will cover recent advances in the knowledge of genetic and environmental risk factors and speculate on how these factors may influence the transition from one stage of disease to another. PMID:25239882

  13. Host immune transcriptional profiles reflect the variability in clinical disease manifestations in patients with Staphylococcus aureus infections.

    Directory of Open Access Journals (Sweden)

    Romain Banchereau

    Full Text Available Staphylococcus aureus infections are associated with diverse clinical manifestations leading to significant morbidity and mortality. To define the role of the host response in the clinical manifestations of the disease, we characterized whole blood transcriptional profiles of children hospitalized with community-acquired S. aureus infection and phenotyped the bacterial strains isolated. The overall transcriptional response to S. aureus infection was characterized by over-expression of innate immunity and hematopoiesis related genes and under-expression of genes related to adaptive immunity. We assessed individual profiles using modular fingerprints combined with the molecular distance to health (MDTH, a numerical score of transcriptional perturbation as compared to healthy controls. We observed significant heterogeneity in the host signatures and MDTH, as they were influenced by the type of clinical presentation, the extent of bacterial dissemination, and time of blood sampling in the course of the infection, but not by the bacterial isolate. System analysis approaches provide a new understanding of disease pathogenesis and the relation/interaction between host response and clinical disease manifestations.

  14. Differential effects of Th1 versus Th2 cytokines in combination with hypoxia on HIFs and angiogenesis in RA

    Science.gov (United States)

    2012-01-01

    Introduction Hypoxia and T-helper cell 1 (Th1) cytokine-driven inflammation are key features of rheumatoid arthritis (RA) and contribute to disease pathogenesis by promoting angiogenesis. The objective of our study was to characterise the angiogenic gene signature of RA fibroblast-like synoviocytes (FLS) in response to hypoxia, as well as Th1 and T-helper cell 2 (Th2) cytokines, and in particular to dissect out effects of combined hypoxia and cytokines on hypoxia inducible transcription factors (HIFs) and angiogenesis. Methods Human angiogenesis PCR arrays were used to screen cDNA from RA FLS exposed to hypoxia (1% oxygen) or dimethyloxalylglycine, which stabilises HIFs. The involvement of HIF isoforms in generating the angiogenic signature of RA FLS stimulated with hypoxia and/or cytokines was investigated using a DNA-binding assay and RNA interference. The angiogenic potential of conditioned media from hypoxia-treated and/or cytokine-treated RA FLS was measured using an in vitro endothelial-based assay. Results Expression of 12 angiogenic genes was significantly altered in RA FLS exposed to hypoxia, and seven of these were changed by dimethyloxalylglycine, including ephrin A3 (EFNA3), vascular endothelial growth factor (VEGF), adipokines angiopoietin-like (ANGPTL)-4 and leptin. These four proangiogenic genes were dependent on HIF-1 in hypoxia to various degrees: EFNA3 >ANGPTL-4 >VEGF >leptin. The Th1 cytokines TNFα and IL-1β induced HIF-1 but not HIF-2 transcription as well as activity, and this effect was additive with hypoxia. In contrast, Th2 cytokines had no effect on HIFs. IL-1β synergised with hypoxia to upregulate EFNA3 and VEGF in a HIF-1-dependent fashion but, despite strongly inducing HIF-1, TNFα suppressed adipokine expression and had minimal effect on EFNA3. Supernatants from RA FLS subjected to hypoxia and TNFα induced fewer endothelial tubules than those from FLS subjected to TNFα or hypoxia alone, despite high VEGF protein levels. The Th2

  15. Posledice kvantnega računalništva

    OpenAIRE

    Malenko, Kokan

    2017-01-01

    Kvantno računalništvo je novo obetavno področje, ki bi lahko prineslo velike izboljšave današnje tehnologije. Vendar pa bi lahko obenem tudi razorožilo nekatere priljubljene kriptografske algoritme. Čeprav uporabnih in stabilnih kvantnih računalnikov še ni, sta njihova potencialna moč in uporabnost spodbudili veliko zanimanje. V tem delu bomo pojasnili osnovne lastnosti kvantnega računalnika, tj. ra-ču-nal-ni-ka, ki izkorišča kvantnomehanske pojave, kot so superpozicija, intefe...

  16. Separation of Ra/Ca by ion exchange; Separacion de Ra/Ca por intercambio ionico

    Energy Technology Data Exchange (ETDEWEB)

    Iturbe, J.L.; Jimenez R, M.; Flores M, J

    1991-04-15

    The radium and the calcium belong to the same group in the periodic classification and as consequence both they present very similar chemical properties, that makes difficult its separation. Both elements are also frequently associate in the nature, the calcium is very abundant, the radium is not it and for that reason it is indispensable its separation to analyze to this last one. The alpha spectroscopy is very appropriate to analyze to the {sup 226} Ra, however to achieve a good resolution of the spectra, the samples should contain small quantities of calcium. The purposes of this work were to know the chromatographic behavior of the alkaline-earthy cations: calcium, barium and radium and to apply these knowledge to the separation of the {sup 226} Ra and its analysis by means of alpha spectroscopy. (Author)

  17. Dosimetry of {sup 223}Ra-chloride: dose to normal organs and tissues

    Energy Technology Data Exchange (ETDEWEB)

    Lassmann, Michael [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Nosske, Dietmar [Federal Office for Radiation Protection (BfS), Department of Radiation and Health, Oberschleissheim (Germany)

    2013-02-15

    {sup 223}Ra-Chloride (also called Alpharadin {sup registered}) targets bone metastases with short range alpha particles. In recent years several clinical trials have been carried out showing, in particular, the safety and efficacy of palliation of painful bone metastases in patients with castration-resistant prostate cancer using {sup 223}Ra-chloride. The purpose of this work was to provide a comprehensive dosimetric calculation of organ doses after intravenous administration of {sup 223}Ra-chloride according to the present International Commission on Radiological Protection (ICRP) model for radium. Absorbed doses were calculated for 25 organs or tissues. Bone endosteum and red bone marrow show the highest dose coefficients followed by liver, colon and intestines. After a treatment schedule of six intravenous injections with 0.05 MBq/kg of {sup 223}Ra-chloride each, corresponding to 21 MBq for a 70 kg patient, the absorbed alpha dose to the bone endosteal cells is about 16 Gy and the corresponding absorbed dose to the red bone marrow is approximately 1.5 Gy. The comprehensive list of dose coefficients presented in this work will assist in comparing and evaluating organ doses from various therapy modalities used in nuclear medicine and will provide a base for further development of patient-specific dosimetry. (orig.)

  18. The identification of point mutations in Duchenne muscular dystrophy patients by using reverse-transcription PCR and the protein truncation test

    Energy Technology Data Exchange (ETDEWEB)

    Gardner, R.J.; Bobrow, M.; Roberts, R.G. [St. Thomas`s Hospitals, London (United Kingdom)

    1995-08-01

    The protein truncation test (PTT) is a mutation-detection method that monitors the integrity of the open reading frame (ORF). More than 60% of cases of Duchenne muscular dystrophy (DMD) result from gross frameshifting deletions in the dystrophin gene that are detectable by multiplex PCR system. It has become apparent that virtually all of the remaining DMD mutations also disrupt the translational reading frame, making the PTT a logical next step toward a comprehensive strategy for the identification of all DMD mutations. We report here a pilot study involving 22 patients and describe the mutations characterized. These constitute 12 point mutations or small insertions/deletions and 4 gross rearrangements. We also have a remaining five patients in whom there does not appear to be mutation in the ORF. We believe that reverse-transcription-PCR/PTT is an efficient method by which to screen for small mutations in DMD patients with no deletion. 29 refs., 2 figs., 3 tabs.

  19. Hypothalamic-pituitary-adrenal axis activity in patients with rheumatoid arthritis.

    NARCIS (Netherlands)

    Eijsbouts, A.M.M.; Hoogen, F.H.J. van den; Laan, R.F.J.M.; Hermus, A.R.M.M.; Sweep, C.G.J.; Putte, L.B.A. van de

    2005-01-01

    OBJECTIVE: To study the hypothalamic-pituitary-adrenal (HPA) axis in patients with rheumatoid arthritis (RA). METHODS: Fifty patients with RA participated in 3 groups: recent onset active RA (n = 20), longstanding active RA (n = 20) and long-standing RA in remission (n = 10), and were compared with

  20. Variants within MECP2, a key transcription regulator, are associated with increased susceptibility to lupus and differential gene expression in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Webb, Ryan; Wren, Jonathan D; Jeffries, Matlock; Kelly, Jennifer A; Kaufman, Kenneth M; Tang, Yuhong; Frank, Mark Barton; Merrill, Joan; Kimberly, Robert P; Edberg, Jeffrey C; Ramsey-Goldman, Rosalind; Petri, Michelle; Reveille, John D; Alarcón, Graciela S; Vilá, Luis M; Alarcón-Riquelme, Marta E; James, Judith A; Vyse, Timothy J; Moser, Kathy L; Gaffney, Patrick M; Gilkeson, Gary S; Harley, John B; Sawalha, Amr H

    2009-04-01

    Both genetic and epigenetic factors play an important role in the pathogenesis of lupus. The aim of this study was to examine methyl-CpG-binding protein 2 gene (MECP2) polymorphisms in a large cohort of patients with lupus and control subjects, and to determine the functional consequences of the lupus-associated MECP2 haplotype. We genotyped 18 single-nucleotide polymorphisms within MECP2, located on chromosome Xq28, in a large cohort of patients with lupus and control subjects of European descent. We studied the functional effects of the lupus-associated MECP2 haplotype by determining gene expression profiles in B cell lines in female lupus patients with and those without the lupus-associated MECP2 risk haplotype. We confirmed, replicated, and extended the genetic association between lupus and genetic markers within MECP2 in a large independent cohort of lupus patients and control subjects of European descent (odds ratio 1.35, P = 6.65 x 10(-11)). MECP2 is a dichotomous transcription regulator that either activates or represses gene expression. We identified 128 genes that are differentially expressed in lupus patients with the disease-associated MECP2 haplotype; most ( approximately 81%) were up-regulated. Genes that were up-regulated had significantly more CpG islands in their promoter regions compared with genes that were down-regulated. Gene ontology analysis using the differentially expressed genes revealed significant association with epigenetic regulatory mechanisms, suggesting that these genes are targets for MECP2 regulation in B cells. Furthermore, at least 13 of the 104 up-regulated genes are regulated by interferon. The disease-risk MECP2 haplotype was associated with increased expression of the MECP2 transcription coactivator CREB1 and decreased expression of the corepressor histone deacetylase 1. Polymorphism in the MECP2 locus is associated with lupus and, at least in part, contributes to the interferon signature observed in lupus patients.

  1. Transforming growth factor-β increases interleukin-13 synthesis via GATA-3 transcription factor in T-lymphocytes from patients with systemic sclerosis.

    Science.gov (United States)

    Baraut, Julie; Farge, Dominique; Jean-Louis, Francette; Masse, Ingrid; Grigore, Elena Ivan; Arruda, Lucas C M; Lamartine, Jérôme; Verrecchia, Franck; Michel, Laurence

    2015-07-31

    Transforming growth factor (TGF)-β and interleukin (IL)-13 play a crucial role in the pathogenesis of systemic sclerosis (SSc), partly through activation of collagen production that leads to fibrosis. The aim of the present study was to determine whether TFG-β alters IL-13 production in T lymphocytes from patients with SSc from that seen in those of healthy donors. IL-13 mRNA and protein synthesis under TFG-β exposure was measured in circulating T lymphocytes from healthy donors and patients with SSc and also in the Jurkat Th2 T-cell line, using quantitative real-time PCR and fluorescence-activated cell sorting analysis, respectively. The involvement of Smad and GATA-3 transcription factors was assessed by using specific inhibitors and small interfering RNA, and the binding capacity of GATA-3 to the IL-13 gene promoter was evaluated by chromatin immunoprecipitation assay. TGF-β induced a significant decrease in IL-13 mRNA and protein levels in lymphocytes from healthy donors (mean [±SD] inhibition of 30% ± 10% and 20% ± 7%, respectively; p T-cell subtypes from patients with SSc, with respective increases of 2.4 ± 0.3-fold, 1.6 ± 0.05-fold and 2.7 ± 0.02-fold. The involvement of the Smad signaling pathway and upregulation of GATA-3 binding capacity on the IL-13 promoter in lymphocytes from patients with SSc contributed to the effect of TGF-β on IL-13 production. These results demonstrate that TGF-β upregulates IL-13 synthesis through GATA-3 expression in the T lymphocytes of patients with SSc, confirming that the GATA-3 transcription factor can be regarded as a novel therapeutic target in patients with SSc.

  2. (223)Ra-dichloride spectrometric characterization: Searching for the presence of long-lived isotopes with radiological protection implications.

    Science.gov (United States)

    Sánchez-Jiménez, J; López-Montes, A; Núñez-Martínez, L; Villa-Abaunza, A; Fraile, L M; Sánchez-Tembleque, V; Udías, J M

    2017-03-01

    (223)Ra-dichloride was approved with the commercial name of Xofigo in 2014 for treatment of metastatic castration-resistant prostate cancer. (223)Ra is obtained by neutron irradiation of (226)Ra yielding (227)Ac, which decays to (227)Th and (223)Fr, both decaying to (223)Ra. Since (223)Ra is predominantly (95.3%) an alpha emitter with a 11.42days long half-life, the radiopharmaceutical, its remnants, the patient, and waste material can be managed and disposed with low radiation protection requirements. (227)Ac is a long-lived (T1/2=21.77years) beta emitter that demands strong radiation protection measures. In particular waste disposal has to follow the International Atomic Energy Agency (IAEA) and European Commission (EC) regulations. Since (227)Ac is involved in the production of (223)Ra, an impurity analysis of each batch is required after production. Due to time restrictions, the manufacturer's detection limit (<0.001%) exceeds the one required to assure that (227)Ac concentrations are below direct disposal levels. To improve the detection limit, long-term accurate spectroscopy is required. Alpha and gamma spectroscopy measurements were carried out at the Complutense University Nuclear Physics Laboratory. After twelve months follow up of a sample, (227)Ac concentration was found to be smaller than 10(-9). This allows for direct waste disposal and no additional radiation protection restrictions than those required for (223)Ra. The presence of contamination by other radioisotopes was also ruled out by this experiment. Specifically (226)Ra, involved in (223)Ra production as the original parent and with a very long-lived (T1/2=1577years) alpha emitter, was also below the experimental detection limit. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  3. Raúl Pepe Verano Montesinos

    Directory of Open Access Journals (Sweden)

    José Luis Luque

    2013-05-01

    Full Text Available El 31 de enero de 2005 falleció en Lima el doctor Raúl Verano. Nacido el 12 de julio de 1940 en Cajatambo, realizó sus estudios superiores en la Universidad Nacional Mayor de San Marcos, graduándose en 1971 de bachiller en Educación y en 1972 obtuvo el grado de bachiller en Biología con la tesis Foraminíferos del litoral del departamento de Lima; optando la profesión de Biólogo en 1973. Empezó sus actividades docentes en 1965 como Ayudante de Prácticas en las cá- tedras de zoología y desde 1971 fue Jefe de Prácticas. Ascendiendo a Auxiliar en 1974, para luego ocupar diversos cargos en la administración universitaria, siendo los más destacados el de Director del Instituto de Investigaciones Antonio Raimondi entre 1981 y 1985 y Decano de la Facultad de Ciencias Biológicas de la Universidad Nacional Mayor de San Marcos en el período 1988 a 1991. Sus actividades de investigación estuvieron alrededor de la ictioparasitología, obteniendo el grado de Doctor en Ciencias Biológicas en 1987 con la tesis Kudoa peruviana Mateo, 1972, redescripción y ultraestructura; Kudoa sarmientae sp. n y Kudoa estela sp. n en peces de la costa peruana

  4. Developing a construct to evaluate flares in rheumatoid arthritis: a conceptual report of the OMERACT RA Flare Definition Working Group.

    Science.gov (United States)

    Alten, Rieke; Pohl, Christof; Choy, Ernest H; Christensen, Robin; Furst, Daniel E; Hewlett, Sarah E; Leong, Amye; May, James E; Sanderson, Tessa C; Strand, Vibeke; Woodworth, Thasia G; Bingham, Clifton O

    2011-08-01

    Rheumatoid arthritis (RA) patients and healthcare professionals (HCP) recognize that episodic worsening disease activity, often described as a "flare," is a common feature of RA that can contribute to impaired function and disability. However, there is no standard definition to enable measurement of its intensity and impact. The conceptual framework of the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA Flare Definition Working Group includes an anchoring statement, developed at OMERACT 9 in 2008: "flare in RA" is defined as worsening of signs and symptoms of sufficient intensity and duration to lead to change in therapy. Subsequently, domains characterizing flare have been identified by comprehensive literature review, patient focus groups, and patient/HCP Delphi exercises. This led to a consensus regarding preliminary domains and a research agenda at OMERACT 10 in May 2010. The conceptual framework of flare takes into account validated approaches to measurement in RA: (1) various disease activity indices (e.g., Disease Activity Score, Clinical Disease Activity Index, Simplified Disease Activity Index); (2) use of patient-reported outcomes (PRO); and (3) characterization of minimally clinically detectable and important differences (MCDD, MCID). The measurement of RA flare is composed of data collection assessing a range of unique domains describing key features of RA worsening at the time of patient self-report of flare, and then periodically for the duration of the flare. The components envisioned are: (1) Patient self-report using a "patient global question" with well characterized and validated anchors; (2) Patient assessment using a flare questionnaire and PRO available at the time of each self-report; (3) Physician/HCP assessment of disease activity status; and (4) Physician's determination whether to change treatment. In randomized controlled trials and observational studies, such a conceptual approach is intended to lead to a valid measure of

  5. Gender and BCR-ABL transcript type are correlated with molecular response to imatinib treatment in patients with chronic myeloid leukemia.

    Science.gov (United States)

    Lin, Han-Xin; Sjaarda, Jenny; Dyck, Jocob; Stringer, Randa; Hillis, Chris; Harvey, Maria; Carter, Ronald; Ainsworth, Peter; Leber, Brian; Pare, Guillaume; Sadikovic, Bekim

    2016-04-01

    Achieving a major molecular response (MMR) is the goal of imatinib therapy for chronic myeloid leukemia. However, the association between gender, BCR-ABL transcript type, and age with MMR is not well understood and often controversial. We retrospectively analyzed 166 patients who have been treated with imatinib for up to 10 yr. Men had a lower MMR rate than women (63.3% vs. 81.6%, P = 0.006) and a shorter time to relapse (median 354 vs. 675 d, P = 0.049), while patients with b3a2 or with both b3a2 and b2a2 break point transcripts had higher MMR rate than those with b2a2 (81.8%, 77.1% vs. 60.7%, P = 0.023 for b3a2 vs. b2a2, P = 0.043 for both vs. b2a2). A striking difference was found between men with b2a2 and women with both b2a2 and b3a2 in terms of MMR rate (43.8% vs. 88.9%), MMR rate within 6 months (7.1% vs. 62.5%) and the time to MMR (median d 493 vs. 159, P = 0.036). Both gender and BCR-ABL transcript, but not age, were significantly associated with the molecular response. Men with b2a2 represent a less favorable group in their response to imatinib treatment and may need alternative therapy regimen and closer monitoring. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Histone Chaperone ASF1A Predicts Poor Outcomes for Patients With Gastrointestinal Cancer and Drives Cancer Progression by Stimulating Transcription of β-Catenin Target Genes

    Directory of Open Access Journals (Sweden)

    Xiuming Liang

    2017-07-01

    Full Text Available Epigenetic mechanisms play a key role in gastrointestinal cancer (GIC development and progression, and most studies have been focused on aberrant DNA methylation and histone modifying enzymes. However, the histone H3–H4 chaperone ASF1A is an important factor regulating chromatin assembling and gene transcription, while it is currently unclear whether ASF1A is involved in cancer pathogenesis. The present study is thus designed to address this issue. Here we showed that ASF1A expression was widespread in GIC-derived cell lines and up-regulated in primary GIC. Higher levels of ASF1A expression predicted significantly shorter patient overall survival in colorectal cancer (P = 0.0012. The further analyses of the GEO dataset validate higher ASF1A expression as a prognostic factor for CRC patients. Mechanistically, ASF1A interacted with β-catenin and promoted the transcription of β-catenin target genes including c-MYC, cyclin D1, ZEB1 and LGR5, thereby stimulating proliferation, stemness and migration/invasion of GIC cells. β-Catenin inhibition abolished these effects of ASF1A. Moreover, the ASF1A-β-catenin-ZEB1 axis down-regulated E-Cadherin expression, thereby contributing to enhanced migration/invasion of GIC cells. ASF1A over-expression and depletion facilitated and inhibited in vivo tumor growth and/or metastasis in mouse xenograft models, respectively. Taken together, ASF1A is aberrantly over-expressed in GIC tumors and plays key roles in GIC development and progression by stimulating the transcription of β-catenin target genes. ASF1A may thus be a novel target for GIC therapy and a potential prognostic marker.

  7. Rheumatoid Arthritis (RA) associated interstitial lung disease (ILD).

    LENUS (Irish Health Repository)

    O'Dwyer, David N

    2013-10-01

    Rheumatoid Arthritis (RA) is the most common Connective Tissue Disease (CTD) and represents an increasing burden on global health resources. Interstitial lung disease (ILD) has been recognised as a complication of RA but its potential for mortality and morbidity has arguably been under appreciated for decades. New studies have underscored a significant lifetime risk of ILD development in RA. Contemporary work has identified an increased risk of mortality associated with the Usual Interstitial Pneumonia (UIP) pattern which shares similarity with the most devastating of the interstitial pulmonary diseases, namely Idiopathic Pulmonary Fibrosis (IPF). In this paper, we discuss recent studies highlighting the associated increase in mortality in RA-UIP. We explore associations between radiological and histopathological features of RA-ILD and the prognostic implications of same. We emphasise the need for translational research in this area given the growing burden of RA-ILD. We highlight the importance of the respiratory physician as a key stakeholder in the multidisciplinary management of this disorder. RA-ILD focused research offers the opportunity to identify early asymptomatic disease and define the natural history of this extra articular manifestation. This may provide a unique opportunity to define key regulatory fibrotic events driving progressive disease. We also discuss some of the more challenging and novel aspects of therapy for RA-ILD.

  8. Activity concentrations of 224Ra, 226Ra, 228Ra and 40K radionuclides in refinery products and the additional radiation dose originated from oil residues in Turkey.

    Science.gov (United States)

    Parmaksiz, A; Agus, Y; Bulgurlu, F; Bulur, E; Yildiz, Ç; Öncü, T

    2013-10-01

    A total of 56 crude oil, refinery product, waste water, sludge and scale samples collected from three refineries were measured by gamma-ray spectrometry. Except for nine samples, all refinery product samples were found to have activity concentrations below the minimum detectable activity (MDA) values. The maximum (224)Ra, (226)Ra, (228)Ra and (40)K activity concentrations in crude oil and refinery product samples were measured as 11.7 ± 4.5, 14.9 ± 3.5, 11.6 ± 4.5, 248.5 ± 18.5 Bq kg(-1), respectively. The maximum (224)Ra, (226)Ra, (228)Ra and (40)K activity concentrations in scale, sludge and water samples were measured as 343.7 ± 11.8, 809.2 ± 29.0, 302.5 ± 21.6, 623.0 ± 80.9 Bq kg(-1), respectively. Radium equivalent activities of the residue samples were calculated up to 1241.8 ± 42.4 Bq kg(-1). The maximum activity concentration index and the alpha index were found to be 4.2 and 4.0, respectively. The annual effective doses of residue samples were calculated below the permitted dose rate for the public, i.e. 1 mSv y(-1).

  9. The potential of {sup 223}Ra and {sup 18}F-fluoride imaging to predict bone lesion response to treatment with {sup 223}Ra-dichloride in castration-resistant prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Murray, Iain; Chittenden, Sarah J.; Denis-Bacelar, Ana M.; Flux, Glenn D. [Royal Marsden NHS Foundation Trust, Joint Department of Physics, Sutton, Surrey (United Kingdom); The Institute of Cancer Research, London (United Kingdom); Hindorf, Cecilia [Royal Marsden NHS Foundation Trust, Joint Department of Physics, Sutton, Surrey (United Kingdom); The Institute of Cancer Research, London (United Kingdom); Skaane University Hospital, Department of Radiation Physics, Lund (Sweden); Parker, Christopher C. [Royal Marsden NHS Foundation Trust, Department of Urology, Sutton (United Kingdom); Chua, Sue [Royal Marsden NHS Foundation Trust, Department of Nuclear Medicine, Sutton (United Kingdom)

    2017-10-15

    The aims of this study were to calculate bone lesion absorbed doses resulting from a weight-based administration of {sup 223}Ra-dichloride, to assess the relationship between those doses and corresponding {sup 18}F-fluoride uptake and to assess the potential of quantitative {sup 18}F-fluoride imaging to predict response to treatment. Five patients received two intravenous injections of {sup 223}Ra-dichloride, 6 weeks apart, at 110 kBq/kg whole-body weight. The biodistribution of {sup 223}Ra in metastatic lesions as a function of time after administration as well as associated lesion dosimetry were determined from serial {sup 223}Ra scans. PET/CT imaging using {sup 18}F-fluoride was performed prior to the first treatment (baseline), and at week 6 immediately before the second treatment and at week 12 after baseline. Absorbed doses to metastatic bone lesions ranged from 0.6 Gy to 44.1 Gy. For individual patients, there was an average factor difference of 5.3 (range 2.5-11.0) between the maximum and minimum lesion dose. A relationship between lesion-absorbed doses and serial changes in {sup 18}F-fluoride uptake was demonstrated (r{sup 2} = 0.52). A log-linear relationship was demonstrated (r{sup 2} = 0.77) between baseline measurements of {sup 18}F-fluoride uptake prior to {sup 223}Ra-dichloride therapy and changes in uptake 12 weeks after the first cycle of therapy. Correlations were also observed between both {sup 223}Ra and {sup 18}F-fluoride uptake in lesions (r = 0.75) as well as between {sup 223}Ra absorbed dose and {sup 18}F-fluoride uptake (r = 0.96). There is both inter-patient and intra-patient heterogeneity of absorbed dose estimates to metastatic lesions. A relationship between {sup 223}Ra lesion absorbed dose and subsequent lesion response was observed. Analysis of this small group of patients suggests that baseline uptake of {sup 18}F-fluoride in bone metastases is significantly correlated with corresponding uptake of {sup 223}Ra, the associated {sup 223

  10. Recovery of Ra-223 from natural thorium irradiated by protons

    Energy Technology Data Exchange (ETDEWEB)

    Vasiliev, Aleksandr N.; Ostapenko, Valentina S. [Lomonosov Moscow State Univ. (Russian Federation); Russian Academy of Sciences, Moscow-Troitsk (Russian Federation). Inst. for Nuclear Research; Lapshina, Elena V.; Ermolaev, Stanislav V.; Zhuikov, Boris L. [Russian Academy of Sciences, Moscow-Troitsk (Russian Federation). Inst. for Nuclear Research; Danilov, Sergey S. [Lomonosov Moscow State Univ. (Russian Federation); Kalmykov, Stepan N. [Lomonosov Moscow State Univ. (Russian Federation); National Research Center ' Kurchatov Institute' (NRC ' Kurchatov Institute' ), Moscow (Russian Federation)

    2016-11-01

    Irradiation of natural thorium with medium-energy protons is considered to be a prospective approach to large-scale production of {sup 225}Ac and {sup 223}Ra. In addition to the earlier-developed method of {sup 225}Ac isolation, the present work focuses on the simultaneous recovery of {sup 223}Ra from the same thorium target. Radiochemical procedure is based on liquid-liquid extraction, cation exchange and extraction chromatography. The procedure provides separation of radium from spallation and fission products generated in the thorium target. High chemical yield (85-90%) and radionuclide purity of {sup 223}Ra (> 99.8% except {sup 224}Ra and {sup 225}Ra isotopes) have been achieved.

  11. Interleukin-1Ra rs2234663 and Interleukin-4 rs79071878 Polymorphisms in Familial Mediterranean Fever.

    Science.gov (United States)

    Nursal, Ayse Feyda; Tekcan, Akin; Kaya, Suheyla Uzun; Sezer, Ozlem; Yigit, Serbulent

    2016-05-15

    Familial Mediterranean Fever (FMF) is an autosomal recessively inherited auto inflammatory disorder. MEFV gene, causing FMF, encodes pyrin that is associated with the interleukin-1 (IL-1) related inflammation cascade. The aim of this study was to investigate the relationship of interleukin-1 receptor antagonist (IL-1Ra) and interleukin-4 (IL-4) polymorphisms with the risk of FMF in the Turkish population. This study included 160 patients with FMF (74 men, 86 women) and 120 healthy controls (50 men, 70 women), respectively. Genotyping of IL-1Ra rs2234663 polymorphism was evaluated by gel electrophoresis after polymerase chain reaction (PCR). The IL-4 rs79071878 polymorphism was determined by PCR-based restriction fragment length polymorphism (PCR-RFLP) analysis. The results of analyses were evaluated for statistical significance. There was no significant difference in IL-1Ra genotype and allele distributions between FMF and the control groups (p>0.05). However, a significant association was observed between FMF patients and control groups according to IL-4 genotype distribution (p=0.016), but no association was found in the allelic frequency of IL-4 between FMF patients and the controls (p>0.05, OR: 1.131, CI 95%: 0.71-1.81). The IL-4 rs79071878 polymorphism, was associated whereas the IL-1Ra rs2234663 polymorphism was not associated with FMF risk in the Turkish population. Larger studies with different ethnicities are needed to determine the impact of IL-1Ra and IL-4 polymorphism on the risk of developing FMF. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. The IL-1Ra gene variable number tandem repeat variant is associated with susceptibility to temporomandibular disorders in Turkish population.

    Science.gov (United States)

    Tumer, Mehmet Kemal; Nursal, Ayse Feyda; Tekcan, Akin; Yerliyurt, Kaan; Geyko, Anastasia; Yigit, Serbulent

    2017-06-14

    Temporomandibular joint disorders (TMD) are a group of disorders involving temporomandibular joint and related structures. Interleukine-1 receptor antagonist (IL-1Ra) is an important anti-inflammatory molecule that competes with other interleukin-1 molecules. This study was designed to investigate the possible association of the IL-1Ra VNTR variant with the risk of TMD in the Turkish population. Peripheral blood samples were collected from 100 patients with TMD (23 males, 77 females) and 110 healthy individuals (35 males, 75 females). Genotyping of IL-1Ra 86 bp VNTR variant was evaluated by gel electrophoresis after polymerase chain reaction (PCR). Our results show that there is a statistically significant difference between TMD patients and control group with respect to IL-1Ra genotype distribution and allele frequencies. 1.2, 1.4, and 4.4 genotypes were more common in patients, while 2.2 and 3.3 genotypes were rarer (P<.000). Frequency of alleles 1 and 4 was higher in patient groups (P<.000), whereas alleles 2 and 3 had a lower frequency in patients with TMD (P<.000). This is the first correlation study that evaluates the association between IL-1Ra gene VNTR variant and TMD. The VNTR variant related to IL-1Ra gene showed a strong pattern of association with TMD that may have a potential impact on disease counseling and management. Larger studies with various ethnicities are needed to establish the impact of IL-1Ra VNTR variant on risk of developing TMD. © 2017 Wiley Periodicals, Inc.

  13. Transcription Factor NFIB Is a Driver of Small Cell Lung Cancer Progression in Mice and Marks Metastatic Disease in Patients

    Directory of Open Access Journals (Sweden)

    Ekaterina A. Semenova

    2016-07-01

    Full Text Available Small cell lung cancer (SCLC is an aggressive neuroendocrine tumor, and no effective treatment is available to date. Mouse models of SCLC based on the inactivation of Rb1 and Trp53 show frequent amplifications of the Nfib and Mycl genes. Here, we report that, although overexpression of either transcription factor accelerates tumor growth, NFIB specifically promotes metastatic spread. High NFIB levels are associated with expansive growth of a poorly differentiated and almost exclusively E-cadherin (CDH1-negative invasive tumor cell population. Consistent with the mouse data, we find that NFIB is overexpressed in almost all tested human metastatic high-grade neuroendocrine lung tumors, warranting further assessment of NFIB as a tumor progression marker in a clinical setting.

  14. Measurement of 224Ra and 226Ra activities in natural waters using a radon-in-air monitor

    Science.gov (United States)

    Kim, G.; Burnett, W.C.; Dulaiova, H.; Swarzenski, P.W.; Moore, W.S.

    2001-01-01

    We report a simple new technique for measuring low-level radium isotopes (224Ra and 226Ra) in natural waters. The radium present in natural waters is first preconcentrated onto MnO2-coated acrylic fiber (Mn fiber) in a column mode. The radon produced from the adsorbed radium is then circulated through a closed air-loop connected to a commercial radon-in-air monitor. The monitor counts alpha decays of radon daughters (polonium isotopes) which are electrostatically collected onto a silicon semiconductor detector. Count data are collected in energy-specific windows, which eliminate interference and maintain very low backgrounds. Radium-224 is measured immediately after sampling via 220Rn (216Po), and 226Ra is measured via 222Rn (218Po) after a few days of ingrowth of 222Rn. This technique is rapid, simple, and accurate for measurements of low-level 224Ra and 226Ra activities without requiring any wet chemistry. Rapid measurements of short-lived 222Rn and 224Ra, along with long-lived 226Ra, may thus be made in natural waters using a single portable system for environmental monitoring of radioactivity as well as tracing of various geochemical and geophysical processes. The technique could be especially useful for the on-site rapid determination of 224Ra which has recently been found to occur at elevated activities in some groundwater wells.

  15. Determination of lactate dehydrogenase (LDH and Bcr-Abl transcript in the follow-up of patients with chronic myeloid leukemia - doi: 10.4025/actascihealthsci.v32i2.6408 Determination of lactate dehydrogenase (LDH and Bcr-Abl transcript in the follow-up of patients with chronic myeloid leukemia - doi: 10.4025/actascihealthsci.v32i2.6408

    Directory of Open Access Journals (Sweden)

    Thiago Cezar Fujita

    2010-09-01

    Full Text Available Chronic myeloid leukemia (CML is a malignant myeloproliferative disorder that originates from a pluripotent stem cell characterized by abnormal release of the expanded, malignant stem cell clone from the bone marrow into the bloodstream. The vast majority of patients with CML present Bcr-Abl transcripts. Lactate dehydrogenase (LDH is considered a biochemical marker common for tumor growth, anaerobic glycolysis and has been considered a poor prognostic factor for acute myeloid leukemia. Therefore, this study aimed to evaluate the concentration of LDH in plasma and the detection of the Bcr-Abl transcripts in patients with CML and healthy donors. We analyzed 22 patients demonstrably diagnosed with CML and 56 healthy donors. LDH concentration in plasma was higher in patients with CML. All patients with CML in this study were under treatment, but even so four patients had the Bcr-Abl (b3a2 transcript in peripheral blood. Two out of the four patients with b3a2 showed higher LDH (486 U L-1 and 589 U L-1. Thus, although the study was conducted with small numbers of samples, it is possible to suggest therapy alteration for two patients who presented transcript b3a2 in the peripheral blood samples and whose LDH concentration was high, in order to improve the disease.Chronic myeloid leukemia (CML is a malignant myeloproliferative disorder that originates from a pluripotent stem cell characterized by abnormal release of the expanded, malignant stem cell clone from the bone marrow into the bloodstream. The vast majority of patients with CML present Bcr-Abl transcripts. Lactate dehydrogenase (LDH is considered a biochemical marker common for tumor growth, anaerobic glycolysis and has been considered a poor prognostic factor for acute myeloid leukemia. Therefore, this study aimed to evaluate the concentration of LDH in plasma and the detection of the Bcr-Abl transcripts in patients with CML and healthy donors. We analyzed 22 patients demonstrably diagnosed

  16. Phosphorylated signal transducer and activator of transcription-1 immunohistochemical expression is associated with improved survival in patients with oral squamous cell carcinoma.

    Science.gov (United States)

    Pappa, Elena; Nikitakis, Nikolaos; Vlachodimitropoulos, Dimitrios; Avgoustidis, Dimitrios; Oktseloglou, Vlasios; Papadogeorgakis, Nikolaos

    2014-01-01

    To estimate whether the immunohistochemical (IHC) expression patterns of the tumor suppressor gene signal transducer and activator of transcription-1 (STAT1) and its active phosphorylated form (PSTAT1) serve as potential prognostic and predictive markers in patients with oral squamous cell carcinoma (OSCC). STAT1 and PSTAT1 protein expressions were examined immunohistochemically in OSCC tumor tissues and adjacent normal mucosa from 49 patients who underwent primary surgery. The IHC scores were correlated with all available clinicopathologic parameters that were obtained from a maximum of 7 years of follow-up, including survival and response to adjuvant therapy treatment. There was a shift toward lower percentages of cells with STAT1 (P normal tissue sites. No association with patients' clinicopathologic characteristics was shown. However, for the group of patients who received adjuvant chemotherapy, increased PSTAT1 intensity of staining in OSCC tumors was strongly associated with better overall survival (P = .008). This is the first study to concurrently evaluate STAT1 and PSTAT1 IHC expression patterns and their prognostic significance in patients with OSCC, highlighting the potential role of PSTAT1 as a biomarker in therapeutic decision making. Large prospective studies are needed to verify these findings. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  17. Modeling the Energy Performance of LoRaWAN

    Directory of Open Access Journals (Sweden)

    Lluís Casals

    2017-10-01

    Full Text Available LoRaWAN is a flagship Low-Power Wide Area Network (LPWAN technology that has highly attracted much attention from the community in recent years. Many LoRaWAN end-devices, such as sensors or actuators, are expected not to be powered by the electricity grid; therefore, it is crucial to investigate the energy consumption of LoRaWAN. However, published works have only focused on this topic to a limited extent. In this paper, we present analytical models that allow the characterization of LoRaWAN end-device current consumption, lifetime and energy cost of data delivery. The models, which have been derived based on measurements on a currently prevalent LoRaWAN hardware platform, allow us to quantify the impact of relevant physical and Medium Access Control (MAC layer LoRaWAN parameters and mechanisms, as well as Bit Error Rate (BER and collisions, on energy performance. Among others, evaluation results show that an appropriately configured LoRaWAN end-device platform powered by a battery of 2400 mAh can achieve a 1-year lifetime while sending one message every 5 min, and an asymptotic theoretical lifetime of 6 years for infrequent communication.

  18. Modeling the Energy Performance of LoRaWAN.

    Science.gov (United States)

    Casals, Lluís; Mir, Bernat; Vidal, Rafael; Gomez, Carles

    2017-10-16

    LoRaWAN is a flagship Low-Power Wide Area Network (LPWAN) technology that has highly attracted much attention from the community in recent years. Many LoRaWAN end-devices, such as sensors or actuators, are expected not to be powered by the electricity grid; therefore, it is crucial to investigate the energy consumption of LoRaWAN. However, published works have only focused on this topic to a limited extent. In this paper, we present analytical models that allow the characterization of LoRaWAN end-device current consumption, lifetime and energy cost of data delivery. The models, which have been derived based on measurements on a currently prevalent LoRaWAN hardware platform, allow us to quantify the impact of relevant physical and Medium Access Control (MAC) layer LoRaWAN parameters and mechanisms, as well as Bit Error Rate (BER) and collisions, on energy performance. Among others, evaluation results show that an appropriately configured LoRaWAN end-device platform powered by a battery of 2400 mAh can achieve a 1-year lifetime while sending one message every 5 min, and an asymptotic theoretical lifetime of 6 years for infrequent communication.

  19. SU-F-J-08: Quantitative SPECT Imaging of Ra-223 in a Phantom

    Energy Technology Data Exchange (ETDEWEB)

    Yue, J; Hobbs, R; Sgouros, G; Frey, E [Johns Hopkins University Baltimore, MD (United States)

    2016-06-15

    Purpose: Ra-223 therapy of prostate cancer bone metastases is being used to treat patients routinely. However, the absorbed dose distribution at the macroscopic and microscopic scales remains elusive, due to the inability to image the small activities injected. Accurate activity quantification through imaging is essential to calculate the absorbed dose in organs and sub-units in radiopharmaceutical therapy, enabling personalized absorbed dose-based treatment planning methodologies and more effective and optimal treatments. Methods: A 22 cm diameter by 20 cm long cylindrical phantom, containing a 3.52 cm diameter sphere, was used. A total of 2.01 MBq of Ra-223 was placed in the phantom with 177.6 kBq in the sphere. Images were acquired on a dual-head Siemens Symbia T16 gamma camera using three 20% full-width energy windows and centered at 84, 154, and 269 keV (120 projections, 360° rotation, 45 s per view). We have implemented reconstruction of Ra-223 SPECT projections using OS-EM (up to 20 iterations of 10 subsets) with compensation for attenuation using CT-based attenuation maps, collimator-detector response (CDR) (including septal penetration, scatter and Pb x-ray modeling), and scatter in the patient using the effective source scatter estimation (ESSE) method. The CDR functions and scatter kernels required for ESSE were computed using the SIMIND MC simulation code. All Ra-223 photon emissions as well as gamma rays from the daughters Rn-219 and Bi-211 were modeled. Results: The sensitivity of the camera in the three combined windows was 107.3 cps/MBq. The visual quality of the SPECT images was reasonably good and the activity in the sphere was 27% smaller than the true activity. This underestimation is likely due to partial volume effect. Conclusion: Absolute quantitative Ra-223 SPECT imaging is achievable with careful attention to compensate for image degrading factors and system calibration.

  20. Inhibition of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway in rheumatoid synovial fibroblasts using small molecule compounds.

    Science.gov (United States)

    Migita, K; Izumi, Y; Torigoshi, T; Satomura, K; Izumi, M; Nishino, Y; Jiuchi, Y; Nakamura, M; Kozuru, H; Nonaka, F; Eguchi, K; Kawakami, A; Motokawa, S

    2013-12-01

    Janus kinase (JAK) inhibitors have been developed as anti-inflammatory agents and have demonstrated clinical efficacy in rheumatoid arthritis (RA). We investigated if JAK-3-selective inhibition alone could disrupt cytokine signalling in rheumatoid synovial fibroblasts. In-vitro studies were performed using synovial fibroblasts isolated from patients with RA. Levels of activated JAK and signal transducer and activator of transcription (STAT) proteins were detected by immunoblot analysis. Target-gene expression levels were measured by reverse transcription-polymerase chain reaction (RT-PCR) or real-time PCR. The JAK inhibitors CP-690,550 and INCB028050 both suppressed activation of JAK-1/-2/-3 and downstream STAT-1/-3/-5, as well as the expression levels of target proinflammatory genes (MCP-I, SAA1/2) in oncostatin-M (OSM)-stimulated rheumatoid synovial fibroblasts. In contrast, the JAK-3-selective inhibitor, PF-956980, suppressed STAT-1/-5 activation but did not affect STAT-3 activation in OSM-stimulated rheumatoid synovial fibroblasts. In addition, PF-956980 significantly suppressed MCP-1 gene expression, but did not block SAA1/2 gene expression in OSM-stimulated rheumatoid synovial fibroblasts. These data suggest that JAK-3-selective inhibition alone is insufficient to control STAT-3-dependent signalling in rheumatoid synovial fibroblasts, and inhibition of JAKs, including JAK-1/-2, is needed to control the proinflammatory cascade in RA. © 2013 British Society for Immunology.

  1. Lower incidence of acute GVHD is associated with the rapid recovery of CD4+CD25+CD45RA+regulatory T cells in patients who received haploidentical allografts from NIMA-mismatched donors: A retrospective (development) and prospective (validation) cohort-based study.

    Science.gov (United States)

    Wang, Yu; Zhao, Xiang-Yu; Xu, Lan-Ping; Zhang, Xiao-Hui; Han, Wei; Chen, Huan; Wang, Feng-Rong; Mo, Xiao-Dong; Zhang, Yuan-Yuan; Zhao, Xiao-Su; Y, Kong; Liua, Kai-Yan; Huang, Xiao-Jun; Yu, Xue-Zhong; Chang, Ying-Jun

    2016-01-01

    To investigate the effects of non-inherited maternal antigen (NIMA) on clinical outcomes and immune recovery, especially of regulatory T cells (Tregs), in patients who underwent unmanipulated haploidentical transplantation. A retrospective cohort (n = 57) and a prospective cohort (n = 88) were included. All patients received haploidentical allografts from sibling donors. Reconstitution of immune subsets, including Tregs, was determined using multicolor flow cytometry. In the retrospective cohort, the cumulative incidence of grades II-IV acute GVHD in patients with NIMA-mismatched donors was significantly lower than that of cases with NIPA-mismatched donors (14.8% vs. 43.30%, p = 0.018). Patients with higher percentages of CD4 + CD25 + CD45RA + T cells (naive Tregs) within CD4 + T cells recovered on day 30 (≥1.55%) experienced a significantly lower incidence of grades II-IV acute GVHD than that of cases with lower percentages of naive Tregs (NIMA mismatch and the percentages of naive Tregs were associated with the incidence of grades II-IV acute GVHD [ p = 0.050, and 0.031, respectively]. In the prospective cohort, the association of NIMA mismatch [HR = 0.365, 95% CI, 0.169-0.786, p = 0.010] or higher percentages of naive Tregs recovered on day 30 (≥1.55%) [HR = 0.114, 95% CI, 0.027-0.479, p = 0.003] with a lower cumulative incidence of grades II-IV acute GVHD was further demonstrated. No effects of NIMA mismatch on chronic GVHD, transplant-related mortality, relapse, disease-free survival, or overall survival were found. Our results confirmed the role of NIMA mismatch in acute GVHD and provided the first demonstration, based on clinical data, that recovered Tregs may be involved in the effects of NIMA on acute GVHD in a haploidentical transplant setting.

  2. Ra: The Sun for Science and Humanity

    Science.gov (United States)

    1996-01-01

    To guide the development of the Ra Strategic Framework, we defined scientific and applications objectives. For our primary areas of scientific interest, we choose the corona, the solar wind, the Sun's effect on the Earth, and solar theory and model development. For secondary areas of scientific interest, we selected sunspots, the solar constant, the Sun's gravitational field, helioseismology and the galactic cosmic rays. We stress the importance of stereoscopic imaging, observations at high spatial, spectral, and temporal resolutions, as well as of long duration measurements. Further exploration of the Sun's polar regions is also important, as shown already by the Ulysses mission. From an applications perspective, we adopted three broad objectives that would derive complementary inputs for the Strategic Framework. These were to identify and investigate: possible application spin-offs from science missions, possible solar-terrestrial missions dedicated to a particular application, and possible future applications that require technology development. The Sun can be viewed as both a source of resources and of threats. Our principal applications focus was that of threat mitigation, by examining ways to improve solar threat monitoring and early warning systems. We compared these objectives to the mission objectives of past, current, and planned international solar missions. Past missions (1962-1980) seem to have been focused on improvement of scientific knowledge, using multiple instrument spacecraft. A ten year gap followed this period, during which the results from previous missions were analyzed and solar study programmes were prepared in international organizations. Current missions (1990-1996) focus on particular topics such as the corona, solar flares, and coronal mass ejections. In planned missions, Sun/Earth interactions and environmental effects of solar activity are becoming more important. The corona is the centre of interest of almost all planned missions

  3. Leaching of 226Ra from components of uranium mill tailings

    Science.gov (United States)

    Landa, E.R.

    1991-01-01

    A sequential extraction procedure was used to characterize the geochemical forms of 226Ra retained by mixtures of quartz sand and a variety of fine-grained rock and mineral species. These mixtures had previously been exposed to the sulfuric acid milling liquor of a simulated acid-leach uranium milling circuit. For most test cases, the major fraction of the 226Ra was extracted with 1 mol/1 NH4Cl and was deemed to be exchangeable. However, 226Ra retained by the barite-containing mixture was resistant to both 1 mol/1 NH4Cl and 1 mol/HCHCl extraction. ?? 1991.

  4. Forenzično računovodstvo u poljoprivredi

    OpenAIRE

    Blaženović, Ivan; Ranogajec, Ljubica

    2016-01-01

    Računovodstveni izvještaji predstavlju glavne izvore informacija o posjedovnoj strani i uspješnosti poduzeća. Manipulacije računovodstvenim informacijama rade se s ciljem prikrivanja stvarnog stanja u poduzeću. U procesu otkrivanja prijevara forenzičari se koriste računalnom opremom i posebno dizajniranim programima za pregled i usporedbu podataka poslovnih knjiga poduzeća koje je pod kontrolom. Ukoliko se uoče nepravilnosti, pokreće se istraga nad tim poduzećem s ciljem sprječavanja kriminal...

  5. Transcription-terminating mutation in telethonin causing autosomal recessive muscular dystrophy type 2G in a European patient.

    Science.gov (United States)

    Olivé, Montse; Shatunov, Alexey; Gonzalez, Laura; Carmona, Olga; Moreno, Dolores; Quereda, Lidia Gonzalez; Martinez-Matos, J A; Goldfarb, Lev G; Ferrer, Isidro

    2008-12-01

    A 27-year-old woman of Moldavian origin presented at the age of 15 with progressive proximal limb weakness and painful cramps in her calf muscles. Clinical examination revealed prominent muscle weakness in proximal muscles of the lower extremities and distal anterior compartment of legs, and mild weakness in shoulder girdle muscles. In addition, she had marked calf hypertrophy, muscle atrophy involving the anterior and posterior compartments of the thighs, and the distal anterior compartment of legs, as well as mild scapular winging and hyperlordosis. A muscle biopsy taken from the biceps brachii showed mild dystrophic changes, absent vacuoles, and abundant lobulated fibers. Immunofluorescence and Western blot assays demonstrated complete telethonin deficiency. Molecular analysis revealed a homozygous Trp25X mutation in the telethonin (TCAP) gene resulting in termination of transcription at an early point. Four families from Brazil with telethonin deficiency have previously been reported and classified as LGMD2G, but the actual frequency of this disease is unknown. With this current identification of a case outside the Brazilian population, telethonin mutation-associated LGMD should be considered worldwide.

  6. Imbalance between HAT and HDAC activities in the PBMCs of patients with ankylosing spondylitis or rheumatoid arthritis and influence of HDAC inhibitors on TNF alpha production.

    Directory of Open Access Journals (Sweden)

    Eric Toussirot

    Full Text Available OBJECTIVE: Acetylation or deacetylation of histone proteins may modulate cytokine gene transcription such as TNF alpha (TNF. We evaluated the balance between histone deacetytlase (HDAC and histone acetyltransferase (HAT in patients with rheumatoid arthritis (RA or ankylosing spondylitis (AS compared to healthy controls (HC and determined the influence of HDAC inhibitors (trichostatin A -TSA- or Sirtinol -Sirt- on these enzymatic activities and on the PBMC production of TNF. METHODS: 52 patients with RA, 21 with AS and 38 HC were evaluated. HAT and HDAC activities were measured on nuclear extracts from PBMC using colorimetric assays. Enzymatic activities were determined prior to and after ex vivo treatment of PBMC by TSA or Sirt. TNF levels were evaluated in PBMC culture supernatants in the absence or presence of TSA or Sirt. RESULTS: HAT and HDAC activities were significantly reduced in AS, while these activities reached similar levels in RA and HC. Ex vivo treatment of PBMC by HDACi tended to decrease HDAC expression in HC, but Sirt significantly reduced HAT in RA. TNF production by PBMC was significantly down-regulated by Sirt in HC and AS patients. CONCLUSION: HAT and HDAC were disturbed in AS while no major changes were found in RA. HDACi may modulate HDAC and HAT PBMC expression, especially Sirt in RA. Sirtinol was able to down regulate TNF production by PBMC in HC and AS. An imbalance between HAT and HDAC activities might provide the rationale for the development of HDACi in the therapeutic approach to inflammatory rheumatic diseases.

  7. Diffusion tensor imaging: the normal evolution of ADC, RA, FA, and eigenvalues studied in multiple anatomical regions of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Loebel, Ulrike [University Hospital Jena, Institute of Diagnostic and Interventional Radiology, Jena (Germany); St. Jude Children' s Research Hospital, Department of Radiological Sciences, Memphis, TN (United States); Sedlacik, Jan [St. Jude Children' s Research Hospital, Department of Radiological Sciences, Memphis, TN (United States); University Hospital Jena, Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena (Germany); Guellmar, Daniel [University Hospital Jena, Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena (Germany); University Hospital Jena, Biomagnetic Center, Department of Neurology, Jena (Germany); Kaiser, Werner A.; Mentzel, Hans-Joachim [University Hospital Jena, Institute of Diagnostic and Interventional Radiology, Jena (Germany); Reichenbach, Juergen R. [University Hospital Jena, Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena (Germany)

    2009-04-15

    The aim of our work was to investigate the process of myelination in healthy patients using the diffusion parameters apparent diffusion coefficient (ADC), relative anisotropy (RA), fractional anisotropy (FA), and eigenvalues. Age-dependent changes were assessed using the slope m of the fit functions that best described the data. Seventy-two patients (3 weeks-19 years) without pathological magnetic resonance imaging findings were selected from all pediatric patients scanned with diffusion tensor imaging over a 5-year period at our institution. ADC, RA, FA, and eigenvalue maps were calculated and regions of interest were selected in anterior/posterior pons, genu/splenium of corpus callosum (CC), anterior/posterior limb of internal capsule (IC), and white matter (WM) regions (frontal, temporal, parietal, occipital WM). Statistical analysis was performed using Spearman correlation coefficient and regression analysis. Mean values ranged 71.6 x 10{sup -5} to 90.3 x 10{sup -5} mm{sup 2}/s (pons/parietal WM) for ADC, 0.32-0.94 (frontal WM/CC) for RA, and 0.36-0.81 (frontal WM/splenium) for FA. Logarithmic fit functions best described the data. Strong age influences were observed for CC, pons, and parietal/frontal WM and changes were significant for all three eigenvalues, most pronounced for perpendicular eigenvalues. Changes in RA and FA differed depending on the structure anisotropy. Changes observed for ADC, RA, FA, and eigenvalues with age were consistent with previous findings. Changes detected for RA and FA varied due to the different scaling of both parameters. We found that the use of the largely linear scaled RA adds more valuable information for the assessment of age-dependent structural changes as compared to FA. Additionally, we report normative values for the diffusion parameters studied. (orig.)

  8. Association of transcription factor 7-like 2 (TCF7L2) gene polymorphism with posttransplant diabetes mellitus in kidney transplant patients medicated with tacrolimus.

    Science.gov (United States)

    Kurzawski, Mateusz; Dziewanowski, Krzysztof; Kędzierska, Karolina; Wajda, Anna; Lapczuk, Joanna; Droździk, Marek

    2011-01-01

    New onset posttransplant diabetes mellitus (PTDM) has a high incidence after kidney transplantation in patients medicated with tacrolimus. PTDM can adversely affect patient and graft survival. The pathophysiology of PTDM closely mimics type 2 diabetes mellitus (T2DM). One of the possible genetic factors predisposing individuals to PTDM might be a polymorphism in the transcription factor 7-like 2 gene (TCF7L2). This polymorphism has previously been associated with increased risk of T2DM in the general population. Therefore, the present study aimed to evaluate TCF7L2 polymorphisms in PTDM in kidney transplant patients medicated with tacrolimus. Non-diabetic kidney transplant patients medicated with tacrolimus (n = 234) were genotyped for the presence of TCF7L2 gene variants (rs12255372 and rs7903146) using TaqMan probes. Of the 234 patients, 66 patients had developed PTDM and 168 had not. Frequencies of the studied single nucleotide polymorphisms (SNPs) did not differ significantly between the study groups. Moreover, haplotype analyses failed to detect any associations between TCF7L2 haplotypes and PTDM. However, in late-onset PTDM (developed later that 2 weeks from transplantation), frequencies of the rs7903146 TT genotype and T minor allele were significantly increased compared to non-PTDM controls (17.9% vs. 5.9%, p = 0.017, OR: 4.13, 95% CI: 1.19-14.33 for TT genotype, 39.3% vs. 25.9%, p = 0.038 for T allele). If the application of TCF7L2 rs7903146 SNPs as a marker for PTDM is confirmed by further independent studies, replacing tacrolimus with other immunosuppressants could be warranted in patients at high risk of PTDM, as diagnosed by TCF7L2 genotyping.

  9. Giver lave Ra-værdier bedre hygiejne?

    DEFF Research Database (Denmark)

    Gram, Lone; Bagge-Ravn, Dorthe; Kold, John

    2004-01-01

    Ifølge vore undersøgelser er der ingen grund til at ændre på den generelle anbefaling om, at Ra bør være mindre end 0,8 µm. Muligvis kan man dog i særlige tilfælde opnå hygiejnemæssige gevinster ved at bruge meget fine poleringer, dvs. Ra mindre end 0,8 µm.......Ifølge vore undersøgelser er der ingen grund til at ændre på den generelle anbefaling om, at Ra bør være mindre end 0,8 µm. Muligvis kan man dog i særlige tilfælde opnå hygiejnemæssige gevinster ved at bruge meget fine poleringer, dvs. Ra mindre end 0,8 µm....

  10. Impossible cartographies: approaching Raúl Ruiz’s cinema

    National Research Council Canada - National Science Library

    Michael Goddard

    2013-01-01

    Raúl Ruiz (1931-2011), while considered one of the world’s most significant filmmakers by several film critics, is yet to be the subject of any thorough academic engagement with his work in English...

  11. LoRA: A Loudspeaker-Based Room Auralization System

    DEFF Research Database (Denmark)

    Favrot, Sylvain Emmanuel; Buchholz, Jörg

    2010-01-01

    that the involved signal processing preserves the temporal, spectral and spatial properties of the room impulse response captured by these parameters. This flexible research platform will be useful for studying auditory processing and perception in normal-hearing and hearing-impaired listeners in fully controlled......In order to study basic human perception in reverberant environments, a novel loudspeaker-based room auralization (LoRA) system is proposed in this paper. The LoRA system efficiently combines modern room acoustic models with high-order Ambisonic auralization. An objective evaluation has been...... carried out demonstrating the applicability of the LoRA system. Room acoustic parameters (reverberation time, clarity, speech transmission index and inter-aural cross correlation coefficients) of room impulse responses were compared at the input and the simulated output of the LoRA system. Results show...

  12. The Microphthalmia-Associated Transcription Factor p.E318K Mutation Does Not Play a Major Role in Sporadic Renal Cell Tumors from Caucasian Patients.

    Science.gov (United States)

    Stoehr, Christine G; Walter, Bernhard; Denzinger, Stefan; Ghiorzo, Paola; Sturm, Richard A; Hinze, Raoul; Moch, Holger; Junker, Kerstin; Hartmann, Arndt; Stoehr, Robert

    2016-01-01

    The transcription factor MITF (microphthalmia-associated transcription factor) is known to induce expression of hypoxia-inducible factor (HIF1-α), which is involved in renal carcinogenesis. The MITF p.E318K mutation leads to deficient SUMOylation of MITF, resulting in enhanced activation of its target genes. A case-control study on melanoma patients who coincidentally were affected by renal cell carcinoma (RCC) has revealed an elevated risk for mutation carriers to be affected by one or both of these malignancies, suggesting a possible role for MITF p.E318K in renal carcinogenesis. The same study described an MITF mutation frequency of 1.5% in a small cohort of sporadic RCC, but comprehensive data on sporadic renal cell tumors are missing. We therefore tested a large cohort of sporadic renal tumors for MITF p.E318K mutation status. Genomic DNA was extracted from 426 formalin-fixed, paraffin-embedded sporadic renal tumors that had been graded according to the 2004 WHO classification of renal tumors and staged according to the 2002 TNM classification. The tumor cohort was enriched with papillary and chromophobe RCC, and also contained benign oncocytomas. DNA was tested for MITF p.E318K by pyrosequencing. Of 403 analyzable tumors, 402 renal tumors were wild-type ones, and only 1 case showed the MITF p.E318K mutation. This tumor was a clear-cell RCC (pT3b N0 M0 G3 according to the TNM classification 2002). The affected patient was male, 61 years old, and had no known coexisting malignancies. The MITF p.E318K mutation does not appear to play a major role in sporadic RCC carcinogenesis, but is possibly restricted to a rare subpopulation of inherited RCC. © 2016 S. Karger AG, Basel.

  13. Transcriptional profiling of peripheral blood mononuclear cells in pancreatic cancer patients identifies novel genes with potential diagnostic utility.

    Directory of Open Access Journals (Sweden)

    Michael J Baine

    2011-02-01

    Full Text Available It is well known that many malignancies, including pancreatic cancer (PC, possess the ability to evade the immune system by indirectly downregulating the mononuclear cell machinery necessary to launch an effective immune response. This knowledge, in conjunction with the fact that the trancriptome of peripheral blood mononuclear cells has been shown to be altered in the context of many diseases, including renal cell carcinoma, lead us to study if any such alteration in gene expression exists in PC as it may have diagnostic utility.PBMC samples from 26 PC patients and 33 matched healthy controls were analyzed by whole genome cDNA microarray. Three hundred eighty-three genes were found to be significantly different between PC and healthy controls, with 65 having at least a 1.5 fold change in expression. Pathway analysis revealed that many of these genes fell into pathways responsible for hematopoietic differentiation, cytokine signaling, and natural killer (NK cell and CD8+ T-cell cytotoxic response. Unsupervised hierarchical clustering analysis identified an eight-gene predictor set, consisting of SSBP2, Ube2b-rs1, CA5B, F5, TBC1D8, ANXA3, ARG1, and ADAMTS20, that could distinguish PC patients from healthy controls with an accuracy of 79% in a blinded subset of samples from treatment naïve patients, giving a sensitivity of 83% and a specificity of 75%.In summary, we report the first in-depth comparison of global gene expression profiles of PBMCs between PC patients and healthy controls. We have also identified a gene predictor set that can potentially be developed further for use in diagnostic algorithms in PC. Future directions of this research should include analysis of PBMC expression profiles in patients with chronic pancreatitis as well as increasing the number of early-stage patients to assess the utility of PBMCs in the early diagnosis of PC.

  14. O pensamento desenvolvimentista de Raúl Prebisch Raúl Prebisch's thought on development

    Directory of Open Access Journals (Sweden)

    Joaquim Miguel Couto

    2007-04-01

    Full Text Available As idéias do economista argentino Raúl Prebisch (1901-1986 sempre estiveram voltadas para a ação. As dificuldades encontradas diante de problemas concretos (durante a crise dos anos 1930, tornaram Prebisch um homem prático. Assim, suas teorias sobre a substituição de importações, o sistema centro-periferia e a criação de um mercado comum latino-americano, possuíam um grande sentido de influenciar a realidade. A única exceção coube a sua "Teoria da Transformação", construída no último decênio de sua vida. Nesta, Prebisch se afasta da realidade e teoriza sobre a criação de um novo sistema econômico, através de uma síntese entre socialismo e liberalismo.The Argentinean economist Raúl Prebisch’s (1901-1986 ideas were always gone back to the action. Difficulties facing concrete problems made him a pragmatic man. Thus, his theories about import substitution, core-periphery system and the creation of a common Latin-American market, were embodied in a great purpose of influencing the reality. The only exception was the "Theory of Transformation", which was built in the last decade of this life. There, Prebisch moves off practical matters and speculates about the creation of a new economic system, through a synthesis of socialism and liberalism.

  15. Identifying Preliminary Domains to Detect and Measure Rheumatoid Arthritis Flares: Report of the OMERACT 10 RA Flare Workshop

    DEFF Research Database (Denmark)

    Bingham, Clifton O; Alten, Rieke; Bartlett, Susan J

    2011-01-01

    an international research project to understand the specific characteristics and impact of episodic disease worsening, or "flare," so that outcome measures can be developed or modified to reflect this uncommonly measured, but very real and sometimes disabling RA disease feature. Patient research partners provided......, a preliminary list of key domains has been identified to evaluate flare. RESULTS: At OMERACT 10, consensus was achieved identifying features of flare in addition to the existing core set for RA, including fatigue, stiffness, symptom persistence, systemic features, and participation. Patient self-report of flare...

  16. Synergistic activation of retinoic acid (RA)-responsive genes and induction of embryonal carcinoma cell differentiation by an RA receptor {alpha} (RAR{alpha})-, RAR{beta}-, or RAR{gamma}-selective ligand in combination with retinoid Z receptor-specific ligand

    Energy Technology Data Exchange (ETDEWEB)

    Roy, B.; Taneja, R.; Chambon, P. [Universite Louis Pasteur, Illkirch (France)

    1995-12-01

    This research indicates thatn retinoic acid receptor (RAR)-retinoid X receptor (RXR) heterodimers activate transcription of RA-responsive genes and induce cell differentiation of P19 and F9 cells in a ligand-dependent manner. 43 refs., 4 figs., 2 tabs.

  17. Transcriptional profiling of fibroblasts from patients with mutations in MCT8 and comparative analysis with the human brain transcriptome

    NARCIS (Netherlands)

    W.E. Visser (Wil Edward); S.M.A. Swagemakers (Sigrid); Z. Özgür (Zeliha); R. Schot (Rachel); F.W. Verheijen (Frans); W.F.J. van IJcken (Wilfred); P.J. van der Spek (Peter)

    2010-01-01

    textabstractThyroid hormone (TH) is crucial for normal brain development. TH transporters control TH homeostasis in brain as evidenced by the complex endocrine and neurological phenotype of patients with mutations in monocarboxylate transporter 8 (MCT8). We investigated the mechanisms of disease by

  18. Feelings of guilt and shame in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    ten Klooster, Peter M.; Christenhusz, Lieke C.A.; Taal, Erik; Eggelmeijer, Frank; van Woerkom, Jan-Maarten; Rasker, Hans J.

    2014-01-01

    This study aims to determine whether patients with rheumatoid arthritis (RA) experience more general feelings of guilt and shame than their peers without RA and to examine possible correlates of guilt and shame in RA. In a cross-sectional survey study, 85 out-patients with RA (77 % female; median

  19. Assessing Medication Adherence in Patients with Rheumatoid Arthritis (RA)

    Science.gov (United States)

    2017-04-26

    DEPARTMENT OF THE AIR FORCE 59TH MEDICAL WING (AETC) JOINT BASE SAN ANTONIO - LACKLAND TEXAS 26 APR 2017 MEMORANDUM FOR SGSP ATrN: MAJ SHAOPING MO...Shaoplng Mo Sumner, Maj , USAF, PharmD San Antonio Combined Military Postgraduate Year One Pharmacy Residency Program .......••Fort Sam Houston, TX

  20. Investigation of $\\alpha$-decay rates of $^{221}$Fr, $^{224}$Ra and $^{226}$Ra in different environments

    CERN Multimedia

    2007-01-01

    It has recently been suggested, and indicated experimentally, that $\\alpha$- decay half-lives are modified by solid state effects in the surrounding environment. We propose here to measure with high accuracy the $\\alpha$-decay half-life of $^{221}$Fr, $^{224}$Ra and $^{226}$Ra in insulators and metals. Furthermore we plan to investigate the temperature dependency of the half-life in these materials (room temperature, 4 K and 10 mK).

  1. HE4 Transcription- and Splice Variants-Specific Expression in Endometrial Cancer and Correlation with Patient Survival

    Directory of Open Access Journals (Sweden)

    Shi-Wen Jiang

    2013-11-01

    Full Text Available We investigated the HE4 variant-specific expression patterns in various normal tissues as well as in normal and malignant endometrial tissues. The relationships between mRNA variants and age, body weight, or survival are analyzed. ICAT-labeled normal and endometrial cancer (EC tissues were analyzed with multidimensional liquid chromatography followed by tandem mass spectrometry. Levels of HE4 mRNA variants were measured by real-time PCR. Mean mRNA levels were compared among 16 normal endometrial samples, 14 grade 1 and 14 grade 3 endometrioid EC, 15 papillary serous EC, and 14 normal human tissue samples. The relationship between levels of HE4 variants and EC patient characteristics was analyzed with the use of Pearson correlation test. We found that, although all five HE4 mRNA variants are detectable in normal tissue samples, their expression is highly tissue-specific, with epididymis, trachea, breast and endometrium containing the highest levels. HE4-V0, -V1, and -V3 are the most abundant variants in both normal and malignant tissues. All variants are significantly increased in both endometrioid and papillary serous EC, with higher levels observed in grade 3 endometrioid EC. In the EC group, HE4-V1, -V3, and -V4 levels inversely correlate with EC patient survival, whereas HE4-V0 levels positively correlate with age. HE4 variants exhibit tissue-specific expression, suggesting that each variant may exert distinct functions in normal and malignant cells. HE4 levels appear to correlate with EC patient survival in a variant-specific manner. When using HE4 as a biomarker for EC management, the effects of age should be considered.

  2. ANTI-HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN B1 (ANTI-RA33 ANTIBODIES IN RHEUMATOID ARTHRITIS AND SYSTEMIC SCLEROSIS

    Directory of Open Access Journals (Sweden)

    P. A. Kuznetsova

    2017-01-01

    Full Text Available Anti-heterogeneous nuclear ribonucleoprotein (RNP autoantibodies (AAbs are encountered in many autoimmune rheumatic diseases (ARDs. The potential diagnostic value of the RA33 AAb complex consisting of RNP A2 and alternative domains of the splicing proteins RNP B1 and RNP B2 is now of interest to rheumatologists. Subjects and methods. The authors studied the frequency of anti-RNP B1 AAbs in 300 patients with systemic ARDs, including those with rheumatoid arthritis (RA, ankylosing spondylitis (AS, systemic lupus erythematosus (SLE, systemic sclerosis (SSc, and Sjö gren's syndrome (SS and in 53 people without ARDs, who constituted a control group. Serum anti-RNP B1 AAbs were assessed by enzyme immunoassay. Results and discussion. The frequency of anti-RNP B1 AAbs in patients with ARDs was much higher than that in the control group: 170/300 (56.6% and 8/53 (13% patients, respectively. Anti-RNP B1 AAbs were detected in 78.5% (113/144 of the patients with RA; 40.3% (23/57 of those with AS, in 67.5% (27/40 of those with SSc, in 36.4% (16/44 of those with SLE, and in 13.3% (2/15 of those with SS. The diagnostic sensitivity of the marker for RA was 78.5%, its diagnostic specificity was 84.9%; the likelihood ratio of positive and negative results was 5.24 and 0.24, respectively. In the patients with RA, the level of anti-RNP B1 AAbs significantly correlated with that of C-reactive protein and erythrocyte sedimentation rate, while in those with SSc the detection of anti-RNP B1 AAbs was related to the rigidity of the vascular wall and the presence of hypertension. The frequency of anti-RNP B1 AAbs among the RA patients seronegative for rheumatoid factor and anti-cyclic citrullinated peptide antibodies was 15.4%. Conclusion. Anti-RNP B1 AAs are a useful laboratory marker (with the upper limit of the normal range being 3.3 U/ml, but are of limited value in the diagnosis of RA. Anti-RNP B1 AAbs may be regarded as an additional diagnostic marker for RA.

  3. Radium isotopes ((226)Ra and (228)Ra) in Na-Cl type groundwaters from Tohoku District (Aomori, Akita and Yamagata Prefectures) in Japan.

    Science.gov (United States)

    Tomita, Jumpei; Zhang, Jing; Yamamoto, Masayoshi

    2014-11-01

    A total of 28 Na-Cl type groundwater samples were collected from Aomori, Akita and Yamagata Prefectures, in the Tohoku District of Japan, and their radium isotope ((226)Ra and (228)Ra) concentrations were measured along with their chemical components and stable isotope ratios (δ(2)H and δ(18)Os). The (226)Ra concentrations in groundwater samples varied widely, ranging from 8.8 to 1587 mBq kg(-1). These concentrations showed an increasing tendency with the increase of the total dissolved solid (TDS) contents. The (228)Ra/(226)Ra activity ratios were in the range from 0.3 to 4.2, with most data being around 0.5-2. These ratios were within those of (232)Th/(238)U found in granitic and related rocks and so on in Japan, indicating that Ra isotopes mainly ejected into the groundwater by the alpha-recoil process. The relationship between (226)Ra and other parameters suggested that Ra isotopes in groundwater samples in this study were mainly constrained by adsorption-desorption reactions depending on salinity with wide variation. Clear correlation between (226)Ra-Ca, (226)Ra-Sr, (226)Ra-Ba and (226)Ra-TDS observed in sulfate-free groundwater samples indicated that Ra isotopes of them were constrained by adsorption-desorption reactions depending on salinity under reducing condition. In contrast, relationship of (226)Ra-Ca, (226)Ra-Sr, (226)Ra-Ba and (226)Ra-TDS in sulfate-containing groundwater samples varied widely, and then, removal or enhanced mobility of Ra isotopes of them were observed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Work disability remains a major problem in rheumatoid arthritis in the 2000s: data from 32 countries in the QUEST-RA Study

    DEFF Research Database (Denmark)

    Sokka, Tuulikki; Kautiainen, Hannu; Pincus, Theodore

    2010-01-01

    of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries. METHODS: The Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8......ABSTRACT: INTRODUCTION: Work disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use......,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K US dollars (USD) per capita) and 16 low-GDP countries (disability status at onset and over the course of RA and clinical status of patients who continued working or had stopped working...

  5. Inflammatory genes TNFα and IL6 display no signs of increased H3K4me3 in circulating monocytes from untreated rheumatoid arthritis patients.

    Science.gov (United States)

    Messemaker, T C; Mikkers, H M M; Huizinga, T W; Toes, R E M; van der Helm-van Mil, A H M; Kurreeman, F

    2017-09-01

    Innate immune cells, such as monocytes, can adopt a long-lasting pro-inflammatory phenotype, a phenomenon called 'trained immunity'. In trained immunity, increased cytokine levels of genes, like interleukin (IL)-6 and tumor necrosis factor (TNF)-α, are observed, which are associated with increased histone 3 lysine 4 trimethylation (H3K4me3) in the promoter region. As systemic IL6 and TNFα levels are increased in rheumatoid arthritis (RA) patients and monocytes are known to be the primary producers of TNFα and IL6, we hypothesized that 'trained immunity' signals may be observed at these genes in monocytes from RA patients. CD14+ monocytes were isolated from untreated RA patients and paired age-matched healthy controls. H3K4me3, mRNA, protein and serum levels of IL6 and TNFα were evaluated by chromatin immunoprecipitation, reverse-transcription quantitative PCR and enzyme-linked immunosorbent assays. Despite elevated serum levels of TNFα and IL6 in the tested RA patients (Ptrained immunity signals in circulating monocytes from untreated RA patients, despite increased IL6 and TNFα serum levels.

  6. Therapy palliative with {sup 2}23Ra without special radiation protection measures?; Palliative Therapie mit {sup 223}Ra ohne besondere Strahlenschutzmassnahmen?

    Energy Technology Data Exchange (ETDEWEB)

    Just, Guenther [Forschungsbuero Radonbalneologie (FRB), Grosspoesna (Germany); Petzold, Juergen

    2015-07-01

    For nearly 2 years now as a therapy of the castration resistant prostata carcinoma a nuclide therapy with {sup 223}Ra-Dichloride (trade-mark Xofigo) is applied. Xofigo is applied by a medical specialist for nuclear medicine altogether 6 times in a monthly distance. The activity used in each case is according to the body weight (50 kBq/kg BW). This therapy is licensed by the supervisory authorities of the German federal countries as an ambulant therapy. Special radiation protection measures are only required when exceeding a given number of 17 patients per year as incorparation measurements.

  7. Decreased mRNA expression of transcription factor forkhead box F2 is an indicator of poor prognosis in patients with resected esophageal squamous cell carcinoma.

    Science.gov (United States)

    Zheng, Yu-Zhen; Wen, Jing; Cao, Xun; Yang, Hong; Luo, Kong-Jia; Liu, Qian-Wen; Huang, Qing-Yuan; Chen, Jun-Ying; Fu, Jian-Hua

    2015-05-01

    The transcription factor forkhead box F2 (FOXF2) is an evolutionarily conserved DNA-binding protein involved in embryogenesis and metabolism. Although recent studies prove that FOXF2 is a tumor suppressor in various human cancers, the role of FOXF2 in esophageal squamous cell carcinoma (ESCC) remains unknown. Therefore, samples were collected from 188 ESCC patients, including 33 pairs of tumor and non-tumor tissues, and FOXF2 mRNA expression was investigated by quantitative polymerase chain reaction. The results demonstrated that FOXF2 mRNA is downregulated in tumor tissues compared to paired non-tumor tissues (P=0.048). The receiver operating characteristic curve analysis indicated 1.2 as a cut-off point and, thus, 125 and 63 tumors were classified as low- and high-level FOXF2 mRNA expression, respectively. We observed that low-level FOXF2 mRNA expression in the tumors was associated with a higher frequency of lymph node metastasis (P=0.044), an effect further suggested by the multivariate logistic regression analysis (P=0.060). According to the univariate Cox analysis, patients harboring tumors with low-level FOXF2 mRNA expression had a significantly increased mortality risk compared to those with high-level expression (hazard ratio=1.700, 95% confidence interval, 1.077-2.681), with 5-year survival rates of 41.1 and 61.9%, respectively. This negative prognostic effect of low-level FOXF2 mRNA expression was further validated in the multivariate Cox analysis (P=0.021). The subgroup analysis demonstrated that the effect of FOX2 mRNA expression was limited to male patients and those with advanced-stage disease. Taken together, these findings suggest that FOXF2 may be an anti-oncogene for ESCC and decreased FOXF2 mRNA expression is associated with a poor prognosis in patients with ESCC.

  8. Elevated interferon-stimulated gene transcription in peripheral blood mononuclear cells occurs in patients infected with genotype 1 but not genotype 3 hepatitis C virus.

    Science.gov (United States)

    Robinson, M W; Swann, R; Sigruener, A; Barclay, S T; Mills, P R; McLauchlan, J; Patel, A H

    2015-04-01

    Hepatitis C virus (HCV) can be classified into seven distinct genotypes that are associated with differing pathologies and respond differently to antiviral therapy. In the UK, genotype 1 and 3 are present in approximately equal proportions. Chronic infection with HCV genotype 3 is associated with increased liver steatosis and reduced peripheral total cholesterol levels, which potentially influences peripheral immune responses. To understand these differences, we investigated host gene transcription in peripheral blood mononuclear cells by microarray and quantitative PCR in patients with genotype 1 (n = 22) or genotype 3 infection (n = 22) and matched healthy controls (n = 15). Enrichment of genes involved in immune response and inflammatory pathways were present in patients infected with HCV genotype 1; however, no differences in genes involved in lipid or cholesterol metabolism were detected. This genotype-specific induction of genes is unrelated to IL28B genotype or previous treatment failure. Our data support the hypothesis that genotype 1 infection drives a skewed Type I interferon response and provides a foundation for future investigations into the host-pathogen interactions that underlie the genotype-specific clinical outcomes of chronic HCV infection. © 2014 The Authors Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.

  9. Splicing factor SF2/ASF rescues IL-2 production in T cells from systemic lupus erythematosus patients by activating IL-2 transcription.

    Science.gov (United States)

    Moulton, Vaishali R; Grammatikos, Alexandros P; Fitzgerald, Lisa M; Tsokos, George C

    2013-01-29

    T cells from patients with systemic lupus erythematosus (SLE) produce insufficient amounts of the vital cytokine IL-2. We previously showed that SLE T cells express decreased levels of the T-cell receptor-CD3ζ chain and forced expression of CD3ζ into SLE T cells restores IL-2 production. We recently showed that the serine arginine protein splicing factor 2/alternative splicing factor (SF2/ASF) enhances the expression of CD3ζ chain by limiting the production of an unstable splice variant. Here we demonstrate that SF2/ASF levels are decreased in patients with SLE and more so in those with active disease. More importantly, we reveal a function of SF2/ASF, independent of T-cell receptor/CD3 signaling, whereby it is recruited to the IL-2 promoter, increases transcriptional activity, and enhances IL-2 production in SLE T cells. Our results demonstrate that SF2/ASF regulates IL-2 production and that decreased SF2/ASF expression in SLE T cells contributes to deficient IL-2 production.

  10. Fully automated joint space width measurement and digital X-ray radiogrammetry in early RA.

    Science.gov (United States)

    Platten, Michael; Kisten, Yogan; Kälvesten, Johan; Arnaud, Laurent; Forslind, Kristina; van Vollenhoven, Ronald

    2017-01-01

    To study fully automated digital joint space width (JSW) and bone mineral density (BMD) in relation to a conventional radiographic scoring method in early rheumatoid arthritis (eRA). Radiographs scored by the modified Sharp van der Heijde score (SHS) in patients with eRA were acquired from the SWEdish FarmacOTherapy study. Fully automated JSW measurements of bilateral metacarpals 2, 3 and 4 were compared with the joint space narrowing (JSN) score in SHS. Multilevel mixed model statistics were applied to calculate the significance of the association between ΔJSW and ΔBMD over 1 year, and the JSW differences between damaged and undamaged joints as evaluated by the JSN. Based on 576 joints of 96 patients with eRA, a significant reduction from baseline to 1 year was observed in the JSW from 1.69 (±0.19) mm to 1.66 (±0.19) mm (p0) joints: 1.68 mm (95% CI 1.70 to 1.67) vs 1.54 mm (95% CI 1.63 to 1.46). Similarly the unadjusted multilevel model showed significant differences in JSW between undamaged (1.68 mm (95% CI 1.72 to 1.64)) and damaged joints (1.63 mm (95% CI 1.68 to 1.58)) (p=0.0048). This difference remained significant in the adjusted model: 1.66 mm (95% CI 1.70 to 1.61) vs 1.62 mm (95% CI 1.68 to 1.56) (p=0.042). To measure the JSW with this fully automated digital tool may be useful as a quick and observer-independent application for evaluating cartilage damage in eRA. NCT00764725.

  11. Profiling of the transcriptional response to all-trans retinoic acid in breast cancer cells reveals RARE-independent mechanisms of gene expression.

    Science.gov (United States)

    Coyle, Krysta Mila; Maxwell, Selena; Thomas, Margaret Lois; Marcato, Paola

    2017-11-30

    Retinoids, derivatives of vitamin A, are key physiological molecules with regulatory effects on cell differentiation, proliferation and apoptosis. As a result, they are of interest for cancer therapy. Specifically, models of breast cancer have varied responses to manipulations of retinoid signaling. This study characterizes the transcriptional response of MDA-MB-231 and MDA-MB-468 breast cancer cells to retinaldehyde dehydrogenase 1A3 (ALDH1A3) and all-trans retinoic acid (atRA). We demonstrate limited overlap between ALDH1A3-induced gene expression and atRA-induced gene expression in both cell lines, suggesting that the function of ALDH1A3 in breast cancer progression extends beyond its role as a retinaldehyde dehydrogenase. Our data reveals divergent transcriptional responses to atRA, which are largely independent of genomic retinoic acid response elements (RAREs) and consistent with the opposing responses of MDA-MB-231 and MDA-MB-468 to in vivo atRA treatment. We identify transcription factors associated with each gene set. Manipulation of the IRF1 transcription factor demonstrates that it is the level of atRA-inducible and epigenetically regulated transcription factors that determine expression of target genes (e.g. CTSS, cathepsin S). This study provides a paradigm for complex responses of breast cancer models to atRA treatment, and illustrates the need to characterize RARE-independent responses to atRA in a variety of models.

  12. Prognostic and Predictive Value of Thyroid Transcription Factor-1, CD56, P40 and Other Clinical Characteristics in Small Cell Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Xin WANG

    2017-08-01

    Full Text Available Background and objective The aim of this study is to explore roles of thyroid transcription factor-1 (TTF-1, CD56, P40 expression and other clinical characteristics predicting response and survival in patients with small cell lung cancer (SCLC. Methods Formalin-fixed, paraffin-embedded biopsy tissues were retrospectively obtained from 198 SCLC patients who were diagnosed first in Xuanwu Hospital. The expressions of TTF-1, CD56 and P40 were detected by immunohistochemistry. The clinical data including age, gender, cancer stage, Eastern Cooperative Oncology Group (ECOG score, smoking or not, superior vena cava syndrome (SVCS due to lung cancer or not were collected. Cox proportional hazard model was used to analyze the relationship between the overall survival (OS and factors. Results Immunohistochemical staining results showed the positive rate of TTF-1, CD56, P40 were 73.2%, 88.4% and 7.1% respectively. TTF-1 expression (OR=0.665, 95%CI: 0.472-0.937, smoking index ≤400 (OR=1.72, 95%CI: 1.061-2.789 and ECOG=2 (OR=3.551, 95%CI: 2.133-5.914, extensive-stage (OR=2.487, 95%CI: 1.793-3.451 and SVCS due to lung cancer (OR=2.394, 95%CI: 1.49-3.846 were independent prognostic factors for SCLC patients. Conclusion Prognosis of SCLC was related to TTF-1 expression independently after adjusting smoking, ECOG score, stage and SVCS due to lung cancer. Detection of TTF-1, CD56 and P40 expression level might be helpful for predict the prognosis of SCLC.

  13. Phase I and biomarker study of OPB-51602, a novel signal transducer and activator of transcription (STAT) 3 inhibitor, in patients with refractory solid malignancies.

    Science.gov (United States)

    Wong, A L; Soo, R A; Tan, D S; Lee, S C; Lim, J S; Marban, P C; Kong, L R; Lee, Y J; Wang, L Z; Thuya, W L; Soong, R; Yee, M Q; Chin, T M; Cordero, M T; Asuncion, B R; Pang, B; Pervaiz, S; Hirpara, J L; Sinha, A; Xu, W W; Yuasa, M; Tsunoda, T; Motoyama, M; Yamauchi, T; Goh, B C

    2015-05-01

    The aim of this study was to determine the maximum-tolerated dose (MTD), safety, pharmacokinetics, and pharmacodynamics of OPB-51602, an oral, direct signal transduction activator of transcription 3 (STAT3) inhibitor, in patients with refractory solid tumors. Three cohorts were studied: cohort A, a sequential dose escalation of OPB-51602 administered intermittently (days 1-14 every 21 days); cohort B, an expansion cohort evaluating the dose lower than the MTD; cohort C, evaluating continuous daily dosing. Fifty-one patients were studied at 2, 4, and 5 mg per day dosing. The MTD was 5 mg; first-cycle dose-limiting toxicities (DLTs) were grade 3 hyponatremia in one patient, and grade 3 dehydration in another. Intermittent dosing of both 2 and 4 mg doses were tolerable, and the recommended phase II dose was 4 mg. Cohort B investigated 4 mg intermittently, whereas cohort C investigated 4 mg continuously. Common toxicities included fatigue, nausea/vomiting, diarrhea, anorexia, and early-onset peripheral neuropathy. Drug-induced pneumonitis occurred in two patients in cohort C. Continuous dosing was associated with a higher incidence of peripheral neuropathy and a lower mean relative dose intensity, compared with intermittent dosing. Steady-state pharmacokinetics was characterized by high oral clearance, mean elimination half-life ranging from 44 to 61 h, and a large terminal-phase volume of distribution. An active metabolite, OPB-51822, accumulated to a greater extent than OPB-51602. Flow cytometry of peripheral blood mononuclear cells demonstrated pSTAT3 (Tyr(705)) inhibition following exposure. Two patients achieved partial responses at 5 mg intermittently and 4 mg continuously; both had epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) with prior EGFR tyrosine kinase inhibitor exposure. OPB-51602 demonstrates promising antitumor activity, particularly in NSCLC. Its long half-life and poorer tolerability of continuous dosing

  14. Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) Family Study: rationale and design for a randomized controlled trial evaluating rheumatoid arthritis risk education to first-degree relatives.

    Science.gov (United States)

    Sparks, Jeffrey A; Iversen, Maura D; Miller Kroouze, Rachel; Mahmoud, Taysir G; Triedman, Nellie A; Kalia, Sarah S; Atkinson, Michael L; Lu, Bing; Deane, Kevin D; Costenbader, Karen H; Green, Robert C; Karlson, Elizabeth W

    2014-09-01

    We present the rationale, design features, and protocol of the Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) Family Study (ClinicalTrials.gov NCT02046005). The PRE-RA Family Study is an NIH-funded prospective, randomized controlled trial designed to compare the willingness to change behaviors in first-degree relatives of rheumatoid arthritis (RA) patients without RA after exposure to RA risk educational programs. Consented subjects are randomized to receive education concerning their personalized RA risk based on demographics, RA-associated behaviors, genetics, and biomarkers or to receive standard RA information. Four behavioral factors associated with RA risk were identified from prior studies for inclusion in the risk estimate: cigarette smoking, excess body weight, poor oral health, and low fish intake. Personalized RA risk information is presented through an online tool that collects data on an individual's specific age, gender, family history, and risk-related behaviors; presents genetic and biomarker results; displays relative and absolute risk of RA; and provides personalized feedback and education. The trial outcomes will be changes in willingness to alter behaviors from baseline to 6 weeks, 6 months, and 12 months in the three intervention groups. The design and the execution of this trial that targets a special population at risk for RA, while incorporating varied risk factors into a single risk tool, offer distinct challenges. We provide the theoretical rationale for the PRE-RA Family Study and highlight particular design features of this trial that utilize personalized risk education as an intervention. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. The impact of gender stereotypes on the evaluation of general practitioners' communication skills: an experimental study using transcripts of physician-patient encounters.

    Science.gov (United States)

    Nicolai, Jennifer; Demmel, Ralf

    2007-12-01

    The present study has been designed to test for the effect of physicians' gender on the perception and assessment of empathic communication in medical encounters. Eighty-eight volunteers were asked to assess six transcribed interactions between physicians and a standardized patient. The effects of physicians' gender were tested by the experimental manipulation of physicians' gender labels in transcripts. Participants were randomly assigned to one of two testing conditions: (1) perceived gender corresponds to the physician's true gender; (2) perceived gender differs from the physician's true gender. Empathic communication was assessed using the Rating Scales for the Assessment of Empathic Communication in Medical Interviews. A 2 (physician's true gender: female vs. male)x2 (physician's perceived gender: female vs. male)x2 (rater's gender: female vs. male) mixed multivariate analysis of variance (MANOVA) yielded a main effect for physician's true gender. Female physicians were rated higher on empathic communication than male physicians irrespective of any gender labels. The present findings suggest that gender differences in the perception of physician's empathy are not merely a function of the gender label. These findings provide evidence for differences in male and female physicians' empathic communication that cannot be attributed to stereotype bias. Future efforts to evaluate communication skills training for general practitioners may consider gender differences.

  16. IL-17RA Signaling in Airway Inflammation and Bronchial Hyperreactivity in Allergic Asthma.

    Science.gov (United States)

    Willis, Cynthia R; Siegel, Lori; Leith, Anh; Mohn, Deanna; Escobar, Sabine; Wannberg, Sharon; Misura, Kira; Rickel, Erika; Rottman, James B; Comeau, Michael R; Sullivan, John K; Metz, Daniela P; Tocker, Joel; Budelsky, Alison L

    2015-12-01

    Asthma is a heterogeneous disease characterized by airway inflammation and hyperreactivity. IL-17 receptor A (IL-17RA) is a shared receptor subunit required for activity of IL-17 family cytokines, including IL-17A and IL-25. IL-17A and IL-25 induce different proinflammatory responses, and concentrations are elevated in subjects with asthma. However, the individual contributions of IL-17A and IL-25 to disease pathogenesis are unclear. We explored proinflammatory activities of the IL-17 pathway in models of pulmonary inflammation and assessed its effects on contractility of human bronchial airway smooth muscle. In two mouse models, IL-17RA, IL-17RB, or IL-25 blockade reduced airway inflammation and airway hyperreactivity. Individually, IL-17A and IL-25 enhanced contractility of human bronchial smooth muscle induced by methacholine or carbachol. IL-17A had more pronounced effects on methacholine-induced contractility in bronchial rings from donors with asthma compared with donors without asthma. Blocking the IL-17 pathway via IL-17RA may be a useful therapy for some patients with asthma by reducing pulmonary inflammation and airway hyperreactivity.

  17. Interleukin-4 (IL4 and Interleukin-4 receptor (IL4RA polymorphisms in asthma: a case control study

    Directory of Open Access Journals (Sweden)

    Lorente Félix

    2005-11-01

    Full Text Available Abstract Background IL4/IL4RA pathway plays an important role in atopy and asthma. Different polymorphisms in IL4 and IL4RA genes have been described. Particularly, -33C>TIL4 and 576Q>RIL4RA SNPs have been independently associated to atopy and asthma. The purpose of this study was to analyse these polymorphisms in a population of patients with a well-characterized asthma phenotype. Methods A total of 212 unrelated Caucasian individuals, 133 patients with asthma and 79 healthy subjects without symptoms or history of asthma or atopy and with negative skin prick tests were recruited. Lung function was measured by spirometry and asthma was specialist physician-diagnosed according to the ATS (American Thoracic Society criteria and classified following the GINA (Global Initiative for Asthma guidelines. Skin prick tests were performed according to EAACI recommendations. -33C>TIL4 was studied with TaqMan assay and 576Q>RIL4RA by PCR-RFLP technique. Hardy-Weinberg equilibrium was analysed in all groups. Dichotomous variables were analysed using χ2, Fisher exact test, Monte Carlo simulation test and odds ratio test. To model the effects of multiple covariates logistic regression was used. Results No statistically significant differences between the group of patients with asthma and the controls were found when the allele and genotype distribution of -33C>TIL4 and 576Q>RIL4RA polymorphisms were compared. However, the T allele of the -33C>TIL4 SNP was more frequent in patients with persistent asthma. Multivariate analysis adjusted for age and sex confirmed that carriers of allele T had an increased risk of persistent asthma (OR:2.77, 95%CI:1.18–6.49; p = 0.019. Analysis of combination of polymorphisms showed that patients carrying both the T allele of -33C>TIL4 and the A allele of 576Q>RIL4RA had an increased risk of asthma. This association was particularly observed in persistent asthma [Fisher's p value = 0.0021, Monte Carlo p value (after 104

  18. Differential Effects of Vitamins A and D on the Transcriptional Landscape of Human Monocytes during Infection.

    Science.gov (United States)

    Klassert, Tilman E; Bräuer, Julia; Hölzer, Martin; Stock, Magdalena; Riege, Konstantin; Zubiría-Barrera, Cristina; Müller, Mario M; Rummler, Silke; Skerka, Christine; Marz, Manja; Slevogt, Hortense

    2017-01-17

    Vitamin A and vitamin D are essential nutrients with a wide range of pleiotropic effects in humans. Beyond their well-documented roles in cellular differentiation, embryogenesis, tissue maintenance and bone/calcium homeostasis, both vitamins have attracted considerable attention due to their association with-immunological traits. Nevertheless, our knowledge of their immunomodulatory potential during infection is restricted to single gene-centric studies, which do not reflect the complexity of immune processes. In the present study, we performed a comprehensive RNA-seq-based approach to define the whole immunomodulatory role of vitamins A and D during infection. Using human monocytes as host cells, we characterized the differential role of both vitamins upon infection with three different pathogens: Aspergillus fumigatus, Candida albicans and Escherichia coli. Both vitamins showed an unexpected ability to counteract the pathogen-induced transcriptional responses. Upon infection, we identified 346 and 176 immune-relevant genes that were regulated by atRA and vitD, respectively. This immunomodulatory activity was dependent on the inflammatory stimulus, allowing us to distinguish regulatory patterns which were specific for each stimulatory setting. Moreover, we explored possible direct and indirect mechanisms of vitamin-mediated regulation of the immune response. Our findings highlight the importance of vitamin-monitoring in critically ill patients. Moreover, our results underpin the potential of atRA and vitD as therapeutic options for anti-inflammatory treatment.

  19. Alterations in Janus kinase (JAK)-signal transducers and activators of transcription (STAT) signaling in patients with end-stage dilated cardiomyopathy.

    Science.gov (United States)

    Podewski, Edith K; Hilfiker-Kleiner, Denise; Hilfiker, Andres; Morawietz, Henning; Lichtenberg, Artur; Wollert, Kai C; Drexler, Helmut

    2003-02-18

    Experimental studies indicate that interleukin-6 (IL-6)-related cytokines, signaling via the shared receptor gp130, Janus kinases (JAKs), and signal transducers and activators of transcription (STATs), provide a critical cardiomyocyte survival pathway in vivo. Little is known about the activation of this signaling pathway in the myocardia of patients with end-stage dilated cardiomyopathy (DCM). We performed a comprehensive expression and activation analysis of IL-6-related cytokines, receptors, signal transducers, and signal transduction inhibitors in left ventricular (LV) myocardia from patients with DCM (n=10) and non-failing (NF) donor hearts (n=5). Differential expression (DCM versus NF) was observed by immunoblotting at each level of the signaling cascade, including receptor ligands (IL-6: -59%, P<0.01; leukemia inhibitory factor [LIF]: +54%, P<0.05), receptor subunits (LIF receptor: -16%, P<0.05), signaling molecules (the Janus kinase TYK2: -48%, P<0.01; STAT3: -47%, P<0.01), and suppressors of cytokine signaling (SOCS1: +97%, P<0.05; SOCS3: -49%, P<0.01). Tyrosine-phosphorylation status of gp130 was increased (+60%, P<0.05), whereas tyrosine-phosphorylation status of JAK2 was reduced in DCM (-72%, P<0.01). Moreover, as shown by immunohistochemistry, the number of STAT3-positive cardiomyocytes was reduced in DCM (-42%, P<0.01). Signaling via gp130 and JAK-STAT is profoundly altered in DCM. Importantly, tyrosine-phosphorylation of JAK2 is reduced in the face of increased gp130 phosphorylation, indicating impaired downstream activation of this critical pathway in DCM.

  20. Clinical value of octamer-binding transcription factor 4 as a prognostic marker in patients with digestive system cancers: A systematic review and meta-analysis.

    Science.gov (United States)

    Chen, Zhiqiang; Zhang, Long; Zhu, Qin; Wang, Xiaowei; Wu, Jindao; Wang, Xuehao

    2017-03-01

    The role of octamer-binding transcription factor 4 (Oct4) has been implicated in the clinical prognosis of various kinds of digestive system cancers, but the results remain controversial. The purpose of this meta-analysis is to assess the potential role of Oct4 as a prognostic marker in digestive system tumors. Relevant articles were retrieved from Pubmed, Web of Science, and Cochrane Library up to July 2016. The software Stata 12.0 was used to analyze the outcomes, including overall survival (OS), disease-free survival, recurrence-free survival, and clinicopathological characteristics. A total of 13 eligible studies with 1538 patients were included. Elevated Oct4 expression was significantly associated with poor OS (pooled hazard ratio [HR] = 2.183, 95% confidence interval [CI]: 1.824-2.612), disease-free survival (pooled HR = 1.973, 95% CI: 1.538-2.532), and recurrence-free survival (pooled HR = 2.209, 95% CI: 1.461-3.338) of digestive system malignancies. Subgroup analyses showed that cancer type, sample size, study quality, and laboratory detection method did not alter the significant prognostic value of Oct4. Additionally, Oct4 expression was found to be an independent predictive factor for OS (HR = 2.068, 95% CI: 1.633-2.619). No significant association was found between Oct4 and clinicopathological features of digestive system malignancies. This study provided evidence of Oct4 and/or its closely related homolog protein as a predictive factor for patients with digestive system cancers. More large-scale clinical studies on the prognostic value of Oct4 are warranted. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  1. Genetic basis of virulence attenuation revealed by comparative genomic analysis of Mycobacterium tuberculosis strain H37Ra versus H37Rv.

    Directory of Open Access Journals (Sweden)

    Huajun Zheng

    2008-06-01

    Full Text Available Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading infectious disease despite the availability of chemotherapy and BCG vaccine. The commonly used avirulent M. tuberculosis strain H37Ra was derived from virulent strain H37 in 1935 but the basis of virulence attenuation has remained obscure despite numerous studies. We determined the complete genomic sequence of H37Ra ATCC25177 and compared that with its virulent counterpart H37Rv and a clinical isolate CDC1551. The H37Ra genome is highly similar to that of H37Rv with respect to gene content and order but is 8,445 bp larger as a result of 53 insertions and 21 deletions in H37Ra relative to H37Rv. Variations in repetitive sequences such as IS6110 and PE/PPE/PE-PGRS family genes are responsible for most of the gross genetic changes. A total of 198 single nucleotide variations (SNVs that are different between H37Ra and H37Rv were identified, yet 119 of them are identical between H37Ra and CDC1551 and 3 are due to H37Rv strain variation, leaving only 76 H37Ra-specific SNVs that affect only 32 genes. The biological impact of missense mutations in protein coding sequences was analyzed in silico while nucleotide variations in potential promoter regions of several important genes were verified by quantitative RT-PCR. Mutations affecting transcription factors and/or global metabolic regulations related to in vitro survival under aging stress, and mutations affecting cell envelope, primary metabolism, in vivo growth as well as variations in the PE/PPE/PE-PGRS family genes, may underlie the basis of virulence attenuation. These findings have implications not only for improved understanding of pathogenesis of M. tuberculosis but also for development of new vaccines and new therapeutic agents.

  2. RA – beskeden genetisk disposition - resultater fra nyt dansk tvillingstudie

    DEFF Research Database (Denmark)

    Svendsen, Anders Jørgen

    2010-01-01

    undersøgelse af RA hos danske tvillinger underbygger vores tidligere observationer, der indikerer, at den genetiske disposition til den gruppe af polyartritter, der samles under betegnelsen reumatoid arthrit, er beskeden. De senere års forskning tyder på, at sygdommen i klinisk, behandlingsmæssig, men også i...

  3. Nuclear structure of 216 Ra at high spin

    Indian Academy of Sciences (India)

    Bi(10B, 3n) reaction at an incident beam energy of 55 MeV and 209Bi(11B, 4n) reaction at incident beam energies ranging from 65 to 78 MeV. Based on coincidence data, the level scheme for 216Ra has been considerably extended up to ...

  4. Kui ei taha, ära õpi? / Peeter Kreitzberg

    Index Scriptorium Estoniae

    Kreitzberg, Peeter, 1948-2011

    2003-01-01

    Autor leiab, et viimase 10 aasta jooksul levinud arusaam - kui ei taha, ära õpi - on tegelikult väga negatiivsete tagajärgedega seisukoht. Haridus ei ole vaid individuaalne hüve ja selle puudumine individuaalne õnnetus, see on kogu ühiskonna probleem

  5. Respuesta a Raúl Martínez Santos

    Directory of Open Access Journals (Sweden)

    Natàlia Balagué Serre

    2014-12-01

    Full Text Available Las autoras del trabajo titulado “Unificar las cièncias del deporte” (núm. 114, julio-sep. 2013, responden a la réplica enviada por el Prof. Raúl Martínez Santos titulada “Reflexiones y condiciones para una unificación de las ciencias del deporte” .

  6. Detection of tumor cell-specific mRNA in the peripheral blood of patients with breast cancer—evaluation of several markers with real-time reverse transcription-PCR.

    Science.gov (United States)

    Andergassen, Ulrich; Hofmann, Simone; Kölbl, Alexandra C; Schindlbeck, Christian; Neugebauer, Julia; Hutter, Stefan; Engelstädter, Verena; Ilmer, Matthias; Friese, Klaus; Jeschke, Udo

    2013-01-08

    It is widely known that cells from epithelial tumors, e.g., breast cancer, detach from their primary tissue and enter blood circulation. We show that the presence of circulating tumor cells (CTCs) in samples of patients with primary and metastatic breast cancer can be detected with an array of selected tumor-marker-genes by reverse transcription real-time PCR. The focus of the presented work is on detecting differences in gene expression between healthy individuals and adjuvant and metastatic breast cancer patients, not an accurate quantification of these differences. Therefore, total RNA was isolated from blood samples of healthy donors and patients with primary or metastatic breast cancer after enrichment of mononuclear cells by density gradient centrifugation. After reverse transcription real-time PCR was carried out with a set of marker genes (BCSP, CK8, Her2, MGL, CK18, CK19). B2M and GAPDH were used as reference genes. Blood samples from patients with metastatic disease revealed increased cytokine gene levels in comparison to normal blood samples. Detection of a single gene was not sufficient to detect CTCs by reverse transcription real-time PCR. Markers used here were selected based on a recent study detecting cancer cells on different protein levels. The combination of such a marker array leads to higher and more specific discovery rates, predominantly in metastatic patients. Identification of CTCs by PCR methods may lead to better diagnosis and prognosis and could help to choose an adequate therapy.

  7. Detection of Tumor Cell-Specific mRNA in the Peripheral Blood of Patients with Breast Cancer — Evaluation of Several Markers with Real-Time Reverse Transcription-PCR

    Directory of Open Access Journals (Sweden)

    Ulrich Andergassen

    2013-01-01

    Full Text Available It is widely known that cells from epithelial tumors, e.g., breast cancer, detach from their primary tissue and enter blood circulation. We show that the presence of circulating tumor cells (CTCs in samples of patients with primary and metastatic breast cancer can be detected with an array of selected tumor-marker-genes by reverse transcription real-time PCR. The focus of the presented work is on detecting differences in gene expression between healthy individuals and adjuvant and metastatic breast cancer patients, not an accurate quantification of these differences. Therefore, total RNA was isolated from blood samples of healthy donors and patients with primary or metastatic breast cancer after enrichment of mononuclear cells by density gradient centrifugation. After reverse transcription real-time PCR was carried out with a set of marker genes (BCSP, CK8, Her2, MGL, CK18, CK19. B2M and GAPDH were used as reference genes. Blood samples from patients with metastatic disease revealed increased cytokine gene levels in comparison to normal blood samples. Detection of a single gene was not sufficient to detect CTCs by reverse transcription real-time PCR. Markers used here were selected based on a recent study detecting cancer cells on different protein levels. The combination of such a marker array leads to higher and more specific discovery rates, predominantly in metastatic patients. Identification of CTCs by PCR methods may lead to better diagnosis and prognosis and could help to choose an adequate therapy.

  8. RAPIDARC (RA) in the uterine cervical cancer; dosimetric gain vs 3D-Crt; RAPIDARC (RA) en el cancer de cervix uterino; ganancia dosimetrica vs 3D-CRT

    Energy Technology Data Exchange (ETDEWEB)

    Ramirez, J.; Garcia, B.; Quispe, K.; Gonzales, A.; Marquina, J., E-mail: jose.ramirez@aliada.com.pe [Clinica Aliada, Oncologia Integral, Av. Jose Galvez Barrenechea 1044, San Isidro, Lima (Peru)

    2014-08-15

    This work aims to quantitatively assess RAPIDARC (RA) treatments versus three dimensional-Conformal Radiation Therapy with field to field technique (3D-Crt-Fin F). 11 patients with cervical cancer treated at our institution radically or adjuvant clinical stages I-III B were evaluated. The prescribed dose was 50 Gy (2 Gy / Fr). The RA plans consisted of two isocentric complete arcs and conformational plans of 4 isocentric fields (previous, subsequent, right side and left side) with 3D-Crt-Fin F technique; both cases carried out ??in the Eclipse version 10 planner with calculation algorithm analytical anisotropic algorithm (AAA) and volumetric optimization software (for VMAT plans). Homogeneity indices (Hi), conformity indices (CI) Sigma indices (S-Index), monitor units (MU) and the time required for each treatment were compared. The mean age was 52 years (32-65) of the 11 patients 9 were clinical stages I-II B. The Hi varied from 0.052 for RA to 0.163 for 3D-Crt-Fin F (p = 0.009), and the CI between 1.005 and 1.35 (p = 0.26), the S-index from 1.2 to 3.7 (p = 0.001) and the H-index of 1.08 to 1.15 (p = 0.24). All dose limits in risk organs were met with a significant difference in the RA plans versus 3D-Crt-Fin F. In patients with cervical cancer the treatment plans quality with the indices aforementioned seems to be better with the RA technique, being observed a significant reduction of radiation to surrounding organs. (author)

  9. Determination of {sup 226}Ra, {sup 228}Ra, and {sup 210}Pb in mushroom from a naturally high radioactive region

    Energy Technology Data Exchange (ETDEWEB)

    Rosa, Mychelle M.L.; Custodio, Luis Gustavo; Cheberle, Luan T.V.; Taddei, Maria Helena T., E-mail: mychelle@cnen.gov.br, E-mail: lgcustodio@hotmail.com, E-mail: lt.cheberle@bol.com.br, E-mail: mhtaddei@cnen.gov.br [Comissao Nacional de Energia Nuclear (LAPOC/CNEN-MG), Pocos de Caldas, MG (Brazil). Laboratorio de Pocos de Caldas; Maihara, Vera A., E-mail: vmaihara@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (CNEN/IPEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Many studies have shown that mushrooms are organisms which efficiently accumulate radionuclides and can be used as indicators of environmental contamination and ecosystem quality. The Pocos de Caldas plateau, in Minas Gerais, is a region that has elevated natural radioactivity due to the presence of radiological anomalies of volcanic origin. Seventy areas of radioactive anomalies have been identified in this region. From the radiological point of view the determination of {sup 226}Ra, {sup 228}Ra, and {sup 210}Pb is relevant because they are decay products of the natural series of {sup 238}U and {sup 232}Th, mainly responsible for natural radioactive exposures of man. The present paper is part of a broader study conducted in the Pocos de Caldas plateau, in which the concentration activities of {sup 226}Ra, {sup 228}Ra, and {sup 210}Pb in mushroom samples were determined. The mushrooms were collected at different points of the plateau under the influence of radioactive anomalies and away from the influence of anomalies. From statistical studies a correlation between the accumulation of radionuclides in mushrooms and anomalies was established and it was possible to confirm the efficiency that the mushrooms present as environmental contamination indicators. (author)

  10. Inventory of {sup 226}Ra, {sup 228}Ra and {sup 210}Pb in marine sediments cores of Southwest Atlantic Ocean

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Alice M.R.; Oliveira, Joselene de, E-mail: alice.costa@usp.br, E-mail: jolivei@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Gerencia de Metrologia das Radiacoes. Lab. de Radiometria Ambiental; Figueira, Rubens C.L.; Mahiques, Michel M.; Sousa, Silvia H.M., E-mail: rfigueira@usp.br, E-mail: mahiques@usp.br, E-mail: smsousa@usp.br [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Instituto Oceanografico

    2015-07-01

    {sup 210}Pb (22.3 y) is a radioactive isotope successfully applied as tracer of sediment dating of the last 100-150 years. The application of {sup 226}Ra and {sup 228}Ra as paleoceanographic tracers (half-lives of 1,600 y and 5.7 y, respectively) also gives some information of ocean's role in past climate change. In this work, it was analyzed 2 sediment cores collect at Southwest Atlantic Ocean. The sediments samples were freeze-dried and acid digested in microwave. It was carried out a radiochemical separation of {sup 226}Ra, {sup 228}Ra and {sup 210}Pb and performed a gross alpha and gross beta measurement of both precipitates Ba(Ra)SO{sub 4} and PbCrO{sub 4} in a low background gas-flow proportional counter. Activity concentrations of {sup 226}Ra ranged from 45 Bq kg{sup -1} to 70 Bq kg{sup -1} in NAP-62 and from 57 Bq kg{sup -1} to 82 Bq kg{sup -1} in NAP-63 samples. The concentration of {sup 228}Ra varied between 37 Bq kg{sup -1} and 150 Bq kg{sup -1} in NAP-62 and between 23 Bq kg{sup -1} and 111 Bq kg{sup -1} in NAP-63 samples. The concentration of total {sup 210}Pb ranged from 126 Bq kg{sup -1} to 256 Bq kg{sup -1} in NAP-62 and from 63 Bq kg{sup -1} to 945 Bq kg{sup -1} in NAP-63 samples. Results of {sup 210}Pb{sub uns} varied from 68 Bq kg{sup -1} to 192 Bq kg{sup -1} for NAP-62, while varied from <4.9 Bq kg{sup -1} to 870 Bq kg{sup -1} in NAP-63 profile. Increased values of {sup 210}Pb{sub uns} were found on the top of both NAP-62 and NAP- 63 sediment profile. (author)

  11. Study of the specific concentrations of {sup 40}K, {sup 224}Ra, {sup 226}Ra and {sup 228}Ra in some seasonings marketed in Rio de Janeiro City

    Energy Technology Data Exchange (ETDEWEB)

    Garcêz, Ricardo W.D.; Lopes, José M.; Silva, Leandro B.; Silva, Ademir X. da [Coordenacao de Pos-Graduacao e Pesquisa de Engenharia (PEN/COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Programa de Engenharia Nuclear; Lima, Marco A.F., E-mail: rgarcez@nuclear.ufrj.br [Universidade Federal Fluminense (UFF), Niterói, RJ (Brazil). Instituto de Biologia

    2017-07-01

    The seasoning are vegetables substances used in foods to enhance their flavor, aroma and color. This work presents an investigation of the activity concentration of Naturally Occurring Radioactive Materials (NORMs) in 28 samples of seasoning utilized by brazilian population. The seasoning samples were measured using gamma spectroscopy technique with a high-purity germanium (HPGe) detector, a non-destructive nuclear method and with the LabSOCS software for the calculation of the efficiency curve. The analysis shows that the activity concentration of {sup 40}K was measured in all samples and ranges from 21.0 Bq/kg to 1288 Bq/kg. The highest concentration activity of {sup 40}K was measured to 'cheiro verde', a local seasoning made of chives (Allium Schoenoprasum) and parsley (Petroselinum Crispum), while annatto, made with the fruit of Bixa Orelhana, had the lowest activity concentration. Brazil nut (Bertholletia Excelsa) presented the highest concentrations for {sup 226}Ra and {sup 228}Ra with 24 Bq/kg and 25.7 Bq/kg, respectively and black pepper (Piper Nigrum) presented the highest concentration for {sup 224}Ra with 33.9 Bq/kg. The highest effective dose for members of the public due to ingestion was 23.5 μSv/y due to Brazil nut and the lowest effective dose was found for annatto: 0.13 μSv/y. The syrian seasoning sample present specific concentration of 6.1±1.1 Bq/kg for {sup 137}Cs and 0.08 μSv/y of effective dose. The values found in this work do not represent a risk to human health. (author)

  12. Screening of Male Patients for Trichomonas vaginalis with Transcription-Mediated Amplification in a Community with a High Prevalence of Sexually Transmitted Infection

    Science.gov (United States)

    Munson, Kimber L.; Napierala, Maureen; Schell, Ronald F.; Kramme, Timothy; Miller, Cheryl; Hryciuk, Jeanne E.

    2013-01-01

    Trichomonas vaginalis infection in males has been largely uncharacterized. Past reports indicated increased susceptibility to other sexually transmitted infection (STI) agents such as human immunodeficiency virus and Neisseria gonorrhoeae with concurrent T. vaginalis infection. This warrants a more thorough review of male T. vaginalis incidence. A retrospective 3-year investigation of transcription-mediated amplification (TMA)-based urethral swab and first-void urine screening for T. vaginalis within a regional health care system was performed to address T. vaginalis prevalence in males. Of 622 total samples tested, 6.6% were positive for T. vaginalis. Delineation of all specimens by ZIP code of patient residence revealed 11 predominant ZIP codes with respect to testing volume and detection rates. Within these 11 ZIP codes, representing 78.3% of total testing volume, urine was the preferred specimen source compared to urethral swabs. Seven of these 11 ZIP codes contained majority African American populations. The aggregate T. vaginalis detection rate trended higher than that of the remaining four ZIP codes, which were comprised primarily of Caucasian populations (8.9% versus 5.0%, respectively; P = 0.15). The average age of a T. vaginalis-infected male (39.9 years) was significantly greater than those for Chlamydia trachomatis or N. gonorrhoeae (27.6 and 25.9 years, respectively; P vaginalis detection, with age distribution analogous to that reported in females, TMA-based detection of T. vaginalis can be a routine constituent within a comprehensive STI screening panel for males in high-prevalence STI communities. PMID:23100348

  13. Clinical and subclinical neuropsychiatric abnormalities in rheumatoid arthritis patients

    Directory of Open Access Journals (Sweden)

    Eman M Khedr

    2015-01-01

    Conclusion Cognitive impairment, depression, anxiety and peripheral neuropathy are common in RA patients. Early diagnosis and management of neuropsychiatric disorders in RA patients may greatly improve the patients′ health-related quality of life.

  14. Directed differentiation of patient-specific induced pluripotent stem cells identifies the transcriptional repression and epigenetic modification of NKX2-5, HAND1, and NOTCH1 in hypoplastic left heart syndrome.

    Directory of Open Access Journals (Sweden)

    Junko Kobayashi

    Full Text Available The genetic basis of hypoplastic left heart syndrome (HLHS remains unknown, and the lack of animal models to reconstitute the cardiac maldevelopment has hampered the study of this disease. This study investigated the altered control of transcriptional and epigenetic programs that may affect the development of HLHS by using disease-specific induced pluripotent stem (iPS cells. Cardiac progenitor cells (CPCs were isolated from patients with congenital heart diseases to generate patient-specific iPS cells. Comparative gene expression analysis of HLHS- and biventricle (BV heart-derived iPS cells was performed to dissect the complex genetic circuits that may promote the disease phenotype. Both HLHS- and BV heart-derived CPCs were reprogrammed to generate disease-specific iPS cells, which showed characteristic human embryonic stem cell signatures, expressed pluripotency markers, and could give rise to cardiomyocytes. However, HLHS-iPS cells exhibited lower cardiomyogenic differentiation potential than BV-iPS cells. Quantitative gene expression analysis demonstrated that HLHS-derived iPS cells showed transcriptional repression of NKX2-5, reduced levels of TBX2 and NOTCH/HEY signaling, and inhibited HAND1/2 transcripts compared with control cells. Although both HLHS-derived CPCs and iPS cells showed reduced SRE and TNNT2 transcriptional activation compared with BV-derived cells, co-transfection of NKX2-5, HAND1, and NOTCH1 into HLHS-derived cells resulted in synergistic restoration of these promoters activation. Notably, gain- and loss-of-function studies revealed that NKX2-5 had a predominant impact on NPPA transcriptional activation. Moreover, differentiated HLHS-derived iPS cells showed reduced H3K4 dimethylation as well as histone H3 acetylation but increased H3K27 trimethylation to inhibit transcriptional activation on the NKX2-5 promoter. These findings suggest that patient-specific iPS cells may provide molecular insights into complex

  15. High intensity exercise or conventional exercise for patients with rheumatoid arthritis?: outcome expectations of patients, rheumatologists, and physiotherapists.

    NARCIS (Netherlands)

    Munneke, M.; Jong, Z. de; Zwinderman, A.H.; Ronday, H.K.; Ende, C.H.M. van den; Vliet Vlieland, T.P.M.; Hazes, J.M.W.

    2004-01-01

    OBJECTIVE: To examine the outcome expectations of RA patients, rheumatologists, and physiotherapists regarding high intensity exercise programmes compared with conventional exercise programmes. METHODS: An exercise outcome expectations questionnaire was administered to 807 RA patients, 153

  16. High intensity exercise or conventional exercise for patients with rheumatoid arthritis? Outcome expectations of patients, rheumatologists, and physiotherapists

    NARCIS (Netherlands)

    Munneke, M.; de Jong, Z.; Zwinderman, A. H.; Ronday, H. K.; van den Ende, C. H. M.; Vliet Vlieland, T. P. M.; Hazes, J. M. W.

    2004-01-01

    OBJECTIVE: To examine the outcome expectations of RA patients, rheumatologists, and physiotherapists regarding high intensity exercise programmes compared with conventional exercise programmes. METHODS: An exercise outcome expectations questionnaire was administered to 807 RA patients, 153

  17. WRKY transcription factors.

    Science.gov (United States)

    Rushton, Paul J; Somssich, Imre E; Ringler, Patricia; Shen, Qingxi J

    2010-05-01

    WRKY transcription factors are one of the largest families of transcriptional regulators in plants and form integral parts of signalling webs that modulate many plant processes. Here, we review recent significant progress in WRKY transcription factor research. New findings illustrate that WRKY proteins often act as repressors as well as activators, and that members of the family play roles in both the repression and de-repression of important plant processes. Furthermore, it is becoming clear that a single WRKY transcription factor might be involved in regulating several seemingly disparate processes. Mechanisms of signalling and transcriptional regulation are being dissected, uncovering WRKY protein functions via interactions with a diverse array of protein partners, including MAP kinases, MAP kinase kinases, 14-3-3 proteins, calmodulin, histone deacetylases, resistance proteins and other WRKY transcription factors. WRKY genes exhibit extensive autoregulation and cross-regulation that facilitates transcriptional reprogramming in a dynamic web with built-in redundancy. 2010 Elsevier Ltd. All rights reserved.

  18. Sexual dimorphism of RA manifestations: genes, hormones and behavior.

    Science.gov (United States)

    Kovacs, William J; Olsen, Nancy J

    2011-05-01

    Women are more likely than men to develop rheumatoid arthritis (RA), and recent data suggest that they also suffer greater disability than men with this disease. The reasons for these sexually dimorphic patterns of disease incidence and progression are unknown, but investigations into the underlying mechanisms could provide useful insights into RA pathogenesis and may also suggest new treatment approaches. The processes of sexual differentiation involve genetic input, gonadal hormone signaling and responses from target cells and tissues. Layered upon these processes are behavioral characteristics of males and females acquired as a result of their social context. Differences in disease presentation between the sexes could be the result of complex combinations of all these factors. Recent research suggests that the developmental processes of sexual differentiation might render women more susceptible than men to similar levels of immune or inflammatory burden by virtue of sex-specific differences in body composition and structure.

  19. Trapping of short lived Ra{sup +} ions

    Energy Technology Data Exchange (ETDEWEB)

    Bekker, H.; Nunes Portela, M.; Seelen, D.; Dermois, O.; Jungmann, K.; Onderwater, C.J.G.; Timmermans, R.G.E.; Willmann, L.; Wilschut, H.W. [KVI, University of Groningen, NL (Germany)

    2012-07-01

    A precision measurement of atomic parity violation in order to determine electroweak mixing angle at low energy scale is underway at the KVI, University of Groningen. The experiment exploits the large sensitivity of a single trapped Ra{sup +} ion. It requires the trapping of short lived radium ions in a Paul trap. Our first laser spectroscopy on an ensemble of trapped short-lived {sup 209-214}Ra{sup +} isotopes employed buffer gas cooled ions in a linear Paul trap. It provided hyperfine structure of the 6d {sup 2}D{sub 3/2} states and isotope shift of the 6d {sup 2}D{sub 3/2}-7p {sup 2}P{sub 1/2} transition. In a next step the buffer gas cooled Ra ions are extracted from the trap and transported in an electrostatic transport system towards a small Paul trap in an UHV environment. Here the ion can be cooled and subsequently microwave transitions between hyperfine states in the 6d {sup 2}D{sub 3/2} manifold can be driven in order to yield high precision results on the hyperfine constants. These results provide input for the ongoing precision atomic structure calculations.

  20. Octupole collectivity in $^{220}$Rn and $^{224}$Ra

    CERN Document Server

    Gaffney, Liam Paul

    Collective properties of the radioactive nuclei $^{220}$Rn and $^{224}$Ra have been studied via Coulomb excitation of a 2.8$\\,$A.MeV radioactive ion beam (RIB) incident upon $^{60}$Ni, $^{112,114}$Cd and $^{120}$Sn targets. The experiments took place at the REX-ISOLDE RIB facility, CERN. De-excitation $\\gamma$-ray yields following multiple-step Coulomb excitation were detected in coincidence with recoiling target nuclei in the Miniball spectrometer. For the first time, B(E3;3$^+ \\rightarrow 0^+$) values have been directly measured with a radioactive ion beam. In the process, $^{224}$Ra becomes the heaviest post-accelerated RIB to date at ISOLDE (with the possible exception of the quasi-stable $^{238}$U). The measurements presented in this thesis represent a tripling of the number of nuclei around Z$\\simeq88$ and N$\\simeq134$, for which direct measurements of the octupole collectivity have been performed. The only previous measurements being for the relatively long-lived $^{226}$Ra. The $\\gamma$-ray yields, in...

  1. Raízes e estruturas da sociedade brasileira

    Directory of Open Access Journals (Sweden)

    Leonor Natividade de Campos Medeiros

    2014-05-01

    Full Text Available Este estudo teve como objetivo conhecer e refletir as raízes e estruturas da sociedade brasileira, na visão de dois grandes pensadores: Sérgio Buarque de Holanda com Raízes do Brasil e Gilberto Freyre com Casa-Grande & Senzala. Holanda dividiu o Brasil em duas fases a primeira da colonização portuguesa e a segunda uma critica ao Estado Novo. Freyre mostra a organização social, política e econômica da época da colonização e desenvolve seus estudos ao final da década de 1920, época em que o ambiente intelectual brasileiro está sob a força do modernismo. Conclui-se que o pensamento de Holanda e Freyre se assemelha em alguns aspectos e diverge em outros.   Sociologia de Freyre; Sociologia de Holanda; Raízes da sociedade brasileira

  2. Shared care or nurse consultations as an alternative to rheumatologist follow-up for rheumatoid arthritis (RA) outpatients with stable low disease-activity RA

    DEFF Research Database (Denmark)

    Sørensen, Jan; Primdahl, J; Horn, Hc

    2014-01-01

    Objectives: To compare the cost-effectiveness of three types of follow-up for outpatients with stable low-activity rheumatoid arthritis (RA). Method: In total, 287 patients were randomized to either planned rheumatologist consultations, shared care without planned consultations, or planned nurse......-effectiveness rates (ICERs) were estimated in comparison with rheumatologist consultations. Results: Changes in disease activity, functional status, and health-related quality of life were not statistically significantly different for the three groups, although the mean scores were better for the shared care...... and nurse care groups compared with the rheumatologist group. Shared care and nurse care were non-significantly less costly than rheumatologist care. As both shared care and nurse care were associated with slightly better EQ-5D improvements and lower costs, they dominated rheumatologist care. At EUR 10 000...

  3. Cell therapy centered on IL-1Ra is neuroprotective in experimental stroke

    DEFF Research Database (Denmark)

    Clausen, Bettina Hjelm; Lambertsen, Kate Lykke; Dagnæs-Hansen, Frederik

    2016-01-01

    irradiated mice with IL-1Ra-producing bone marrow cells is associated with neuroprotection and recruitment of IL-1Ra-producing leukocytes after stroke. Neuroprotection is also achieved by therapeutic injection of IL-1Ra-producing bone marrow cells 30 min after stroke onset, additionally improving...... production of IL-1Ra and IL-1α/β identifies microglia, not infiltrating leukocytes, as the major sources of IL-1Ra after experimental stroke, and shows IL-1Ra and IL-1β to be produced by segregated subsets of microglia with a small proportion of these cells co-expressing IL-1α. Reconstitution of whole body...... by demonstration of IL-1Ra-producing cells in the human cortex early after ischemic stroke. Taken together, our results attribute distinct neuroprotective or neurotoxic functions to segregated subsets of microglia and suggest that treatment strategies increasing the production of IL-1Ra by infiltrating leukocytes...

  4. High-Linear Energy Transfer Irradiation Targeted to Skeletal Metastases by the Alpha Emitter Ra-223: Adjuvant or Alternative to Conventional Modalities?

    Energy Technology Data Exchange (ETDEWEB)

    Bruland, Oyvind S.; Nilsson, Sten; Fisher, Darrell R.; Larsen, Roy H.

    2006-10-15

    The bone-seeking, alpha-particle emitting radiopharmaceutical Alpharadin, 223RaCl2 (t1/2 = 11.4 days) is under clinical development as a novel treatment for skeletal metastases from breast and prostate cancer. This paper summarizes the current status of preclinical and clinical research on 223RaCl2. Potential advantages of 223Ra to that of external beam irradiation or registered beta-emitting bone-seekers are discussed. Published data of 223Ra dosimetry in mice and a therapeutic study in a skeletal metastases model in nude rats have indicated significant therapeutic potential of bone-seeking alpha-emitters. This paper provides short-term and long-term results from the first clinical single dosage trial. We present data from a repeated dosage study of five consecutive injections of 50 kBq/kg bodyweight, once every third week, or two injections of 125 kBq/kg bodyweight, six weeks apart. Furthermore, preliminary results are given for a randomized phase II trial involving 64 patients with hormone-refractory prostate cancer and painful skeletal metastases who received four monthly injections of 223Ra or saline as an adjuvant to external beam radiotherapy. Also presented are preliminary dose estimates for 223Ra in humans. Results indicate that repeated dosing is feasible and that opportunities are available for combined treatment strategies.

  5. U-Th-Ra disequilibria at the Masaya (Nicaragua); Desequilibres U-Th-Ra au Masaya (Nicaragua)

    Energy Technology Data Exchange (ETDEWEB)

    Sigmarsson, O.; Condomines, M. [Centre de Recherches Volcanologiques, CNRS URA-10, 63 - Clermont Ferrand (France)

    1996-12-31

    {sup 238}U-{sup 230}Th-{sup 226}Ra radioactive disequilibria were measured in several basalt samples of the post-caldera flows of the Masaya volcano (Nicaragua). {sup 230}Th/{sup 232}Th ratios are from the highest known in the world (about 2.53) with {sup 230}Th/{sup 238}U ratios close to 1. These exceptionally high isotopic thorium ratios from the Masaya and other neighboring volcanoes (Conception, Cerro Negro, Momotombo) are followed by very high {sup 10}Be/{sup 9}Be ratios (60 10{sup -11} for the 1722 flow). These geochemical characteristics with {delta}{sup 18}O of typical mantle origin (5.55) suggest an influence of the subducted sediments fluids in the magma source. The age of the metasomatism ranges from 10 to 0.3 Ma. Initial {sup 226}Ra/{sup 230}Th ratios measured in four historical flows vary from 1.3 to 1.4 and are anti-correlated with the Th content. These variations are probably linked to the fractionated crystallisation of plagioclase minerals. The initial {sup 226}Ra/Ba ratio remains constant and suggests the existence of a huge stationary magmatic reservoir. This hypothesis is also confirmed by the disproportion between the SO{sub 2} quantity emitted by the volcano and by the degassing of lavas on the ground. The {sup 226}Ra excess observed in the Masaya lavas can be the result of a second stage of metasomatism which occurred less than 8000 years B.P. during partial fusion. Abstract only. (J.S.).

  6. An evaluation of ²²⁶Ra and ²²⁸Ra in drinking water in several counties in Texas, USA.

    Science.gov (United States)

    Landsberger, S G; George, G

    2013-11-01

    Naturally Occurring Radioactive Material (NORM) or Technology Enhanced Naturally Occurring Radioactive Material (TENORM) can be a potential health risk. It is now well known that the underlying geology in many parts of Texas has given rise to levels of (226)Ra and (228)Ra that often exceed the limits set by the US Environmental Protection Agency. A detailed literature search was undertaken to assess the levels of (226)Ra and (228)Ra in all of the Texas counties. Several statistical evaluations of the data were performed. The Hickory aquifer in the Llano Uplift region of Texas has consistently had the highest number of (226)Ra and (228)Ra concentrations above the legal limit. As well many of the affected rural communities may not have the financial resources to rectify the problem. Copyright © 2013. Published by Elsevier Ltd.

  7. Filovirus replication and transcription

    OpenAIRE

    Mühlberger, Elke

    2007-01-01

    The highly pathogenic filoviruses, Marburg and Ebola virus, belong to the nonsegmented negative-sense RNA viruses of the order Mononegavirales. The mode of replication and transcription is similar for these viruses. On one hand, the negative-sense RNA genome serves as a template for replication, to generate progeny genomes, and, on the other hand, for transcription, to produce mRNAs. Despite the similarities in the replication/transcription strategy, filoviruses have evolved structural and fu...

  8. Radiochemical determination and separation or total radium, 226Ra and 224Ra; Analisis Radioquimico de Radio total, Radio-226 y Radio-224

    Energy Technology Data Exchange (ETDEWEB)

    Suarez, J. A.; Gonzalez, J. A.; Pablo, M. A. de

    1987-07-01

    Radiochemical purification and separation of radium has been carried out and the determination of total radium solubilized in aqueous samples has been studied assuming that all the alpha emitters of the sample have their origin in the 226Ra and elements of its desintegration chain. Also, the activities of 22Ra and 226 Ra have been evaluated separately doing a measurement after the chemical separation of the radium and another one 10 days after. (Author) 9 refs.

  9. WRKY transcription factors

    Science.gov (United States)

    Bakshi, Madhunita; Oelmüller, Ralf

    2014-01-01

    WRKY transcription factors are one of the largest families of transcriptional regulators found exclusively in plants. They have diverse biological functions in plant disease resistance, abiotic stress responses, nutrient deprivation, senescence, seed and trichome development, embryogenesis, as well as additional developmental and hormone-controlled processes. WRKYs can act as transcriptional activators or repressors, in various homo- and heterodimer combinations. Here we review recent progress on the function of WRKY transcription factors in Arabidopsis and other plant species such as rice, potato, and parsley, with a special focus on abiotic, developmental, and hormone-regulated processes. PMID:24492469

  10. Homeobox transcription factor muscle segment homeobox 2 (Msx2) correlates with good prognosis in breast cancer patients and induces apoptosis in vitro.

    LENUS (Irish Health Repository)

    Lanigan, Fiona

    2010-01-01

    The homeobox-containing transcription factor muscle segment homeobox 2 (Msx2) plays an important role in mammary gland development. However, the clinical implications of Msx2 expression in breast cancer are unclear. The aims of this study were to investigate the potential clinical value of Msx2 as a breast cancer biomarker and to clarify its functional role in vitro.

  11. Ra+ ion trapping : toward an atomic parity violation measurement and an optical clock

    NARCIS (Netherlands)

    Portela, M. Nunez; Dijck, E. A.; Mohanty, A.; Bekker, H.; van den Berg, Joost E.; Giri, G. S.; Hoekstra, S.; Onderwater, C. J. G.; Schlesser, S.; Timmermans, R.G.E.; Versolato, O. O.; Willmann, L.; Wilschut, H. W.; Jungmann, K.

    2014-01-01

    A single Ra+ ion stored in a Paul radio frequency ion trap has excellent potential for a precision measurement of the electroweak mixing angle at low momentum transfer and as the most stable optical clock. The effective transport and cooling of singly charged ions of the isotopes Ra-209 to Ra-214 in

  12. Selective extraction of naturally occurring radioactive Ra2+ from aqueous waste streams

    NARCIS (Netherlands)

    van Leeuwen, F.W.B.

    2005-01-01

    This thesis describes the design and selectivity of new Ra2+ extractants. The results presented provide insight in both the requirements needed to give Ra2+ selectivity and in the achievable Ra2+/Mn+ (Mn+ = alkali(ne earth) cation) separations.

  13. Raça e lesão de órgãos-alvo da hipertensão arterial em pacientes atendidos em um ambulatório universitário de referência na cidade de Salvador Race and hypertensive target-organ damage in patients from an university-affiliated outpatient care referral clinic in the city of Salvador

    Directory of Open Access Journals (Sweden)

    Antonio Carlos Beisl Noblat

    2004-02-01

    Full Text Available OBJETIVO: Avaliar se a raça do paciente estaria associada à presença de hipertrofia ventricular esquerda, acidente vascular cerebral e insuficiência renal crônica em hipertensos atendidos em ambulatório de referência em Salvador-BA. MÉTODOS: Analisados dados de 622 pacientes com o primeiro atendimento em ambulatório de hipertensão, entre 1982 e 1986, e identificados os com história prévia ou seqüela de acidente vascular cerebral, hipertrofia ventricular esquerda ou insuficiência renal (creatinina sérica > 1,4 mg/dL. Modelos de regressão logística foram utilizados para estimar odds ratio (OR da associação entre raça (mulatos ou negros vs brancos e lesão de órgãos-alvo de hipertensão, ajustadas para sexo e idade. RESULTADOS: A média de idade dos pacientes foi 53,8±14,3 anos, 74,1% mulheres. Quanto à raça, 15,1% eram brancos, 65,9% mulatos e 19,0% negros. Acidente vascular cerebral foi significantemente mais freqüente em negros ou mulatos do que em brancos (odds ratio ajustada (ORa=3,44; intervalo de confiança (IC 95%=1,23-9,67. Quanto às associações envolvendo raça com os eventos hipertrofia ventricular esquerda e insuficiência renal as ORa não foram estatisticamente significantes, mas foram consistentes com maior prevalência de hipertrofia ventricular esquerda e insuficiência renal em negros e mulatos. CONCLUSÃO: Negros e mulatos hipertensos têm maior risco de lesão de órgão alvo do que brancos, com diferença racial maior para acidente vascular cerebral não fatal. Deve ser avaliada se diferenças raciais em mortalidade relacionada a complicações da hipertensão influenciam as associações observadas entre raça e lesão de órgãos-alvo.OBJECTIVE: To assess whether a patient's race is associated with the presence of left ventricular hypertrophy, stroke, and renal failure in hypertensive patients from an outpatient care referral clinic in the city of Salvador in the state of Bahia. METHODS: We

  14. Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA.

    Science.gov (United States)

    Suzuki, Takuji; Sakagami, Takuro; Rubin, Bruce K; Nogee, Lawrence M; Wood, Robert E; Zimmerman, Sarah L; Smolarek, Teresa; Dishop, Megan K; Wert, Susan E; Whitsett, Jeffrey A; Grabowski, Gregory; Carey, Brenna C; Stevens, Carrie; van der Loo, Johannes C M; Trapnell, Bruce C

    2008-11-24

    Primary pulmonary alveolar proteinosis (PAP) is a rare syndrome characterized by accumulation of surfactant in the lungs that is presumed to be mediated by disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling based on studies in genetically modified mice. The effects of GM-CSF are mediated by heterologous receptors composed of GM-CSF binding (GM-CSF-Ralpha) and nonbinding affinity-enhancing (GM-CSF-Rbeta) subunits. We describe PAP, failure to thrive, and increased GM-CSF levels in two sisters aged 6 and 8 yr with abnormalities of both GM-CSF-Ralpha-encoding alleles (CSF2RA). One was a 1.6-Mb deletion in the pseudoautosomal region of one maternal X chromosome encompassing CSF2RA. The other, a point mutation in the paternal X chromosome allele encoding a G174R substitution, altered an N-linked glycosylation site within the cytokine binding domain and glycosylation of GM-CSF-Ralpha, severely reducing GM-CSF binding, receptor signaling, and GM-CSF-dependent functions in primary myeloid cells. Transfection of cloned cDNAs faithfully reproduced the signaling defect at physiological GM-CSF concentrations. Interestingly, at high GM-CSF concentrations similar to those observed in the index patient, signaling was partially rescued, thereby providing a molecular explanation for the slow progression of disease in these children. These results establish that GM-CSF signaling is critical for surfactant homeostasis in humans and demonstrate that mutations in CSF2RA cause familial PAP.

  15. Transcription Factor Pathways and Congenital Heart Disease

    Science.gov (United States)

    McCulley, David J.; Black, Brian L.

    2013-01-01

    Congenital heart disease is a major cause of morbidity and mortality throughout life. Mutations in numerous transcription factors have been identified in patients and families with some of the most common forms of cardiac malformations and arrhythmias. This review discusses factor pathways known to be important for normal heart development and how abnormalities in these pathways have been linked to morphological and functional forms of congenital heart defects. A comprehensive, current list of known transcription factor mutations associated with congenital heart disease is provided, but the review focuses primarily on three key transcription factors, Nkx2-5, GATA4, and Tbx5, and their known biochemical and genetic partners. By understanding the interaction partners, transcriptional targets, and upstream activators of these core cardiac transcription factors, additional information about normal heart formation and further insight into genes and pathways affected in congenital heart disease should result. PMID:22449847

  16. Osteoblastic potential of infrapatellar fat pad-derived mesenchymal stem cells from rheumatoid arthritis and osteoarthritis patients.

    Science.gov (United States)

    Skalska, Urszula; Prochorec-Sobieszek, Monika; Kontny, Ewa

    2016-06-01

    To evaluate the osteoblastic potential of adipose-derived mesenchymal stem cells (ASCs) from infrapatellar fat pad (IPFP) of rheumatoid arthritis (RA) patients in comparison to osteoarthritis (OA) patients, as well as the influence of tumor necrosis factor alpha (TNFα) on osteoblastic ASC differentiation in vitro. ASCs were isolated from IPFP of RA and OA patients. After expansion, cells were cultured in osteogenic medium with or without TNFα. After 2 weeks, expression of BMP-2, Runx-2, osterix (Osx), collagen 1a1 (Col1a1) and osteopontin (OPN) messenger RNA (mRNA) was assessed by reverse transcription polymerase chain reaction and calcium deposition by alizarin red staining. Dickkopf-1 (DKK-1) and osteoprotegerin (OPG) protein concentrations were measured in culture supernatants using enzyme-linked immunosorbent assay. Both RA- and OA-ASCs cultured in osteogenic medium showed calcium deposition. The expression of Runx2 and OPN mRNA was increased in RA-ASCs. These cells expressed significantly more Osx and OPN than OA-ASCs. TNFα potentiated calcium deposition, up-regulated Runx2 and BMP-2 but down-regulated Col1a1 and OPN expression. In osteogenic cultures DKK-1 concentration was increased but that of OPG decreased, whereas TNFα elevated secretion of both cytokines. RA-ASCs have comparable or slightly stronger osteogenic potential than OA-ASCs. RA-ASCs seem to be more sensitive to TNFα treatment. TNFα exerts complex effects on ASC osteoblastogenesis, enhances expression of early osteogenic markers and calcium deposition, inhibits expression of mRNA coding for non-mineral bone components and alters ASC secretory activity. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  17. The Transcription Factor Encyclopedia

    DEFF Research Database (Denmark)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I

    2012-01-01

    ABSTRACT: Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130...

  18. The transcriptional landscape

    DEFF Research Database (Denmark)

    Nielsen, Henrik

    2011-01-01

    The application of new and less biased methods to study the transcriptional output from genomes, such as tiling arrays and deep sequencing, has revealed that most of the genome is transcribed and that there is substantial overlap of transcripts derived from the two strands of DNA. In protein codi...

  19. Addition of the Neurokinin-1-Receptor Antagonist (RA) Aprepitant to a 5-Hydroxytryptamine-RA and Dexamethasone in the Prophylaxis of Nausea and Vomiting Due to Radiation Therapy With Concomitant Cisplatin

    Energy Technology Data Exchange (ETDEWEB)

    Jahn, Franziska, E-mail: franziska.jahn@uk-halle.de [Department of Hematology/Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany); Riesner, Anica [Department of Gastroenterology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany); Jahn, Patrick [Nursing Research Unit, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany); Sieker, Frank; Vordermark, Dirk [Department of Radiation Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany); Jordan, Karin [Department of Hematology/Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany)

    2015-08-01

    Purpose: To assess, in a prospective, observational study, the safety and efficacy of the addition of the neurokinin-1-receptor antagonist (NK1-RA) aprepitant to concomitant radiochemotherapy, for the prophylaxis of radiation therapy–induced nausea and vomiting. Patients and Methods: This prospective observational study compared the antiemetic efficacy of an NK1-RA (aprepitant), a 5-hydroxytryptamine-RA, and dexamethasone (aprepitant regimen) versus a 5-hydroxytryptamine-RA and dexamethasone (control regimen) in patients receiving concomitant radiochemotherapy with cisplatin at the Department of Radiation Oncology, University Hospital Halle (Saale), Germany. The primary endpoint was complete response in the overall phase, defined as no vomiting and no use of rescue therapy in this period. Results: Fifty-nine patients treated with concomitant radiochemotherapy with cisplatin were included in this study. Thirty-one patients received the aprepitant regimen and 29 the control regimen. The overall complete response rates for cycles 1 and 2 were 75.9% and 64.5% for the aprepitant group and 60.7% and 54.2% for the control group, respectively. Although a 15.2% absolute difference was reached in cycle 1, a statistical significance was not detected (P=.22). Furthermore maximum nausea was 1.58 ± 1.91 in the control group and 0.73 ± 1.79 in the aprepitant group (P=.084); for the head-and-neck subset, 2.23 ± 2.13 in the control group and 0.64 ± 1.77 in the aprepitant group, respectively (P=.03). Conclusion: This is the first study of an NK1-RA–containing antiemetic prophylaxis regimen in patients receiving concomitant radiochemotherapy. Although the primary endpoint was not obtained, the absolute difference of 10% in efficacy was reached, which is defined as clinically meaningful for patients by international guidelines groups. Randomized phase 3 studies are necessary to further define the potential role of an NK1-RA in this setting.

  20. Investigation of Telomerase/Telomeres system in Bone Marrow Mesenchymal Stem Cells derived from IPF and RA-UIP

    Directory of Open Access Journals (Sweden)

    Antoniou Katerina M

    2012-07-01

    Full Text Available Abstract Objective Idiopathic Pulmonary Fibrosis and Rheumatoid Arthritis associated usual interstitial pneumonia seem to have the same poor outcome as there is not an effective treatment. The aim of the study is to explore the reparative ability of bone marrow mesenchymal stem cells by evaluating the system telomerase/telomeres and propose a novel therapeutic approach. Methods BM-MSCs were studied in 6 IPF patients, 7 patients with RA-UIP and 6 healthy controls. We evaluated the telomere length as well as the mRNA expression of both components of telomerase (human telomerase reverse transcriptase, h-TERT and RNA template complementary to the telomeric loss DNA, h-TERC. Results We found that BM-MSCs from IPF, RA-UIP cases do not present smaller telomere length than the controls (p = 0.170. There was no significant difference regarding the expression of both h-TERT and h-TERC genes between patients and healthy controls (p = 0.107 and p = 0.634 respectively. Conclusions We demonstrated same telomere length and telomerase expression in BM-MSCs of both IPF and RA-UIP which could explain similarities in pathogenesis and prognosis. Maintenance of telomere length in these cells could have future implication in cell replacement treatment with stem cells of these devastating lung disorders.

  1. Mechanical Properties of Transcription.

    Science.gov (United States)

    Sevier, Stuart A; Levine, Herbert

    2017-06-30

    The mechanical properties of transcription have recently been shown to play a central role in gene expression. However, a full physical characterization of this central biological process is lacking. In this Letter, we introduce a simple description of the basic physical elements of transcription where RNA elongation, RNA polymerase rotation, and DNA supercoiling are coupled. The resulting framework describes the relative amount of RNA polymerase rotation and DNA supercoiling that occurs during RNA elongation. Asymptotic behavior is derived and can be used to experimentally extract unknown mechanical parameters of transcription. Mechanical limits to transcription are incorporated through the addition of a DNA supercoiling-dependent RNA polymerase velocity. This addition can lead to transcriptional stalling and resulting implications for gene expression, chromatin structure and genome organization are discussed.

  2. Calculation of P,T-odd interaction effect in ^{225}RaO

    CERN Document Server

    Kudashov, A D; Skripnikov, L V; Mosyagin, N S; Titov, A V

    2012-01-01

    The 10-electron generalized relativistic effective core potential and the corresponding correlation spin-orbital basis sets are generated for the Ra atom and the relativistic coupled cluster calculations for the RaO molecule are performed. The main goal of the study is to evaluate the P,T-odd parameter X characterized by the molecular electronic structure and corresponding to a "volume effect" in the interaction of the ^{225}Ra nucleus Schiff moment with electronic shells of RaO. Our final result for X(^{225}RaO) is -7532 which is surprisingly close to that in ^{205}TlF but has different sign. The obtained results are discussed and the quality of the calculations is analyzed. The value is of interest for a proposed experiment on RaO [PRA 77, 024501 (2008)] due to a very large expected Schiff moment of the ^{225}Ra nucleus.

  3. Rapid Reagentless Detection of M. tuberculosis H37Ra in Respiratory Effluents

    Energy Technology Data Exchange (ETDEWEB)

    Adams, K L; Steele, P T; Bogan, M J; Sadler, N M; Martin, S; Martin, A N; Frank, M

    2008-01-29

    Two similar mycobacteria, Mycobacteria tuberculosis H37Ra and Mycobacteria smegmatis are rapidly detected and identified within samples containing a complex background of respiratory effluents using Single Particle Aerosol Mass Spectrometry (SPAMS). M. tuberculosis H37Ra (TBa), an avirulent strain, is used as a surrogate for virulent tuberculosis (TBv); M. smegmatis (MSm) is utilized as a near neighbor confounder for TBa. Bovine lung surfactant and human exhaled breath condensate are used as first-order surrogates for infected human lung expirations from patients with pulmonary tuberculosis. This simulated background sputum is mixed with TBa or MSm and nebulized to produce conglomerate aerosol particles, single particles that contain a bacterium embedded within a background respiratory matrix. Mass spectra of single conglomerate particles exhibit ions associated with both respiratory effluents and mycobacteria. Spectral features distinguishing TBa from MSm in pure and conglomerate particles are shown. SPAMS pattern matching alarm algorithms are able to distinguish TBa containing particles from background matrix and MSm for >50% of the test particles, which is sufficient to enable a high probability of detection and a low false alarm rate if an adequate number of such particles are present. These results indicate the potential usefulness of SPAMS for rapid, reagentless tuberculosis screening.

  4. The investigation of association between IL-1Ra and ACE I/D polymorphisms in carpal tunnel syndrome.

    Science.gov (United States)

    Cevik, Betul; Tekcan, Akin; Inanir, Ahmet; Kurt, Semiha Gulsum; Yigit, Serbulent

    2017-03-29

    Carpal tunnel syndrome (CTS) is a common neurologic impairment caused by injury on the median nerve in the wrist, characterized by pain and loss of sensory. CTS usually occurs through three factors, such as a mechanical pressure on median nerve, immunologic changes, and oxidative stress. The aim of this study was to evaluate the influence of interleukin-1 receptor antagonist (IL-1Ra) and angiotensin-converting enzyme (ACE) I/D polymorphisms on the susceptibility of patients to the CTS. One hundred fifty-eight patients with CTS and 151 healthy controls were enrolled in this study. Each patient was analyzed according to diseases symptoms, such as gender, a positive Tinel's sign, a positive Phalen maneuver, disease sides, EMG findings, and clinical stage. We applied the polymerase chain reaction (PCR) to determine the polymorphisms of IL-1Ra and ACE I/D. The statistically significant relation was not found between IL-1Ra, ACE I/D polymorphisms and CTS (respectively, P>.05; P>.05, OR: 1.51, CI: 0.82-1.61). Additionally, in the result of the statistical analysis compared with gene polymorphisms and clinical characteristics, we did not find any correlation (P>.05). Our findings showed that there are no associations of IL-1Ra and ACE I/D polymorphisms with susceptibility of a person for the development of CTS. So, it means that these polymorphisms do not create a risk for the development of CTS. Further studies with larger populations will be required to confirm these findings in different study populations. © 2017 Wiley Periodicals, Inc.

  5. Osteoporosis diagnostics in patients with rheumatoid arthritis

    OpenAIRE

    Małgorzata Węgierska; Marta Dura; Einat Blumfield; Paweł Żuchowski; Marzena Waszczak; Sławomir Jeka

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic systemic connective tissue disease. The development of comorbidities often occurs in the course of RA. One of them is osteoporosis, which has serious social and economic effects and may contribute to the increase in the degree of disability and premature death of the patient. Due to the young age in which RA disease occurs, densitometry (DXA) of the lumbar spine is the basic examination in osteoporosis diagnostics. In the course of RA, much more frequent...

  6. Raúl Castro a la hora de las decisiones

    Directory of Open Access Journals (Sweden)

    Janette HABEL

    2010-01-01

    Full Text Available Este artículo trata sobre el nuevo rol político de Raúl Castro en Cuba. Su misión no es fácil. Debe redefinir un proyecto de desarrollo viable en condiciones históricas y geopolíticas nuevas; garantizar la estabilidad del país; organizar el relevo entre los antiguos dirigentes históricos y las nuevas generaciones; y, además, iniciar negociaciones con la administración Obama. ¿Se podrá hablar en adelante de un «raulismo» o se seguirá imponiendo el «fidelismo»? Asimismo, ¿cómo salvaguardar la soberanía e independencia, junto a las principales conquistas sociales desde hace cincuenta años, mientras al mismo tiempo se llevan a cabo las reformas «estructurales » y se intenta normalizar relaciones con el continente, específicamente con Estados Unidos? Esa respuesta, que no es obvia, la debe dar Raúl Castro.

  7. Wt1 controls retinoic acid signalling in embryonic epicardium through transcriptional activation of Raldh2

    Science.gov (United States)

    Guadix, Juan Antonio; Ruiz-Villalba, Adrián; Lettice, Laura; Velecela, Victor; Muñoz-Chápuli, Ramón; Hastie, Nicholas D.; Pérez-Pomares, José María; Martínez-Estrada, Ofelia M.

    2011-01-01

    Epicardial-derived signals are key regulators of cardiac embryonic development. An important part of these signals is known to relate to a retinoic acid (RA) receptor-dependent mechanism. RA is a potent morphogen synthesised by Raldh enzymes, Raldh2 being the predominant one in mesodermal tissues. Despite the importance of epicardial retinoid signalling in the heart, the molecular mechanisms controlling cardiac Raldh2 transcription remain unknown. In the current study, we show that Wt1-null epicardial cells display decreased expression of Raldh2 both in vivo and in vitro. Using a RA-responsive reporter, we have confirmed that Wt1-null epicardial cells actually show reduced synthesis of RA. We also demonstrate that Raldh2 is a direct transcriptional target of Wt1 in epicardial cells. A secondary objective of this study was to identify the status of RA-related receptors previously reported to be critical to epicardial biology (PDGFRα,β; RXRα). PDGFRα and PDGFRβ mRNA and protein levels are downregulated in the absence of Wt1, but only Pdgfra expression is rescued by the addition of RA to Wt1-null epicardial cells. RXRα mRNA levels are not affected in Wt1-null epicardial cells. Taken together, our results indicate that Wt1 critically regulates epicardial RA signalling via direct activation of the Raldh2 gene, and identify a role for Wt1 in the regulation of morphogen receptors involved in the proliferation, migration, and differentiation of epicardial and epicardially-derived cells (EPDC). PMID:21343363

  8. Tumor Necrosis Factor (TNF Bioactivity at the Site of an Acute Cell-Mediated Immune Response Is Preserved in Rheumatoid Arthritis Patients Responding to Anti-TNF Therapy

    Directory of Open Access Journals (Sweden)

    Rachel Byng-Maddick

    2017-08-01

    Full Text Available The impact of anti-tumor necrosis factor (TNF therapies on inducible TNF-dependent activity in humans has never been evaluated in vivo. We aimed to test the hypothesis that patients responding to anti-TNF treatments exhibit attenuated TNF-dependent immune responses at the site of an immune challenge. We developed and validated four context-specific TNF-inducible transcriptional signatures to quantify TNF bioactivity in transcriptomic data. In anti-TNF treated rheumatoid arthritis (RA patients, we measured the expression of these biosignatures in blood, and in skin biopsies from the site of tuberculin skin tests (TSTs as a human experimental model of multivariate cell-mediated immune responses. In blood, anti-TNF therapies attenuated TNF bioactivity following ex vivo stimulation. However, at the site of the TST, TNF-inducible gene expression and genome-wide transcriptional changes associated with cell-mediated immune responses were comparable to that of RA patients receiving methotrexate only. These data demonstrate that anti-TNF agents in RA patients do not inhibit inducible TNF activity at the site of an acute inflammatory challenge in vivo, as modeled by the TST. We hypothesize instead that their therapeutic effects are limited to regulating TNF activity in chronic inflammation or by alternative non-canonical pathways.

  9. Tumor Necrosis Factor (TNF) Bioactivity at the Site of an Acute Cell-Mediated Immune Response Is Preserved in Rheumatoid Arthritis Patients Responding to Anti-TNF Therapy.

    Science.gov (United States)

    Byng-Maddick, Rachel; Turner, Carolin T; Pollara, Gabriele; Ellis, Matthew; Guppy, Naomi J; Bell, Lucy C K; Ehrenstein, Michael R; Noursadeghi, Mahdad

    2017-01-01

    The impact of anti-tumor necrosis factor (TNF) therapies on inducible TNF-dependent activity in humans has never been evaluated in vivo. We aimed to test the hypothesis that patients responding to anti-TNF treatments exhibit attenuated TNF-dependent immune responses at the site of an immune challenge. We developed and validated four context-specific TNF-inducible transcriptional signatures to quantify TNF bioactivity in transcriptomic data. In anti-TNF treated rheumatoid arthritis (RA) patients, we measured the expression of these biosignatures in blood, and in skin biopsies from the site of tuberculin skin tests (TSTs) as a human experimental model of multivariate cell-mediated immune responses. In blood, anti-TNF therapies attenuated TNF bioactivity following ex vivo stimulation. However, at the site of the TST, TNF-inducible gene expression and genome-wide transcriptional changes associated with cell-mediated immune responses were comparable to that of RA patients receiving methotrexate only. These data demonstrate that anti-TNF agents in RA patients do not inhibit inducible TNF activity at the site of an acute inflammatory challenge in vivo, as modeled by the TST. We hypothesize instead that their therapeutic effects are limited to regulating TNF activity in chronic inflammation or by alternative non-canonical pathways.

  10. Determination of Ra-223 in human excretion samples by means of α-spectrometry; Bestimmung von {sup 223}Ra in Ausscheidungsproben mittels α-Spektrometrie

    Energy Technology Data Exchange (ETDEWEB)

    Zoriy, M.V.; Froning, M.; Hill, P. [Forschungszentrum Juelich GmbH (Germany). Geschaeftsbereich Strahlenschutz und Sicherheit

    2015-07-01

    To ensure the safety of occupationally exposed person for possible incorporation of {sup 223}Ra during the handling with Alpharadin / Xofigo {sup registered}, the determination of {sup 223}Ra activity in its excretion sample (e.g, in a stool sample) might be of great importance. To assess the {sup 223}Ra activity in human faeces samples a new analytical method was developed in our laboratory. The determination is performed by means of grid-ionization a-spectrometry. After a relatively simple sample preparation procedure (usually within max. 6 hours) and the addition of an internal standard, a direct determination of {sup 223}Ra with the grid ionization chamber (GIK) is possible. The method was optimized and successfully tested. The procedure-related LOD for {sup 223}Ra in a 24-hour faeces sample was 0.1 Bq/Probe.

  11. A Novel Single-Cell FISH-Flow Assay Identifies Effector Memory CD4+ T cells as a Major Niche for HIV-1 Transcription in HIV-Infected Patients

    Directory of Open Access Journals (Sweden)

    Judith Grau-Expósito

    2017-07-01

    Full Text Available Cells that actively transcribe HIV-1 have been defined as the “active viral reservoir” in HIV-infected individuals. However, important technical limitations have precluded the characterization of this specific viral reservoir during both treated and untreated HIV-1 infections. Here, we used a novel single-cell RNA fluorescence in situ hybridization-flow cytometry (FISH-flow assay that requires only 15 million unfractionated peripheral blood mononuclear cells (PBMCs to characterize the specific cell subpopulations that transcribe HIV RNA in different subsets of CD4+ T cells. In samples from treated and untreated HIV-infected patients, effector memory CD4+ T cells were the main cell population supporting HIV RNA transcription. The number of cells expressing HIV correlated with the plasma viral load, intracellular HIV RNA, and proviral DNA quantified by conventional methods and inversely correlated with the CD4+ T cell count and the CD4/CD8 ratio. We also found that after ex vivo infection of unstimulated PBMCs, HIV-infected T cells upregulated the expression of CD32. In addition, this new methodology detected increased numbers of primary cells expressing viral transcripts and proteins after ex vivo viral reactivation with latency reversal agents. This RNA FISH-flow technique allows the identification of the specific cell subpopulations that support viral transcription in HIV-1-infected individuals and has the potential to provide important information on the mechanisms of viral pathogenesis, HIV persistence, and viral reactivation.

  12. A Novel Single-Cell FISH-Flow Assay Identifies Effector Memory CD4+ T cells as a Major Niche for HIV-1 Transcription in HIV-Infected Patients

    Science.gov (United States)

    Grau-Expósito, Judith; Serra-Peinado, Carla; Miguel, Lucia; Navarro, Jordi; Curran, Adrià; Burgos, Joaquin; Ocaña, Imma; Ribera, Esteban; Torrella, Ariadna; Planas, Bibiana; Badía, Rosa; Castellví, Josep; Falcó, Vicenç; Crespo, Manuel

    2017-01-01

    ABSTRACT Cells that actively transcribe HIV-1 have been defined as the “active viral reservoir” in HIV-infected individuals. However, important technical limitations have precluded the characterization of this specific viral reservoir during both treated and untreated HIV-1 infections. Here, we used a novel single-cell RNA fluorescence in situ hybridization-flow cytometry (FISH-flow) assay that requires only 15 million unfractionated peripheral blood mononuclear cells (PBMCs) to characterize the specific cell subpopulations that transcribe HIV RNA in different subsets of CD4+ T cells. In samples from treated and untreated HIV-infected patients, effector memory CD4+ T cells were the main cell population supporting HIV RNA transcription. The number of cells expressing HIV correlated with the plasma viral load, intracellular HIV RNA, and proviral DNA quantified by conventional methods and inversely correlated with the CD4+ T cell count and the CD4/CD8 ratio. We also found that after ex vivo infection of unstimulated PBMCs, HIV-infected T cells upregulated the expression of CD32. In addition, this new methodology detected increased numbers of primary cells expressing viral transcripts and proteins after ex vivo viral reactivation with latency reversal agents. This RNA FISH-flow technique allows the identification of the specific cell subpopulations that support viral transcription in HIV-1-infected individuals and has the potential to provide important information on the mechanisms of viral pathogenesis, HIV persistence, and viral reactivation. PMID:28698276

  13. Temporomandibular Joint Disorders in Patients with Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Yi-Chun Lin

    2007-12-01

    Conclusion: There was a high prevalence of TMD in RA patients. The severity of TMD variably correlated with RA severity. Clinically, a high score of hand-joint space narrowing may serve as an early indicator of RA patients at risk of severe TMD. This may facilitate early management and prevent the functional impairment of the temporomandibular joint.

  14. Sodium excretion is higher in patients with rheumatoid arthritis than in matched controls

    National Research Council Canada - National Science Library

    Sarah Marouen; Guilhem du Cailar; Rachel Audo; Cedric Lukas; Gaelle Vial; Anne Tournadre; Emmanuel Barrat; Jean Ribstein; Bernard Combe; Jacques Morel; Claire I Daien

    2017-01-01

    .... We aimed to compare sodium intake in patients with rheumatoid arthritis (RA) vs. matched controls. Methods This case-control study included 24 patients with RA at diagnosis and 24 controls matched by age, gender and body mass index...

  15. Periodontitis in established rheumatoid arthritis patients: a cross-sectional clinical, microbiological and serological study

    Science.gov (United States)

    2012-01-01

    Introduction The association between rheumatoid arthritis (RA) and periodontitis is suggested to be linked to the periodontal pathogen Porphyromonas gingivalis. Colonization of P. gingivalis in the oral cavity of RA patients has been scarcely considered. To further explore whether the association between periodontitis and RA is dependent on P. gingivalis, we compared host immune responses in RA patients with and without periodontitis in relation to presence of cultivable P. gingivalis in subgingival plaque. Methods In 95 RA patients, the periodontal condition was examined using the Dutch Periodontal Screening Index for treatment needs. Subgingival plaque samples were tested for presence of P. gingivalis by anaerobic culture technique. IgA, IgG and IgM antibody titers to P. gingivalis were measured by ELISA. Serum and subgingival plaque measures were compared to a matched control group of non-RA subjects. Results A higher prevalence of severe periodontitis was observed in RA patients in comparison to matched non-RA controls (27% versus 12%, p periodontitis had higher DAS28 scores than RA patients with no or moderate periodontitis (p periodontitis had higher IgG- and IgM-anti P. gingivalis titers than non-RA controls with severe periodontitis (p periodontitis is related to severity of RA. RA patients with severe periodontitis have a more robust antibody response against P. gingivalis than non-RA controls, but not all RA patients have cultivable P. gingivalis. PMID:23075462

  16. Pleuropulmonary manifestation in patients with rheumatoid arthritis in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Omer S. B. Alamoudi

    2017-01-01

    Conclusions: Pneumonia, bronchiectasis, and interstitial lung disease were the most common abnormalities seen in RA patients. The presence of comorbidity, male gender, and ExRA was significantly associated with lung involvement.

  17. Eukaryotic transcription factors

    DEFF Research Database (Denmark)

    Staby, Lasse; O'Shea, Charlotte; Willemoës, Martin

    2017-01-01

    Gene-specific transcription factors (TFs) are key regulatory components of signaling pathways, controlling, for example, cell growth, development, and stress responses. Their biological functions are determined by their molecular structures, as exemplified by their structured DNA-binding domains...

  18. Depression in patients with rheumatoid arthritis: description, causes and mechanisms

    OpenAIRE

    Margaretten, Mary; Julian, Laura; Katz, Patricia; YELIN, EDWARD

    2011-01-01

    Two sets of contributory factors to depression among patients with rheumatoid arthritis (RA) are generally examined – the social context of the individual and the biologic disease state of that person’s RA. This article will review the evidence for both. RA affects patients both physically and psychologically. Comorbid depression is common with RA and leads to worse health outcomes. Low socioeconomic status, gender, age, race/ethnicity, functional limitation, pain and poor clinical status hav...

  19. Transcriptional regulation of metabolism.

    Science.gov (United States)

    Desvergne, Béatrice; Michalik, Liliane; Wahli, Walter

    2006-04-01

    Our understanding of metabolism is undergoing a dramatic shift. Indeed, the efforts made towards elucidating the mechanisms controlling the major regulatory pathways are now being rewarded. At the molecular level, the crucial role of transcription factors is particularly well-illustrated by the link between alterations of their functions and the occurrence of major metabolic diseases. In addition, the possibility of manipulating the ligand-dependent activity of some of these transcription factors makes them attractive as therapeutic targets. The aim of this review is to summarize recent knowledge on the transcriptional control of metabolic homeostasis. We first review data on the transcriptional regulation of the intermediary metabolism, i.e., glucose, amino acid, lipid, and cholesterol metabolism. Then, we analyze how transcription factors integrate signals from various pathways to ensure homeostasis. One example of this coordination is the daily adaptation to the circadian fasting and feeding rhythm. This section also discusses the dysregulations causing the metabolic syndrome, which reveals the intricate nature of glucose and lipid metabolism and the role of the transcription factor PPARgamma in orchestrating this association. Finally, we discuss the molecular mechanisms underlying metabolic regulations, which provide new opportunities for treating complex metabolic disorders.

  20. Dosimetry of bone metastases in targeted radionuclide therapy with alpha-emitting {sup 223}Ra-dichloride

    Energy Technology Data Exchange (ETDEWEB)

    Pacilio, Massimiliano [Azienda Ospealiera San Camillo Forlianini, Rome (Italy). Dept. of Medical Physics; Ventroni, Guido; Mango, Lucio [Azienda Ospealiera San Camillo Forlianini, Rome (Italy). Dept. of Nuclear Medicin; De Vincentis, Giuseppe; Di Castro, Elisabetta; Frantellizzi, Viviana; Follacchio, Giulia Anna; Garkavaya, Tatiana [Rome Univ. (Italy). Dept. of Radiological, Oncological and Anatomo Pathological Sciences; Cassano, Bartolomeo; Lorenzon, Leda [Rome Univ. (Italy). Postgraduate School of Medical Physics; Pellegrini, Rosanna; Pani, Roberto [Rome Univ. (Italy). Dept. of Molecular Medicine; Ialongo, Pasquale [Azienda Ospealiera San Camillo Forlianini, Rome (Italy). Dept. of Radiology

    2016-01-15

    Ra-dichloride is an alpha-emitting radiopharmaceutical used in the treatment of bone metastases from castration-resistant prostate cancer. Image-based dosimetric studies remain challenging because the emitted photons are few. The aim of this study was to implement a methodology for in-vivo quantitative planar imaging, and to assess the absorbed dose to lesions using the MIRD approach. The study included nine Caucasian patients with 24 lesions (6 humeral head lesions, 4 iliac wing lesions, 2 scapular lesions, 5 trochanter lesions, 3 vertebral lesions, 3 glenoid lesions, 1 coxofemoral lesion). The treatment consisted of six injections (one every 4 weeks) of 50 kBq per kg body weight. Gamma-camera calibrations for {sup 223}Ra included measurements of sensitivity and transmission curves. Patients were statically imaged for 30 min, using an MEGP collimator, double-peak acquisition, and filtering to improve the image quality. Lesions were delineated on {sup 99m}Tc-MDP whole-body images, and the ROIs superimposed on the {sup 223}Ra images after image coregistration. The activity was quantified with background, attenuation, and scatter correction. Absorbed doses were assessed deriving the S values from the S factors for soft-tissue spheres of OLINDA/EXM, evaluating the lesion volumes by delineation on the CT images. In 12 lesions with a wash-in phase the biokinetics were assumed to be biexponential, and to be monoexponential in the remainder. The optimal timing for serial acquisitions was between 1 and 5 h, between 18 and 24 h, between 48 and 60 h, and between 7 and 15 days. The error in cumulated activity neglecting the wash-in phase was between 2 % and 12 %. The mean effective half-life (T{sub 1/2eff}) of {sup 223}Ra was 8.2 days (range 5.5-11.4 days). The absorbed dose (D) after the first injection was 0.7 Gy (range 0.2-1.9 Gy). Considering the relative biological effectiveness (RBE) of alpha particles (RBE = 5), D{sub RBE} = 899 mGy/MBq (range 340-2,450 mGy/MBq). The

  1. An implanted $^{228}$Ra source for response characterization of bolometers

    CERN Multimedia

    TeO$_{2}$ crystals are used as bolometers in experiments searching for Double $\\beta$ Decay without emission of neutrinos. One of the most important issues in this extremely delicate kind of experiments is the discrimination of the background from the real signal. A deep knowledge of the bolometric response to $\\alpha$-particles is therefore needed to recognize and discard them, since it has been proven that $\\alpha$ surface contamination could be a major contribution in our background budget. We would like to use ISOLDE’s capability of implanting $^{228}$Ra to make a long-lived source feeding several monochromatic $\\alpha$- and recoiling nuclei, with little or no $\\alpha$-peak broadening due to the source itself, for tests of our detectors in Milano and Gran Sasso INFN National Lab.

  2. Loe-ära-loe! Eesti lastekirjandus 2007 / Jaanika Palm

    Index Scriptorium Estoniae

    Palm, Jaanika, 1973-

    2008-01-01

    Hainsalu, Lehte. Rõõmuratas (TEA Kirjastus) ; Vilep, Heiki. Katus sõidab (Vilep & Vallik) ; Vaiksoo, Jaanus. Onu Heino eksis ära (Koolibri) ; Vallik, Aidi. Tirtsti ja turtsti (TEA Kirjastus) ; Trull, Ilmar. Järvevaht ja joogivesi (Eesti Ekspressi Kirjastus) ; Kassel, Riina. Kalliralli (Ilo) ; Kumberg, Krista. Autopõnn Anto lemmiktoit (Koolibri) ; Ojar, Triinu. Suur must koer = Suur must pini (Päike ja Pilv) ; Pervik, Aino. Suleline, Puhuja ja must Munk (Tänapäev) ; Tomusk, Ilmar. Tere, Volli! (Tänapäev) ; Ausman, Piia. Tähtsad asjad (Haus Galerii) ; Ulman, Mihkel. Võlur taskust (Elmatar) ; Tangsoo, Jaan. Kotermann Juko imeline reis läbi Eestimaa (Varrak) ; Made, Reet. Tuhin tiibades (Koolibri) ; Vallik, Aidi. Mis sinuga juhtus, Ann? (Tänapäev)

  3. The Paran\\'a Ra'anga expedition

    CERN Document Server

    Gangui, Alejandro; Vena, Pablo

    2013-01-01

    Paran\\'a Ra'anga (the image of Paran\\'a, in Guaran\\'i) is the name of a cultural and scientific expedition that traveled the rivers: R\\'io de la Plata, Paran\\'a and Paraguay, from Buenos Aires to Asunci\\'on, during March 2010. The project brought together some forty scientists and artists from three countries in a slow and enriching cruise, putting in active contact actors from different backgrounds and disciplines -which usually run separately- in the framework of an unusual space-time experience. The project recovers the historical tradition of the trip as an instrument of knowledge and collaboration between the arts and sciences, necessary to build new ways of seeing and understanding the river and its banks. This article reports on the motivations of this project and its projection.

  4. Transcriptional profiles discriminate patients with pulmonary tuberculosis from non-tuberculous individuals depending on the presence of non-insulin diabetes mellitus.

    Science.gov (United States)

    Serrano, Carmen J; Cuevas-Córdoba, Betzaida; Macías-Segura, Noé; González-Curiel, Rosa Angélica; Martínez-Balderas, Víctor Yordani; Enciso-Moreno, Leonor; Small, Peter; Hernández-Pando, Rogelio; Enciso-Moreno, José Antonio

    2016-01-01

    Our objective was to identify transcriptional biomarkers in peripheral blood mononuclear cells (PBMC) that discriminate individuals with latent tuberculosis infection (LTBI) from those with pulmonary tuberculosis (PTB) in subjects with non-insulin-dependent diabetes mellitus (NIDDM) and in individuals without NIDDM. Using gene expression microarrays we identified differentially expressed genes from lungs of mice infected with Mycobacterium tuberculosis (Mtb) or a mutant (ΔsigH) representing a non-inflammatory model. Genes expressed in blood, with inflammatory related functions were evaluated in humans by RT-qPCR. NCF1 and ORM transcripts have the better discriminatory capacity to identify PTB subjects from LTBI and non-infected controls (NICs) independently of the presence of NIDDM. The sequential evaluation of the mRNA levels of NCF1 and ORM as multiple diagnostic tests showed 95% Sensitivity (Se) and 80% Specificity (Sp). In addition, FPR2 promises to be a good biomarker for the PTB detection in subjects with NIDDM (Se=100%; Sp=90%). Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Annual intakes of (226)Ra, (228)Ra and (40)K in staple foodstuffs from a high background radiation area in the southwest region of Cameroon.

    Science.gov (United States)

    Ele Abiama, P; Ben-Bolie, G H; Amechmachi, N; Najib, F; El Khoukhi, T; Owono Ateba, P

    2012-08-01

    Concentrations of naturally occurring radionuclides (226)Ra, (228)Ra and (40)K were determined in five most consumed vegetables in a high-level background radiation area (HLBRA) in the southwest region of Cameroon. A total of 25 foodstuff samples collected from Akongo, Ngombas, Awanda, Bikoué and Lolodorf rural districts were analyzed by gamma spectrometry. The average activity concentration values of (226)Ra, (228)Ra and (40)K were respectively 2.30, 1.50 and 140.40 Bq kg(-1) fresh-weights. The effective dose for individual consumption of the investigated foodstuff types was calculated on an estimated annual intake of such diets in the study area. The estimated total daily effective doses from the ingestion of the investigated foodstuffs for each studied long-life natural radionuclide were respectively 0.41 μSv for (226)Ra, 0.84 μSv for (228)Ra and 0.71 μSv for (40)K. The total annual effective dose was estimated at 0.70 mSv y(-1). (228)Ra (44%) and (40)K (36%) were found to be the main sources for internal irradiation which is very likely due to the specific uptake of these radionuclides by the studied plants. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Development of a liquid scintillation method for in vitro determination of {sup 226}Ra and {sup 228} Ra in bioassay samples

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, Paulo Cesar P.; Sousa, Wanderson O.; Juliao, Ligia M.Q.C.; Dantas, Bernardo M., E-mail: pcesar@ird.gov.b [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2011-07-01

    Radium isotopes are dispersed in the environment according to their physicochemical characteristics. The intake of {sup 226}Ra and {sup 228}Ra in humans can occur by inhalation and ingestion and the risk of internal exposure are related to their long half-lives, characteristics of the emission and biokinetics of the isotopes in the human body. The goal of this work is to develop a methodology for the analysis of {sup 226}Ra and {sup 228}Ra in excreta samples (urine and feces), using liquid scintillation technique. Excreta samples were provided by non-exposed humans for the purpose of standardizing the methodology and the establishment of a background level of radium excretion. Radium isotopes were concentrated and separated from the constituents of the sample by co-precipitation with barium sulphate. The precipitate of Ba(Ra)SO{sub 4} was filtrated and weighted for the determination of the chemical yield. The filter containing the precipitate was transferred to a scintillation vial. In the scintillation vial, 8 mL of water, 8 mL of Instagel XF and 4 mL of UltimaGold were added, forming a gel suspension, after stirring the solution. The {sup 226}Ra and {sup 228}Ra activities were determined 21 days after the precipitation of samples. The samples were counted in a liquid scintillation spectrometer. The technique presented adequate sensitivity and reproducibility for the analysis of urine and feces. The activities of {sup 226}Ra and {sup 228}Ra in excreta samples provide useful information for the identification of the main route of intake and for the assessment of the internal exposure of occupationally exposed workers and inhabitants of high background areas. (author)

  7. 21 CFR 12.98 - Official transcript.

    Science.gov (United States)

    2010-04-01

    ... a verbatim stenographic transcript of oral testimony and for necessary copies of the transcript. (b... the transcript of oral testimony. Corrections are permitted only for transcription errors. The...

  8. A window of opportunity for abatacept in RA: is disease duration an independent predictor of low disease activity/remission in clinical practice?

    Science.gov (United States)

    Harrold, Leslie R; Litman, Heather J; Connolly, Sean E; Kelly, Sheila; Hua, Winnie; Alemao, Evo; Rosenblatt, Lisa; Rebello, Sabrina; Kremer, Joel M

    2017-06-01

    The objective of the study was to examine whether disease duration independently predicts treatment response among biologic-naïve patients with rheumatoid arthritis (RA) initiating abatacept in clinical practice. Using the Corrona RA registry (February 2006-January 2015), biologic-naïve patients with RA initiating abatacept with 12-month (±3 months) follow-up and assessment of disease activity (Clinical Disease Activity Index [CDAI]) at initiation and at 12 months were identified. The primary outcome was mean change in CDAI (ΔCDAI) from baseline to 12 months. Secondary outcomes at 12 months included achievement of low disease activity (LDA; CDAI ≤10 in patients with moderate/high disease activity at initiation) and remission (CDAI ≤2.8 in patients with low, moderate or high disease activity at initiation). Linear and logistic regression analyses were performed to examine the relationship between disease duration and response to abatacept. There were 281 biologic-naïve patients with RA initiating abatacept (disease duration 0-2 years, n = 107; 3-5 years, n = 45; 6-10 years, n = 50; >10 years, n = 79). Increased disease duration was associated with older age (p = 0.047), and the median number of prior conventional disease-modifying antirheumatic drugs used was lowest in the 0- to 2-year duration group (p 10 years. In adjusted analyses, shorter disease duration was significantly associated with greater mean ΔCDAI (p = 0.015) and greater likelihood of achieving LDA (p = 0.048). In biologic-naïve patients with RA initiating abatacept, earlier disease (shorter disease duration) was associated with greater ΔCDAI and likelihood of achieving LDA.

  9. Keitel Functional Test for patients with rheumatoid arthritis: translation, reliability, validity, and responsiveness

    DEFF Research Database (Denmark)

    Holm, Bente; Jacobsen, S.; Skjodt, H.

    2008-01-01

    ) 15 patients with long-lasting (median=6 years) active RA, tested before and after 2, 6, and 14 weeks of anti-tumor necrosis factor alpha (TNF-alpha) inhibitor therapy, and (2) 35 patients with early (median=0.25 year) RA, tested at years 0, 0.5, 1, and 2. Twenty-three patients in the early RA group...

  10. Transcriptional activation of the human ucp1 gene in a rodent cell line. Synergism of retinoids, isoproterenol, and thiazolidinedione is mediated by a multipartite response element.

    Science.gov (United States)

    del Mar Gonzalez-Barroso, M; Pecqueur, C; Gelly, C; Sanchis, D; Alves-Guerra, M C; Bouillaud, F; Ricquier, D; Cassard-Doulcier, A M

    2000-10-13

    Uncoupling protein 1 (UCP1) is uniquely expressed in brown adipocytes and generates heat production by uncoupling respiration from ATP synthesis. The activatory effects of norepinephrine and retinoic acid (RA) on rodent ucp1 gene transcription have been well characterized. These effects are mediated by a 211-base pair (bp) enhancer which is also sufficient to restrict expression to brown adipose tissue. The molecular mechanisms controlling the transcription of the human ucp1 gene are unknown. In order to study the transcriptional regulation of the human gene, we set up chloramphenicol acetyltransferase constructs containing the entire or deleted 5' regions upstream of the transcriptional start site of the gene. These constructs were transiently transfected in a mouse cell line. A 350-bp hormone response region showing a significant homology with the rat ucp1 enhancer and located between the BclI polymorphic site and an AatII site (bp -3820/-3470) was detected. This region was sufficient to mediate the stimulation by RA and by combined treatments (RA + isoproterenol (ISO), RA + thiazolidinedione (TZD), or RA + ISO + TZD). The highest stimulation, a 26-fold increase in basal activity, was obtained by RA + ISO + TZD treatment. In contrast to the rodent gene, under our conditions, the effect of ISO and/or TZD is dependent on RA stimulation. Analysis of 105 bp inside the 350-bp element by site-directed mutagenesis and gel retardation experiments demonstrated that a multipartite response element mediates the drug stimulation. This region binds RARs and RXRs nuclear factors, CREB/ATF factors, and also PPARgamma despite the absence of a consensus peroxisome-proliferator response element. The activation of the human ucp1 gene transcription by certain hormones or drugs, and the identification of the cis-elements involved, will help to identify new compounds activating fat oxidation and energy expenditure in humans.

  11. The Expression of Nuclear Transcription Factor Kappa B (NF-κB) in the Case of Critically Ill Polytrauma Patients with Sepsis and Its Interactions with microRNAs.

    Science.gov (United States)

    Papurica, Marius; Rogobete, Alexandru Florin; Sandesc, Dorel; Cradigati, Carmen Alina; Sarandan, Mirela; Crisan, Dan Ciprian; Horhat, Florin George; Boruga, Ovidiu; Dumache, Raluca; Nilima, Kundnani Rajpal; Nitu, Razvan; Stanca, Horia; Bedreag, Ovidiu Horea

    2016-08-01

    Critical polytrauma patients present a series of pathophysiological disturbances, biochemical and molecular dysfunction, which comprise to be the major cause of intensive care unit admission. In regard to molecular damage, there exists a series of factors, which all together contribute to the aggravation of the clinical status leading to increased mortality rate in these patients. One of the most important biochemical factors involved is the nuclear transcription factor B (NF-κB). Impaired NF-κB functioning is reflected on the clinical status of the patient through increased production of pro-inflammatory molecule, leading to multiple organ dysfunction syndrome. In addition to this, through microRNAs interactions, various pathophysiological as well as biochemical disturbances are produced, which altogether further reduce the patient's survival rate. In this paper, we would like to present the modifications seen in the expression of NF-κB in critically polytraumatized patients with sepsis. In additions to this, we would like to discuss the correlation between the microRNAs and its further implications in clinical status of these patients.

  12. Impact of foliage on LoRa 433MHz propagation in tropical environment

    Science.gov (United States)

    Ahmad, Khairol Amali; Salleh, Mohd Sharil; Segaran, Jivitraa Devi; Hashim, Fakroul Ridzuan

    2018-02-01

    LoRa is being considered as one of the promising system for Low-Power-Wide-Area-Network (LPWAN) to support the growth of Internet of Things (IoT) applications. Designed to operate in the industrial, scientific and medical (ISM) bands, LoRa had been tested and evaluated mainly in Europe and US in the 868 MHz and 915 MHz modulation bands. Using chirp spread spectrum technology, LoRa is expected to be robust against degredation. This paper provides some early results in the performance of LoRa signal propagation of 433 MHz modulation in tropical foliage environments.

  13. First Measurement of the Atomic Electric Dipole Moment of $^{225}$Ra

    CERN Document Server

    Parker, R H; Kalita, M R; Lemke, N D; Bailey, K G; Bishof, M N; Greene, J P; Holt, R J; Korsch, W; Lu, Z -T; Mueller, P; O'Connor, T P; Singh, J T

    2015-01-01

    The radioactive radium-225 ($^{225}$Ra) atom is a favorable case to search for a permanent electric dipole moment (EDM). Due to its strong nuclear octupole deformation and large atomic mass, $^{225}$Ra is particularly sensitive to interactions in the nuclear medium that violate both time-reversal symmetry and parity. We have developed a cold-atom technique to study the spin precession of $^{225}$Ra atoms held in an optical dipole trap, and demonstrated the principle of this method by completing the first measurement of its atomic EDM, reaching an upper limit of $|$$d$($^{225}$Ra)$|$ $<$ $5.0\\!\\times\\!10^{-22}$ $e \\cdot$cm (95$\\%$ confidence).

  14. Tracking suspended particle transport via radium isotopes ((226)Ra and (228)Ra) through the Apalachicola-Chattahoochee-Flint River system.

    Science.gov (United States)

    Peterson, Richard N; Burnett, William C; Opsahl, Stephen P; Santos, Isaac R; Misra, Sambuddha; Froelich, Philip N

    2013-02-01

    Suspended particles in rivers can carry metals, nutrients, and pollutants downstream which can become bioactive in estuaries and coastal marine waters. In river systems with multiple sources of both suspended particles and contamination sources, it is important to assess the hydrologic conditions under which contaminated particles can be delivered to downstream ecosystems. The Apalachicola-Chattahoochee-Flint (ACF) River system in the southeastern United States represents an ideal system to study these hydrologic impacts on particle transport through a heavily-impacted river (the Chattahoochee River) and one much less impacted by anthropogenic activities (the Flint River). We demonstrate here the utility of natural radioisotopes as tracers of suspended particles through the ACF system, where particles contaminated with arsenic (As) and antimony (Sb) have been shown to be contributed from coal-fired power plants along the Chattahoochee River, and have elevated concentrations in the surficial sediments of the Apalachicola Bay Delta. Radium isotopes ((228)Ra and (226)Ra) on suspended particles should vary throughout the different geologic provinces of this river system, allowing differentiation of the relative contributions of the Chattahoochee and Flint Rivers to the suspended load delivered to Lake Seminole, the Apalachicola River, and ultimately to Apalachicola Bay. We also use various geochemical proxies ((40)K, organic carbon, and calcium) to assess the relative composition of suspended particles (lithogenic, organic, and carbonate fractions, respectively) under a range of hydrologic conditions. During low (base) flow conditions, the Flint River contributed 70% of the suspended particle load to both the Apalachicola River and the bay, whereas the Chattahoochee River became the dominant source during higher discharge, contributing 80% of the suspended load to the Apalachicola River and 62% of the particles entering the estuary. Neither of these hydrologic

  15. The transcription of MGAT4A glycosyl transferase is increased in white cells of peripheral blood of Type 2 Diabetes patients

    Directory of Open Access Journals (Sweden)

    Cruz Miguel

    2007-10-01

    Full Text Available Abstract Background Human glycosylase IV is involved in GLUT2 transporter regulation in pancreatic β cells. A KO of this gene along with a high fat diet in a mice model has been associated with the development of type 2 diabetes (T2D. The aims of this study were to measure and compare the MGAT4A mRNA levels in white blood cells (WBC from T2D subjects and healthy subjects (T2NB, and to measure the half-life of the MGAT4A mRNA. Results We studied a sample of 73 individuals, 40 T2D subjects and 33 T2NB subjects. Anthropometrical and biochemical profiles were registered. The MGAT4A mRNA levels in WBC and the transcript half-life in Jurkat T cells were determined by Real-Time PCR. A blood differential cell counting was made for each individual. Cell counting showed T2D subjects exhibited an increased number of WBC compared to T2NB subjects (P = 0.0001. Biochemical parameters such as fasting glucose (P = 0.0001, and triglycerides (P = 0.002 were statistically significant. T2D subjects had 4.2-fold more MGAT4A transcript compared to T2NB subjects (P = 0.002. The MGAT4A mRNA had a half-life of 2.04 h in Jurkat T cells. Conclusion The results of this work suggest that in T2D subjects, high levels of glucose and triglycerides are accompanied by an increase on MGAT4A mRNA levels and WBC count; condition that suggests a pro-inflammatory state due to a chronic metabolic stress.

  16. Regulation of Transcript Elongation

    Science.gov (United States)

    Belogurov, Georgiy A.; Artsimovitch, Irina

    2015-01-01

    Bacteria lack subcellular compartments and harbor a single RNA polymerase that synthesizes both structural and protein-coding RNAs, which are cotranscriptionally processed by distinct pathways. Nascent rRNAs fold into elaborate secondary structures and associate with ribosomal proteins, whereas nascent mRNAs are translated by ribosomes. During elongation, nucleic acid signals and regulatory proteins modulate concurrent RNA-processing events, instruct RNA polymerase where to pause and terminate transcription, or act as roadblocks to the moving enzyme. Communications among complexes that carry out transcription, translation, repair, and other cellular processes ensure timely execution of the gene expression program and survival under conditions of stress. This network is maintained by auxiliary proteins that act as bridges between RNA polymerase, ribosome, and repair enzymes, blurring boundaries between separate information-processing steps and making assignments of unique regulatory functions meaningless. Understanding the regulation of transcript elongation thus requires genome-wide approaches, which confirm known and reveal new regulatory connections. PMID:26132790

  17. Deciphering Transcriptional Regulation

    DEFF Research Database (Denmark)

    Valen, Eivind

    control spanning the range from completely muted to cranked up to maximum. The volume, in this case, is the production rate of proteins. This production is the result of a two step procedure: i) transcription, in which a small part of DNA from the genome (a gene) is transcribed into an RNA molecule (an mRNA...... prediction and provide tools that help investigators use these. In addition, a de novo motif discovery tool was developed that locates these patterns in DNA sequences. This compared favorably to many contemporary methods. A novel experimental method, cap-analysis of gene expression (CAGE), was recently......); and ii) translation, in which the mRNA is translated into a protein. This thesis focus on the ¿rst of these steps, transcription, and speci¿cally the initiation of this. Simpli¿ed, initiation is preceded by the binding of several proteins, known as transcription factors (TFs), to DNA. This takes place...

  18. Coccidioides immitis meningitis in a patient with hyperimmunoglobulin E syndrome due to a novel mutation in signal transducer and activator of transcription.

    Science.gov (United States)

    Powers, Annie E; Bender, Jeffrey M; Kumánovics, Attila; Ampofo, Krow; Augustine, Nancy; Pavia, Andrew T; Hill, Harry R

    2009-07-01

    Hyperimmunoglobulin E syndrome (HIES) is a rare primary immunodeficiency characterized by recurrent skin and lung infections. We report the first case of Coccidioides immitis meningitis in a patient with HIES. Coccidioides should be included in the differential diagnosis for central nervous system infections in HIES patients.

  19. IL-15 expression on RA synovial fibroblasts promotes B cell survival.

    Directory of Open Access Journals (Sweden)

    Marta Benito-Miguel

    Full Text Available INTRODUCTION: The purpose of this study was to examine the role of RA Synovial Fibroblast (RASFib IL-15 expression on B cell survival. METHODS: Magnetically sorted peripheral blood memory B cells from 15 healthy subjects were cocultured with RASFib. RESULTS: RASFib constitutively expressed membrane IL-15. Survival of isolated B cells cultured for 6 days, below 5%, was extended in coculture with RASFib to 52+/-8% (p<0.001. IL-15 neutralizing agents but not isotype controls, reduced this rate to 31+/-6% (p<0.05. Interestingly, rhIL-15 had no effect on isolated B cells but significantly increased their survival in coculture with RASFib. In parallel, B cell IL-15R chains were upregulated in cocultures. BAFF and VCAM-1, that are expressed on RASFib, were tested as potential candidates involved in upregulating B cell IL-15R. Culture of B cells in the presence of rhBAFF or rhVCAM-1 resulted in significantly increased survival, together with upregulation of all three IL-15R chains; in parallel, rhIL-15 potentiated the anti-apoptotic effect of BAFF and VCAM-1. Both BAFF and VCAM-1 neutralizing agents downmodulated the effect of RASFib on B cell survival and IL-15R expression. In parallel, rhIL-15 had a lower effect on the survival of B cells cocultured with RASFib in the presence of BAFF or VCAM-1 neutralizing agents. Peripheral blood B cells from 15 early RA patients demonstrated an upregulated IL-15R and increased survival in cocultures. CONCLUSION: IL-15 expression on RASFib significantly contributes to the anti-apoptotic effect of RASFib on B cells. IL-15 action is facilitated by BAFF and VCAM-1 expressed on RASFib, through an upregulation of IL-15R chains.

  20. Sedentary behaviour in patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Thomsen, Tanja; Beyer, Nina; Aadahl, Mette

    2015-01-01

    BACKGROUND: Despite increasing interest in investigating sedentary behaviour (SB) in the general population and in patients with rheumatoid arthritis (RA), there is little documentation of the subjective experiences of SB in patients with RA. This study aimed to examine how patients with RA...... modification of physical activity level causing increase in SB, especially during periods of disease flare. Prioritizing and planning of SB also functioned as part of self-management strategies. 3) It has nothing to do with my arthritis; for some patients, SB was not related to RA, but simply reflected a way...

  1. Impossible cartographies: approaching Raúl Ruiz’s cinema

    Directory of Open Access Journals (Sweden)

    Michael Goddard

    2013-06-01

    Full Text Available Raúl Ruiz (1931-2011, while considered one of the world’s most significant filmmakers by several film critics, is yet to be the subject of any thorough academic engagement with his work in English. My book Impossible Cartographies sets out on this task by mapping, as fully as possible, Ruiz’s cinematic trajectory across more than five decades of prolific work ranging from his earliest work in Chile to high budget ‘European’ costume dramas culminating in the recent Mysteries of Lisbon (2010. It does this by treating Ruiz’s work, with its surrealist, magic realist, popular cultural and neo-Baroque sources, as a type of ‘impossible’ cinematic cartography, mapping real, imaginary and virtual spaces, and crossing between different cultural contexts, aesthetic strategies, and technical media. In argues that across the different phases of Ruiz’s work identified, there are key continuities such as the invention of singular cinematic images and the interrogation of their possible and impossible combinations. This article will present some of the key themes of Ruiz’s cinema and use ideas of virtual cartography, tableaux vivants and the neo-baroque to illuminate a range of Ruiz’s films from the Hypothesis of the Stolen Painting (1978 to Mysteries of Lisbon, his last major project.

  2. Precision measurement of the RaE shape factor

    Energy Technology Data Exchange (ETDEWEB)

    Grau, C.A. [CIEMAT, Madrid (Spain). Direccion de Tecnologia; Grau, M.A. [Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas (CIEMAT), Madrid (Spain). Inst. de Investigacion Basica

    1996-01-01

    We apply to RaE a new method to determine the shape factor coefficients of pure beta transitions with energies over the Cherenkov threshold of water. This method is based on the precision measurement of one observable, the ft-value, and two quasi-observables, the Cherenkov counting efficiency and the position of the maximum point of the liquid-scintillation logarithmic pulse-height spectrum. We found for the revised shape factor function that the ground state wave function vertical stroke {sup 210}Bi, 1{sup -} right angle is the combination of the three wave functions vertical stroke 1h{sub 9/2}2g{sub 9/2} right angle, vertical stroke 1h{sub 9/2} 1i{sub 11/2} right angle and vertical stroke 1h{sub 9/2}2g{sub 7/2} right angle. This result is also confirmed by the excellent agreement we obtain with experiment for the longitudinal electron polarization. (orig.).

  3. RA diagnostics applying optical tomography in frequency domain

    Science.gov (United States)

    Klose, Alexander D.; Prapavat, Viravuth; Minet, Olaf; Beuthan, Juergen; Mueller, Gerhard J.

    1998-01-01

    Our aim is to reconstruct the optical parameters in a slice of a finger joint phantom for further investigations about rheumatoid arthritis (RA). Therefore, we have developed a flexible NIR scanning system in order to collect amplitude and phase delay of photon density waves in frequency-domain. A cylindrical finger joint phantom was embedded in a container of Intralipid solution due to the application of an inverse method for infinite geometry. The joint phantom was investigated by a laser beam obtaining several projections. The average optical parameters of each projection was calculated. Using different reconstruction techniques, e.g. ART and SIRT with a special projection operator, we reconstructed the optical parameters in a slice. The projection operator can be heuristically described by a photon path density function of a homogeneous media with infinite geometry. Applied to an object with an unknown distribution of optical parameters it calculates the expectation value of the investigated object. The potentials and limits of these fast reconstruction methods will be presented.

  4. Background Characterization for Thermal Ion Release Experiments with 224Ra

    Energy Technology Data Exchange (ETDEWEB)

    Kwong, H.; /Stanford U., Phys. Dept.; Rowson, P.; /SLAC

    2005-12-15

    The Enriched Xenon Observatory for neutrinoless double beta decay uses {sup 136}Ba identification as a means for verifying the decay's occurrence in {sup 136}Xe. A current challenge is the release of Ba ions from the Ba extraction probe, and one possible solution is to heat the probe to high temperatures to release the ions. The investigation of this method requires a characterization of the alpha decay background in our test apparatus, which uses a {sup 228}Th source that produces {sup 224}Ra daughters, the ionization energies of which are similar to those of Ba. For this purpose, we ran a background count with our apparatus maintained at a vacuum, and then three counts with the apparatus filled with Xe gas. We were able to match up our alpha spectrum in vacuum with the known decay scheme of {sup 228}Th, while the spectrum in xenon gas had too many unresolved ambiguities for an accurate characterization. We also found that the alpha decays occurred at a near-zero rate both in vacuum and in xenon gas, which indicates that the rate was determined by {sup 228}Th decays. With these background measurements, we can in the future make a more accurate measurement of the temperature dependency of the ratio of ions to neutral atoms released from the hot surface of the probe, which may lead to a successful method of Ba ion release.

  5. Rhythm quantization for transcription

    NARCIS (Netherlands)

    Cemgil, A.T.; Desain, P.W.M.; Kappen, H.J.

    1999-01-01

    Automatic Music Transcription is the extraction of an acceptable notation from performed music. One important task in this problem is rhythm quantization which refers to categorization of note durations. Although quantization of a pure mechanical performance is rather straightforward, the task

  6. Actinomycin and DNA transcription.

    OpenAIRE

    Sobell, H M

    1985-01-01

    Recent advances in understanding how actinomycin binds to DNA have suggested its mechanism of action. Actinomycin binds to a premelted DNA conformation present within the transcriptional complex. This immobilizes the complex, interfering with the elongation of growing RNA chains. The model has a number of implications for understanding RNA synthesis.

  7. Actinomycin and DNA transcription.

    Science.gov (United States)

    Sobell, H M

    1985-01-01

    Recent advances in understanding how actinomycin binds to DNA have suggested its mechanism of action. Actinomycin binds to a premelted DNA conformation present within the transcriptional complex. This immobilizes the complex, interfering with the elongation of growing RNA chains. The model has a number of implications for understanding RNA synthesis. Images PMID:2410919

  8. transcriptional regulatory element

    African Journals Online (AJOL)

    ARL

    2012-06-12

    Jun 12, 2012 ... Further test of the effect of WPRE on plasmid-mediated gene expression with two therapeutic proteins showed substantial ... promoter-independent, and provide valuable information to improve vectors for efficient and stable gene expression in ... transcriptional events concerning the recombinant. mRNA.

  9. Bayesian Music Transcription

    NARCIS (Netherlands)

    Cemgil, A.T.

    2004-01-01

    Music transcription refers to extraction of a human readable and interpretable description from a recording of a music performance. The final goal is to implement a program that can automatically infer a musical notation that lists the pitch levels of notes and corresponding score positions in any

  10. Actinomycin and DNA transcription

    Energy Technology Data Exchange (ETDEWEB)

    Sobell, H.M.

    1985-08-01

    Recent advances in understanding how actinomycin binds to DNA have suggested its mechanism of action. Actinomycin binds to a premelted DNA conformation present within the transcriptional complex. This immobilizes the complex, interfering with the elongation of growing RNA chains. The model has a number of implications for understanding RNA synthesis.

  11. HMM_RA: An Improved Method for Alpha-Helical Transmembrane Protein Topology Prediction

    Directory of Open Access Journals (Sweden)

    Changhui Yan

    2008-01-01

    Full Text Available α-helical transmembrane (TM proteins play important and diverse functional roles in cells. The ability to predict the topology of these proteins is important for identifying functional sites and inferring function of membrane proteins. This paper presents a Hidden Markov Model (referred to as HMM_RA that can predict the topology of α-helical transmembrane proteins with improved performance. HMM_RA adopts the same structure as the HMMTOP method, which has five modules: inside loop, inside helix tail, membrane helix, outside helix tail and outside loop. Each module consists of one or multiple states. HMM_RA allows using reduced alphabets to encode protein sequences. Thus, each state of HMM_RA is associated with n emission probabilities, where n is the size of the reduced alphabet set. Direct comparisons using two standard data sets show that HMM_RA consistently outperforms HMMTOP and TMHMM in topology prediction. Specifically, on a high-quality data set of 83 proteins, HMM_RA outperforms HMMTOP by up to 7.6% in topology accuracy and 6.4% in α-helices location accuracy. On the same data set, HMM_RA outperforms TMHMM by up to 6.4% in topology accuracy and 2.9% in location accuracy. Comparison also shows that HMM_RA achieves comparable performance as Phobius, a recently published method.

  12. Persistence of octupole correlations in sup 2 sup 3 sup 1 Ra

    CERN Document Server

    Fraile-Prieto, L M; Mach, H; Boutami, R; Aas, A J; Fogelberg, B; García-Raffi, L M; Grant, I S; Gulda, K; Hageboe, E; Kurcewicz, W; Kvasil, J; López, M J; Løvhøiden, G; Martínez, T; Rubio, B; Taín, J L; Tengblad, O

    2001-01-01

    The structure of sup 2 sup 3 sup 1 Ra, the heaviest odd Ra nucleus currently accessible for detailed spectroscopic investigation, has been studied in the beta sup - decay of sup 2 sup 3 sup 1 Fr. The main purpose has been to verify whether fast B(E1) rates and significant octupole correlations recently established in sup 2 sup 2 sup 9 Ra persist in sup 2 sup 3 sup 1 Ra. The excited states in sup 2 sup 3 sup 1 Ra have been determined for the first time. Spins and parities have been deduced from conversion electron measurements, while level half-lives in the ps and ns ranges have been measured with the Advanced Time Delayed beta gamma gamma(t) method. The moderately fast B(E1) rates found for transitions connecting the lowest-lying K suppi=5/2 sup+- and K suppi=1/2 sup+- bands, reveal the persistence of octupole collective effects in sup 2 sup 3 sup 1 Ra, although the B(E1) rates are lower than in sup 2 sup 2 sup 9 Ra. These findings reinforce the differences in the B(E1) systematics between isotonic Ra and Th ...

  13. Association of Variants in IL2RA With Progression of Joint Destruction in Rheumatoid Arthritis

    NARCIS (Netherlands)

    Knevel, R.; de Rooy, D. P. C.; Zhernakova, A.; Grondal, G.; Krabben, A.; Steinsson, K.; Wijmenga, C.; Cavet, G.; Toes, R. E. M.; Huizinga, T. W. J.; Gregersen, P. K.; van der Helm-van Mil, A. H. M.

    ObjectiveHeritability studies have suggested an important role of genetic predisposition in the progression of joint destruction in rheumatoid arthritis (RA); the heritability is estimated at 45-58%. Several single-nucleotide polymorphisms (SNPs) have been identified as being associated with RA

  14. Demand Side Management Using the Internet of Energy Based on LoRaWAN Technology

    DEFF Research Database (Denmark)

    Shahryari, Kolsoom; Anvari-Moghaddam, Amjad; Shahryari, Shadi

    2017-01-01

    into cloud because of a long range, low power, wide area and low bit rate wireless telecommunication system which is called LoRaWAN. All devices in fog domain are connected by long range wide area network (LoRa) into a smart gateway. The gateway which bridges fog domain and cloud, is introduced...

  15. Gender, body mass index and rheumatoid arthritis disease activity: results from the QUEST-RA Study

    DEFF Research Database (Denmark)

    Jawaheer, D; Olsen, J; Lahiff, M

    2010-01-01

    To investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific manner.......To investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific manner....

  16. Selective 226Ra2+ ionophores provided by self-assembly of guanosine and isoguanosine derivatives.

    Science.gov (United States)

    van Leeuwen, Fijs W B; Verboom, Willem; Shi, Xiaodong; Davis, Jeffery T; Reinhoudt, David N

    2004-12-22

    The self-assembled guanosine (G 1)-based hexadecamers and isoguanosine (isoG 2)-based decamers are excellent 226Ra2+ selective ionophores even in the presence of excess alkali (Na+, K+, Rb+, and Cs+) and alkaline earth (Mg2+, Ca2+, Sr2+, and Ba2+) cations over the pH range 3-11. G 1 requires additional picrate anions to provide a neutral assembly, whereas the isoG 2 assembly extracts 226Ra2+ cations without any such additives. Both G 1-picrate and isoG 2 assemblies show 226Ra2+ extraction even at a 0.35 x 10(6) fold excess of Na+, K+, Rb+, Cs+, Mg2+, or Ca2+ (10(-2) M) to 226Ra2+ (2.9 x 10(-8) M) and at a 100-fold salt to ionophore excess. In the case of the G 1-picrate assembly, more competition was observed from Sr2+ and Ba2+, as extraction of 226Ra2+ ceased at an M2+/226Ra2+ ratio of 10(6) and 10(4), respectively. With the isoG 2 assembly, 226Ra2+ extraction also occurred at a Sr2+/226Ra2+ ratio of 10(6) but ceased at a 10(6) excess of Ba2+. The results clearly demonstrate the power of molecular self-assembly for the construction of highly selective ionophores.

  17. {sup 226}Ra measurement by thermal ionisation mass spectrometry: Use of {sup 226}Ra and {sup 14}C for groundwater dating

    Energy Technology Data Exchange (ETDEWEB)

    Dever, L. [Universite Paris-SUD, Orsay, (France). Lab d`Hydrologie et Geochemie Isotopique; Hillaire-Marcel, C. [Geotop, Universite du Quebec a Montreal, Montreal (Canada)

    1997-10-01

    Recent developments in thermal ionisation mass spectrometry (TIMS) and in chemical separation Ra and Ba allow to analyse {sup 226}Ra on smaller water samples (<200 ml) than with conventional counting techniques (10{sup 3} litres). The sampling has been realised on the Chalk aquifer of the Paris basin. The water samples have been collected in the unsaturated zone using in situ filtering devices and in the unconfined and confined parts of the aquifer in the boreholes used for public water supply. {sup 226}Ra contents vary from 0.064{+-}0.02 dpm/kg (n=6) in the unsaturated zone to 0.119{+-}0.069 dpm/kg (n=7) in the unconfined aquifer and 0.319{+-}0.057 dpm/kg (n=9) in the confined aquifer. For all the samples the {sup 226}Ra/{sup 238}U activity ratios are much lower than the secular equilibrium. This points out that the two isotopes have different input function in the water during the mineralisation of the solution. The good correlation (r{sup 2}=0.9) between the {sup 226}Ra and Sr indicates that dissolution of Chalk is the dominant mechanism of mineralisation in {sup 226}Ra of the solution. In the Chalk the mineralisation of the water occurs in the first metres of the unsaturated zone, during the water percolation the water rock interaction takes place through dissolution and precipitation of calcite in a non steady state. According to his distribution coefficient Sr is then a better tracer of dissolution/precipitation process than Ba. Using a geochemical model based on {sup 226}Ra/Sr and Sr/Ca ratios an `age` of the water could be determined. With {sup 226}Ra half life of 1620 years we obtain `ages` varying from 150 years to 1950 years in the unconfined aquifer. For the confined part of the aquifer where the redox condition is different it is necessary to use a geochemical model based on the U concentration in the water, the {sup 226}Ra gives in such case ages varying from 1.8ka to 12.8ka. The radiocarbon ages obtained through usual chemical and/or isotopic models

  18. A non-synonymous single-nucleotide polymorphism in the gene encoding Toll-like Receptor 3 (TLR3) is associated with sero-negative Rheumatoid Arthritis (RA) in a Danish population

    DEFF Research Database (Denmark)

    Laska, Magdalena Janina; Hansen, Bettina; Troldborg, Anne

    2014-01-01

    BACKGROUND: It has been suggested that polymorphisms in Toll-like Receptors (TLRs) are associated with Rheumatoid Arthritis (RA), but the implicated alleles have differed between studies. The aim of this investigation was to explore whether polymorphisms of TLR genes are associated with RA...... in a predominantly Caucasian population from Denmark using a case-control approach. FINDINGS: DNA samples (3 university hospital outpatient clinics) were obtained from patients with RA (n = 704) and healthy controls (n = 639) in a Danish population. TLR single nucleotide polymorphisms (SNPs) were selected based...... on the previously reported associations with chronic autoimmune diseases. Genotyping for the TLR SNPs was performed using Sequenom Multiplex technology.We identified one SNP in TLR3, [(rs3775291, P = 0.02, OR (95% CI) 1.31 (1.1087-1.5493)] significantly associated with the whole RA cohort. Subgroup analysis...

  19. Ion neutralisation mass-spectrometry route to radium monofluoride (RaF)

    CERN Document Server

    Isaev, T A; Willmann, L; Berger, R

    2013-01-01

    The diatomic molecule radium monofluoride (RaF) has recently been proposed as a versatile probe for physics beyond the current standard model. Herein, a route towards production of a RaF molecular beam via radium ions is proposed. It takes advantage of the special electronic structure expected for group 2 halides and group 2 hydrides: The electronic ground state of neutral RaF and its monocation differ in occupation of a non-bonding orbital of $\\sigma$ symmetry. This implies similar equilibrium distances and harmonic vibrational wavenumbers in the two charge states and thus favourable Franck--Condon factors for neutralisation without dissociation in neutralising collisions. According to the calculated ionisation energy of RaF, charge exchange collisions of RaF$^+$ with sodium atoms are almost iso-enthalpic, resulting in large cross-sections for the production of neutral radium monofluoride.

  20. Distribution of 226Ra Radionuclide in Upwelling Event Off Ulsan, Gampo and Pohang, Korea

    Directory of Open Access Journals (Sweden)

    Muslim

    2009-07-01

    Full Text Available Upwelling is an important event in the sea for it makes the area to become more productive. The objective of this study is to determine the distribution of radium-226 as radiotoxic in the upwelling area in the summer season. Measurements of the horizontal and vertical activities of 226Ra in the Ulsan, Gampo and Pohang waters were conducted in June, August 1999 and June 2000 when the upwelling event was expected to occur. Water temperature, salinity and dissolved oxygen (DO were also measured concurrently. The thermocline layer or the layer where the temperature decreased drastically occurred at a depth between 30 m to 100 m for samples dated June 1999 and 30 m to more than 100 m for samples dated August 1999 and June 2000. The salinity decreased with depth but the DO concentration increased in this layer. The condition affected the vertical distribution of 226Ra in the study area, where the 226Ra activities showed to be relatively homogeneous vertically in each station. This indicates that the upwelling which occurred in the study area was capable to distribute the 226Ra activities from the bottom to the surface. Thus, the 226Ra distribution at that time did not increase with depth, opposite to what usually occurs in the ocean at normal condition. The 226Ra activities also did not decrease after elapsed time of one year, in fact, it increased. However, horizontally the 226Ra activities decreased with increasing distance from the coastal zone. Based on these results, it can be concluded that the upwelling event in the Ulsan, Gampo and Pohang was effective for increasing the 226Ra activities and was capable to create homogeneous 226Ra activities from the bottom to the surface in the water column, and the source of 226Ra was likely to originate from outside area (i.e. coastal zone and bottom area.

  1. Mitochondrial haplogroups in patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Duhn, Pernille Hurup; Sode, Jacob; Hagen, Christian Munch

    2017-01-01

    Objective To describe the distribution of specific mitochondrial DNA (mtDNA) haplogroups (hgs) in a cohort of patients with rheumatoid arthritis (RA). Methods Two-hundred nineteen consecutive patients with RA had mtDNA isolated from their blood, sequenced and haplotyped. Patients were diagnosed...

  2. Transcriptional responses in the adaptation to ischaemia-reperfusion injury: a study of the effect of ischaemic preconditioning in total knee arthroplasty patients

    LENUS (Irish Health Repository)

    Murphy, Terence

    2010-05-10

    Abstract Background Ischaemic preconditioning (IPC) has emerged as a method of reducing ischaemia-reperfusion injury. However, the complex mechanism through which IPC elicits this protection is not fully understood. The aim of this study was to investigate the genomic response induced by IPC in muscle biopsies taken from the operative leg of total knee arthroplasty patients in order to gain insight into the IPC mechanism. Methods Twenty patients, undergoing primary total knee arthroplasty, were randomly assigned to IPC (n = 10) and control (n = 10) groups. Patients in the IPC group received ischaemic preconditioning immediately prior to surgery. IPC was induced by three five-minute cycles of tourniquet insufflation interrupted by five-minute cycles of reperfusion. A muscle biopsy was taken from the operative knee of control and IPC-treated patients at the onset of surgery and, again, at one hour into surgery. The gene expression profile of muscle biopsies was determined using the Affymetrix Human U113 2.0 microarray system and validated using real-time polymerase chain reaction (RT-PCR). Measurements of C-reactive protein (CRP), erythrocyte sedimentation (ESR), white cell count (WCC), cytokines and haemoglobin were also made pre- and post-operatively. Results Microarray analysis revealed a significant increase in the expression of important oxidative stress defence genes, immediate early response genes and mitochondrial genes. Upregulation of pro-survival genes was also observed and correlated with a downregulation of pro-apoptotic gene expression. CRP, ESR, WCC, cytokine and haemoglobin levels were not significantly different between control and IPC patients. Conclusions The findings of this study suggest that IPC of the lower limb in total knee arthroplasty patients induces a protective genomic response, which results in increased expression of immediate early response genes, oxidative stress defence genes and pro-survival genes. These findings indicate that

  3. Transcriptional responses in the adaptation to ischaemia-reperfusion injury: a study of the effect of ischaemic preconditioning in total knee arthroplasty patients

    Directory of Open Access Journals (Sweden)

    Doran Peter P

    2010-05-01

    Full Text Available Abstract Background Ischaemic preconditioning (IPC has emerged as a method of reducing ischaemia-reperfusion injury. However, the complex mechanism through which IPC elicits this protection is not fully understood. The aim of this study was to investigate the genomic response induced by IPC in muscle biopsies taken from the operative leg of total knee arthroplasty patients in order to gain insight into the IPC mechanism. Methods Twenty patients, undergoing primary total knee arthroplasty, were randomly assigned to IPC (n = 10 and control (n = 10 groups. Patients in the IPC group received ischaemic preconditioning immediately prior to surgery. IPC was induced by three five-minute cycles of tourniquet insufflation interrupted by five-minute cycles of reperfusion. A muscle biopsy was taken from the operative knee of control and IPC-treated patients at the onset of surgery and, again, at one hour into surgery. The gene expression profile of muscle biopsies was determined using the Affymetrix Human U113 2.0 microarray system and validated using real-time polymerase chain reaction (RT-PCR. Measurements of C-reactive protein (CRP, erythrocyte sedimentation (ESR, white cell count (WCC, cytokines and haemoglobin were also made pre- and post-operatively. Results Microarray analysis revealed a significant increase in the expression of important oxidative stress defence genes, immediate early response genes and mitochondrial genes. Upregulation of pro-survival genes was also observed and correlated with a downregulation of pro-apoptotic gene expression. CRP, ESR, WCC, cytokine and haemoglobin levels were not significantly different between control and IPC patients. Conclusions The findings of this study suggest that IPC of the lower limb in total knee arthroplasty patients induces a protective genomic response, which results in increased expression of immediate early response genes, oxidative stress defence genes and pro-survival genes. These findings

  4. From palliative therapy to prolongation of survival: (223)RaCl2 in the treatment of bone metastases.

    Science.gov (United States)

    Liepe, Knut; Shinto, Ajit

    2016-07-01

    Patients with hormone-refractory prostate cancer often have multiple bone metastases. The resulting bone pain is associated with reduced life quality, increased cost of therapy and impairment of overall survival. Trials with bone-targeting β-emitters have mostly showed an effect on alleviation of bone pain along with prolongation in survival, documented in only a limited number of patients. A randomized phase III trial (ALSYMPCA) using the α-emitter (223)RaCl2 (Xofigo®) showed for the first time, a longer overall survival of 3.6 months in treated patients as a sign of an antitumor effect. The time to first skeletal-related events was also significantly longer in the therapy group compared with placebo. Because of the short range of α-emitter, the bone marrow toxicity of radium therapy is low, and so this radionuclide could also be a candidate for combination with chemotherapy. The elimination of (223)RaCl2 is mainly through the gastrointestinal tract and side effects are mainly in this area. The procedure is similar to treatment with other bone-seeking agents and consists of six administrations of 50 kBq/kg bodyweight Xofigo®, repeated every 4 weeks. At present Xofigo® is only approved for hormone-refractory prostate cancer.

  5. Methotrexate intolerance in the treatment of rheumatoid arthritis (RA): effect of adding caffeine to the management regimen.

    Science.gov (United States)

    Malaviya, Anand Narayan

    2017-02-01

    The aim of this study was to investigate the effect of caffeine on the symptoms of methotrexate (MTX) intolerance in patients with RA. The follow-up patients with RA seen over a period of 11 months were included in this work. The degree of MTX intolerance, if present, was classified as 'moderate' and 'severe'. Those with intolerance were advised caffeine (coffee or dark chocolate) synchronised with the MTX dose. The effect was assessed as 'very good', 'good' or 'none'. Among 855 patients seen during this period, 313 (36.6 %) did not have any MTX intolerance, 542 (63.4 %) patients had some degree of MTX intolerance, 422 (77.8 %; 49.3 % of the total patients) had 'minimal' intolerance not requiring any intervention. The remaining 120 (22.1 %) of the 542 (14 % of the total 855) patients had 'moderate' or 'severe' MTX intolerance. Among these, 55 % had complete relief of symptoms and were able to continue taking the advised dose of MTX; 13.3 % had partial improvement and continued taking MTX but only with antiemetics; 7.5 % were minimally better but were somehow managing; 10 % were complete caffeine failure without any relief; 14.2 % did not like caffeine (coffee or dark chocolate) and did not want to take it. Caffeine relieved the symptoms of MTX intolerance in 55 % and partial relief in 13 % of the patients. A significant number of patients did not like to take caffeine (coffee or dark chocolate). It is of note that northern part of India is primarily a tea-drinking population where coffee is not a favourite drink.

  6. Skin expression of mammalian target of rapamycin and forkhead box transcription factor O1, and serum insulin-like growth factor-1 in patients with acne vulgaris and their relationship with diet.

    Science.gov (United States)

    Agamia, N F; Abdallah, D M; Sorour, O; Mourad, B; Younan, D N

    2016-06-01

    Acne vulgaris is a multifactorial disorder of the pilosebaceous units. Several studies have reported that insulin-like growth factor (IGF)-1, forkhead box transcription factor (Fox)O1 and mammalian target of rapamycin (mTOR) interactions may be the key to understanding the links between genetic and environmental factors in acne vulgaris. To evaluate the immunohistochemical detection of mTOR and FoxO1 in the skin, and the serum level of IGF-1 in patients with acne vulgaris. This study was carried out on 60 participants, including 40 patients with acne and 20 controls. A diet questionnaire was administered to the patients and controls. Serum levels of IGF-1 were measured using enzyme-linked immunosorbent assay, and skin biopsies were taken from lesions on the backs of the patients and controls. FoxO1 and mTOR expression was detected using immunohistochemistry. A significantly higher serum IGF-1 level was found in the patients with acne than in the controls. The cytoplasmic expression of FoxO1 was found to be significantly greater in the acne group, whereas in the control subjects this expression was likely to be nuclear. Both the cytoplasmic expression and the nuclear expression of mTOR were significantly more intense in the patients with acne than in the controls. Excess consumption of a high-glycaemic-load diet was significantly associated with higher serum levels of IGF-1 and cytoplasmic expression of FoxO1 and mTOR. These results suggest that FoxO1, mTOR, serum IGF-1 and a high-glycaemic-load diet may play a role in acne pathogenesis. © 2016 British Association of Dermatologists.

  7. DNA Topoisomerases in Transcription

    DEFF Research Database (Denmark)

    Rødgaard, Morten Terpager

    2015-01-01

    This Ph.D. thesis summarizes the main results of my studies on the interplay between DNA topoisomerases and transcription. The work was performed from 2011 to 2015 at Aarhus University in the Laboratory of Genome Research, and was supervised by associate professor Anni H. Andersen. Most of the ex......This Ph.D. thesis summarizes the main results of my studies on the interplay between DNA topoisomerases and transcription. The work was performed from 2011 to 2015 at Aarhus University in the Laboratory of Genome Research, and was supervised by associate professor Anni H. Andersen. Most...... topoisomerase-DNA cleavage complex. The second study is an investigation of how topoisomerases influence gene regulation by keeping the genome in an optimal topological state....

  8. Study of the Effect of an Oral Formulation of Fig and Olive on Rheumatoid Arthritis (RA) Remission Indicators: A Randomized Clinical Trial.

    Science.gov (United States)

    Bahadori, Shahnaz; Salamzadeh, Jamshid; Kamalinejad, Mohammad; Shams Ardekani, Mohammad Reza; Keshavarz, Mansoor; Ahmadzadeh, Arman

    2016-01-01

    This study was designed to explore the complementary effects of a combination formulation of olive oil, olive and fig fruits on RA remission indicators. A randomized controlled clinical trial was designed. Adult RA patients were randomly divided into two groups receiving routine Disease-modifying antirheumatic drugs (DMARDs) regimen (control group) and routine DMARDs regimen plus the herbal supplementary formulation of olive oil, fig and olive fruits (intervention group). Patients were followed every 4 weeks for total study period of 16 weeks. In addition to demographic and medical history of the patients, the Disease Activity Score with 28-joint counts based on Erythrocyte Sedimentation Rate (DAS28_ESR) were recorded. SPSS (version 22.0) software was used to analyze data, assuming polive and fig products, with a longer follow up periods.

  9. Alpha beta but not gamma delta T cell clones in synovial fluids of patients with reactive arthritis show active transcription of tumour necrosis factor alpha and interferon gamma

    NARCIS (Netherlands)

    Rihl, M.; Gu, J.; Baeten, D.; Märker-Hermann, E.; Goodall, J. C.; Gaston, J. S. H.; Kuipers, J. G.; Zeidler, H.; Yu, D. T. Y.

    2004-01-01

    OBJECTIVE: To compare the cytokine expression profile of three CD8+, three CD4+, and three gammadelta+ T cell clones all derived from the synovial fluids of three patients with reactive arthritis (ReA). METHODS: Complementary DNA based microarrays containing the specific sequence of 56 cytokine

  10. Spanish dialects: phonetic transcription

    OpenAIRE

    Moreno Bilbao, M. Asunción; Mariño Acebal, José Bernardo

    1998-01-01

    It is well known that canonical Spanish, the dialectal variant `central' of Spain, so called Castilian, can be transcribed by rules. This paper deals with the automatic grapheme to phoneme transcription rules in several Spanish dialects from Latin America. Spanish is a language spoken by more than 300 million people, has an important geographical dispersion compared among other languages and has been historically influenced by many native languages. In this paper authors expand the Castilian ...

  11. Identification and validation of differentially expressed transcripts by RNA-sequencing of formalin-fixed, paraffin-embedded (FFPE) lung tissue from patients with Idiopathic Pulmonary Fibrosis.

    Science.gov (United States)

    Vukmirovic, Milica; Herazo-Maya, Jose D; Blackmon, John; Skodric-Trifunovic, Vesna; Jovanovic, Dragana; Pavlovic, Sonja; Stojsic, Jelena; Zeljkovic, Vesna; Yan, Xiting; Homer, Robert; Stefanovic, Branko; Kaminski, Naftali

    2017-01-12

    Idiopathic Pulmonary Fibrosis (IPF) is a lethal lung disease of unknown etiology. A major limitation in transcriptomic profiling of lung tissue in IPF has been a dependence on snap-frozen fresh tissues (FF). In this project we sought to determine whether genome scale transcript profiling using RNA Sequencing (RNA-Seq) could be applied to archived Formalin-Fixed Paraffin-Embedded (FFPE) IPF tissues. We isolated total RNA from 7 IPF and 5 control FFPE lung tissues and performed 50 base pair paired-end sequencing on Illumina 2000 HiSeq. TopHat2 was used to map sequencing reads to the human genome. On average ~62 million reads (53.4% of ~116 million reads) were mapped per sample. 4,131 genes were differentially expressed between IPF and controls (1,920 increased and 2,211 decreased (FDR < 0.05). We compared our results to differentially expressed genes calculated from a previously published dataset generated from FF tissues analyzed on Agilent microarrays (GSE47460). The overlap of differentially expressed genes was very high (760 increased and 1,413 decreased, FDR < 0.05). Only 92 differentially expressed genes changed in opposite directions. Pathway enrichment analysis performed using MetaCore confirmed numerous IPF relevant genes and pathways including extracellular remodeling, TGF-beta, and WNT. Gene network analysis of MMP7, a highly differentially expressed gene in both datasets, revealed the same canonical pathways and gene network candidates in RNA-Seq and microarray data. For validation by NanoString nCounter® we selected 35 genes that had a fold change of 2 in at least one dataset (10 discordant, 10 significantly differentially expressed in one dataset only and 15 concordant genes). High concordance of fold change and FDR was observed for each type of the samples (FF vs FFPE) with both microarrays (r = 0.92) and RNA-Seq (r = 0.90) and the number of discordant genes was reduced to four. Our results demonstrate that RNA sequencing of RNA

  12. 226Ra and 228Ra tracer study on material transport in the east coast of Hainan Island, China: a case of nutrients

    Directory of Open Access Journals (Sweden)

    Ni SU

    2011-06-01

    Full Text Available Material fluxes (e.g. nutrients from coast to offshore play an important role in controlling the water quality in the concerned adjacent sea not only by the increase of nutrient concentration but by the change of nutrient structure. In the present work, naturally occurring isotopes (226Ra and 228Ra had been measured by alpha spectrometry in Wenjiao/Wenchang and Wanquan river estuaries and adjacent sea water of the east coast of Hainan Island. The excess dissolved 226Ra and 228Ra activities were observed in comparison with the values expected from the conservative mixing of freshwater and seawater end-members in both estuaries. Using 1-Dimensional Diffusion model, the estimated horizontal eddy diffusion coefficients (Kh derived from 228Ra activities away from its sources was 3.16?105 cm2 s-1. Furthermore, the corresponding nutrient fluxes into the coastal area were assessed. The results can provide useful information for the processes of mixing and exchange of coastal water as well as the transportation of dissoluble pollutants in this sea area.

  13. 'If I didn't have RA I wouldn't give them house room': the relationship between RA, footwear and clothing choices.

    Science.gov (United States)

    Goodacre, Lynne J; Candy, Fiona J

    2011-03-01

    The aim of this study was to develop a greater understanding of the impact of RA on women's self-image and self-presentation via an exploration of their clothing choices. Located within a qualitative symbolic interactionist approach, 15 women with RA (age range 38-74 years, disease duration 1-47 years) each participated in two interviews. The first explored the impact of RA on their feelings about their bodies and their appearance; the second explored the factors that informed their clothing choices and the way they presented themselves. All interviews were digitally recorded and transcribed verbatim, digital photographs of the women's clothes and shoes were taken. Data were analysed jointly by both authors using thematic network analysis. Shoes were identified as greatly influencing the women's clothing choices and how they presented themselves. Three themes were identified that explored the structural and symptomatic impact of RA on the women's feet, the strategies they had developed to resolve their footwear needs outside of prescription footwear and the significant impact that footwear had on their clothing choices and self-presentation. Insights from these data highlight the polarity that exists between the clinical, functional attitudes towards shoes and their social status. While aesthetic issues challenge the acceptability of prescription footwear, problems also exist with the functionality and comfort of footwear available on high streets. A more collaborative approach to the design of footwear is required for both prescription and mainstream footwear to meet the needs of women with RA.

  14. Studies on sup(226) Ra and sup(210) Pb activities and the concentration factors of sup(226) Ra in the surface organic layers of the estuarine sediments of Mindola and Purna rivers in India

    Digital Repository Service at National Institute of Oceanography (India)

    Joshi, L.U.; Zingde, M.D.; Desai, B.N.

    consumed by humans The sampling techniques, experimental procedures and the distribution of the isotopes of sup(226) Ra and sup(210) Pb in the estuarine regions and the concentration factors of sup(226) Ra in the region are detailed....

  15. Mechanochemical ATPases and transcriptional activation

    National Research Council Canada - National Science Library

    Zhang, X; Chaney, M; Wigneshweraraj, Siva R; Schumacher, J; Bordes, P; Cannon, W; Buck, M

    2002-01-01

    ... transcription from other ATP‐independent activation mechanisms that rely on the recruitment of RNAP by transcription factors. As described below, productive interactions between σ 54 and its a...

  16. Nucleocytoplasmic shuttling of transcription factors

    DEFF Research Database (Denmark)

    Cartwright, P; Helin, K

    2000-01-01

    To elicit the transcriptional response following intra- or extracellular stimuli, the signals need to be transmitted to their site of action within the nucleus. The nucleocytoplasmic shuttling of transcription factors is a mechanism mediating this process. The activation and inactivation of the t......To elicit the transcriptional response following intra- or extracellular stimuli, the signals need to be transmitted to their site of action within the nucleus. The nucleocytoplasmic shuttling of transcription factors is a mechanism mediating this process. The activation and inactivation...... transcription factor families are regulated by similar mechanisms, there are several differences that allow for the specific activation of each transcription factor. This review discusses the general import and export pathways found to be common amongst many different transcription factors, and highlights...... a select group of transcription factors that demonstrate the diversity displayed in their mode of activation and inactivation....

  17. ATP-dependent chromatin remodeling by the Cockayne syndrome B DNA repair-transcription-coupling factor

    NARCIS (Netherlands)

    E. Citterio (Elisabetta); V. van den Boom (Vincent); G. Schnitzler; R. Kanaar (Roland); E. Bonte (Edgar); R.E. Kingston; W. Vermeulen (Wim); J.H.J. Hoeijmakers (Jan)

    2000-01-01

    textabstractThe Cockayne syndrome B protein (CSB) is required for coupling DNA excision repair to transcription in a process known as transcription-coupled repair (TCR). Cockayne syndrome patients show UV sensitivity and severe neurodevelopmental abnormalities. CSB is a

  18. Transcriptional networks controlling adipocyte differentiation

    DEFF Research Database (Denmark)

    Siersbæk, R; Mandrup, Susanne

    2011-01-01

    Adipocyte differentiation is regulated by a complex cascade of signals that drive the transcriptional reprogramming of the fibroblastic precursors. Genome-wide analyses of chromatin accessibility and binding of adipogenic transcription factors make it possible to generate "snapshots" of the trans......Adipocyte differentiation is regulated by a complex cascade of signals that drive the transcriptional reprogramming of the fibroblastic precursors. Genome-wide analyses of chromatin accessibility and binding of adipogenic transcription factors make it possible to generate "snapshots...

  19. Sanshool on The Fingertip Interferes with Vibration Detection in a Rapidly-Adapting (RA Tactile Channel.

    Directory of Open Access Journals (Sweden)

    Scinob Kuroki

    Full Text Available An Asian spice, Szechuan pepper (sanshool, is well known for the tingling sensation it induces on the mouth and on the lips. Electrophysiological studies have revealed that its active ingredient can induce firing of mechanoreceptor fibres that typically respond to mechanical vibration. Moreover, a human behavioral study has reported that the perceived frequency of sanshool-induced tingling matches with the preferred frequency range of the tactile rapidly adapting (RA channel, suggesting the contribution of sanshool-induced RA channel firing to its unique perceptual experience. However, since the RA channel may not be the only channel activated by sanshool, there could be a possibility that the sanshool tingling percept may be caused in whole or in part by other sensory channels. Here, by using a perceptual interference paradigm, we show that the sanshool-induced RA input indeed contributes to the human tactile processing. The absolute detection thresholds for vibrotactile input were measured with and without sanshool application on the fingertip. Sanshool significantly impaired detection of vibrations at 30 Hz (RA channel dominant frequency, but did not impair detection of higher frequency vibrations at 240 Hz (Pacinian-corpuscle (PC channel dominant frequency or lower frequency vibrations at 1 Hz (slowly adapting 1 (SA1 channel dominant frequency. These results show that the sanshool induces a peripheral RA channel activation that is relevant for tactile perception. This anomalous activation of RA channels may contribute to the unique tingling experience of sanshool.

  20. SU-E-T-588: Optimization of Imaging Following 223Ra Administration in Targeted Alpha-Emitting Radionuclide Therapy of Bone Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Benabdallah, N; Bernardini, M [Hopital Europeen George Pompidou, Paris, Ile de France (France); Desbree, A [Institut de Radioprotection et de Surete Nucleaire, Fontenay-aux-roses, Ile-de-France (France); Labriolle-Vaylet, C de [Hopital Trousseau, Paris, Ile de France (France); Franck, D [Institut de Radioprotection et de Suretu Nucleaire, Fontenay Aux Roses, Ile de France (France)

    2015-06-15

    Purpose: With a growing demand of alpha-emitting radiopharmaceuticals, especially Xofigo ({sup 223}RaCl{sub 2}) which is used in the treatment of metastatic bone disease, the optimization of dosimetry becomes necessary. Indeed, in Europe, as stated on the council directive 2013/59/euratom, exposures of target volumes for radiotherapeutic purposes shall be individually planned taking into account that doses to non-target volumes and tissues shall be as low as reasonably achievable. To that aim, the possibility of imaging {sup 223}Ra was first investigated. Methods: The experiments were conducted at the Hopital Europeen Georges Pompidou with an Infinia Hawkeye 4 gamma camera, equipped with a medium-energy collimator. Imaging parameters, such as sensibility, spatial resolution and energy spectrum, were determined using several physical phantoms with a source of 6 MBq of {sup 223}Ra. Bone metastases were modeled with a NEMA Body Phantom to investigate image degradation based on the concentration of {sup 223}Ra. Results: The acquired energy spectrum allowed to visualize several photon peaks: at 85, 154 and 270 keV. Camera sensitivity measured from the phantom study was 102.3 cps/MBq for the 85 keV ± 20 %, 89.9 cps/MBq for the 154 ± 20 % window and 65.4 cps/MBq for the 270 ± 10 % window. The spatial resolution (full-width at half-maximum) was respectively 1.7, 1.9 and 1.8 cm for the three energy windows. SPECT/CT images of NEMA Body Phantom without and with attenuation have permitted to determine the best reconstruction parameters. Conclusion: This study has demonstrated that it is possible to obtain clinically relevant information from images of {sup 223}Ra. All these results will be valuable to analyze biodistribution imaging of the radiopharmaceutical in the patient body and go further in the reconstruction of patient images in order to personalize the dosimetry.

  1. Evaluation of the IL2/IL21, IL2RA and IL2RB genetic variants influence on the endogenous non-anterior uveitis genetic predisposition.

    Science.gov (United States)

    Cénit, María Carmen; Márquez, Ana; Cordero-Coma, Miguel; Fonollosa, Alejandro; Adán, Alfredo; Martínez-Berriotxoa, Agustín; Llorenç, Victor; Díaz Valle, David; Blanco, Ricardo; Cañal, Joaquín; Díaz-Llopis, Manuel; García Serrano, José Luis; de Ramón, Enrique; del Rio, María José; Begoña Gorroño-Echebarría, Marina; Martín-Villa, José Manuel; Ortego-Centeno, Norberto; Martín, Javier

    2013-05-15

    Recently, different genetic variants located within the IL2/IL21 genetic region as well as within both IL2RA and IL2RB loci have been associated to multiple autoimmune disorders. We aimed to investigate for the first time the potential influence of the IL2/IL21, IL2RA and IL2RB most associated polymorphisms with autoimmunity on the endogenous non-anterior uveitis genetic predisposition. A total of 196 patients with endogenous non-anterior uveitis and 760 healthy controls, all of them from Caucasian population, were included in the current study. The IL2/IL21 (rs2069762, rs6822844 and rs907715), IL2RA (2104286, rs11594656 and rs12722495) and IL2RB (rs743777) genetic variants were genotyped using TaqMan® allelic discrimination assays. A statistically significant difference was found for the rs6822844 (IL2/IL21 region) minor allele frequency in the group of uveitis patients compared with controls (P(-value)=0.02, OR=0.64 CI 95%=0.43-0.94) although the significance was lost after multiple testing correction. Furthermore, no evidence of association with uveitis was detected for the analyzed genetic variants of the IL2RA or IL2RB loci. Our results indicate that analyzed IL2/IL21, IL2RA and IL2RB polymorphisms do not seem to play a significant role on the non-anterior uveitis genetic predisposition although further studies are needed in order to clear up the influence of these loci on the non-anterior uveitis susceptibility.

  2. An update on hearing impairment in patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Emamifar, Amir; Jensen Hansen, Inger Marie

    2018-01-01

    Rheumatoid arthritis (RA) is a systemic, autoimmune disease that present with intra-articular and extra-articular manifestations. Auditory system may be involved during the course of RA disease due to numbers of pathologies. The link between hearing impairment and RA has been discussed in the pre......Rheumatoid arthritis (RA) is a systemic, autoimmune disease that present with intra-articular and extra-articular manifestations. Auditory system may be involved during the course of RA disease due to numbers of pathologies. The link between hearing impairment and RA has been discussed...... in the previous literature. In this study we provide an update on the clinical aspect of hearing impairment in RA. We suggest to test hearing in all newly diagnosed RA patients at diagnosis as well as regularly during the course of disease....

  3. Guayaquil au temps du choléra

    Directory of Open Access Journals (Sweden)

    1996-01-01

    Full Text Available L’épidémie de choléra survenue en 1991 en Équateur a frappé certaines villes et régions plus que d’autres sur la Côte. Guayaquil, la première ville du pays par le nombre de ses habitants (1 600 000 habitants, a connu le record de cas. L’analyse de la répartition des malades hospitalisés dans la ville montre que les quartiers pauvres, récents et, de surcroît, bâtis sur les eaux polluées du delta ne sont pas les plus frappés alors que la zone centrale taudifiée a concentré un nombre de cas élevé. Les pratiques sociales sont-elles davantage responsables de cette situation que les facteurs pourtant très contraignants ici de l’environnement ? GUAYAQUIL EN LOS TIEMPOS DEL CÓLERA. La epidemia del cólera, ocurrida en 1991 en Ecuador, ha golpeado mucho más algunas ciudades y regiones de la Costa. Guayaquil, la primera ciudad del país con 1 600 000 habitantes, ha conocido un número de casos record. El análisis de la distribución de los enfermos hospitalizados en la ciudad revela que los barrios pobres, recientes y además construidos sobre las aguas contaminadas del delta no son los más afectados por esta epidemia en relación con la parte central tugurizada. Las prácticas sociales tal vez tienen más responsabilidad en esta situación que las condiciones particularmente difíciles del medio ambiente. GUAYAQUIL DURING THE CHOLERA. The cholera epidemic, which occured in 1991, impacted some cities and regions of the coast much more than others. Guayaquil, inhabitants Ecuador's largest city with a population of some 1, 6000 000 inhabitants, experienced a record number of cases. An analysis of the sick hospitalized in this city reveals that the poor urban sections, which were built recently and moreover were constructed upon the contaminated waters of the delta, were not the most affected by this epidemic, particularly when compared to the congested central part of the city. This suggests that social practices were more

  4. Cancer-type dependent expression of CK2 transcripts.

    Directory of Open Access Journals (Sweden)

    Melissa M J Chua

    Full Text Available A multitude of proteins are aberrantly expressed in cancer cells, including the oncogenic serine-threonine kinase CK2. In a previous report, we found increases in CK2 transcript expression that could explain the increased CK2 protein levels found in tumors from lung and bronchus, prostate, breast, colon and rectum, ovarian and pancreatic cancers. We also found that, contrary to the current notions about CK2, some CK2 transcripts were downregulated in several cancers. Here, we investigate all other cancers using Oncomine to determine whether they also display significant CK2 transcript dysregulation. As anticipated from our previous analysis, we found cancers with all CK2 transcripts upregulated (e.g. cervical, and cancers where there was a combination of upregulation and/or downregulation of the CK2 transcripts (e.g. sarcoma. Unexpectedly, we found some cancers with significant downregulation of all CK2 transcripts (e.g. testicular cancer. We also found that, in some cases, CK2 transcript levels were already dysregulated in benign lesions (e.g. Barrett's esophagus. We also found that CK2 transcript upregulation correlated with lower patient survival in most cases where data was significant. However, there were two cancer types, glioblastoma and renal cell carcinoma, where CK2 transcript upregulation correlated with higher survival. Overall, these data show that the expression levels of CK2 genes is highly variable in cancers and can lead to different patient outcomes.

  5. Recombinant Rhipicephalus appendiculatus gut (Ra86) and salivary gland cement (Trp64) proteins as candidate antigens for inclusion in tick vaccines: protective effetcs of Ra86 on infestation with adult R. appendiculatus.

    NARCIS (Netherlands)

    Saimo, M.; Odongo, D.O.; Mwaura, S.; Vlak, J.M.; Musoke, A.J.; Lubega, G.W.; Bishop, R.P.; Oers, van M.M.

    2011-01-01

    Rhipicephalus appendiculatus gut protein Ra86 (variants Ra85A and Ra92A) and the salivary gland cement protein (Trp64) were expressed in the baculovirus-insect cell system. The recombinant gut proteins expressed as soluble proteins and the recombinant cement protein, as insoluble inclusion bodies,

  6. Vertikalna raščlanjenost reljefa kopnenog dijela Republike Hrvatske

    OpenAIRE

    Lozić, Sanja

    1995-01-01

    U ovom radu dana je analiza vertikalne raščlanjenosti reljefa kopnenog dijela Republike Hrvatske. Vertikalna raščlanjenost numerički je parametar reljefa i određena je visinskom razlikom najviše i najniže točke unutar jedinične površine terena. Kao izraz morfostrukturnih i morfogenetskih osobina reljefa dinamičkog karaktera, značajan je kvantitativni indikator geomorfoloških osobina i procesa koji se odvijaju u reljefu. Rezultati analize vertikalne raščlanjenosti reljefa Hrvatske omogućuj...

  7. Localization of powdery mildew resistance gene Ml-ra on barley chromosome 5

    DEFF Research Database (Denmark)

    Doll, Hans; Jensen, Hans Peter

    1986-01-01

    Evidence is presented that the powdery mildew resistance gene called Ml-(41/145) represents a unique, unnamed locus, which we suggest to be designated Ml-ra with reference to variety 'Ragusa b' [Hordeum vulgare]. Ml-ra is located on the short arm of chormosome 5 near powdery mildew resistance loc...... Ml-a and the seed storage protein loci Hor1 and Hor2. The most likely order of the loci is Hor1, Ml-a, Ml-ra, and Hor2....

  8. Ra and the average effective strain of surface asperities deformed in metal-working processes

    DEFF Research Database (Denmark)

    Bay, Niels; Wanheim, Tarras; Petersen, A. S

    1975-01-01

    and γ0. View the MathML sourcege is highly dependent on γ0, View the MathML sourcege increasing with increasing γ0. It is shown that the Ra-value and the strain are hardly affected by the normal pressure until interacting deformation of the asperities begins, that is until the limit of Amonton's law...... is reached. After that Ra decreases and the strain increases rapidly with the normal pressure, Ra approaching zero whilst View the MathML sourcege approaches a limiting value depending on the initial slope of the asperities....

  9. Determination of natural radionuclides, U, Th-232, Ra-226, Ra-228, Pb-210 and K-40 in sediments from CananÉIa-Iguape System, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Jesus, Gleyka J.D.; Chiozzini, Vitor G.; Saueia, Cátia H.R.; Nisti, Marcelo B.; Braga, Elisabete S.; Fávaro, Deborah I.T., E-mail: gjdjesus@ipen.br, E-mail: chsaueia@ipen.br, E-mail: mbnisti@ipen.br, E-mail: defavaro@ipen.br, E-mail: vitor.chio@usp.br, E-mail: edsbraga@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Universidade de São Paulo (USP), SP (Brazil). Instituto Oceanográfico

    2017-07-01

    The Cananéia-Iguape estuarine-lagoon complex, located in the south of São Paulo State, Brazil, is a protected area recognized by UNESCO as part of the Biosphere Reserve, due to its importance as a natural ecosystem. However, along the years, the mining activities in the region affected the river basin, to such an extent that contamination was observed for As, Cu, Pb and Zn. Since the mining activities can also enhance the levels of natural radioactivity in the sediments, this study aimed to determine the activity concentration of the natural radionuclides (K-40, U, Ra-226, Pb-210, Th-232 and Ra-228) in 34 bottom sediments samples collected in the Cananéia-Iguape system. The samples were measured by gamma spectrometry, using a HPGe for the determination of K-40, Ra-226, Pb-210 and Ra-228. The concentration of U and Th-232 was determined by instrumental neutron activation analysis. The activity concentration of K-40 varied from 119 ± 17 to 522 ± 74 Bq kg{sup -1}; U-238 varied from 0.31 ± 0.05 to 5.8 ± 0.3 mg kg{sup -1}; Ra-226 varied from 3.7 ± 0.3 to 43.3 ± 1.5 Bq kg{sup -1}; Pb-210 varied from 5.8 ± 2.6 to 118 ± 12 Bq kg{sup -1}; Th-232 varied from 0.67 ± 0.02 to 16.6 ± 0.4 mg kg{sup -1} and Ra-228 varied from 3.5 ± 0.6 to 64.9 ± 2.4 Bq kg{sup -1}. These results were compared with literature values for the region, indicating that they are the background of the region and no contamination was observed from NORM (Naturally Occurring Radioactive Material) industries. (author)

  10. Vitamin D Receptor gene (VDR) transcripts in bone, cartilage, muscles and blood and microarray analysis of vitamin D responsive genes expression in paravertebral muscles of Juvenile and Adolescent Idiopathic Scoliosis patients

    Science.gov (United States)

    2012-01-01

    Background VDR may be considered as a candidate gene potentially related to Idiopathic Scoliosis susceptibility and natural history. Transcriptional profile of VDR mRNA isoforms might be changed in the structural tissues of the scoliotic spine and potentially influence the expression of VDR responsive genes. The purpose of the study was to determine differences in mRNA abundance of VDR isoforms in bone, cartilage and paravertebral muscles between tissues from curve concavity and convexity, between JIS and AIS and to identify VDR responsive genes differentiating Juvenile and Adolescent Idiopathic Scoliosis in paravertebral muscles. Methods In a group of 29 patients with JIS and AIS, specimens of bone, cartilage, paravertebral muscles were harvested at the both sides of the curve apex together with peripheral blood samples. Extracted total RNA served as a matrix for VDRs and VDRl mRNA quantification by QRT PCR. Subsequent microarray analysis of paravertebral muscular tissue samples was performed with HG U133A chips (Affymetrix). Quantitative data were compared by a nonparametric Mann Whitney U test. Microarray results were analyzed with GeneSpring 11GX application. Matrix plot of normalized log-intensities visualized the degree of differentiation between muscular tissue transcriptomes of JIS and AIS group. Fold Change Analysis with cutoff of Fold Change ≥2 identified differentially expressed VDR responsive genes in paravertebral muscles of JIS and AIS. Results No significant differences in transcript abundance of VDR isoforms between tissues of the curve concavity and convexity were found. Statistically significant difference between JIS and AIS group in mRNA abundance of VDRl isoform was found in paravertebral muscles of curve concavity. Higher degree of muscular transcriptome differentiation between curve concavity and convexity was visualized in JIS group. In paravertebral muscles Tob2 and MED13 were selected as genes differentially expressed in JIS and AIS

  11. Vitamin D Receptor gene (VDR transcripts in bone, cartilage, muscles and blood and microarray analysis of vitamin D responsive genes expression in paravertebral muscles of Juvenile and Adolescent Idiopathic Scoliosis patients

    Directory of Open Access Journals (Sweden)

    Nowak Roman

    2012-12-01

    Full Text Available Abstract Background VDR may be considered as a candidate gene potentially related to Idiopathic Scoliosis susceptibility and natural history. Transcriptional profile of VDR mRNA isoforms might be changed in the structural tissues of the scoliotic spine and potentially influence the expression of VDR responsive genes. The purpose of the study was to determine differences in mRNA abundance of VDR isoforms in bone, cartilage and paravertebral muscles between tissues from curve concavity and convexity, between JIS and AIS and to identify VDR responsive genes differentiating Juvenile and Adolescent Idiopathic Scoliosis in paravertebral muscles. Methods In a group of 29 patients with JIS and AIS, specimens of bone, cartilage, paravertebral muscles were harvested at the both sides of the curve apex together with peripheral blood samples. Extracted total RNA served as a matrix for VDRs and VDRl mRNA quantification by QRT PCR. Subsequent microarray analysis of paravertebral muscular tissue samples was performed with HG U133A chips (Affymetrix. Quantitative data were compared by a nonparametric Mann Whitney U test. Microarray results were analyzed with GeneSpring 11GX application. Matrix plot of normalized log-intensities visualized the degree of differentiation between muscular tissue transcriptomes of JIS and AIS group. Fold Change Analysis with cutoff of Fold Change ≥2 identified differentially expressed VDR responsive genes in paravertebral muscles of JIS and AIS. Results No significant differences in transcript abundance of VDR isoforms between tissues of the curve concavity and convexity were found. Statistically significant difference between JIS and AIS group in mRNA abundance of VDRl isoform was found in paravertebral muscles of curve concavity. Higher degree of muscular transcriptome differentiation between curve concavity and convexity was visualized in JIS group. In paravertebral muscles Tob2 and MED13 were selected as genes differentially

  12. Exploración de raíces sacras: indicaciones, técnica y resultados

    National Research Council Canada - National Science Library

    Arlandis Guzmán, S; Alapont Alacreu, J.M; Bonillo García, M.Á; Ruiz Cerdá, J.L; Martínez Agulló, E; Jiménez Cruz, F

    2003-01-01

    ... eléctricos aplicados sobre las raíces sacras. La exploración de raíces sacras (ERS) es fundamental para considerar a un paciente candidato al implante definitivo del estimulador de la raíz sacra...

  13. Analysis of the interaction between transcription factor 7-like 2 genetic variants with nopal and wholegrain fibre intake: effects on anthropometric and metabolic characteristics in type 2 diabetes patients.

    Science.gov (United States)

    López-Ortiz, M M; Garay-Sevilla, M E; Tejero, M E; Perez-Luque, E L

    2016-09-01

    The transcription factor 7-like 2 (TCF7L2) genetic variants have shown differential effect on low-fat and high-fat diet in obese subjects. Nopal is a Mexican variety of cactus that is a traditional food and has been used in the treatment of diabetes. Its hypoglycaemic effect may be because of its soluble fibre (mucopolysaccharide) content. This study analysed the effects of the rs7903146 and rs12255372 TCF7L2 variants on anthropometric, metabolic and hormonal parameters in type 2 diabetes mellitus patients who consumed fibre from either nopal tortilla or wholegrain bread for 8 weeks. We followed-up seventy-four patients who consumed an individualised isoenergetic diet that included nopal tortilla (Diet 1) and sixty-three patients with a diet that included wholegrain bread (Diet 2). Anthropometric, metabolic and hormonal measures were collected at baseline and final intervention. The size effect and carry-over effect were estimated. To assess the interaction of genotype and diets, we used a general linear model repeated-measures analysis. Minor allele frequency of rs7903146T was 0·27 and for rs12255372T it was 0·13. At 8 weeks after Diet 1 intake, weight, BMI, waist and hip circumference decreased (P=0·00015) in rs7903146CC and rs12255372GG genotypes. In particular, patients carrying of the rs7903146CC and consuming Diet 1 showed a reduction in waist circumference of more than 2·5 cm compared with Diet 2 (P<0·001). No significant interaction between rs7903146 or rs12255372 and diet was seen in this study. In conclusion, in the carriers of the rs7903146CC and rs12255372GG wild types, significant changes in all anthropometric measures were observed, and had better response to both diets.

  14. Microorganisms in respiratory tract of patients diagnosed with atypical pneumonia: results of a research based on the use of reverse transcription polymerase chain reaction (RT-PCR) DNA microarray method and enzyme-linked immunosorbent assay.

    Science.gov (United States)

    Tokman, Hrisi Bahar; Aslan, Mustafa; Ortaköylü, Gönenç; Algingil, Reyhan Calişkan; Yüksel, Pelin; Karakullukçu, Asiye; Kalayci, Fatma; Saribaş, Suat; Cakan, Hüseyin; Demir, Tuncalp; Kocazeybek, Bekir S

    2014-01-01

    Numerous molecular-based tests were applied for the laboratory-based diagnosis of viruses. In this cross-sectional case control study, in addition to bacteria, we aimed to determine respiratory viruses using, for the first time in our country, the Reverse Transcription PCR DNA Microarray method, and we also aimed to evaluate its diagnostic performance. Respiratory viruses were investigated from nasopharyngeal swabs of 76 patients diagnosed with atypical pneumonia and 64 healthy controls using the CLART Pneumovir (Genomica, Spain) kit and from 10 mL blood samples of the same subjects. M. pneumoniae IgM was detected by ELISA and L. pneumophila IgM and C. pneumoniae IgM by indirect immunofluorescence. Person's chi-square test was used for statistical analysis. Our results showed that the specificity (100%) and the positive predictive value (100%) of the CLART Pneumovir kit were high, but its sensitivity (53%), its negative predictive value (64%), and its kappa value (50%) were low. Parainfluenza Virus type 3 and M. pneumoniae were found alone or together as the most common microorganisms while no cases of human bocavirus, adenovirus, rhinovirus, or coronavirus were detected. Our results demonstrated that, during the study period, most of our patients had atypical pneumonia due to Parainfluenza Virus type 3 and M. pneumoniae co-infection.

  15. BAFF (B cell activating factor) transcript level in peripheral blood of patients with SLE is associated with same-day disease activity as well as global activity over the next year.

    Science.gov (United States)

    Zollars, Eric; Bienkowska, Jadwiga; Czerkowicz, Julie; Allaire, Norm; Ranger, Ann M; Magder, Laurence; Petri, Michelle

    2015-01-01

    Quantitating gene expression is a potential method of developing biomarkers in systemic lupus erythematosus (SLE). Because of the known pathological role of B cell activating factor (BAFF) in SLE, we explored the association between BAFF gene expression and clinical activity in SLE. A total of 275 patients with SLE completed this phase of a prospective observational study. At entry into the study, the BAFF gene expression levels were determined in peripheral blood RNA. Serum concentration of BAFF protein was also measured. We then determined clinical associations with SLE disease history, SLE activity on the same day and SLE activity over the course of the next year. Elevated BAFF gene expression was associated with a history of more leucopenia and serologically with more autoantibodies (anti-dsDNA, anti-Sm, anti-Ro, anti-La and anti-RNP) and low complement. Patients with higher amounts of BAFF transcript had higher measured levels of clinical disease activity. Initial high levels of BAFF gene expression also predicted increased disease activity over the course of the next year. In contrast, serum concentration of BAFF protein was not strongly associated with same-day global disease activity or with future disease activity. BAFF gene expression level is associated with clinical and serological SLE activity on the same day and predictive of clinical activity over the next year. BAFF gene expression is a better measure and predictor of SLE disease activity than the serum BAFF protein level.

  16. Blood levels of CD11b+ memory T lymphocytes are selectively upregulated in patients with active rheumatoid arthritis

    DEFF Research Database (Denmark)

    Nielsen, H; Petersen, A A; Skjødt, H

    1999-01-01

    The adhesion molecules CD11b (a beta2-integrin component) and CD54 (ICAM-1) on blood leukocytes were studied by flow cytometry in patients with rheumatoid arthritis (RA). The fractions of CD4+ cells co-expressing CD11b were elevated in 16 patients with active RA compared with those in 16 RA...

  17. Towards a precise measurement of atomic parity violation in a single Ra{sup +} ion

    Energy Technology Data Exchange (ETDEWEB)

    Nunez Portela, M., E-mail: nunez@kvi.nl; Berg, J. E. van den; Bekker, H.; Boell, O.; Dijck, E. A.; Giri, G. S.; Hoekstra, S.; Jungmann, K.; Mohanty, A.; Onderwater, C. J. G.; Santra, B.; Schlesser, S.; Timmermans, R. G. E.; Versolato, O. O.; Wansbeek, L. W.; Willmann, L.; Wilschut, H. W. [Kernfysisch Versneller Instituut (KVI) (Netherlands)

    2013-03-15

    A single trapped Ra{sup + } (Z = 88) ion provides a very promising route towards a most precise measurement of Atomic Parity Violation (APV), since APV effects grow faster than Z{sup 3}. This experiment promises the best determination of the electroweak coupling constant at the lowest accessible energies. Such a measurement provides a sensitive test of the Standard Model in particle physics. At the present stage of the experiment, we focus on trapping and laser cooling stable Ba{sup + } ions as a precursor for radioactive Ra{sup + }. Online laser spectroscopy of the isotopes {sup 209 - 214}Ra{sup + } in a linear Paul trap has provided information on transition wavelengths, fine and hyperfine structures and excited state lifetimes as test of atomic structure calculations. Additionaly, a single trapped Ra{sup + } ion could function as a very stable clock.

  18. Data of evolutionary structure change: 1C5RA-3BSQC [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1C5RA-3BSQC 1C5R 3BSQ A C IVGGYTCGANTVPYQVSLNSG-YHFCGGSLINSQWVVSA...AHCYKSGIQVRLGEDNINVVEGNEQFISASKSIVHPSYNSNTLNNDIMLIKLKSAASLNSRVASISLPTSCASAGTQCLISGWGNTKSSGTSYPDVLKCLKAPILSDS... 3BSQ C 3BSQC 3BSQ C 3BSQC VSW...VID> 2 3BSQ C 3BSQC

  19. Hispaania võib oma väed Iraagist ära tuua / Erkki Bahovski

    Index Scriptorium Estoniae

    Bahovski, Erkki, 1970-

    2004-01-01

    Hispaania parlamendivalimised võitnud sotsialistliku partei liider, arvatav uus peaminister Jose Luis Rodriguez Zapatero lubas Hispaania väed Iraagist ära tuua. Diagrammid: Hispaania valimistulemused

  20. Ajakohatu küsimine kunsti algupära järele / Leo Luks

    Index Scriptorium Estoniae

    Luks, Leo, 1976-

    2002-01-01

    Rets.: Martin Heidegger. Kunstiteose algupära. Saksa keelest tõlkinud Ülo Matjus. Tartu, 2002 (Avatud Eesti Raamat). Konkreetse Heideggeri teose mõistmiseks vajalikust taustast. Kogumikust - Kaasaegne poliitiline filosoofia

  1. I-RaCM: A Fully Integrated Risk and Lifecycle Cost Model Project

    Data.gov (United States)

    National Aeronautics and Space Administration — SpaceWorks Engineering, Inc. (SEI) proposes development of the Integrated Risk and Cost Model I-RaCM, as the innovation to meet the need for integrated cost and risk...

  2. Peeter ei võta lapsi ära / Peeter Kreitzberg

    Index Scriptorium Estoniae

    Kreitzberg, Peeter, 1948-2011

    2001-01-01

    Vastukaja ajalehes "Eesti Ekspress" 29. märtsil ilmunud artiklile "Peeter Kreitzberg: võtame vaestelt lapsed ära!" ja ajalehes "SL Õhtuleht" ilmunud Imbi Paju artiklile "Põhjala igavus ja Eesti hiilgus"

  3. The space (reorganization in Guaíra after the end of “Sete Quedas”

    Directory of Open Access Journals (Sweden)

    Edson Belo Clemente de Souza

    2007-12-01

    Full Text Available This article analyses the space (re organization in themunicipality of Guaíra – PR after the formation of Itaipu Lakewith consequent immersions of the “Sete Quedas”. Due tothe socio-environmental impact caused by the flood, a newphase of development is going to be implemented in Guaírabased on the Directory Plans of 1980 and 1992, reorganizingthe geographic area of Guaíra in a corollary way.

  4. Ra isotopes in trees: Their application to the estimation of heartwood growth rates and tree ages

    Science.gov (United States)

    Hancock, Gary J.; Murray, Andrew S.; Brunskill, Gregg J.; Argent, Robert M.

    2006-12-01

    The difficulty in estimating growth rates and ages of tropical and warm-temperate tree species is well known. However, this information has many important environmental applications, including the proper management of native forests and calculating uptake and release of atmospheric carbon. We report the activities of Ra isotopes in the heartwood, sapwood and leaves of six tree species, and use the radial distribution of the 228Ra/226Ra activity ratio in the stem of the tree to estimate the rate of accretion of heartwood. A model is presented in which dissolved Ra in groundwater is taken up by tree roots, translocated to sapwood in a chemically mobile (ion-exchangeable) form, and rendered immobile as it is transferred to heartwood. Uptake of 232Th and 230Th (the parents of 228Ra and 226Ra) is negligible. The rate of heartwood accretion is determined from the radioactive decay of 228Ra (half-life 5.8 years) relative to long-lived 226Ra (half-life 1600 years), and is relevant to growth periods of up to 50 years. By extrapolating the heartwood accretion rate to the entire tree ring record the method also appears to provide realistic estimates of tree age. Eight trees were studied (three of known age, 72, 66 and 35 years), including three Australian hardwood eucalypt species, two mangrove species, and a softwood pine (P. radiata). The method indicates that the rate of growth ring formation is species and climate dependent, varying from 0.7 rings yr-1 for a river red gum (E. camaldulensis) to around 3 rings yr-1 for a tropical mangrove (X. mekongensis).

  5. Bioavailability of radionuclides {sup 226}Ra, {sup 228}Ra and {sup 210}Pb present in the brazilian phosphate fertilizers and phosphogypsum; Avaliacao da biodisponibilidade dos radionuclideos {sup 226}Ra, {sup 228}Ra e {sup 210}Pb presentes nos fertilizantes fosfatados e no fosfogesso de procedencia nacional

    Energy Technology Data Exchange (ETDEWEB)

    Russo, Ana Carolina

    2013-08-01

    Phosphogypsum, also called gypsum, by-product of the phosphate fertilizer industry, can be used as soil conditioner since it provides improvements in the soil-plant system. However, this by-product concentrates radionuclides of the U and Th series, present in the phosphate rock used as raw material, which can impact the environment. In order to study the bioavailability of radionuclides, samples of phosphogypsum and phosphate fertilizers (monoammonium phosphate and triple superphosphate) were analyzed. The concentration of {sup 226}Ra, {sup 228}Ra and {sup 210}Pb were determined by gamma spectrometry. The samples were leached with a mild EDTA solution and the radionuclides present in the final solution were determined by total alpha and beta counting on a gas flow proportional counter. The percentage of extraction varied from 1.6% to 1.7% for {sup 210}Pb, from 0.5% to 1.4% for {sup 226}Ra and from 0.1% to 1.0% for the {sup 228}Ra in phosphogypsum samples. The low percentage of extraction obtained for the radionuclides can be partly explained by the low solubility of phosphogypsum, which ranged from 7.7% to 16%. For the monoammonium phosphate samples the percentage of extraction were less than 26% for {sup 226}Ra, less than 10% for '2{sup 28}Ra and less than 10% for {sup 210}Pb. In spite of the high solubility of 77% of monoammonium phosphate in the EDTA solution, low concentrations of radionuclides were observed in the leached solution. For the triple superphosphate samples, the percentage of extraction was 2.3% for {sup 226}Ra, 1.2% for {sup 228}Ra and 11.3% for {sup 210}Pb. In spite of the high solubility of 66% of triple superphosphate in the EDTA solution, low concentrations of radionuclides were observed in the leached solution. (author)

  6. Joint Program on Rapid Prototyping. RaPIER (Rapid Prototyping to Investigate End-User Requirements).

    Science.gov (United States)

    1985-03-28

    for reuse. The Ada langauge contains a rich set of features that support reusability. Some of the most important ones are: o packages, o separate...telephone consultants for RaPIER at least through the fifth year of this project. Beyond that, the Computer Sciences Center will need to transfer...motivated to exploit them, can/will become a RaPIER skilled user; 6. deals with requirements; T . deals with new products; 8. is part of the contractor’s

  7. Oceanographic profile data collected from CTD casts aboard RA-3, RA-4 and NOAA Ship RAINIER as part of project OPR-R976-RA-15 in the Beaufort Sea and Bering Sea from 2015-06-22 to 2015-08-22 (NCEI Accession 0131250)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NCEI Accession 0131250 includes physical and profile data collected aboard the RA-3, RA-4 and NOAA Ship RAINIER during project OPR-R976-RA-15 in the Beaufort Sea and...

  8. Isolated right atrial appendage (RAA rupture in blunt trauma – a case report and an anatomic study comparing RAA and right atrium (RA wall thickness

    Directory of Open Access Journals (Sweden)

    Jatene Fabio B

    2007-02-01

    Full Text Available Abstract Background Heart chambers rupture in blunt trauma is uncommon and is associated with a high mortality. The determinant factors, and the incidence of isolated heart chambers rupture remains undetermined. Isolated rupture of the right atrium appendage (RAA is very rare, with 8 cases reported in the reviewed literature. The thin wall of the RAA has been presumed to render this chamber more prone to rupture in blunt trauma. Objective To report a case of isolated RAA rupture in blunt trauma, and to compare right atrium (RA and RAA wall thickness in a necropsy study. Methods The thickness of RA and RAA wall of hearts from cadavers of fatal penetrating head trauma victims was measured. Our case of isolated RAA rupture is presented. The main findings of the 8 cases reported in the literature, and the findings of our case, were organized in a table. Result The comparison of the data showed that wall thickness of the RAA (0.53 ± 0.33 mm was significantly thinner than that of RA (1.11 ± 0.42 mm (p Comments In all these 9 cases of isolated RAA rupture, cardiac tamponade occurred, RAA rupture was diagnosed intraoperatively and sutured, and the patients survived. Main mechanisms hypothesized for heart chamber rupture include mechanical compression coincident with phases of cardiac cycle, leading to high hydrostatic pressure inside the chamber. Published series include numerous cases of RA rupture, and only a few cases of RAA rupture. Conclusion Thus, our data suggests that wall thickness is not a determinant factor for RA or RAA rupture in blunt trauma.

  9. Targeting bcr-abl transcripts with siRNAs in an imatinib-resistant chronic myeloid leukemia patient: challenges and future directions.

    Science.gov (United States)

    Koldehoff, Michael

    2015-01-01

    Within the recent years, RNA interference (RNAi) has become an almost standard method for in vitro knockdown of any target gene of interest. Now, one major focus is to further explore its potential therapeutic use. From the mechanism, it becomes clear that small interfering RNAs (siRNAs) play a pivotal role in triggering RNAi. This chapter describes the in vivo application of targeted non-virally delivered synthetic bcr-abl siRNA in a female patient with recurrent Philadelphia chromosome positive chronic myeloid leukemia (CML) resistant to imatinib (Y253F mutation) and chemotherapy after allogeneic hematopoietic stem cell transplantation. A remarkable inhibition of the overexpressed bcr-abl oncogene resulting in increased apoptosis of CML cells was found. In vivo siRNA application was well tolerated without any clinically adverse events. The current findings imply that the clinical application of synthetic siRNA is feasible and safe and has real potential for genetic-based therapies using synthetic non-viral carriers.

  10. Distribution and retention in bone of /sup 226/Ra and comparison with the ICRP 20 model

    Energy Technology Data Exchange (ETDEWEB)

    Holtzman, R.B.; Rundo, J.; Sha, J.Y.; Spaletto, M.I.

    1981-01-01

    Analyses are presented of the ratios of /sup 226/Ra to calcium in over 650 samples of compact and cancellous bone from 66 female and 26 male subjects who had died from less than one to 60 years after first exposure to radium. The /sup 226/Ra/Ca ratios were normalized to the terminal /sup 226/Ra skeletal content. The /sup 226/Ra/Ca ratios for vertebrae were essentialy identical to those for other cancellous bone for a given subject. Comparisons of the data with predictions of the ICRP model of alkaline earth metabolism show that for female cancellous bone the normalized /sup 226/Ra/Ca ratios tended to be greater than predicted, while those for female cortical bone (femoral and tibial shaft) tended to be less. The data for males were fitted better by the model. A modification of the model to reduce the amount of radium deposited in soft tissue fitted the data better in some respects. A straight line linear least squares fit to the data appeared to fit as well as, or better than, the models. A radiation effect was suggested in that the normalized /sup 226/Ra/Ca ratio for vertebrae relative to the ratio expected increased with skeletal absorbed dose for vertebra. However, no such effect was apparent for compact bone or for the cancellous bone as a whole.

  11. An easy method for Ra-226 determination in river waters by liquid-scintillation counting

    Science.gov (United States)

    Moreno, H. P.; Vioque, I.; Manjón, G.; García-Tenorio, R.

    1999-01-01

    226Ra activity concentration in river water was determined using a low background liquid scintillation counter. Radium was extracted from the samples as Ra-BaSO4 precipitate which, afterwards, was dissolved with EDTA in ammonia medium. Solution was transferred into a low potassium glass vial and then mixed with a scintillation cocktail. Two different scintillation cocktails were selected for comparison. Efficiency, recovery yield and α/β separation were studied with both liquid scintillation cocktails. One single measurement, made one month after radium separation, allows to calculate the226Ra concentration as well as to assess the presence of alpha contamination of the sample. In the case of negligible interferences,224Ra concentrations can be subsequently evaluated in the same sample by the measurement made just after chemical separation of radium. This method has been applied for the determination of226Ra and224Ra activity concentrations in river water collected from different locations along the Odiel river estuary area (South-west of Spain). The presence of chemical industry, the wastes of which are released into the river, could be connected with radium activity concentration enhancements in the water.

  12. Cardiovascular disease in patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Naranjo, Antonio; Sokka, Tuulikki; Descalzo, Miguel

    2008-01-01

    ABSTRACT: INTRODUCTION: We analyzed the prevalence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA) and its association with traditional CV risk factors, clinical features of RA, and the use of disease-modifying antirheumatic drugs (DMARDs) in a multinational cross......-sectional cohort of nonselected consecutive outpatients with RA (The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis Program, or QUEST-RA) who were receiving regular clinical care. METHODS: The study involved a clinical assessment by a rheumatologist and a self-report questionnaire...

  13. Internalised stigma in people with rheumatoid arthritis: a cross sectional study to establish the psychometric properties of the ISMI-RA.

    Science.gov (United States)

    Corker, Elizabeth; Henderson, R Claire; Lempp, Heidi; Brown, June S L

    2016-06-02

    Internalised stigma is theorized to be the internalisation and legitimisation of stereotypes of the diagnosis held in society and has not been quantified within patients with Rheumatoid Arthritis. This study aimed to: validate a modified version of a measure of internalised stigma, (the Internalised Stigma of Mental Illness scale, ISMI) for use in a group of patients diagnosed with rheumatoid arthritis; establish the consistency of the construct being measured, and to explore the levels of internalised stigma within this group. A cross-sectional survey was conducted in London, UK with participants receiving out-patient treatment for Rheumatoid Arthritis. Participants completed the ISMI-Rheumatoid Arthritis (ISMI-RA) and a measure of self-esteem. One hundred respondents were interviewed by phone. The ISMI-RA was found to be reliable using a measure of internal consistency (α = 0.85) showed concurrent validity with the Index of Self Esteem (r = 0.58, p gender (t = 1.43, p = 0.61). A quarter of respondents reported internalised stigma to a 'severe' level. Acceptability and feasibility were established. A confirmatory factor analysis provided some support for the model of internalised stigma. The application of the ISMI-RA among the Rheumatoid Arthritis population looks promising. Internalised stigma was found to be present within this group. More research is needed to generalize these results and to explore the effects of internalised stigma on treatment adherence and quality of life.

  14. A mutation at IVS1 + 5 of the von Hippel-Lindau gene resulting in intron retention in transcripts is not pathogenic in a patient with a tongue cancer?: case report

    Directory of Open Access Journals (Sweden)

    Asakawa Takeshi

    2012-03-01

    Full Text Available Abstract Background Von Hippel-Lindau disease (VHL is a dominantly inherited familial cancer syndrome predisposing the patient to a variety of malignant and benign neoplasms, most frequently hemangioblastoma, renal cell carcinoma, pheochromocytoma, and pancreatic tumors. VHL is caused by mutations of the VHL tumor suppressor gene on the short arm of chromosome 3, and clinical manifestations develop if both alleles are inactivated according to the two-hit hypothesis. VHL mutations are more frequent in the coding region and occur occasionally in the splicing region of the gene. Previously, we reported that the loss of heterozygosity (LOH of the VHL gene is common in squamous cell carcinoma tissues of the tongue. Case Presentation We describe a case of squamous cell carcinoma in the tongue caused by a point mutation in the splicing region of the VHL gene and discuss its association with VHL disease. Sequence analysis of DNA extracted from the tumor and peripheral blood of the patient with squamous cell carcinoma revealed a heterozygous germline mutation (c. 340 + 5 G > C in the splice donor sequence in intron 1 of the VHL gene. RT-PCR analysis of the exon1/intron1 junction in RNA from tumor tissue detected an unspliced transcript. Analysis of LOH using a marker with a heterozygous mutation of nucleotides (G or C revealed a deletion of the mutant C allele in the carcinoma tissues. Conclusions The fifth nucleotide G of the splice donor site of the VHL gene is important for the efficiency of splicing at that site. The development of tongue cancer in this patient was not associated with VHL disease because the mutation occurred in only a single allele of the VHL gene and that allele was deleted in tumor cells.

  15. Inhibition of the all-trans Retinoic Acid (atRA) Hydroxylases CYP26A1 and CYP26B1 Results in Dynamic, Tissue-Specific Changes in Endogenous atRA Signaling.

    Science.gov (United States)

    Stevison, Faith; Hogarth, Cathryn; Tripathy, Sasmita; Kent, Travis; Isoherranen, Nina

    2017-07-01

    All-trans retinoic acid (atRA), the active metabolite of vitamin A, is a ligand for several nuclear receptors and acts as a critical regulator of many physiologic processes. The cytochrome P450 family 26 (CYP26) enzymes are responsible for atRA clearance, and are potential drug targets to increase concentrations of endogenous atRA in a tissue-specific manner. Talarozole is a potent inhibitor of CYP26A1 and CYP26B1, and has shown some success in clinical trials. However, it is not known what magnitude of change is needed in tissue atRA concentrations to promote atRA signaling changes. The aim of this study was to quantify the increase in endogenous atRA concentrations necessary to alter atRA signaling in target organs, and to establish the relationship between CYP26 inhibition and altered atRA concentrations in tissues. Following a single 2.5-mg/kg dose of talarozole to mice, atRA concentrations increased up to 5.7-, 2.7-, and 2.5-fold in serum, liver, and testis, respectively, resulting in induction of Cyp26a1 in the liver and testis and Rar β and Pgc 1β in liver. The increase in atRA concentrations was well predicted from talarozole pharmacokinetics and in vitro data of CYP26 inhibition. After multiple doses of talarozole, a significant increase in atRA concentrations was observed in serum but not in liver or testis. This lack of increase in atRA concentrations correlated with an increase in CYP26A1 expression in the liver. The increased atRA concentrations in serum without a change in liver suggest that CYP26B1 in extrahepatic sites plays a key role in regulating systemic atRA exposure. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  16. Impact of rheumatoid arthritis on receiving a diagnosis of hypertension among patients with regular primary care.

    Science.gov (United States)

    Bartels, Christie M; Johnson, Heather; Voelker, Katya; Thorpe, Carolyn; McBride, Patrick; Jacobs, Elizabeth A; Pandhi, Nancy; Smith, Maureen

    2014-09-01

    Despite numerous studies reporting increased cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA), the impact of RA on managing modifiable CVD risk factors remains understudied. We tested the hypothesis that RA is a risk factor for not receiving a hypertension diagnosis. Using a cohort design, we studied adult patients with and without RA/inflammatory arthritis from a large academic multispecialty practice. All were seen regularly in primary care and met clinical guideline hypertension criteria, but lacked prior hypertension diagnosis/treatment. The primary outcome was time to International Classification of Diseases, Ninth Revision code for hypertension or elevated blood pressure, or antihypertensive medication prescription. Kaplan-Meier survival curve analysis and Cox proportional hazards modeling were used to examine the impact of RA on diagnosis of hypertension. Among 14,974 patients with undiagnosed hypertension, 201 patients had RA codes. RA patients had equivalent primary care visits and more total visits compared to patients without RA. At the end of the study, the likelihood of hypertension diagnosis was 36% in RA patients compared to 51% in patients without RA. In adjusted Cox models, RA patients had a 29% lower hypertension diagnosis hazard (hazard ratio 0.71, 95% confidence interval 0.55-0.93), reflecting more undiagnosed hypertension than with other comorbidities. Among patients meeting guideline-based hypertension criteria, RA patients were less likely to be diagnosed despite more visits than those without RA. Given heightened CVD risks in RA and the importance of hypertension diagnosis as a first step toward controlling risk, rheumatologists should collaborate to improve rates of diagnosis for this modifiable CVD risk factor. Copyright © 2014 by the American College of Rheumatology.

  17. Differential effects of infliximab on absolute circulating blood leucocyte counts of innate immune cells in early and late rheumatoid arthritis patients

    Science.gov (United States)

    Coulthard, L R; Geiler, J; Mathews, R J; Church, L D; Dickie, L J; Cooper, D L; Wong, C; Savic, S; Bryer, D; Buch, M H; Emery, P; Morgan, A W; McDermott, M F

    2012-01-01

    Anti-tumour necrosis factor (TNF) biologics have revolutionized therapy of rheumatoid arthritis (RA). We compared the effects of infliximab on numbers of circulating leucocyte subsets in early RA (disease/symptom duration of ≤1 year) and late RA patients (>1 year). A control group consisted of early RA patients treated with a combination of methotrexate (MTX) and methylprednisolone. Blood samples were obtained at baseline (pre-therapy) from all RA patients, divided into three groups: (i) late RA receiving infliximab/MTX, (ii) early RA–infliximab/MTX, (iii) early RA–steroid/MTX, and also from follow-up patients at 2 and 14 weeks. Significant differences in absolute counts of monocytes and granulocytes were observed between healthy controls and RA patients. At baseline CD14bright monocytes and CD16+ granulocytes were increased in both early RA and late RA patients. CD4+ T cells, CD8+ T cells and B cells were all increased at baseline in early RA, but not in late RA. At 2 weeks following infliximab treatment decreased granulocytes were observed in both early and late RA and decreased natural killer (NK) cells in late RA. CD16+ granulocytes and NK cells were also decreased at 14 weeks post-infliximab in early RA. Biotinylated infliximab was used to detect membrane-associated TNF (mTNF)-expressing leucocytes in RA patients. CD16+ granulocytes, NK cells and CD14dim monocytes all expressed higher levels of mTNF in RA patients. In summary infliximab is associated with decreased CD16+ granulocyte and NK cell counts, possibly through binding of mTNF. Differential effects of infliximab between early and late RA suggest that pathogenic mechanisms change as disease progresses. PMID:22943199

  18. IL-1RA gene-transfected bone marrow-derived mesenchymal stem cells in APA microcapsules could alleviate rheumatoid arthritis.

    Science.gov (United States)

    Hu, Jianhua; Li, Hongjian; Chi, Guanhao; Yang, Zhao; Zhao, Yi; Liu, Wei; Zhang, Chao

    2015-01-01

    In order to investigate the encapsulation of interleukin 1 receptor antagonist (IL-RA) gene-modified mesenchymal stem cells (MSCs) in alginate-poly-L-lysine (APA) microcapsules for the persistent delivery of interleukin 1 receptor antagonist (IL-RA) to treat Rheumatoid arthritis (RA). We transfect mesenchymal stem cells with IL-RA gene, and quantify the IL-RA proteins released from the encapsulated cells followed by microencapsulation of recombinant mesenchymal stem cells, and thus observe the permeability of APA microcapsules and evaluate clinical effects after induction and treatment of collagen-induced arthritis (CIA). The concentration of IL-RA in the supernatant was determined by IL-RA ELISA kit by run in technical triplicates using samples from three separate mice. Encapsulated IL-RA gene-transfected cells were capable of constitutive delivery of IL-RA proteins for at least 30 days. Moreover, the APA microcapsules could inhibit the permeation of fluorescein isothiocyanate-conjuncted immunoglobulin G. Also, it has been found that the APA microcapsules can significantly attenuate collagen induced arthritis after delivering of APA microcapsules to rats. Our results demonstrated that the nonautologous IL-RA gene-transfected stem cells are of potential utility for RA therapy.

  19. Migration area of the Tsushima Warm Current Branches within the Sea of Japan: Implications from transport of 228Ra

    Science.gov (United States)

    Inoue, M.; Shirotani, Y.; Furusawa, Y.; Fujimoto, K.; Kofuji, H.; Yoshida, K.; Nagao, S.; Yamamoto, M.; Hamajima, Y.; Honda, N.; Morimoto, A.; Takikawa, T.; Shiomoto, A.; Isoda, Y.; Minakawa, M.

    2017-07-01

    We investigated lateral profiles of 228Ra (half-life; 5.75 years) activity and 228Ra/226Ra (1600 years) activity ratio using 241 surface water samples collected in/around the Sea of Japan and the East China Sea (ECS) during June-October of 2009-2014. In the ECS, the 228Ra/226Ra ratio in the surface waters exhibited markedly wide variation (mixing between the 228Ra-rich continental shelf water and the 228Ra-depleted Kuroshio Current water. In July, the surface waters of the central Sea of Japan (135-138°E) became separated into three currents: the Offshore Branch of the Tsushima Warm Current (OBTWC) (228Ra/226Ra =0.7-1.2) at 39-41°N, the Coastal Branch of the TWC (CBTWC) ( 0.7) on the southern side, and sub-Arctic Current ( 0.7) on the northern side. From the central to northeastern Sea of Japan, the 228Ra/226Ra ratio at the surface (0.8-1.0) was within a range between that of the CBTWC and OBTWC. The fraction of continental shelf water in the CBTWC, OBTWC, and in their combined current was estimated to be 11-16%, 8%, and 10-11%, respectively.

  20. Transcriptional Regulation in Haematopoiesis:

    DEFF Research Database (Denmark)

    Lauridsen, Felicia K B

    in transplantation studies. Consistent with this, transcriptome profiling revealed very low expression of cell cycle genes in these reporter-dim HSCs. Sequencing of >1200 single HSCs confirmed that the main source of transcriptional heterogeneity was the cell cycle. It also revealed a low-level expression...... of distinct lineage affiliated genes in the otherwise highly purified HSCs. Taken together, these studies demonstrate the use of our model as a tool for isolating superior HSCs, and show that low-level expression of mature lineage markers is inherent in the highly purified stem cell compartment. In the second...... study we profiled the global DNA binding sites of two major players in myeloid differentiation – PU.1 and C/EBPα - together with histone modifications in four successive stages of myeloid differentiation (LSK, preGM, GMP and mature granulocytes). Consistent with their haematopoietic expression patterns...

  1. Euglena Transcript Processing.

    Science.gov (United States)

    McWatters, David C; Russell, Anthony G

    2017-01-01

    RNA transcript processing is an important stage in the gene expression pathway of all organisms and is subject to various mechanisms of control that influence the final levels of gene products. RNA processing involves events such as nuclease-mediated cleavage, removal of intervening sequences referred to as introns and modifications to RNA structure (nucleoside modification and editing). In Euglena, RNA transcript processing was initially examined in chloroplasts because of historical interest in the secondary endosymbiotic origin of this organelle in this organism. More recent efforts to examine mitochondrial genome structure and RNA maturation have been stimulated by the discovery of unusual processing pathways in other Euglenozoans such as kinetoplastids and diplonemids. Eukaryotes containing large genomes are now known to typically contain large collections of introns and regulatory RNAs involved in RNA processing events, and Euglena gracilis in particular has a relatively large genome for a protist. Studies examining the structure of nuclear genes and the mechanisms involved in nuclear RNA processing have revealed that indeed Euglena contains large numbers of introns in the limited set of genes so far examined and also possesses large numbers of specific classes of regulatory and processing RNAs, such as small nucleolar RNAs (snoRNAs). Most interestingly, these studies have also revealed that Euglena possesses novel processing pathways generating highly fragmented cytosolic ribosomal RNAs and subunits and non-conventional intron classes removed by unknown splicing mechanisms. This unexpected diversity in RNA processing pathways emphasizes the importance of identifying the components involved in these processing mechanisms and their evolutionary emergence in Euglena species.

  2. INTERLEUKIN 28 RECEPTOR GENE ALPHA IL28RA AND PSORIASIS: ASSOCIATION WITH DISEASE SEVERITY AND AGE AT ONSET

    Directory of Open Access Journals (Sweden)

    E. S. Galimova

    2015-01-01

    Full Text Available Molecular basis still remains unclear for psoriasis, a chronic inflammatory skin disease. It biological features are presented by abnormal differentiation of epidermal keratinocytes, overgrowth and dilation of blood vessels, and leukocyte infiltration of dermal and epidermal skin layers. These events appear to be driven, mainly, by various cytokines and chemokines released by activated T cell populations. The aim of this replication study was to determine, whether the rs4649203 SNP of IL28RA gene is associated with susceptibility to psoriasis. A total of 341 patients with psoriasis and 407 matched healthy controls were enrolled to carry out a case control study. Genotyping was performed using a Real-Time PCR assay. Our preliminary data suggest that the polymorphism located in IL28RA gene, known to be related to inflammatory and immunity processes, showed an association with patients’ age at onset and the disease severity. The results of this study are promising, with respect to development of a personalized approach to psoriasis treatment.

  3. In vivo study of the HC-TN strain of hepatitis C virus recovered from a patient with fulminant hepatitis: RNA transcripts of a molecular clone (pHC-TN) are infectious in chimpanzees but not in Huh7.5 cells

    DEFF Research Database (Denmark)

    Sakai, Akito; Takikawa, Shingo; Thimme, Robert

    2007-01-01

    Both viral and host factors are thought to influence the pathogenesis of hepatitis C virus (HCV) infection. We studied strain HC-TN (genotype 1a), which caused fulminant hepatic failure in a patient and, subsequently, severe hepatitis in a chimpanzee (CH1422), to analyze the relationship between...... disease severity, host immune response, viral evolution, and outcome. A second chimpanzee (CH1581) was infected from CH1422 plasma, and a third chimpanzee (CH1579) was infected from RNA transcripts of a consensus cDNA of HC-TN (pHC-TN). RNA transcripts of pHC-TN did not replicate in Huh7.5 cells, which...

  4. Promoter-mediated transcriptional dynamics.

    Science.gov (United States)

    Zhang, Jiajun; Zhou, Tianshou

    2014-01-21

    Genes in eukaryotic cells are typically regulated by complex promoters containing multiple binding sites for a variety of transcription factors, but how promoter dynamics affect transcriptional dynamics has remained poorly understood. In this study, we analyze gene models at the transcriptional regulation level, which incorporate the complexity of promoter structure (PS) defined as transcriptional exits (i.e., ON states of the promoter) and the transition pattern (described by a matrix consisting of transition rates among promoter activity states). We show that multiple exits of transcription are the essential origin of generating multimodal distributions of mRNA, but promoters with the same transition pattern can lead to multimodality of different modes, depending on the regulation of transcriptional factors. In turn, for similar mRNA distributions in the models, the mean ON or OFF time distributions may exhibit different characteristics, thus providing the supplemental information on PS. In addition, we demonstrate that the transcriptional noise can be characterized by a nonlinear function of mean ON and OFF times. These results not only reveal essential characteristics of promoter-mediated transcriptional dynamics but also provide signatures useful for inferring PS based on characteristics of transcriptional outputs. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  5. Initiation of HIV Reverse Transcription

    Directory of Open Access Journals (Sweden)

    Roland Marquet

    2010-01-01

    Full Text Available Reverse transcription of retroviral genomes into double stranded DNA is a key event for viral replication. The very first stage of HIV reverse transcription, the initiation step, involves viral and cellular partners that are selectively packaged into the viral particle, leading to an RNA/protein complex with very specific structural and functional features, some of which being, in the case of HIV-1, linked to particular isolates. Recent understanding of the tight spatio-temporal regulation of reverse transcription and its importance for viral infectivity further points toward reverse transcription and potentially its initiation step as an important drug target.

  6. The post-transcriptional operon

    DEFF Research Database (Denmark)

    2011-01-01

    A post-transcriptional operon is a set of monocistronic mRNAs encoding functionally related proteins that are co-regulated by a group of RNA-binding proteins and/or small non-coding RNAs so that protein expression is coordinated at the post-transcriptional level. The post-transcriptional operon...... model (PTO) is used to describe data from an assortment of methods (e.g. RIP-Chip, CLIP-Chip, miRNA profiling, ribosome profiling) that globally address the functionality of mRNA. Several examples of post-transcriptional operons have been documented in the literature and demonstrate the usefulness...

  7. Anti-Toxoplasma antibodies in Egyptian rheumatoid arthritis patients.

    Science.gov (United States)

    El-Henawy, Abeer A; Hafez, Eman Abdel Razek; Nabih, Nairmen; Shalaby, Naglaa M; Mashaly, Mervat

    2017-05-01

    To assess seroprevalence of anti-Toxoplasma gondii antibodies; both IgG and IgM in Egyptian rheumatoid arthritis (RA) patients versus a non-RA group and to compare anti-Toxoplasma antibodies seroprevalence among RA patients receiving traditional treatment and RA patients treated with biologic drug. 60 RA patients and 60 healthy controls were enrolled in the study. Patients were categorized into two groups: one group included 30 patients receiving disease modifying anti-rheumatic drugs (DMARDs), while the other group included 30 patients receiving biologic agent, infliximab, a TNF-α antagonist. Serum samples of all investigated persons were examined for anti-Toxoplasma antibodies. RA activity markers including rheumatoid factor, anti-cyclic citrullinated protein antibodies, C reactive protein, ESR in addition to disease activity score 28 (DAS28) of RA patients were also evaluated to explore their association with Toxoplasma seropositivity. Anti-Toxoplasma IgG antibodies were detected among 46/60 RA patients (76.7%) versus 29/60 controls (48.3%), (p = 0.001). Anti-Toxoplasma IgG titre was higher among RA group [median, (range) = 232.940 (8.949-653.242) IU/ml] than among controls [median, (range) = 68.820 (2.450-318.945) IU/ml], (p Toxoplasma IgG antibodies. No positive anti-Toxoplasma IgM was detected. A positive correlation was detected between anti-Toxoplasma IgG titre and disease activity markers. Higher seroprevalence of anti-Toxoplasma IgG antibodies among RA patients compared to controls reflects an association between latent Toxoplasma infection and RA. Our findings support previous studies and necessitate future large-scale studies to elucidate the exact role of Toxoplasma whether a trigger of autoimmunity in RA or an effect of immunosuppression.

  8. HIV-1 transcription and latency: an update.

    Science.gov (United States)

    Van Lint, Carine; Bouchat, Sophie; Marcello, Alessandro

    2013-06-26

    Combination antiretroviral therapy, despite being potent and life-prolonging, is not curative and does not eradicate HIV-1 infection since interruption of treatment inevitably results in a rapid rebound of viremia. Reactivation of latently infected cells harboring transcriptionally silent but replication-competent proviruses is a potential source of persistent residual viremia in cART-treated patients. Although multiple reservoirs may exist, the persistence of resting CD4+ T cells carrying a latent infection represents a major barrier to eradication. In this review, we will discuss the latest reports on the molecular mechanisms that may regulate HIV-1 latency at the transcriptional level, including transcriptional interference, the role of cellular factors, chromatin organization and epigenetic modifications, the viral Tat trans-activator and its cellular cofactors. Since latency mechanisms may also operate at the post-transcriptional level, we will consider inhibition of nuclear RNA export and inhibition of translation by microRNAs as potential barriers to HIV-1 gene expression. Finally, we will review the therapeutic approaches and clinical studies aimed at achieving either a sterilizing cure or a functional cure of HIV-1 infection, with a special emphasis on the most recent pharmacological strategies to reactivate the latent viruses and decrease the pool of viral reservoirs.

  9. Rheumatoid arthritis patients' experiences of wearing therapeutic footwear - A qualitative investigation

    Directory of Open Access Journals (Sweden)

    Nester Christopher J

    2007-11-01

    Full Text Available Background Specialist 'therapeutic' footwear is recommended for patients with diseases such as rheumatoid arthritis (RA as a beneficial intervention for reducing foot pain, improving foot health, and increasing general mobility. However, many patients choose not to wear this footwear. Recommendations from previous studies have been implemented but have had little impact in improving this situation. The aim of this study was to explore RA patients' experiences of this footwear to ascertain the factors which influence their choice to wear it or not. Method Ten females and three males with RA and experience of wearing specialist footwear were recruited from four National Health Service orthotic services. Semi-structured interviews were carried out in the participants own homes. A hermeneutic phenomenological analysis of the transcripts was carried out to identify themes. Results The analysis revealed two main themes from both the female and male groups. These were the participants' feelings about their footwear and their experiences of the practitioner/s involved in providing the footwear. In addition, further themes were revealed from the female participants. These were feelings about their feet, behaviour associated with the footwear, and their feelings about what would have improved their experience. Conclusion Unlike any other intervention specialist therapeutic footwear replaces something that is normally worn and is part of an individual's body image. It has much more of a negative impact on the female patients' emotions and activities than previously acknowledged and this influences their behaviour with it. The patients' consultations with the referring and dispensing practitioners are pivotal moments within the patient/practitioner relationship that have the potential to influence whether patients choose to wear the footwear or not.

  10. Synthetic transcription elongation factors license transcription across repressive chromatin.

    Science.gov (United States)

    Erwin, Graham S; Grieshop, Matthew P; Ali, Asfa; Qi, Jun; Lawlor, Matthew; Kumar, Deepak; Ahmad, Istaq; McNally, Anna; Teider, Natalia; Worringer, Katie; Sivasankaran, Rajeev; Syed, Deeba N; Eguchi, Asuka; Ashraf, Md; Jeffery, Justin; Xu, Mousheng; Park, Paul M C; Mukhtar, Hasan; Srivastava, Achal K; Faruq, Mohammed; Bradner, James E; Ansari, Aseem Z

    2017-11-30

    Releasing a paused RNA polymerase II into productive elongation is tightly-regulated, especially at genes that impact human development and disease. To exert control over this rate-limiting step, we designed sequence-specific synthetic transcription elongation factors (Syn-TEFs). These molecules are composed of programmable DNA-binding ligands flexibly tethered to a small molecule that engages the transcription elongation machinery. By limiting activity to targeted loci, Syn-TEFs convert constituent modules from broad-spectrum inhibitors of transcription into gene-specific stimulators. We present Syn-TEF1, a molecule that actively enables transcription across repressive GAA repeats that silence frataxin expression in Friedreich's ataxia, a terminal neurodegenerative disease with no effective therapy. Furthermore, the modular design of Syn-TEF1 defines a general framework for developing a class of molecules that license transcription elongation at targeted genomic loci. Copyright © 2017, American Association for the Advancement of Science.

  11. Reconstruction of blood propagation in three-dimensional rotational X-ray angiography (3D-RA).

    Science.gov (United States)

    Schmitt, Holger; Grass, Michael; Suurmond, Rolf; Köhler, Thomas; Rasche, Volker; Hähnel, Stefan; Heiland, Sabine

    2005-10-01

    This paper presents a framework of non-interactive algorithms for the mapping of blood flow information to vessels in 3D-RA images. With the presented method, mapping of flow information to 3D-RA images is done automatically without user interaction. So far, radiologists had to perform this task by extensive image comparisons and did not obtain visualizations of the results. In our approach, flow information is reconstructed by forward projection of vessel pieces in a 3D-RA image to a two-dimensional projection series capturing the propagation of a short additional contrast agent bolus. For accurate 2D-3D image registration, an efficient patient motion compensation technique is introduced. As an exemplary flow-related quantity, bolus arrival times are reconstructed for the vessel pieces by matching of intensity-time curves. A plausibility check framework was developed which handles projection ambiguities and corrects for noisy flow reconstruction results. It is based on a linear programming approach to model the feeding structure of the vessel. The flow reconstruction method was applied to 12 cases of cerebral stenoses, AVMs and aneurysms, and it proved to be feasible in the clinical environment. The propagation of the injected contrast agent was reconstructed and visualized in three-dimensional images. The flow reconstruction method was able to visualize different types of useful information. In cases of stenosis of the middle cerebral artery (MCA), flow reconstruction can reveal impeded blood flow depending on the severeness of the stenosis. With cases of AVMs, flow reconstruction can clarify the feeding structure. The presented methods handle the problems imposed by clinical demands such as non-interactive algorithms, patient motion compensation, short reconstruction times, and technical requirements such as correction of noisy bolus arrival times and handling of overlapping vessel pieces. Problems occurred mainly in the reconstruction and segmentation of 3D-RA

  12. MobC of conjugative RA3 plasmid from IncU group autoregulates the expression of bicistronic mobC-nic operon and stimulates conjugative transfer.

    Science.gov (United States)

    Godziszewska, Jolanta; Kulińska, Anna; Jagura-Burdzy, Grażyna

    2014-09-04

    The IncU conjugative transfer module represents highly efficient promiscuous system widespread among conjugative plasmids of different incompatibility groups. Despite its frequent occurrence the mechanisms of relaxosome formation/action are far from understood. Here we analyzed the putative transfer auxiliary protein MobC of the conjugative plasmid RA3 from the IncU incompatibility group. MobC is a protein of 176 amino acids encoded in the bicistronic operon mobC-nic adjacent to oriT. MobC is homologous to prokaryotic transcription factors of the ribbon-helix-helix (RHH) superfamily. Conserved LxxugxNlNQiaxxLn motif clusters MobC with the clade of conjugative transfer auxilliary proteins of MobP relaxases. MobC forms dimers in solution and autoregulates the expression of mobCp by binding to an imperfect palindromic sequence (OM) located between putative -35 and -10 motifs of the promoter. Medium-copy number test plasmid containing the oriT-mobCp region is mobilized with a high frequency by the RA3 conjugative system. The mutations introduced into OM that abolished MobC binding in vitro decreased 2-3 fold the frequency of mobilization of the test plasmids. The deletion of OM within the RA3 conjugative module had no effect on transfer if the mobC-nic operon was expressed from the heterologous promoter. If only nic was expressed from the heterologous promoter (no mobC) the conjugative transfer frequency of such plasmid was 1000-fold lower. The MobC is an auxiliary transfer protein of dual function. It autoregulates the expression of mobC-nic operon while its presence significantly stimulates transfer efficiency.

  13. Transcription cofactors TRIM24, TRIM28, and TRIM33 associate to form regulatory complexes that suppress murine hepatocellular carcinoma.

    Science.gov (United States)

    Herquel, Benjamin; Ouararhni, Khalid; Khetchoumian, Konstantin; Ignat, Mihaela; Teletin, Marius; Mark, Manuel; Béchade, Guillaume; Van Dorsselaer, Alain; Sanglier-Cianférani, Sarah; Hamiche, Ali; Cammas, Florence; Davidson, Irwin; Losson, Régine

    2011-05-17

    TRIM24 (TIF1α), TRIM28 (TIF1β), and TRIM33 (TIF1γ) are three related cofactors belonging to the tripartite motif superfamily that interact with distinct transcription factors. TRIM24 interacts with the liganded retinoic acid (RA) receptor to repress its transcriptional activity. Germ line inactivation of TRIM24 in mice deregulates RA-signaling in hepatocytes leading to the development of hepatocellular carcinoma (HCC). Here we show that TRIM24 can be purified as at least two macromolecular complexes comprising either TRIM33 or TRIM33 and TRIM28. Somatic hepatocyte-specific inactivation of TRIM24, TRIM28, or TRIM33 all promote HCC in a cell-autonomous manner in mice. Moreover, HCC formation upon TRIM24 inactivation is strongly potentiated by further loss of TRIM33. These results demonstrate that the TIF1-related subfamily of TRIM proteins interact both physically and functionally to modulate HCC formation in mice.

  14. Analytical study of (226)Ra activity concentration in market consuming foodstuffs of Ramsar, Iran.

    Science.gov (United States)

    Gooniband Shooshtari, M; Deevband, M R; Kardan, M R; Fathabadi, N; Salehi, A A; Naddafi, K; Yunesian, M; Nabizadeh Nodehi, R; Karimi, M; Hosseini, S S

    2017-01-01

    Ramsar, a city of Iran located on the coast of the Caspian Sea, has been considered to be enormously important due to its high natural radioactivity levels. People living in High Level Natural Radiation Areas (HLNRAs) have been exposed by several sources, one of which could be foodstuff. However, many studies have been carried out to measure the environmental radioactivity in Ramsar, but no survey has been conducted in all stapled consumed foods yet. This study was dedicated to determine (226)Ra activity concentration in the daily diets of Ramsar residents as a probable exposure. Approximately 70 different market samples were collected during the four seasons based on the daily consumption patterns of residents which have the highest consumption and their availability in the seasons. All samples, after washing, drying and pretreatment, were analyzed for (226)Ra radionuclide determination by α-spectrometry. The mean radioactivity concentration of (226)Ra ranged between 7 ± 1 mBq Kg(-1) wet weight in meat, and 318 ± 118 mBq Kg(-1) for tea dry leaves. The (226)Ra activity concentrations in collected samples varied from below the minimum detectable activity up to 530 ± 30 mBq Kg(-1). To compare the results with United Nations Scientific Committee on Effects of Atomic Radiation (UNSCEAR) reference values, the (226)Ra activity concentrations concluded from the results appear to be higher in milk, chicken and eggs and less in grain products, vegetables, fruits and fish products. These results indicate that no significant (226)Ra contamination is present in market foodstuffs and provide reference values for the foodstuffs in Ramsar. Of the total daily dietary (226)Ra exposure from market consuming foodstuffs for adults in Ramsar, the largest percentage was from wheat. The residents consuming wheat and manufacturing wheat products such as bread, pasta, porridge, crackers, biscuits, pancakes, pies, pastries, cakes, cookies, muffins, rolls, doughnuts, breakfast

  15. Single Ra{sup +} ion spectroscopy - towards a measurement of atomic parity violation

    Energy Technology Data Exchange (ETDEWEB)

    Nunez Portela, Mayerlin; Mohanti, A.; Dijck, E.A.; Bekker, H.; Boell, O.; Berg, J. van den; Giri, G.S.; Jungmann, K.; Onderwater, C.J.G.; Santra, B.; Timmermans, R.G.E.; Versolato, O.O.; Wansbeek, L.W.; Willmann, L.; Wilschut, H.W. [KVI, University of Groningen, Groningen (Netherlands)

    2013-07-01

    The sensitivity of the Atomic Parity Violation (APV) signal grows faster than the third power of the atomic number Z. Ra{sup +} (Z=88) is heaviest alkaline earth ion available. A single trapped Ra{sup +} ion opens a very promising path for a measurement atomic parity violation. One of the experimental challenges is the localization of the ion within a fraction of an optical wavelength. For this the current experiments are focused on trapping and laser cooling of Ba{sup +} ions as a precursor for Ra{sup +}. Ba{sup +} ions are trapped and laser cooled in a precision hyperbolic Paul trap. Work towards single Ba{sup +} ion localization and detection is in progress. Recently the hyperfine structure of the 6d{sub 2}D{sub 3/2} states and the isotope shift of the 6d{sub 2}D{sub 3/2}-7p{sub 2}P{sub 1/2} transition in the isotopes {sup 209-214}Ra{sup +} has been measured in online laser spectroscopy experiments at the KVI AGOR/TRIμP facility. These results are essential for the interpretation of an APV measurement in Ra{sup +}.

  16. A Dual Key-Based Activation Scheme for Secure LoRaWAN

    Directory of Open Access Journals (Sweden)

    Jaehyu Kim

    2017-01-01

    Full Text Available With the advent of the Internet of Things (IoT era, we are experiencing rapid technological progress. Billions of devices are connected to each other, and our homes, cities, hospitals, and schools are getting smarter and smarter. However, to realize the IoT, several challenging issues such as connecting resource-constrained devices to the Internet must be resolved. Recently introduced Low Power Wide Area Network (LPWAN technologies have been devised to resolve this issue. Among many LPWAN candidates, the Long Range (LoRa is one of the most promising technologies. The Long Range Wide Area Network (LoRaWAN is a communication protocol for LoRa that provides basic security mechanisms. However, some security loopholes exist in LoRaWAN’s key update and session key generation. In this paper, we propose a dual key-based activation scheme for LoRaWAN. It resolves the problem of key updates not being fully supported. In addition, our scheme facilitates each layer in generating its own session key directly, which ensures the independence of all layers. Real-world experimental results compared with the original scheme show that the proposed scheme is totally feasible in terms of delay and battery consumption.

  17. Castration modulates singing patterns and electrophysiological properties of RA projection neurons in adult male zebra finches

    Directory of Open Access Journals (Sweden)

    Songhua Wang

    2014-04-01

    Full Text Available Castration can change levels of plasma testosterone. Androgens such as testosterone play an important role in stabilizing birdsong. The robust nucleus of the arcopallium (RA is an important premotor nucleus critical for singing. In this study, we investigated the effect of castration on singing patterns and electrophysiological properties of projection neurons (PNs in the RA of adult male zebra finches. Adult male zebra finches were castrated and the changes in bird song assessed. We also recorded the electrophysiological changes from RA PNs using patch clamp recording. We found that the plasma levels of testosterone were significantly decreased, song syllable’s entropy was increased and the similarity of motif was decreased after castration. Spontaneous and evoked firing rates, membrane time constants, and membrane capacitance of RA PNs in the castration group were lower than those of the control and the sham groups. Afterhyperpolarization AHP time to peak of spontaneous action potential (AP was prolonged after castration.These findings suggest that castration decreases song stereotypy and excitability of RA PNs in male zebra finches.

  18. La Realidad Aumentada (RA. Recursos y propuestas para la innovación educativa

    Directory of Open Access Journals (Sweden)

    Javier J. Maquilón Sánchez

    2017-01-01

    Full Text Available Este artículo contiene una propuesta de experiencia práctica de enseñanza-­‐aprendizaje, basada en la realidad aumentada (RA como recurso didáctico innovador. RA es tanto un concepto como una tecnología 3D interactiva actualmente en desarrollo. Por este motivo, en primer lugar se ha expuesto, por un lado, qué es la RA y, por otro lado, cuáles son las variantes tecnológicas actuales principales. Seguidamente, se ha hecho un análisis reflexivo de varios aspectos, que el docente ha de considerar respecto a la RA como tecnología aplicada a la educación, destacando la aportación innovadora de la RA como recurso didáctico. Finalmente se presenta el diseño y la elaboración de la actividad, tipo webquest que incluye un blog de aula.

  19. Knock-Down of IL-1Ra in Obese Mice Decreases Liver Inflammation and Improves Insulin Sensitivity

    Science.gov (United States)

    Franck, Niclas; Maris, Michael; Nalbandian, Sarah; Talukdar, Saswata; Schenk, Simon; Hofmann, Hans-Peter; Bullough, David; Osborn, Olivia

    2014-01-01

    Interleukin 1 Receptor antagonist (IL-1Ra) is highly elevated in obesity and is widely recognized as an anti-inflammatory cytokine. While the anti-inflammatory role of IL-1Ra in the pancreas is well established, the role of IL-1Ra in other insulin target tissues and the contribution of systemic IL-1Ra levels to the development of insulin resistance remains to be defined. Using antisense knock down of IL-1Ra in vivo, we show that normalization of IL-1Ra improved insulin sensitivity due to decreased inflammation in the liver and improved hepatic insulin sensitivity and these effects were independent of changes in body weight. A similar effect was observed in IL1-R1 KO mice, suggesting that at high concentrations of IL-1Ra typically observed in obesity, IL-1Ra can contribute to the development of insulin resistance in a mechanism independent of IL-1Ra binding to IL-1R1. These results demonstrate that normalization of plasma IL-1Ra concentration improves insulin sensitivity in diet- induced obese mice. PMID:25244011

  20. Knock-down of IL-1Ra in obese mice decreases liver inflammation and improves insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Niclas Franck

    Full Text Available Interleukin 1 Receptor antagonist (IL-1Ra is highly elevated in obesity and is widely recognized as an anti-inflammatory cytokine. While the anti-inflammatory role of IL-1Ra in the pancreas is well established, the role of IL-1Ra in other insulin target tissues and the contribution of systemic IL-1Ra levels to the development of insulin resistance remains to be defined. Using antisense knock down of IL-1Ra in vivo, we show that normalization of IL-1Ra improved insulin sensitivity due to decreased inflammation in the liver and improved hepatic insulin sensitivity and these effects were independent of changes in body weight. A similar effect was observed in IL1-R1 KO mice, suggesting that at high concentrations of IL-1Ra typically observed in obesity, IL-1Ra can contribute to the development of insulin resistance in a mechanism independent of IL-1Ra binding to IL-1R1. These results demonstrate that normalization of plasma IL-1Ra concentration improves insulin sensitivity in diet- induced obese mice.

  1. Adaptation with transcriptional regulation

    Science.gov (United States)

    Shi, Wenjia; Ma, Wenzhe; Xiong, Liyang; Zhang, Mingyue; Tang, Chao

    2017-02-01

    Biochemical adaptation is one of the basic functions that are widely implemented in biological systems for a variety of purposes such as signal sensing, stress response and homeostasis. The adaptation time scales span from milliseconds to days, involving different regulatory machineries in different processes. The adaptive networks with enzymatic regulation (ERNs) have been investigated in detail. But it remains unclear if and how other forms of regulation will impact the network topology and other features of the function. Here, we systematically studied three-node transcriptional regulatory networks (TRNs), with three different types of gene regulation logics. We found that the topologies of adaptive gene regulatory networks can still be grouped into two general classes: negative feedback loop (NFBL) and incoherent feed-forward loop (IFFL), but with some distinct topological features comparing to the enzymatic networks. Specifically, an auto-activation loop on the buffer node is necessary for the NFBL class. For IFFL class, the control node can be either a proportional node or an inversely-proportional node. Furthermore, the tunability of adaptive behavior differs between TRNs and ERNs. Our findings highlight the role of regulation forms in network topology, implementation and dynamics.

  2. [Pattern of serum cytokines in patients with rheumatoid artritis according to PPD reactivity].

    Science.gov (United States)

    de León Pandolfi, Darío Ponce; Pastor Asurza, César; Beraun, Yasmina; Acevedo-Vásquez, Eduardo; Sánchez-Torres, Alfredo; Alfaro Lozano, José; Perich Campos, Risto; Cucho Venegas, Mariano; Gutiérrez Villafuerte, César; Sánchez Schwartz, César

    2006-11-01

    We demonstrated, in a recently published study, far more PPD negative reactivity among patients who had RA (70%) than among controls (30%). To evaluate the hypothesis that different response to PPD in RA patients is associated with different profiles of serum cytokines, we compared the serum levels of IL-2, IL-4, IL-6, IL-10, TNF alpha and IFN gamma from PPD negative and PPD positive RA patients. We also evaluated any correlations between serum cytokines and RA activity. Forty RA patients and 21 controls were enrolled. Those with an induration < 5mm were considered as negative and those with ≥ 5mm as positive PPD. Disease activity was calculated using DAS28. Plasma levels of cytokines were determined using the multiplex BD TM Cytometric Bead Array Kit Assay. Of the RA patients, 27 (67.5%) had negative reaction to PPD and 13 (32.5%) a positive reaction to PPD. There was no statistical difference in sex profile, age or activity index between both negative and positive PPD RA patients. There was no significant difference in all the cytokines measured between PPD positive and PPD negative RA patients. Index activity show a positive correlation with IFN gamma (r = 0.433; p = 0.005) and IL-6 (r = 0.325; p = 0.041) in RA patients. Positive and negative tuberculin RA patients seem to show a similar cytokine serum profile. Copyright © 2006 Elsevier España S.L. Barcelona. Published by Elsevier Espana. All rights reserved.

  3. Transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers.

    Science.gov (United States)

    Bloom, Chloe I; Graham, Christine M; Berry, Matthew P R; Rozakeas, Fotini; Redford, Paul S; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A; Wilkinson, Robert J; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Valeyre, Dominique; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-Pei; Lipman, Marc; O'Garra, Anne

    2013-01-01

    New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment.

  4. Disease Characteristics and Rheumatoid Arthritis Development in Patients with Early Undifferentiated Arthritis: A 2-year Followup Study.

    Science.gov (United States)

    Brinkmann, Gina H; Norli, Ellen S; Kvien, Tore K; Haugen, Anne J; Grøvle, Lars; Nygaard, Halvor; Bjørneboe, Olav; Thunem, Cathrine; Mjaavatten, Maria D; Lie, Elisabeth

    2017-02-01

    To examine the 2-year disease course in patients with undifferentiated arthritis (UA) focusing on fulfillment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) rheumatoid arthritis (RA) classification criteria. Data were provided by the Norwegian Very Early Arthritis Clinic study, which included patients presenting with ≥ 1 swollen joint of ≤ 16 weeks' duration. UA was defined as patients not fulfilling the 2010 ACR/EULAR RA criteria and who did not have a clinical diagnosis other than RA at baseline. The main outcome was fulfillment of the 2010 RA criteria. Secondary outcomes were disease-modifying antirheumatic drug (DMARD) use, resolution of synovitis without use of DMARD during followup, and final clinical diagnosis. We included 477 patients with UA of whom 47 fulfilled the 2010 ACR/EULAR RA criteria during followup (UA-RA) and 430 did not (UA-non-RA). Of the UA-RA patients, 70% fulfilled the criteria within the first 6 months. UA-RA patients were older, more often positive for rheumatoid factor and anticitrullinated protein antibodies, female, and ever smokers, and they more often presented with polyarticular arthritis, small joint involvement, and a swollen shoulder joint. During followup, 53% of UA-RA patients vs 13% of UA-non-RA patients used DMARD (p arthritis resolved without use of DMARD.

  5. Effects of natural mutations in the ramRA locus on invasiveness of epidemic fluoroquinolone-resistant Salmonella enterica serovar Typhimurium isolates.

    Science.gov (United States)

    Giraud, Etienne; Baucheron, Sylvie; Virlogeux-Payant, Isabelle; Nishino, Kunihiko; Cloeckaert, Axel

    2013-03-01

    Fluoroquinolone (FQ) resistance is increasing worldwide among Salmonella species. Among the mechanisms involved, increased efflux via the tripartite AcrAB-TolC efflux system is mainly modulated through control of expression via the ramRA regulatory locus gene products. Interestingly, in some reference strains these have also been experimentally shown to regulate cell invasion-related genes of the type III secretion system 1 (T3SS-1). In this study, we investigated whether natural mutations occurring in this locus in FQ-resistant S. enterica serovar Typhimurium epidemic clones resulted in the same effects. Quantitative reverse transcription polymerase chain reaction and cell invasion assays were used to study 3 clinical FQ-resistant S. Typhimurium isolates representative of the DT104 and DT204 epidemic clones. For comparison, 3 control reference quinolone-susceptible strains were included. As previously shown, the investigated mutations altering RamR or its DNA-binding site increased expression of efflux genes dependently on ramA. However, the decreased expression of T3SS-1 genes previously reported was not always observed and seemed to be dependent on the genetic background of the FQ-resistant isolate. Indeed, a ramA-dependent decreased invasion of intestinal epithelial cells was only observed for a particular clinical ramR mutant. ramRA mutations occurring in clinical FQ-resistant S. Typhimurium isolates may negatively modulate their invasiveness but this is strain-dependent.

  6. Mitotic bookmarking by transcription factors.

    Science.gov (United States)

    Kadauke, Stephan; Blobel, Gerd A

    2013-04-02

    Mitosis is accompanied by dramatic changes in chromatin organization and nuclear architecture. Transcription halts globally and most sequence-specific transcription factors and co-factors are ejected from mitotic chromatin. How then does the cell maintain its transcriptional identity throughout the cell division cycle? It has become clear that not all traces of active transcription and gene repression are erased within mitotic chromatin. Many histone modifications are stable or only partially diminished throughout mitosis. In addition, some sequence-specific DNA binding factors have emerged that remain bound to select sites within mitotic chromatin, raising the possibility that they function to transmit regulatory information through the transcriptionally silent mitotic phase, a concept that has been termed "mitotic bookmarking." Here we review recent approaches to studying potential bookmarking factors with regards to their mitotic partitioning, and summarize emerging ideas concerning the in vivo functions of mitotically bound nuclear factors.

  7. Impact of 5-HT(3) RA selection within triple antiemetic regimens on uncontrolled highly emetogenic chemotherapy-induced nausea/vomiting.

    Science.gov (United States)

    Schwartzberg, Lee; Jackson, James; Jain, Gagan; Balu, Sanjeev; Buchner, Deborah

    2011-08-01

    It is recommended that patients initiate triple antiemetic therapy with one of the 5-hydroxytryptamine receptor antagonists (5-HT(3) RAs), aprepitant (or its intravenous prodrug fosaprepitant) and dexamethasone prior to the start of highly emetogenic chemotherapy (HEC). However, the impact of 5-HT(3) RA selection within triple antiemetic regimens on the risk of uncontrolled chemotherapy-induced nausea and vomiting (CINV) with HEC has not been well studied. To assess the likelihood of an uncontrolled CINV event following antiemetic prophylaxis with the 5-HT(3) RA palonosetron + aprepitant/fosaprepitant + dexamethasone (palonosetron cohort) versus any of the other 5-HT(3) RAs + aprepitant/fosaprepitant + dexamethasone (other 5-HT(3) RA cohort) among single-day HEC cycles. Single-day HEC cycles (a gap of at least 5 days between two administrations) among patients with a cancer diagnosis and receiving antiemetic prophylaxis with the aforementioned regimens between 1/1/2006 and 6/30/2010 were identified from the IMS LifeLink claims database. Uncontrolled CINV events were identified through ICD-9-CM codes (nausea and vomiting), Current Procedural Terminology codes (hydration), rescue medications and/or use of antiemetic therapy from days 2-5 following HEC administration. Risks for an uncontrolled CINV event among all patients, and within breast cancer and multiple cancer subpopulations, were analyzed at cycle level using logistic multivariate regression models. A total of 8018 cycles for the palonosetron cohort and 1926 cycles for the other 5-HT(3) RA cohort (3574 and 978 patients, respectively) were analyzed. Single-day HEC cycles received by the palonosetron cohort had a significantly lower unadjusted risk of an uncontrolled CINV event (17.5 vs 20.7% for the other 5-HT(3) RA cohort; p = 0.0010), with a 17% lower adjusted risk for palonosetron-administered cycles (odds ratio: 0.83; 95% CI: 0.73-0.94; p = 0.0042). Results in the breast cancer and multiple cancer

  8. Angiopoietin-1 upregulates de novo expression of IL-1β and Il1-Ra, and the exclusive release of Il1-Ra from human neutrophils.

    Science.gov (United States)

    Haddad, Lydia E; Sirois, Martin G

    2014-01-01

    The expression of the angiopoietin (Ang) receptor, Tie2, on both endothelial and inflammatory cells supports the idea that Ang signaling may play a fundamental role in initiating and maintaining the inflammatory response. We have previously shown that Ang1 and/or Ang2 alter the innate immune response by enhancing human neutrophil survival, chemotaxis and production of inflammatory cytokine interleukin-8 (IL-8) in vitro. Thus, we hypothesized that Ang1 and Ang2 could modulate other inflammatory signals in neutrophils, a possibility we explored through a gene-based assay looking at changes in the mRNA expression of 84 inflammatory cytokines and their receptors. We observed that Ang1 (10(-8) M), but not Ang2, increased mRNA expression of prominent pro-inflammatory cytokine IL-1β and its natural antagonist IL-1RA, by up to 32.6- and 10.0-fold respectively, compared to PBS-control. The effects of Ang1 extended to the proteins, as Ang1 increased intracellular levels of precursor and mature IL-1β, and extracellular levels of IL-1RA proteins, by up to 4.2-, 5.0- and 4.4-fold respectively, compared to PBS-control. Interestingly, Ang1 failed at inducing IL-1β protein release or at increasing intracellular IL-1RA, but the ratio of IL-1RA to mature IL-1β remained above 100-fold molar excess inside and outside the cells. The above-noted effects of Ang1 were mediated by MAP kinases, whereby inhibiting MEK1/2 lead to up to 70% effect reduction, whereas the blockade of p38MAPK activity doubled Ang1's effect. These findings suggest that Ang1 selectively alters the balance of neutrophil-derived inflammatory cytokines, favoring the blockade of IL-1 activity, a consideration for future therapies of inflammatory diseases.

  9. Angiopoietin-1 upregulates de novo expression of IL-1β and Il1-Ra, and the exclusive release of Il1-Ra from human neutrophils.

    Directory of Open Access Journals (Sweden)

    Lydia E Haddad

    Full Text Available The expression of the angiopoietin (Ang receptor, Tie2, on both endothelial and inflammatory cells supports the idea that Ang signaling may play a fundamental role in initiating and maintaining the inflammatory response. We have previously shown that Ang1 and/or Ang2 alter the innate immune response by enhancing human neutrophil survival, chemotaxis and production of inflammatory cytokine interleukin-8 (IL-8 in vitro. Thus, we hypothesized that Ang1 and Ang2 could modulate other inflammatory signals in neutrophils, a possibility we explored through a gene-based assay looking at changes in the mRNA expression of 84 inflammatory cytokines and their receptors. We observed that Ang1 (10(-8 M, but not Ang2, increased mRNA expression of prominent pro-inflammatory cytokine IL-1β and its natural antagonist IL-1RA, by up to 32.6- and 10.0-fold respectively, compared to PBS-control. The effects of Ang1 extended to the proteins, as Ang1 increased intracellular levels of precursor and mature IL-1β, and extracellular levels of IL-1RA proteins, by up to 4.2-, 5.0- and 4.4-fold respectively, compared to PBS-control. Interestingly, Ang1 failed at inducing IL-1β protein release or at increasing intracellular IL-1RA, but the ratio of IL-1RA to mature IL-1β remained above 100-fold molar excess inside and outside the cells. The above-noted effects of Ang1 were mediated by MAP kinases, whereby inhibiting MEK1/2 lead to up to 70% effect reduction, whereas the blockade of p38MAPK activity doubled Ang1's effect. These findings suggest that Ang1 selectively alters the balance of neutrophil-derived inflammatory cytokines, favoring the blockade of IL-1 activity, a consideration for future therapies of inflammatory diseases.

  10. Identification of activated cytokine pathways in the blood of systemic lupus erythematosus, myositis, rheumatoid arthritis, and scleroderma patients.

    Science.gov (United States)

    Higgs, Brandon W; Zhu, Wei; Richman, Laura; Fiorentino, David F; Greenberg, Steven A; Jallal, Bahija; Yao, Yihong

    2012-02-01

    To develop genomic signatures of seven cytokines involved in the pathogenesis of rheumatic diseases such as systemic lupus erythematosus (SLE), dermatomyositis (DM), polymyositis (PM), rheumatoid arthritis (RA), or systemic scleroderma (SSc) that could potentially help identify patients likely to respond to therapies that target these individual cytokines. Over-expressed transcripts in the whole blood (WB) were identified from 262 SLE, 44 DM, 33 PM, 38 SSc and 89 RA subjects and compared to 24 healthy subjects using Affymetrix arrays. Cytokine-inducible gene signatures such as type I interferon (IFN), tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-10, IL-13, IL-17, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were assessed in the WB of these subjects to identify subpopulations showing activation of specific cytokine pathways. Significant activation of the type I IFN pathway in a population of five diseases studied was universally observed. The TNF-α and IL-1β pathways were activated in subgroups of PM and RA subjects, respectively, with another subgroup of RA subjects showing activation of the IL-13 pathway. The GM-CSF pathway was activated in a subgroup of SSc subjects and the IL-17 pathway was activated in subgroups of all diseases except SLE. A novel gene expression measurement of activated cytokines in five different rheumatic diseases is presented. Characterizing the cytokine pathways most activated in specific patient subpopulations has the potential to help target the appropriate patient populations for corresponding anti-cytokine therapies. © 2011 The Authors. International Journal of Rheumatic Diseases © 2011 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd.

  11. IL-17A induces signal transducers and activators of transcription-6-independent airway mucous cell metaplasia.

    Science.gov (United States)

    Newcomb, Dawn C; Boswell, Madison G; Sherrill, Taylor P; Polosukhin, Vasiliy V; Boyd, Kelli L; Goleniewska, Kasia; Brody, Steven L; Kolls, Jay K; Adler, Kenneth B; Peebles, R Stokes

    2013-06-01

    Mucous cell metaplasia is a hallmark of asthma, and may be mediated by signal transducers and activators of transcription (STAT)-6 signaling. IL-17A is increased in the bronchoalveolar lavage fluid of patients with severe asthma, and IL-17A also increases mucus production in airway epithelial cells. Asthma therapeutics are being developed that inhibit STAT6 signaling, but the role of IL-17A in inducing mucus production in the absence of STAT6 remains unknown. We hypothesized that IL-17A induces mucous cell metaplasia independent of STAT6, and we tested this hypothesis in two murine models in which increased IL-17A protein expression is evident. In the first model, ovalbumin (OVA)-specific D011.10 Th17 cells were adoptively transferred into wild-type (WT) or STAT6 knockout (KO) mice, and the mice were challenged with OVA or PBS. WT-OVA and STAT6 KO-OVA mice demonstrated increased airway IL-17A and IL-13 protein expression and mucous cell metaplasia, compared with WT-PBS or STAT6 KO-PBS mice. In the second model, WT, STAT1 KO, STAT1/STAT6 double KO (DKO), or STAT1/STAT6/IL-17 receptor A (RA) triple KO (TKO) mice were challenged with respiratory syncytial virus (RSV) or mock viral preparation, and the mucous cells were assessed. STAT1 KO-RSV mice demonstrated increased airway mucous cell metaplasia compared with WT-RSV mice. STAT1 KO-RSV and STAT1/STAT6 DKO-RSV mice also demonstrated increased mucous cell metaplasia, compared with STAT1/STAT6/IL17RA TKO-RSV mice. We also treated primary murine tracheal epithelial cells (mTECs) from WT and STAT6 KO mice. STAT6 KO mTECs showed increased periodic acid-Schiff staining with IL-17A but not with IL-13. Thus, asthma therapies targeting STAT6 may increase IL-17A protein expression, without preventing IL-17A-induced mucus production.

  12. Dysregulation of RNA polymerase I transcription during disease.

    Science.gov (United States)

    Hannan, K M; Sanij, E; Rothblum, L I; Hannan, R D; Pearson, R B

    2013-01-01

    Transcription of the ribosomal RNA genes by the dedicated RNA polymerase I enzyme and subsequent processing of the ribosomal RNA are fundamental control steps in the synthesis of functional ribosomes. Dysregulation of Pol I transcription and ribosome biogenesis is linked to the etiology of a broad range of human diseases. Diseases caused by loss of function mutations in the molecular constituents of the ribosome, or factors intimately associated with RNA polymerase I transcription and processing are collectively termed ribosomopathies. Ribosomopathies are generally rare and treatment options are extremely limited tending to be more palliative than curative. Other more common diseases are associated with profound changes in cellular growth such as cardiac hypertrophy, atrophy or cancer. In contrast to ribosomopathies, altered RNA polymerase I transcriptional activity in these diseases largely results from dysregulated upstream oncogenic pathways or by direct modulation by oncogenes or tumor suppressors at the level of the RNA polymerase I transcription apparatus itself. Ribosomopathies associated with mutations in ribosomal proteins and ribosomal RNA processing or assembly factors have been covered by recent excellent reviews. In contrast, here we review our current knowledge of human diseases specifically associated with dysregulation of RNA polymerase I transcription and its associated regulatory apparatus, including some cases where this dysregulation is directly causative in disease. We will also provide insight into and discussion of possible therapeutic approaches to treat patients with dysregulated RNA polymerase I transcription. This article is part of a Special Issue entitled: Transcription by Odd Pols. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Histological features of rheumatoid arthritis patients having antibodies to enterobacterial common antigens: correlation of antibody levels with semiquantitative histologic scores and laboratory markers.

    Science.gov (United States)

    Aoki, S; Mitsui, T

    2005-01-01

    To ascertain whether clinically diagnosed rheumatoid arthritis (RA) patients having antibodies to enterobacterial common antigens (ECA) in synovial fluid (SF) have a histological appearance characteristic of RA synovitis. Twenty-five RA patients for which synovial biopsy specimens were preserved, were selected from 58 patients with RA tested for antibodies to ECA in SF The synovial tissue specimens were examined histologically using a semiquantitative scoring system with quantitative counts. The correlation of anti-ECA antibody levels with total scores for synovitis and laboratory markers in three RA patient groups (markedly positive, moderately to slightly positive, and negative according to anti-ECA antibody levels) was analyzed statistically. Histologic examination in the markedly positive RA group (total score for synovitis, range 18-20 points) revealed typical histological features of rheumatoid synovitis. Total scores for synovitis were significantly higher in both the markedly positive and moderately to slightly positive RA groups than in the negative RA group. A comparison of anti-ECA antibody levels with total scores for synovitis revealed a strong and significant correlation. Furthermore, levels of anti-ECA antibodies were also correlated with rheumatoid factor and C-reactive protein. Clinically diagnosed RA patients having anti-ECA antibodies in SF showed typical or characteristic histological features of RA synovitis. Our data suggest that a group of RA patients with an entrobacterial etiology exists in larger groups of patients with RA which is thought to be a heterogeneous disease.

  14. A comparative study of different radiometric methodologies for the determination of 226Ra in water

    Directory of Open Access Journals (Sweden)

    Ibrahim F. Al-Hamarneh

    2018-02-01

    Full Text Available An evaluation of various radiometric methods to analyze 226Ra in water has been employed on a set of 10 standard solutions of different concentrations in the range of 1–10 Bq/L−1. The analysis was carried out using well-established procedures by means of gamma-ray, alpha-particle and liquid scintillation spectrometry. The feasibility of the various methods has been quantified in terms of relative standard error and percentage error. Correlations between the various methods have been presented and discussed. In general, good agreement was found in the results of various methodologies, which assures the accuracy of the methods and allows for the validation of instrumentation and procedures. Of the different methods adopted here, a combined procedure for the determination of 226Ra along with 228Ra using Quantulus 1220 ultra-low level background liquid scintillation counting gave the most accurate results.

  15. Determination of {sup 226}Ra in urine samples by alpha spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Kehagia, K.; Potiriadis, C.; Bratakos, S.; Koukouliou, V.; Drikos, G. [Greek Atomic Energy Commission, PO Box 60092, Agia Paraskevi, Attiki 15310 (Greece)

    2007-07-01

    A radiation protection system to assess the internal contamination of workers during decontamination activities in an abounded fertilizer industry in the region of Attika, Greece, has been implemented. This system concerns, among other radionuclides, {sup 226}Ra. Because of the low {sup 226}Ra activities in urine, alpha spectrometry was used as the determination method after radiochemical separation. Radium was co precipitated with lead sulphate and purified using anion and cation exchange techniques. The source for the alpha spectrometric measurement was prepared by the electrodeposition of radium, from an aqueous/ethanol solution, onto stainless steel. The tracer used was {sup 229}Th. The chemical yield and the activity concentration were calculated via its daughter radionuclide {sup 217}At. Using the time-evolution formulas to calculate the {sup 217}At growth from its parent radionuclide {sup 225}Ra, a computer software was developed. This software was incorporated in a database, which automatically calculates and stores the results. (authors)

  16. Geology and Topography of Ra Patera, Io, in the Voyager era: Prelude to Eruption

    Science.gov (United States)

    Schenk, Paul M.; McEwen, Alfred; Davies, A. G.; Davenport, Trevor; Jones, Kevin; Fessler, Brian

    1997-01-01

    Voyager era stereo images are used to map the geology and topography of Ra Patera (a major active volcanic center and possible site of sulfur eruptions on Io). The summit of Ra Patera reaches only approx.1 km above the surrounding plains. Pre-Voyager-era lava flows occur on slopes of 0.1-0.3 deg, comparable to the lunar mare. These flows were emplaced at either low viscosities, high eruption rates, or both. A 600- km-long ridged mountain unit (rising to approx. 8 km near Carancho Patera) forms a 60 by 90 km wide plateau approx. 0.5 km high 50 km east of Ra Patera. The new lava flows observed by Galileo flowed around the southern edge of this plateau.

  17. A Study of LoRa: Long Range & Low Power Networks for the Internet of Things

    Directory of Open Access Journals (Sweden)

    Aloÿs Augustin

    2016-09-01

    Full Text Available LoRa is a long-range, low-power, low-bitrate, wireless telecommunications system, promoted as an infrastructure solution for the Internet of Things: end-devices use LoRa across a single wireless hop to communicate to gateway(s, connected to the Internet and which act as transparent bridges and relay messages between these end-devices and a central network server. This paper provides an overview of LoRa and an in-depth analysis of its functional components. The physical and data link layer performance is evaluated by field tests and simulations. Based on the analysis and evaluations, some possible solutions for performance enhancements are proposed.

  18. Lasercooled RaF as a promising candidate to measure molecular parity violation

    CERN Document Server

    Isaev, T A; Berger, R

    2010-01-01

    The parameter $W_\\mathrm{a}$, which characterizes nuclear spin-dependent parity violation effects within the effective molecular spin-rotational Hamiltonian, was computed for the electronic ground state of radium fluoride (RaF) and found to be one of the largest absolute values predicted so far. These calculations were performed with the complex generalised Hartree-Fock method within a two-component (quasi-relativistic) zeroth-order regular approximation framework. Peculiarities of the molecular electronic structure of RaF lead to highly diagonal Franck-Condon matrices between vibrational states of the electronic ground and first excited states, which renders the molecule in principle suitable for direct laser cooling. As a trapped gas of cold molecules offers a superior coherence time, RaF can be considered a promising candidate for high-precision spectroscopic experiments aimed at the search of molecular parity-violation effects.

  19. A Study of LoRa: Long Range & Low Power Networks for the Internet of Things.

    Science.gov (United States)

    Augustin, Aloÿs; Yi, Jiazi; Clausen, Thomas; Townsley, William Mark

    2016-09-09

    LoRa is a long-range, low-power, low-bitrate, wireless telecommunications system, promoted as an infrastructure solution for the Internet of Things: end-devices use LoRa across a single wireless hop to communicate to gateway(s), connected to the Internet and which act as transparent bridges and relay messages between these end-devices and a central network server. This paper provides an overview of LoRa and an in-depth analysis of its functional components. The physical and data link layer performance is evaluated by field tests and simulations. Based on the analysis and evaluations, some possible solutions for performance enhancements are proposed.

  20. Production of Ac-225 for cancer therapy by photon-induced transmutation of Ra-226.

    Science.gov (United States)

    Melville, G; Meriarty, H; Metcalfe, P; Knittel, T; Allen, B J

    2007-09-01

    The increasing application of Ac-225 for cancer therapy indicates the potential need for its increased production and availability. The production of Ac-225 has been achieved using bremsstrahlung photons from an 18 MV medical linear accelerator (linac) to bombard a Ra-226 target. A linac dose of 2800 Gy produced about 64 microCi of Ra-225, which decays to Ac-225. This result, while consistent with the theoretical calculations, is far too low to be of practical use. A more powerful linac is required that runs at a higher current, longer pulse length and higher frequency for practical production. This process could also lead to the reduction of the nuclear waste product Ra-226.

  1. Diatom species composition in the Raška river (Southwestern Serbia

    Directory of Open Access Journals (Sweden)

    Vidaković Danijela P.

    2015-01-01

    Full Text Available The paper presents data on the composition of epilithic diatoms in the Raška River. Samples were collected by scraping stone surfaces with a brush from 5 localities along the Raška River in April, June, August and November 2011 and March and May 2012. Diatom frustules were cleaned using cold acid method, and mounted on permanent slides. An investigation of the Raška River resulted in description of 106 diatom taxa. The most species rich genera are Navicula (10, Gomphonema (10 and Nitzschia (9, while other genera are presented with one or more species. Detailed floristic analysis of the benthic diatom flora in this river has not been conducted before. Therefore, this paper provides a groundwork for future researches. [Projekat Ministarstva nauke Republike Srbije, br. TR 037009

  2. A survey on LPWA technology: LoRa and NB-IoT

    Directory of Open Access Journals (Sweden)

    Rashmi Sharan Sinha

    2017-03-01

    Full Text Available By 2020, more than twenty five billion devices would be connected through wireless communications. In accordance with the rapid growth of the internet of things (IoT market, low power wide area (LPWA technologies have become popular. In various LPWA technologies, narrowband (NB-IoT and long range (LoRa are two leading technologies. In this paper, we provide a comprehensive survey on NB-IoT and LoRa as efficient solutions connecting the devices. It is shown that unlicensed LoRa has advantages in terms of battery lifetime, capacity, and cost. Meanwhile, licensed NB-IoT offers benefits in terms of QoS, latency, reliability, and range.

  3. The multiple sclerosis susceptibility genes TAGAP and IL2RA are regulated by vitamin D in CD4+ T cells.

    Science.gov (United States)

    Berge, T; Leikfoss, I S; Brorson, I S; Bos, S D; Page, C M; Gustavsen, M W; Bjølgerud, A; Holmøy, T; Celius, E G; Damoiseaux, J; Smolders, J; Harbo, H F; Spurkland, A

    2016-03-01

    Multiple sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system that develops in genetically susceptible individuals. The majority of the MS-associated gene variants are located in genetic regions with importance for T-cell differentiation. Vitamin D is a potent immunomodulator, and vitamin D deficiency has been suggested to be associated with increased MS disease susceptibility and activity. In CD4+ T cells, we have analyzed in vitro vitamin D responsiveness of genes that contain an MS-associated single-nucleotide polymorphism (SNP) and with one or more vitamin D response elements in their regulatory regions. We identify IL2RA and TAGAP as novel vitamin D target genes. The vitamin D response is observed in samples from both MS patients and controls, and is not dependent on the genotype of MS-associated SNPs in the respective genes.

  4. Smoking and polymorphisms of genes encoding mannose-binding lectin and surfactant protein-D in patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Kristiansen, Malthe; Frisch, Morten; Madsen, Hans Ole

    2014-01-01

    To investigate whether polymorphisms in genes coding for mannose-binding lectin (MBL) and surfactant protein-D (SP-D) are associated directly or by interaction with smoking with rheumatoid arthritis (RA), anti-citrullinated peptide antibody (ACPA) positive RA, and erosive RA. MBL2 genotypes, SFTPD...... genotype at codon 11, and HLA-shared epitope were determined in 456 patients with rheumatoid arthritis and 533 sex- and age-matched controls. Patients were grouped according to the presence of ACPA antibodies and RA-associated bone erosions and sub-stratified according to smoking status as never or ever...... with RA but with erosive RA by interaction with smoking. The genetic disposition for high MBL production was associated with ACPA positive RA irrespective of shared epitope. The findings need to be replicated but do as such offer further explanations for the clinical heterogeneity of RA....

  5. Monitoring anti-TNF{alpha} treatment in RA: Responsiveness of magnetic resonance imaging and ultrasonography of the dominant wrist compared to conventional measures of disease activity and structural damage

    DEFF Research Database (Denmark)

    Haavardsholm, Espen A; Ostergaard, Mikkel; Hammer, Hilde Berner

    2008-01-01

    OBJECTIVES: The objective of this study was to evaluate the responsiveness of magnetic resonance imaging (MRI) and ultrasonography (US) compared to conventional measures of disease activity and structural damage in RA patients during the first year of anti-TNFalpha treatment. METHODS: A cohort...

  6. Evaluation of the activity concentration of {sup 226}Ra, {sup 228}Ra and {sup 210}Pb in sediments from Antarctica in the Admiralty bay region; Avaliacao da concentracao de atividade de Ra-226, Ra-228 e Pb-210 em sedimentos provenientes da Antartica na regiao da baia do Almirantado

    Energy Technology Data Exchange (ETDEWEB)

    Mora, Tamires de Araujo

    2015-07-01

    The natural radionuclides from radioactive series of {sup 238}U, {sup 235}U and {sup 232}Th have been applied as tracers in environmental studies for understanding the dynamics that occur in both marine and terrestrial environment, as for example, in research of oceanic processes and management of the coastal region. In the marine environment, these radionuclides can be used to estimate biogeochemical fluxes of marine particles and nutrients that occur in the water column as well as in the sediment. Several research works applied the distribution and the respective disequilibrium degree of natural radionuclides in the environment, including geochronological models for obtaining historical information on samples of certain sediment profile. In this study we performed a radiochemical characterization of the distribution of {sup 226}Ra, {sup 228}Ra and {sup 210}Pb from a sedimentary column called 1B (248 cm long) collected in the Admiralty Bay, Antarctic Peninsula region. The methodology used included the acid leaching of sediment samples followed by the radiochemical sequential separation of {sup 226}Ra and {sup 228}Ra by co-precipitation with Ba(Ra)SO{sub 4} and {sup 210}Pb by co-precipitation with PbCrO{sub 4}. All measurements were carried out by counting of gross alpha and gross beta measures in a low background gas flow proportional detector. The activity concentrations of {sup 226}Ra and {sup 210}Pb were used to estimate the unsupported {sup 210}Pb activities present in sediment profile 1 B. Based on unsupported {sup 210}Pb data and the application of the CIC model (Constant Initial Concentration), it was possible to determine the sedimentation rate of 0.59 ± 0.05 cm /year. (author)

  7. Validity of rheumatoid arthritis diagnoses in the Danish National Patient Registry

    DEFF Research Database (Denmark)

    Pedersen, Line Merete Blak; Klarlund, Mette; Jacobsen, Søren

    2004-01-01

    Discharge diagnoses following hospital admissions in Denmark are recorded in the Danish National Patient Registry (NPR). Such routine hospitalization records may serve as useful research tools in epidemiological studies. The aim of the study was to provide measures of the validity and completeness...... of rheumatoid arthritis (RA) diagnoses recorded in the NPR. We identified medical records for 217 patients recorded as having RA in the NPR between 1977 and 2001. Using two definitions of RA (clinically confirmed RA and fulfilment of the American College of Rheumatology (ACR) 1987 diagnostic criteria for RA...... to RA satisfying the ACR 1987 classification criteria was estimated to 26%. Our conclusion is that with careful attention to the limitations in the data, discharge diagnoses for patients with records of RA in the Danish NPR can be used for epidemiological research purposes; however, our findings prompt...

  8. 7 CFR 614.12 - Transcripts.

    Science.gov (United States)

    2010-01-01

    ... verbatim transcript must pay for the transcription service and provide a copy of the transcript to NRCS at... participant may obtain a verbatim transcript as provided in paragraph (b) of this section. (b) Any party to an informal hearing appeal under § 614.9 may request that a verbatim transcript is made of the hearing...

  9. miRA: adaptable novel miRNA identification in plants using small RNA sequencing data.

    Science.gov (United States)

    Evers, Maurits; Huttner, Michael; Dueck, Anne; Meister, Gunter; Engelmann, Julia C

    2015-11-05

    MicroRNAs (miRNAs) are short regulatory RNAs derived from longer precursor RNAs. miRNA biogenesis has been studied in animals and plants, recently elucidating more complex aspects, such as non-conserved, species-specific, and heterogeneous miRNA precursor populations. Small RNA sequencing data can help in computationally identifying genomic loci of miRNA precursors. The challenge is to predict a valid miRNA precursor from inhomogeneous read coverage from a complex RNA library: while the mature miRNA typically produces many sequence reads, the remaining part of the precursor is covered very sparsely. As recent results suggest, alternative miRNA biogenesis pathways may lead to a more diverse miRNA precursor population than previously assumed. In plants, the latter manifests itself in e.g. complex secondary structures and expression from multiple loci within precursors. Current miRNA identification algorithms often depend on already existing gene annotation, and/or make use of specific miRNA precursor features such as precursor lengths, secondary structures etc. Consequently and in view of the emerging new understanding of a more complex miRNA biogenesis in plants, current tools may fail to characterise organism-specific and heterogeneous miRNA populations. miRA is a new tool to identify miRNA precursors in plants, allowing for heterogeneous and complex precursor populations. miRA requires small RNA sequencing data and a corresponding reference genome, and evaluates precursor secondary structures and precursor processing accuracy; key parameters can be adapted based on the specific organism under investigation. We show that miRA outperforms the currently best plant miRNA prediction tools both in sensitivity and specificity, for data involving Arabidopsis thaliana and the Volvocine algae Chlamydomonas reinhardtii; the latter organism has been shown to exhibit a heterogeneous and complex precursor population with little cross-species miRNA sequence conservation, and

  10. Extração de ecdisterona em raízes de ginseng brasileiro

    OpenAIRE

    Flores, Rejane; Nicoloso,Fernando Teixeira; Brondani, Daniela; Maldaner, Joseila; Cezarotto,Verciane; Giacomelli, Sandro Rogério

    2009-01-01

    Este estudo teve como objetivo otimizar a extração de ecdisterona em raízes de ginseng brasileiro. Primeiramente, para se avaliar a eficiência do solvente extrator, amostras de raízes dois acessos (BRA e JB-UFSM) de P. glomerata foram extraídas em Soxhlet com metanol e clorofórmio, separadamente, durante 4 horas. No segundo ensaio, com o intuito de se escolher o método extrator, a extração foi conduzida em Soxhlet e em ultrassom, utilizando metanol como solvente. Em P. tuberosa, as amostras f...

  11. Performance Comparisons of Improved Regular Repeat Accumulate (RA and Irregular Repeat Accumulate (IRA Turbo Decoding

    Directory of Open Access Journals (Sweden)

    Ahmed Abdulkadhim Hamad

    2017-08-01

    Full Text Available In this paper, different techniques are used to improve the turbo decoding of regular repeat accumulate (RA and irregular repeat accumulate (IRA codes. The adaptive scaling of a-posteriori information produced by Soft-output Viterbi decoder (SOVA is proposed. The encoded pilots are another scheme that applied for short length RA codes. This work also suggests a simple and a fast method to generate a random interleaver having a free 4 cycle Tanner graph. Progressive edge growth algorithm (PEG is also studied and simulated to create the Tanner graphs which have a great girth.

  12. Coverage and Capacity Analysis of Sigfox, LoRa, GPRS, and NB-IoT

    DEFF Research Database (Denmark)

    Vejlgaard, Benny; Lauridsen, Mads; Nguyen, Huan Cong

    2017-01-01

    In this paper the coverage and capacity of SigFox, LoRa, GPRS, and NB-IoT is compared using a real site deployment covering 8000 km2 in Northern Denmark. Using the existing Telenor cellular site grid it is shown that the four technologies have more than 99 % outdoor coverage, while GPRS...... uplink and downlink connectivity with less than 5 % failure rate, while SigFox is able to provide an unacknowledged uplink data service with about 12 % failure rate. Both GPRS and LoRa struggle to provide sufficient indoor coverage and capacity....

  13. Determination of specific activities of U-238, Ra-226, Ra-228 e Th-228 in samples of mineral fertilizers with phosphorus; Determinacao das atividades especificas de U-238, Ra-226, Ra-228 e Th-228 em amostras de fertilizantes minerais com fosforo

    Energy Technology Data Exchange (ETDEWEB)

    Garcez, R.W.D.; Lopes, J.M.; Silva, A.X. da, E-mail: rgarcez@nuclear.ufrj.br [Coordenacao dos Programas de Pos-Graduacao em Engenharoa (COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Programa de Engenharia Nuclear; Domingues, A.M.; Lima, M.A.F. [Universidade Federal Fluminense (UFF),Niteroi, RJ (Brazil)

    2016-07-01

    Samples were analyzed by gamma spectrometry mineral fertilizers with the HPGe detector and aid LabSOCS software for calculating the detection efficiency curve. Specific activities found for Pa-234m, Ra-226, Ra-228 and Th-228 in samples of phosphate fertilizers were 505 Bq.kg{sup -1}, 458 Bq.kg{sup -1}, 450 Bq.kg{sup -1} and 394 Bq.kg{sup -1}, respectively. And for the NPK fertilizer samples were found average values of 390 Bq.kg{sup -1}, 252 Bq.kg{sup -1}, 280 Bq.kg{sup -1} and 268 Bq.kg{sup -1}, respectively. (author)

  14. Membangun Karakter AUD dalam Pengembangan Nilai Agama dan Moral di RA Masyithoh Pabelan Kab. Semarang

    Directory of Open Access Journals (Sweden)

    Amin Sabi'ati

    2016-06-01

    Full Text Available This article is intended to reveal the importance of character building of children through the development of religious and moral values ​​in early childhood in RA Masyithoh Pabelan Semarang regency, the factors that influence the character building, the process of the development of moral and religious values, behavioral changes, and its implementation in the system for early childhood learning. The results showed that the learning that emphasizes hands-on learning and do as habituation, very influential in improving the development of religious and moral values early childhood in RA (Kindergarten Masyithoh Pabelan Semarang District.

  15. A rapid analysis of {sup 226}Ra in raw materials and by-products using gamma-ray spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Chung Sup; Chung, Kun Ho; Kim, Chang Jong; Ji, Young Yong [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2017-03-15

    A gamma-ray peak of {sup 226}Ra (186.2 keV) overlaps with one of {sup 235}U (185.7 keV) in a gamma-ray spectrometry system. Though reference peaks of {sup 235}U can be used to correct the peak interference of {sup 235}U in the analysis of {sup 226}Ra, this requires a complicated calculation process and a high limit of quantitation. On the other hand, evaluating {sup 226}Ra using the correction constant in the overlapped peak can make a rapid measurement of {sup 226}Ra without the complicated calculation process as well as overcome the disadvantage in the indirect measurement of {sup 214}Bi, which means the confinement of {sup 222}Rn gas in a sample container and a time period to recover the secular equilibrium. About 93 samples with 6 species for raw-materials and by-products were prepared to evaluate the activity of {sup 226}Ra using the correction constant. The results were compared with the activity of {sup 214}Bi, which means the indirect measurement of {sup 226}Ra, to validate the method of the direct measurement of {sup 226}Ra using the correction constant. The difference between the direct and indirect measurement of {sup 226}Ra was generally below about ± 20%. However, in the case of the phospho gypsum, a large error of about 50% was found in the comparison results, which indicates the disequilibrium between {sup 238}U and {sup 226}Ra in the materials. Application results of the contribution ratio of {sup 226}Ra were below about ± 10% . The direct measurement of {sup 226}Ra using the correction constant can be an effective method for its rapid measurement of raw materials and by-products because the activity of {sup 226}Ra can be produced with a simple calculation without the consi