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Sample records for factor baff level

  1. Serum B cell-activating factor (BAFF) level in connective tissue disease associated interstitial lung disease.

    Science.gov (United States)

    Hamada, Tsutomu; Samukawa, Takuya; Kumamoto, Tomohiro; Hatanaka, Kazuhito; Tsukuya, Go; Yamamoto, Masuki; Machida, Kentaro; Watanabe, Masaki; Mizuno, Keiko; Higashimoto, Ikkou; Inoue, Yoshikazu; Inoue, Hiromasa

    2015-09-30

    Interstitial lung diseases (ILDs) are common in patients with connective tissue diseases (CTDs). Although the diagnosis of an underlying CTD in ILD (CTD-ILD) affects both prognosis and treatment, it is sometimes difficult to distinguish CTD-ILD from chronic fibrosing interstitial pneumonia (CFIP). B cell-activating factor belonging to the tumour necrosis factor family (BAFF) plays a crucial role in B cell development, survival, and antibody production. We examined serum levels of BAFF, surfactant protein D (SP-D), and Krebs von den Lungen-6 (KL-6) in 33 patients with CTD-ILD, 16 patients with undifferentiated CTD-ILD, 19 patients with CFIP, and 26 healthy volunteers. And we analysed the relationship between serum BAFF levels and pulmonary function, as well as the expression of BAFF in the lung tissue of patients with CTD-ILD. Serum levels of BAFF were significantly higher in CTD-ILD patients compared to healthy subjects and CFIP patients. However, there were no significant differences in serum levels of SP-D and KL-6. Furthermore, serum BAFF levels in CTD-ILD patients were inversely correlated with pulmonary function. BAFF was strongly expressed in the lungs of CTD-ILD patients, but weakly in normal lungs. This is the first study to demonstrate that serum BAFF levels were significantly higher in CTD-ILD patients compared to healthy subjects and CFIP patients. Furthermore, serum BAFF levels were correlated with pulmonary function. We consider that serum BAFF levels in patients with CTD-ILD reflect the presence of ILDs disease activity and severity. These finding suggest that BAFF may be a useful marker for distinguishing CTD-ILD from CFIP.

  2. Changes in Blood B Cell-Activating Factor (BAFF) Levels in Multiple Sclerosis: A Sign of Treatment Outcome.

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    Kannel, Karin; Alnek, Kristi; Vahter, Liina; Gross-Paju, Katrin; Uibo, Raivo; Kisand, Kalle V

    2015-01-01

    Multiple sclerosis (MS) is mediated primarily by autoreactive T cells. However, evidence suggesting the involvement of humoral immunity in brain diseases has increased interest in the role of B cells and their products during MS pathogenesis. The major survival factor for B cells, BAFF has been shown to play a role in several autoimmune conditions. Elevated BAFF levels have been reported in MS animal model and during MS relapse in patients. Moreover, disease-modifying treatments (DMT) reportedly influence blood BAFF levels in MS patients, but the significance of these changes remains unclear. The present study addresses how blood BAFF levels are associated with the clinical course of relapsing-remitting MS and the effectiveness of DMT and short-term steroid treatment. During a prospective longitudinal follow-up of 2.3 years, BAFF was measured in the blood of 170 MS patients in the stable phase and within 186 relapses. BAFF levels were significantly higher in MS patients compared to healthy controls. However, stable MS patients without relapses exhibited significantly higher BAFF levels than relapsing patients. Treatment with interferon-β and immunosuppressants raised BAFF blood levels. Interestingly, a similar effect was not seen in patients treated with glatiramer acetate. Short-term treatment with high doses of intravenous methylprednisolone did not significantly alter plasma BAFF levels in 65% of relapsing-remitting MS patients. BAFF were correlated weakly but significantly with monocyte and basophil counts, but not with other blood cell types (neutrophils, lymphocytes, or eosinophils) or inflammatory biomarkers. To our knowledge, this is the first report demonstrating that higher blood BAFF levels may reflect a more stable and effective MS treatment outcome. These results challenge hypotheses suggesting that elevated blood BAFF levels are associated with more severe disease presentation and could explain the recent failure of pharmaceutical trials targeting

  3. Changes in Blood B Cell-Activating Factor (BAFF Levels in Multiple Sclerosis: A Sign of Treatment Outcome.

    Directory of Open Access Journals (Sweden)

    Karin Kannel

    Full Text Available Multiple sclerosis (MS is mediated primarily by autoreactive T cells. However, evidence suggesting the involvement of humoral immunity in brain diseases has increased interest in the role of B cells and their products during MS pathogenesis. The major survival factor for B cells, BAFF has been shown to play a role in several autoimmune conditions. Elevated BAFF levels have been reported in MS animal model and during MS relapse in patients. Moreover, disease-modifying treatments (DMT reportedly influence blood BAFF levels in MS patients, but the significance of these changes remains unclear. The present study addresses how blood BAFF levels are associated with the clinical course of relapsing-remitting MS and the effectiveness of DMT and short-term steroid treatment. During a prospective longitudinal follow-up of 2.3 years, BAFF was measured in the blood of 170 MS patients in the stable phase and within 186 relapses. BAFF levels were significantly higher in MS patients compared to healthy controls. However, stable MS patients without relapses exhibited significantly higher BAFF levels than relapsing patients. Treatment with interferon-β and immunosuppressants raised BAFF blood levels. Interestingly, a similar effect was not seen in patients treated with glatiramer acetate. Short-term treatment with high doses of intravenous methylprednisolone did not significantly alter plasma BAFF levels in 65% of relapsing-remitting MS patients. BAFF were correlated weakly but significantly with monocyte and basophil counts, but not with other blood cell types (neutrophils, lymphocytes, or eosinophils or inflammatory biomarkers. To our knowledge, this is the first report demonstrating that higher blood BAFF levels may reflect a more stable and effective MS treatment outcome. These results challenge hypotheses suggesting that elevated blood BAFF levels are associated with more severe disease presentation and could explain the recent failure of pharmaceutical

  4. The strength of the antibody response to the nematode Ascaris lumbricoides inversely correlates with levels of B-Cell Activating Factor (BAFF).

    Science.gov (United States)

    Bornacelly, Adriana; Mercado, Dilia; Acevedo, Nathalie; Caraballo, Luis

    2014-06-07

    B-Cell Activating Factor (BAFF) is a cytokine regulating antibody production. Polymorphisms in the gene encoding BAFF were associated with the antibody response to Ascaris but not to mite allergens. In the present study we evaluated the relationship between BAFF and specific antibodies against Ascaris and mites in 448 controls and 448 asthmatics. Soluble BAFF was measured by ELISA and BAFF mRNA by qPCR. Surface expression of BAFF and its receptor (BAFF-R) was analyzed by flow cytometry. Individuals with specific IgE levels to Ascaris >75th percentile had lower levels of soluble BAFF; those with specific IgG levels to Ascaris >75th percentile had reduced BAFF mRNA. Total IgE and specific IgE to mites were not related to BAFF levels. There were no differences in soluble BAFF or mRNA levels between asthmatics and controls. There was an inverse relationship between the cell-surface expression of BAFF-R on CD19+ B cells and BAFF levels at the transcriptional and protein level. These findings suggest that differences in BAFF levels are related to the strength of the antibody response to Ascaris.

  5. The strength of the antibody response to the nematode Ascaris lumbricoides inversely correlates with levels of B-Cell Activating Factor (BAFF)

    Science.gov (United States)

    2014-01-01

    Background B-Cell Activating Factor (BAFF) is a cytokine regulating antibody production. Polymorphisms in the gene encoding BAFF were associated with the antibody response to Ascaris but not to mite allergens. In the present study we evaluated the relationship between BAFF and specific antibodies against Ascaris and mites in 448 controls and 448 asthmatics. Soluble BAFF was measured by ELISA and BAFF mRNA by qPCR. Surface expression of BAFF and its receptor (BAFF-R) was analyzed by flow cytometry. Results Individuals with specific IgE levels to Ascaris >75th percentile had lower levels of soluble BAFF; those with specific IgG levels to Ascaris >75th percentile had reduced BAFF mRNA. Total IgE and specific IgE to mites were not related to BAFF levels. There were no differences in soluble BAFF or mRNA levels between asthmatics and controls. There was an inverse relationship between the cell-surface expression of BAFF-R on CD19+ B cells and BAFF levels at the transcriptional and protein level. Conclusions These findings suggest that differences in BAFF levels are related to the strength of the antibody response to Ascaris. PMID:24906685

  6. B-cell activating factor (BAFF) plasma level at the time of chronic GvHD diagnosis is a potential predictor of non-relapse mortality.

    Science.gov (United States)

    Saliba, R M; Sarantopoulos, S; Kitko, C L; Pawarode, A; Goldstein, S C; Magenau, J; Alousi, A M; Churay, T; Justman, H; Paczesny, S; Reddy, P; Couriel, D R

    2017-07-01

    Biological markers for risk stratification of chronic GvHD (cGvHD) could improve the care of patients undergoing allogeneic hematopoietic stem cell transplantation. Increased plasma levels of B-cell activating factor (BAFF), chemokine (C-X-C motif) ligand 9 (CXCL9) and elafin have been associated with the diagnosis, but not with outcome in patients with cGvHD. We evaluated the association between levels of these soluble proteins, measured by ELISA at the time of cGvHD diagnosis and before the initiation of therapy, with non-relapse-mortality (NRM). Based on the log-transformed values, factor levels were divided into tertiles defined respectively as low, intermediate, and high levels. On univariable analysis, BAFF levels were significantly associated with NRM, whereas CXCL9 and elafin levels were not. Both low (⩽2.3 ng/mL, hazard ratio (HR)=5.8, P=0.03) and high (>5.7 ng/mL, HR=5.4, P=0.03) BAFF levels were associated with a significantly higher NRM compared with intermediate BAFF level. The significant effect of high or low BAFF levels persisted in multivariable analysis. A subset of cGvHD patients had persistently low BAFF levels. In conclusion, our data show that BAFF levels at the time of cGvHD diagnosis are associated with NRM, and also are potentially useful for risk stratification. These results warrant confirmation in larger studies.

  7. BAFF level increased in patients with autoimmune hemolytic anemia.

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    Zhao, Yu-Bing; Li, Jun-Min; Wei, Bei-Wen; Xu, Zi-Zhen

    2015-01-01

    BAFF (B-cell activating factor of the TNF family), an important regulator of B-cell, has been observed to be over-expressed in a variety of autoimmune diseases. Autoimmune hemolytic anemia (AIHA) is an acquired autoimmune disease occurred when antibodies directed against autologous red blood cells. We assessed serum levels of BAFF in AIHA patients with different serological characteristics. Serum BAFF levels were measured in 44 AIHA patients with different direct antiglobulin test (DAT) results and 25 healthy controls. The correlation of BAFF expression with DAT results and serological characteristics was assessed. Serum levels of BAFF in AIHA patients were significantly higher than in healthy subjects (AIHA: 1382.7 ± 1412.8 pg/ml, healthy control: 725.0 ± 415.7 pg/ml, P = 0.0057). Serum BAFF levels were significantly higher in patients with IgG(+)C3(+) or IgG(+) than healthy controls (DAT: negative) (P = 0.012, 0.004, respectively). No significant correlations were presented between serum BAFF levels and four serological parameters: hemoglobine, percentage of reticulocyte, total serum bilirubin, and lactate dehydrogenase. AIHA patients present higher serum BAFF levels than healthy controls, especially for those of IgG(+)C3(+) DAT result. This might lead to a new approach of AIHA treatment.

  8. 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.

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    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.

  9. Expression of BAFF-R, but not BAFF, is an independent prognostic factor in diffuse large B-cell lymphoma patients treated with R-CHOP.

    Science.gov (United States)

    Wang, Yu; Li, Ya-Jun; Jiang, Wen-Qi; Rao, Hui-Lan; Huang, Jia-Jia; Xia, Yi; Bi, Xiwen; Sun, Peng; Huang, Hui-Qiang; Lin, Tong-Yu; Guan, Zhong-Zhen; Li, Zhi-Ming

    2015-11-01

    B-cell activating factor (BAFF) and BAFF-receptor (BAFF-R) play crucial roles in the progression of malignant B-cells. The aim of the present study was to evaluate the expression profiles and the clinical significance of BAFF and BAFF-R in diffuse large B-cell lymphoma (DLBCL). Paraffin-embedded specimens from 136 patients with newly diagnosed DLBCL, treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP), were examined for BAFF and BAFF-R expression by immunohistochemistry. BAFF and BAFF-R were expressed in 72.1 % (98/136) and 47.1 % (64/136) of the DLBCL tissues, respectively. Negative BAFF-R expression was significantly correlated with elevated serum lactate dehydrogenase (LDH) levels (P = 0.036), an International Prognostic Index (IPI) score of 2 or higher (P BAFF-R expression than in those with negative BAFF-R expression (73.4 vs. 56.9 %, P = 0.045). Negative expression of BAFF-R, but not of BAFF, was significantly associated with inferior progression-free survival (PFS; P = 0.020) and overall survival (OS; P = 0.028). Only negative BAFF-R expression was correlated with inferior PFS and OS in multivariate analysis (P = 0.049 and 0.040, respectively). Taken together, our results showed that the majority and approximate one-half of patients with DLBCL were positive for BAFF and BAFF-R, respectively. Negative expression of BAFF-R, but not of BAFF, could be an independent risk factor for PFS and OS in patients with DLBCL treated with standard R-CHOP.

  10. The strength of the antibody response to the nematode Ascaris lumbricoides inversely correlates with levels of B-Cell Activating Factor (BAFF)

    OpenAIRE

    Bornacelly, Adriana; Mercado, Dilia; Acevedo, Nathalie; Caraballo, Luis

    2014-01-01

    Background B-Cell Activating Factor (BAFF) is a cytokine regulating antibody production. Polymorphisms in the gene encoding BAFF were associated with the antibody response to Ascaris but not to mite allergens. In the present study we evaluated the relationship between BAFF and specific antibodies against Ascaris and mites in 448 controls and 448 asthmatics. Soluble BAFF was measured by ELISA and BAFF mRNA by qPCR. Surface expression of BAFF and its receptor (BAFF-R) was analyzed by flow cytom...

  11. Serum BAFF and APRIL levels in patients with autoimmune hemolytic anemia and their clinical significance.

    Science.gov (United States)

    Xu, Zi-Zhen; Zhao, Bing-Bing; Xiong, Hong; Wei, Bei-Wen; Wang, Ye-Fei

    2015-10-01

    B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) play crucial roles in B cell development, survival, and antibody production. Autoimmune hemolytic anemia (AIHA) is an acquired autoimmune disease that occurs when antibodies target autologous red blood cells. Here, we analyzed the serum levels of BAFF and APRIL and their respective clinical associations in patients with AIHA. Serum BAFF and APRIL levels in patients with AIHA were significantly higher (P BAFF and APRIL levels were significantly augmented in patients with lower hemoglobin levels (hemoglobin was 480 IU/mL). Glucocorticoid treatment dramatically reduced serum levels of BAFF and APRIL. Thus, serum BAFF and APRIL levels may reflect the clinical activity of this disease. Our results indicate that analysis of serum concentrations of BAFF and APRIL potentially represents a useful tool for the assessment of AIHA disease activity and progression.

  12. Increased levels of BAFF in patients with systemic lupus erythematosus are associated with acute-phase reactants, independent of BAFF genetics: a case-control study.

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    Eilertsen, Gro Ø; Van Ghelue, Marijke; Strand, Harald; Nossent, Johannes C

    2011-12-01

    To determine whether increased levels of B-cell activating factor (BAFF) in patients with SLE are due to disease activity or genetic variations in the promoter region of the BAFF gene and BAFF gene expression. The case-control study included 101 SLE patients and 111 healthy controls. Five single nucleotide polymorphisms (SNPs) in the BAFF promoter region were investigated by melting point analysis: c.-2841 (T > C), c.-2704 (T > C), c.-2701 (A > T), c.-871 (C > T) and c.-514 (A > G). BAFF mRNA levels were determined by real-time PCR (BAFF-RQ) and serum BAFF (s-BAFF) levels were measured by ELISA. Independent predictors that might be correlated with increased s-BAFF in SLE patients were analysed by multivariate regression methods. RESULTS; Although s-BAFF levels were increased in SLE patients (1.73 vs 0.98 ng/μl, P acute-phase responses, CRP and haemoglobin, but probably not dependent on BAFF genotype or expression. This indicates that s-BAFF production occurs at sites of inflammation.

  13. B Cell Activating Factor (BAFF) and BAFF Receptor Expression in Autoimmune and Nonautoimmune Thyroid Diseases.

    Science.gov (United States)

    Campi, Irene; Tosi, Delfina; Rossi, Stefania; Vannucchi, Guia; Covelli, Danila; Colombo, Federico; Trombetta, Elena; Porretti, Laura; Vicentini, Leonardo; Cantoni, Gianmaria; Currò, Nicola; Beck-Peccoz, Paolo; Bulfamante, Gaetano; Salvi, Mario

    2015-09-01

    The B cell activating factor (BAFF) is a member of the tumor necrosis factor family, which controls the survival/proliferation of B cells and is involved in the pathogenesis of a number of autoimmune diseases. The objective of the present study was to investigate the expression of BAFF and BAFF receptor (BAFF-R) in the thyroid tissue of patients affected with autoimmune thyroid disorders (AITD) or multinodular goiter (MNG) compared with those with normal thyroids. Immunohistochemistry was performed using a panel of antibodies against BAFF, BAFF-R, CD3, CD4, CD8, CD20, CD34, CD79a, CD1a, CD68, and CD163 on the thyroid sections of 27 patients affected with Graves' disease (GD), 23 with Hashimoto's thyroiditis (HT), 16 with nontoxic nodular goiter (NTG), and 15 with toxic nodular goiter (TG), submitted to total thyroidectomy between 2000 and 2011. The overall BAFF-R expression in thyrocytes was weak and not different in AITD and MNG. Conversely, a stronger BAFF expression was observed in MNG compared with AITD. BAFF and BAFF-R expression in the infiltrating lymphocytes was higher in AITD compared with MNG. Interestingly, in lymphocytes of follicular-like structures observed in HT, BAFF and BAFF-R were localized in the germinal center or in the mantle, respectively. This study shows that BAFF and BAFF-R are expressed in the thyrocytes derived from patients with either AITD or MNG, in addition to the expected expression of BAFF and its receptor in the infiltrating immune cells of GD and HT. These findings suggest a possible involvement of BAFF and its receptors in the pathophysiology of AITD.

  14. Clinical Significance of Pre- and Post-Transplant BAFF Levels in Kidney Transplant Recipients.

    Directory of Open Access Journals (Sweden)

    Ji Won Min

    Full Text Available It is well known that pre-transplant B cell activating factor (BAFF levels are associated with the development of de novo anti-HLA antibodies and antibody mediated rejection post-transplant. However, the clinical significance of BAFF values at allograft rejection has not been determined. In this study, we investigated the clinical significance of pre-transplant BAFF level as well as post-transplant BAFF levels measured when indication biopsy was done. We checked for anti-HLA antibodies in 115 kidney transplant recipients who required allograft biopsy due to an increase in serum creatinine. With the same serum specimen, we measured BAFF levels, and in 78 of these patients, pre-transplant BAFF and anti-HLA antibody levels were detected as well. Patients in each group were divided into tertiles according to BAFF levels. We investigated the relationship between BAFF levels and the occurrence of anti-HLA antibodies. Pre-transplant BAFF levels showed significant association with pre-transplant sensitization, and also with early rejection (Tertile 3, 26.9% vs. Tertile 1, 11.5%; P<0.05. Post-transplant BAFF levels showed significant association with pre-transplant sensitization, but did not show association with anti-HLA antibodies and positive donor-specific antibodies at the time of biopsy. We did not find any association between post-transplant BAFF levels and allograft biopsy results, Banff scores and microvascular inflammation scores. In conclusion, pre-transplant BAFF levels are associated with pre-transplant sensitization and are useful in predicting allograft rejection. But post-transplant BAFF levels measured at the time of indication biopsy are not associated with the appearance of de novo HLA-DSA, allograft rejection, biopsy findings and other allograft outcomes.

  15. Clinical Significance of Pre- and Post-Transplant BAFF Levels in Kidney Transplant Recipients.

    Science.gov (United States)

    Min, Ji Won; Kim, Kyoung Woon; Kim, Bo-Mi; Doh, Kyoung Chan; Choi, Min Seok; Choi, Bum Soon; Park, Cheol Whee; Yang, Chul Woo; Kim, Yong-Soo; Oh, Eun-Jee; Chung, Byung Ha

    2016-01-01

    It is well known that pre-transplant B cell activating factor (BAFF) levels are associated with the development of de novo anti-HLA antibodies and antibody mediated rejection post-transplant. However, the clinical significance of BAFF values at allograft rejection has not been determined. In this study, we investigated the clinical significance of pre-transplant BAFF level as well as post-transplant BAFF levels measured when indication biopsy was done. We checked for anti-HLA antibodies in 115 kidney transplant recipients who required allograft biopsy due to an increase in serum creatinine. With the same serum specimen, we measured BAFF levels, and in 78 of these patients, pre-transplant BAFF and anti-HLA antibody levels were detected as well. Patients in each group were divided into tertiles according to BAFF levels. We investigated the relationship between BAFF levels and the occurrence of anti-HLA antibodies. Pre-transplant BAFF levels showed significant association with pre-transplant sensitization, and also with early rejection (Tertile 3, 26.9% vs. Tertile 1, 11.5%; PBAFF levels showed significant association with pre-transplant sensitization, but did not show association with anti-HLA antibodies and positive donor-specific antibodies at the time of biopsy. We did not find any association between post-transplant BAFF levels and allograft biopsy results, Banff scores and microvascular inflammation scores. In conclusion, pre-transplant BAFF levels are associated with pre-transplant sensitization and are useful in predicting allograft rejection. But post-transplant BAFF levels measured at the time of indication biopsy are not associated with the appearance of de novo HLA-DSA, allograft rejection, biopsy findings and other allograft outcomes.

  16. Pretransplant serum BAFF levels are associated with pretransplant HLA immunization and renal allograft survival.

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    Friebus-Kardash, Justa; Wilde, Benjamin; Keles, Deniz; Heinold, Andreas; Kribben, Andreas; Witzke, Oliver; Heinemann, Falko Markus; Eisenberger, Ute

    2018-04-01

    The essential function of B cell-activating factor (BAFF) is regulating the survival and differentiation of B cells. The link between pretransplant BAFF levels and pretransplant alloimmunization and its value to predict subsequent acute antibody-mediated rejection (AMR) and outcome after renal transplantation is not fully understood. Objective of our retrospective single-center study was to determine, by ELISA analysis of pretransplant serum BAFF levels in 249 patients undergoing renal transplantation, association between preformed anti-human leukocyte antigen (HLA) antibodies, occurrence of acute antibody mediated rejection (AMR) and renal allograft survival. Pretransplant serum BAFF levels were significantly higher in presensitized recipients with anti-HLA antibodies (3262±2796pg/ml) than in recipients without occurrence of anti-HLA antibodies (2252±1425pg/ml; pBAFF levels correlated with cumulative MFI values of anti-HLA antibodies (r=0.2966, p=0.0025). Patients with high pretransplant BAFF levels (≥2137pg/ml) experienced significantly lower allograft survival rates compared to low pretransplant BAFF levels (80% vs. 91%; p=0.01). Coexistence of high pretransplant BAFF levels and posttransplant AMR was associated with the worst allograft survival rates (56%). Relative risk (RR) for allograft loss was associated with high serum BAFF levels (RR 2.3; p=0.02), presence of anti-HLA antibodies (RR 2.5; p=0.007) or anti-HLA -donor-specific antibodies (DSAs) (RR 2.6; p=0.003) before transplant and AMR post transplant (RR 2.5; p=0.007). AMR was the strongest independent risk factor for allograft failure (RR 2.6; p=0.03). Elevated pretransplant serum BAFF levels negatively affect renal allograft survival and represent a risk factor for allosensitization and subsequent AMR. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Associations of B cell-activating factor (BAFF) and anti-BAFF autoantibodies with disease activity in multi-ethnic Asian systemic lupus erythematosus patients in Singapore.

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    Howe, H S; Thong, B Y H; Kong, K O; Chng, H H; Lian, T Y; Chia, F L; Tay, K S S; Lau, T C; Law, W G; Koh, E T; Leung, B P

    2017-09-01

    To measure the levels of B cell-activating factor (BAFF) and endogenous anti-BAFF autoantibodies in a cohort of multi-ethnic Asian systemic lupus erythematosus (SLE) patients in Singapore, to determine their correlation with disease activity. Serum samples from 121 SLE patients and 24 age- and sex-matched healthy controls were assayed for BAFF and anti-BAFF immunoglobulin (Ig)G antibody levels by enzyme-linked immunosorbent assay (ELISA). The lowest reliable detection limit for anti-BAFF-IgG antibody levels was defined as 2 standard deviations (s.d.) from blank. Correlation of serum BAFF and anti-BAFF IgG levels with disease activity [scored by SLE Activity Measure revised (SLAM-R)], and disease manifestations were determined in these 121 patients. SLE patients had elevated BAFF levels compared to controls; mean 820 ± 40 pg/ml and 152 pg ± 45/ml, respectively [mean ± standard error of the mean (s.e.m.), P < 0·01], which were correlated positively with anti-dsDNA antibody levels (r = 0·253, P < 0·03), and SLAM-R scores (r = 0·627, P < 0·01). In addition, SLE patients had significantly higher levels of anti-BAFF IgG, which were correlated negatively with disease activity (r = -0·436, P < 0·01), levels of anti-dsDNA antibody (r = -0·347, P < 0·02) and BAFF (r = -0·459, P < 0·01). The majority of patients in this multi-ethnic Asian SLE cohort had elevated levels of BAFF and anti-BAFF antibodies. Anti-BAFF autoantibody levels correlated negatively with clinical disease activity, anti-dsDNA and BAFF levels, suggesting that they may be disease-modifying. Our results provide further information about the complexity of BAFF pathophysiology in different SLE disease populations and phenotypes, and suggest that studies of the influence of anti-cytokine antibodies in different SLE populations will be required when selecting patients for trials using targeted anti-cytokine therapies. © 2017 British Society for

  18. Soluble BAFF Cytokine Levels and Antibody-Mediated Rejection of the Kidney Allograft.

    Science.gov (United States)

    Slavcev, Antonij; Brozova, Jitka; Slatinska, Janka; Sekerkova, Zuzana; Honsova, Eva; Skibova, Jelena; Striz, Ilja; Viklicky, Ondrej

    2016-12-01

    The B-cell activating factor (BAFF) cytokine has important functions for the survival and maturation of B lymphocytes, which implies that this cytokine might play a role in the development of antibody-mediated rejection (AMR) after kidney transplantation. In our study, we compared the concentrations of the soluble BAFF cytokine in kidney graft recipients with AMR and patients without rejection with the goal of testing the hypothesis whether BAFF level measurement might be useful as a diagnostic marker of AMR. The study included a cohort of 19 high-risk patients with diagnosed AMR and 17 control patients free of rejection. BAFF was measured in all patients before transplantation, during the rejection episodes, and three months after transplantation in patients free of rejection using the Luminex technique. Before transplantation, the serum concentrations of BAFF in patients with AMR and kidney recipients without rejection did not significantly differ. After transplantation, however, BAFF levels were significantly lower in patients with AMR and also in patients with concurrent humoral and cellular rejection compared with patients without rejection (p BAFF and the production of donor-specific antibodies (DSA) before and after transplantation. Patients experiencing AMR and simultaneous cellular and AMR had significantly lower concentrations of BAFF in comparison with patients free of rejection.

  19. Antibodies That Block or Activate Mouse B Cell Activating Factor of the Tumor Necrosis Factor (TNF) Family (BAFF), Respectively, Induce B Cell Depletion or B Cell Hyperplasia*

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    Kowalczyk-Quintas, Christine; Schuepbach-Mallepell, Sonia; Vigolo, Michele; Willen, Laure; Tardivel, Aubry; Smulski, Cristian R.; Zheng, Timothy S.; Gommerman, Jennifer; Hess, Henry; Gottenberg, Jacques-Eric; Mackay, Fabienne; Donzé, Olivier

    2016-01-01

    B cell activating factor of the TNF family (BAFF), also known as B lymphocyte stimulator, is a ligand required for the generation and maintenance of B lymphocytes. In this study, the ability of different monoclonal antibodies to recognize, inhibit, or activate mouse BAFF was investigated. One of them, a mouse IgG1 named Sandy-2, prevented the binding of BAFF to all of its receptors, BAFF receptor, transmembrane activator and calcium modulating ligand interactor, and B cell maturation antigen, at a stoichiometric ratio; blocked the activity of mouse BAFF on a variety of cell-based reporter assays; and antagonized the prosurvival action of BAFF on primary mouse B cells in vitro. A single administration of Sandy-2 in mice induced B cell depletion within 2 weeks, down to levels close to those observed in BAFF-deficient mice. This depletion could then be maintained with a chronic treatment. Sandy-2 and a previously described rat IgG1 antibody, 5A8, also formed a pair suitable for the sensitive detection of endogenous circulating BAFF by ELISA or using a homogenous assay. Interestingly, 5A8 and Sandy-5 displayed activities opposite to that of Sandy-2 by stimulating recombinant BAFF in vitro and endogenous BAFF in vivo. These tools will prove useful for the detection and functional manipulation of endogenous mouse BAFF and provide an alternative to the widely used BAFF receptor-Fc decoy receptor for the specific depletion of BAFF in mice. PMID:27451394

  20. Elevated serum BAFF levels in patients with localized scleroderma in contrast to other organ-specific autoimmune diseases.

    Science.gov (United States)

    Matsushita, Takashi; Hasegawa, Minoru; Matsushita, Yukiyo; Echigo, Takeshi; Wayaku, Takamasa; Horikawa, Mayuka; Ogawa, Fumihide; Takehara, Kazuhiko; Sato, Shinichi

    2007-02-01

    Serum levels of B-cell activating factor belonging to the tumor necrosis factor family (BAFF), a potent B-cell survival factor, are elevated in patients with systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis and systemic sclerosis (SSc). The objective of this study was to determine serum BAFF levels and relate the results to the clinical features in patients with organ-specific autoimmune diseases of the skin, such as localized scleroderma and autoimmune bullous diseases. Serum BAFF levels were examined by enzyme-linked immunosorbent assay in 44 patients with localized scleroderma, 20 with pemphigus vulgaris/pemphigus foliaceus, 20 with bullous pemphigoid and 30 healthy controls. Twenty patients with SSc and 20 with SLE were also examined as disease controls. Serum BAFF levels were elevated in localized scleroderma patients compared with healthy controls. Concerning localized scleroderma subgroups, patients with generalized morphea, the severest form of localized scleroderma, had higher serum BAFF levels than linear scleroderma or morphea patients. The BAFF levels of generalized morphea were comparable with those of SSc or SLE. Furthermore, serum BAFF levels correlated positively with antihistone antibody levels and the severity of skin lesion as well as the number of skin lesions. By contrast, serum BAFF levels were not significantly elevated in patients with pemphigus or pemphigoid. These results suggest that BAFF may be contributing to autoimmunity and disease development in localized scleroderma.

  1. The Expression of BAFF Is Controlled by IRF Transcription Factors.

    Science.gov (United States)

    Sjöstrand, Maria; Johansson, Alina; Aqrawi, Lara; Olsson, Tomas; Wahren-Herlenius, Marie; Espinosa, Alexander

    2016-01-01

    Patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) are typically characterized by the presence of autoantibodies and an IFN-signature. The strength of the IFN-signature positively correlates with disease severity, suggesting that type I IFNs are active players in these diseases. BAFF is a cytokine critical for development and proper selection of B cells, and the targeting of BAFF has emerged as a successful treatment strategy of SLE. Previous reports have suggested that BAFF expression is directly induced by type I IFNs, but the precise mechanism for this remains unknown. In this article, we demonstrate that BAFF is a bona fide ISG and that IFN regulatory factors (IRFs) control the expression of BAFF. We identify IRF1 and IRF2 as positive regulators of BAFF transcription and IRF4 and IRF8 as potent repressors; in addition, we have mapped the precise binding site for these factors in the BAFF promoter. IFN-β injections induced BAFF expression mainly in neutrophils and monocytes, and BAFF expression in neutrophils from pSS patients strongly correlated with the strength of the IFN-signature. In summary, we show that BAFF expression is directly induced by type I IFNs via IRF1 and IRF2, whereas IRF4 and IRF8 are negative regulators of BAFF expression. These data suggest that type I IFN blockade in SLE and pSS patients will lead to downregulation of BAFF and a consequential reduction of autoreactive B cell clones and autoantibodies. Copyright © 2015 by The American Association of Immunologists, Inc.

  2. Serum BAFF levels, Methypredsinolone therapy, Epstein-Barr Virus and Mycobacterium avium subsp. paratuberculosis infection in Multiple Sclerosis patients.

    Science.gov (United States)

    Mameli, Giuseppe; Cocco, Eleonora; Frau, Jessica; Arru, Giannina; Caggiu, Elisa; Marrosu, Maria Giovanna; Sechi, Leonardo A

    2016-07-07

    Elevated B lymphocyte activating factor BAFF levels have been reported in multiple sclerosis (MS) patients; moreover, disease-modifying treatments (DMT) have shown to influence blood BAFF levels in MS patients, although the significance of these changes is still controversial. In addition, BAFF levels were reported increased during infectious diseases. In our study, we wanted to investigate on the serum BAFF concentrations correlated to the antibody response against Mycobacterium avium subspecies paratuberculosis (MAP), Epstein-Barr virus (EBV) and their human homologous epitopes in MS and in patients affected with other neurological diseases (OND), divided in Inflammatory Neurological Diseases (IND), Non Inflammatory Neurological Diseases (NIND) and Undetermined Neurological Diseases (UND), in comparison to healthy controls (HCs). Our results confirmed a statistically significant high BAFF levels in MS and IND patients in comparison to HCs but not NIND and UND patients. Interestingly, BAFF levels were inversely proportional to antibodies level against EBV and MAP peptides and the BAFF levels significantly decreased in MS patients after methylprednisolone therapy. These results implicate that lower circulating BAFF concentrations were present in MS patients with humoral response against MAP and EBV. In conclusion MS patients with no IgGs against EBV and MAP may support the hypothesis that elevated blood BAFF levels could be associated with a more stable disease.

  3. B-cell activating factor BAFF reflects patients' immunological risk profile after kidney transplantation.

    Science.gov (United States)

    Schuster, A; Jung, B; Hofbauer, J; Kühne, L; Zecher, D; Banas, B; Bergler, T

    2017-12-01

    The B-cell activating factor BAFF plays an important role in the development and maturation of B-lymphocytes, which can contribute to the generation of donor-specific antibodies and thus may influence graft function and graft survival. Inconsistent data on the role of BAFF levels after renal transplantation for the formation of donor-specific antibodies and the contribution for allograft rejection exist. The aim of the current study was to determine to what extent the degree of pre-immunization is reflected by each patient's BAFF levels before transplantation and in the follow-up. Furthermore, the impact of BAFF on allograft rejection frequency as well as severity and resulting allograft function over time was analyzed. Additionally, the impact of viral infections on BAFF levels after transplantation - as a potential confounder - was examined. For this purpose, a group of pre-sensitized patients (PRA>0%, (52±24% on average), n=40) was compared with non-sensitized patients (PRA=0%, n=62) and in a subsequent analysis stratification in accordance to the detected BAFF level was performed. Pre-sensitized patients had significantly higher BAFF levels before transplantation and suffered significantly more often from early steroid-resistant, mainly antibody-mediated rejections. A result which was confirmed also in highly sensitized patients with PRA levels >50%. Additionally, in the follow-up patients with either rising BAFF levels over time or BAFF levels above the median also had significantly more often antibody mediated rejections. Additionally, patients with BAFF levels above detected median even displayed impaired creatinine values as well as an induced eGFR slope up to month 48 after transplantation. The occurrence of viral infections (CMV, BKV) was only an additional influencing factor in the absence of concomitant allograft rejections. Therefore, the B-cell proliferation factor BAFF appears not only to reflect the immunological risk profile of patients in the

  4. B cell activating factor (BAFF) and BAFF receptors: fakes and facts.

    Science.gov (United States)

    Ferraccioli, G; Gremese, E

    2017-12-01

    Analysis of B cell activating factor (BAFF) receptors before and after B cell depletion therapy (BCDT) might offer a clue to the understanding of whether some B cell subsets may represent useful biomarkers of biological and clinical responses. Among the BAFF receptors in a cohort of rheumatoid arthritis (RA) patients, the AA have shown, by fluorescence activated cell sorter (FACS) analysis of median fluorescence intensity (MFI), that transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA) do not change, whereas the most important, BAFF receptor 3 (BR3), appears to be decreased before as well as after BCDT in all B cell subsets but not in plasmablasts, the most important subset, depleted by BCDT. © 2017 British Society for Immunology.

  5. B cell activating factor of the tumor necrosis factor family (BAFF behaves as an acute phase reactant in acute pancreatitis.

    Directory of Open Access Journals (Sweden)

    Georg Pongratz

    Full Text Available To determine if B cell activating factor of the tumor necrosis factor family (BAFF acts as an acute phase reactant and predicts severity of acute pancreatitis.40 patients with acute pancreatitis were included in this single center cohort pilot study. Whole blood and serum was analyzed on day of admission and nine consecutive days for BAFF, c-reactive protein (CRP, interleukin-6 (IL-6, procalcitonin (PCT, and leucocyte numbers. Different severity Scores (Ranson, APACHE II, SAPS II, SAPS III and the clinical course of the patient (treatment, duration of stay, duration ICU were recorded.Serum BAFF correlates with CRP, an established marker of severity in acute pancreatitis at day of admission with a timecourse profil similar to IL-6 over the first nine days. Serum BAFF increases with Ranson score (Kruskal-Wallis: Chi2 = 10.8; p = 0.03 similar to CRP (Kruskal-Wallis: Chi2 = 9.4; p = 0.05 . Serum BAFF, IL-6, and CRP levels are elevated in patients that need intensive care for more than seven days and in patients with complicated necrotizing pancreatitis. Discriminant analysis and receiver operator characteristics show that CRP (wilks-lambda = 0.549; ROC: AUC 0.948 and BAFF (wilks-lambda = 0.907; ROC: AUC 0.843 serum levels at day of admission best predict severe necrotizing pancreatitis or death, outperforming IL-6, PCT, and number of leucocytes.This study establishes for the first time BAFF as an acute phase reactant with predictive value for the course of acute pancreatitis. BAFF outperforms established markers in acute pancreatitis, like IL-6 and PCT underscoring the important role of BAFF in the acute inflammatory response.

  6. B cell activating factor of the tumor necrosis factor family (BAFF) behaves as an acute phase reactant in acute pancreatitis.

    Science.gov (United States)

    Pongratz, Georg; Hochrinner, Hannah; Straub, Rainer H; Lang, Stefanie; Brünnler, Tanja

    2013-01-01

    To determine if B cell activating factor of the tumor necrosis factor family (BAFF) acts as an acute phase reactant and predicts severity of acute pancreatitis. 40 patients with acute pancreatitis were included in this single center cohort pilot study. Whole blood and serum was analyzed on day of admission and nine consecutive days for BAFF, c-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), and leucocyte numbers. Different severity Scores (Ranson, APACHE II, SAPS II, SAPS III) and the clinical course of the patient (treatment, duration of stay, duration ICU) were recorded. Serum BAFF correlates with CRP, an established marker of severity in acute pancreatitis at day of admission with a timecourse profil similar to IL-6 over the first nine days. Serum BAFF increases with Ranson score (Kruskal-Wallis: Chi2 = 10.8; p = 0.03) similar to CRP (Kruskal-Wallis: Chi2 = 9.4; p = 0.05 ). Serum BAFF, IL-6, and CRP levels are elevated in patients that need intensive care for more than seven days and in patients with complicated necrotizing pancreatitis. Discriminant analysis and receiver operator characteristics show that CRP (wilks-lambda = 0.549; ROC: AUC 0.948) and BAFF (wilks-lambda = 0.907; ROC: AUC 0.843) serum levels at day of admission best predict severe necrotizing pancreatitis or death, outperforming IL-6, PCT, and number of leucocytes. This study establishes for the first time BAFF as an acute phase reactant with predictive value for the course of acute pancreatitis. BAFF outperforms established markers in acute pancreatitis, like IL-6 and PCT underscoring the important role of BAFF in the acute inflammatory response.

  7. Antibodies That Block or Activate Mouse B Cell Activating Factor of the Tumor Necrosis Factor (TNF) Family (BAFF), Respectively, Induce B Cell Depletion or B Cell Hyperplasia.

    Science.gov (United States)

    Kowalczyk-Quintas, Christine; Schuepbach-Mallepell, Sonia; Vigolo, Michele; Willen, Laure; Tardivel, Aubry; Smulski, Cristian R; Zheng, Timothy S; Gommerman, Jennifer; Hess, Henry; Gottenberg, Jacques-Eric; Mackay, Fabienne; Donzé, Olivier; Schneider, Pascal

    2016-09-16

    B cell activating factor of the TNF family (BAFF), also known as B lymphocyte stimulator, is a ligand required for the generation and maintenance of B lymphocytes. In this study, the ability of different monoclonal antibodies to recognize, inhibit, or activate mouse BAFF was investigated. One of them, a mouse IgG1 named Sandy-2, prevented the binding of BAFF to all of its receptors, BAFF receptor, transmembrane activator and calcium modulating ligand interactor, and B cell maturation antigen, at a stoichiometric ratio; blocked the activity of mouse BAFF on a variety of cell-based reporter assays; and antagonized the prosurvival action of BAFF on primary mouse B cells in vitro A single administration of Sandy-2 in mice induced B cell depletion within 2 weeks, down to levels close to those observed in BAFF-deficient mice. This depletion could then be maintained with a chronic treatment. Sandy-2 and a previously described rat IgG1 antibody, 5A8, also formed a pair suitable for the sensitive detection of endogenous circulating BAFF by ELISA or using a homogenous assay. Interestingly, 5A8 and Sandy-5 displayed activities opposite to that of Sandy-2 by stimulating recombinant BAFF in vitro and endogenous BAFF in vivo These tools will prove useful for the detection and functional manipulation of endogenous mouse BAFF and provide an alternative to the widely used BAFF receptor-Fc decoy receptor for the specific depletion of BAFF in mice. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Interferon-beta increases systemic BAFF levels in multiple sclerosis without increasing autoantibody production

    DEFF Research Database (Denmark)

    Hedegaard, Chris J; Sellebjerg, Finn; Krakauer, Martin

    2011-01-01

    Background: Treatment with interferon-beta (IFN-beta) increases B-cell activating factor of the TNF family (BAFF) expression in multiple sclerosis (MS), raising the concern that treatment of MS patients with IFN-beta may activate autoimmune B cells and stimulate the production of MS-associated au......Background: Treatment with interferon-beta (IFN-beta) increases B-cell activating factor of the TNF family (BAFF) expression in multiple sclerosis (MS), raising the concern that treatment of MS patients with IFN-beta may activate autoimmune B cells and stimulate the production of MS......-associated autoantibodies. Objective: To investigate whether BAFF levels are associated with disease severity/activity in untreated MS patients, and to assess the effect of IFN-beta therapy on circulating BAFF and anti-myelin basic protein (MBP) autoantibody levels. Results: Twenty-three patients with relapsing......-remitting MS (RRMS) were followed longitudinally from initiation of IFN-beta therapy. Their blood levels of BAFF correlated positively at baseline with the expanded disability status scale (p

  9. B cell activation factor (BAFF) is a novel adipokine that links obesity and inflammation

    OpenAIRE

    Kim, Yu-Hee; Choi, Bong-Hyuk; Cheon, Hyae-Gyeong; Do, Myoung-Sool

    2009-01-01

    B cell activation factor (BAFF) is a novel member of the TNF ligand superfamily, mainly produced by myeloid cells. BAFF has been shown to participate in B-cell survival and B- and T-cell maturation. BAFF expression in adipocytes has been recently demonstrated. In the current study, we verified that BAFF expression is increased during adipocyte differentiation. BAFF expression was augmented by TNF-α treatment and was decreased by rosiglitazone treatment. BAFF secretion in lean and in ob/ob mic...

  10. Expression of BAFF and BAFF-R in Follicular Lymphoma: Correlation with Clinicopathologic Characteristics and Survival Outcomes

    Science.gov (United States)

    Rao, Hui-Lan; Huang, Jia-Jia; Xia, Yi; Huang, Hui-Qiang; Lin, Tong-Yu; Xia, Zhong-Jun; Li, Su; Li, Zhi-Ming

    2012-01-01

    Background B-cell activation factor (BAFF) and BAFF-receptor (BAFF-R) play crucial roles in the viability and proliferation of malignant lymphoma cells. Limited information exists regarding expression profiles and the prognostic role of BAFF and BAFF-R in follicular lymphoma (FL). We sought to determine the expression profiles of BAFF and BAFF-R in FL and to evaluate the correlation of BAFF and BAFF-R expression with clinicopathologic characteristics and outcome of FL. Correlation between expression levels of BAFF detected by immunohistochemical (IHC) and serum levels of BAFF was also evaluated. Methods Paraffin-embedded specimens from 115 patients were immunohistochemically examined for BAFF and BAFF-R expression. Expression levels were dichotomized into low versus high categories based on immunostaining intensity. The correlation of BAFF and BAFF-R expression with clinicopathologic characteristics and patient outcome was assessed. Serum levels of BAFF in 35 of the 115 patients with IHC data were measured by Enzyme-linked Immunosorbent assay (ELISA). Results BAFF and BAFF-R were expressed in 88.7% (102/115) and 87.8% (101/115) of the cases, respectively. BAFF expression was significantly correlated with only one clinicopathologic feature: Ann Arbor stage. No significant correlation was found between expression levels of BAFF detected by IHC and serum levels of BAFF detected by ELISA. High expression of BAFF-R, but not BAFF, was significantly correlated with inferior progression-free survival (PFS; P = 0.013) and overall survival (OS; P = 0.03). High expression of BAFF-R, bulky disease, and elevated lactate dehydrogenase were correlated with inferior PFS and OS in multivariate analysis. A prognostic scoring system incorporating these 3 risk factors identified 3 distinct prognostic groups with 5-year PFS of 59.4%, 41.9%, and 10.7% and OS of 91.3%, 79.7%, and 45.8%, respectively. Conclusions Most patients with FL variably express BAFF and BAFF-R. High

  11. Unexpected Potency Differences between B-Cell-Activating Factor (BAFF) Antagonist Antibodies against Various Forms of BAFF: Trimer, 60-Mer, and Membrane-Bound.

    Science.gov (United States)

    Nicoletti, Amy M; Kenny, Cynthia Hess; Khalil, Ashraf M; Pan, Qi; Ralph, Kerry L M; Ritchie, Julie; Venkataramani, Sathyadevi; Presky, David H; DeWire, Scott M; Brodeur, Scott R

    2016-10-01

    Therapeutic agents antagonizing B-cell-activating factor/B-lymphocyte stimulator (BAFF/BLyS) are currently in clinical development for autoimmune diseases; belimumab is the first Food and Drug Administration-approved drug in more than 50 years for the treatment of lupus. As a member of the tumor necrosis factor superfamily, BAFF promotes B-cell survival and homeostasis and is overexpressed in patients with systemic lupus erythematosus and other autoimmune diseases. BAFF exists in three recognized forms: membrane-bound and two secreted, soluble forms of either trimeric or 60-mer oligomeric states. To date, most in vitro pharmacology studies of BAFF neglect one or more of these forms. Here, we report a comprehensive in vitro cell-based analysis of BAFF in assay systems that measure all forms of BAFF-mediated activation. We demonstrate the effects of these BAFF forms in both a primary human B-cell proliferation assay and in nuclear factor κB reporter assay systems in Chinese hamster ovary cells expressing BAFF receptors and transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI). In contrast to the mouse system, we find that BAFF trimer activates the human TACI receptor. Further, we profiled the activities of two clinically advanced BAFF antagonist antibodies, belimumab and tabalumab. Unexpectedly, we revealed differences in inhibitory potencies against the various BAFF forms, in particular that belimumab does not potently inhibit BAFF 60-mer. Through this increased understanding of the activity of BAFF antagonists against different forms of BAFF, we hope to influence the discovery of BAFF antagonist antibodies with distinct therapeutic mechanisms for improvement in the treatment of lupus or other related autoimmune pathologies. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  12. Blood stage Plasmodium falciparum antigens induce T cell independent immunoglobulin production via B cell activation factor of the TNF family (BAFF) pathway.

    Science.gov (United States)

    Kumsiri, Ratchanok; Potup, Pachuen; Chotivanich, Kesinee; Petmitr, Songsak; Kalambaheti, Thareerat; Maneerat, Yaowapa

    2010-12-01

    T independent (TI) antigens (Ags) activate monocytes to produce a cytokine, termed B cell activation factor (BAFF), involved in immunoglobulin (Ig) production. This study aimed to investigate whether the soluble schizont fraction of Plasmodium falciparum antigen (sPfAg) and hemozoin (HZ) could act as TI Ag to induce P. falciparum (Pf) specific Ig production via BAFF pathway. Co-cultures of monocytes and naïve B cells from 6 healthy donors were stimulated with sPfAg (10mg/ml) or HZ (10μM). At interval times, the expressions of BAFF on activated monocytes, BAFF receptor (BAFF-R) and proliferation nuclear Ag in activated B cells were determined by flow cytometry. The soluble BAFF (sBAFF), total and specific IgG levels in the supernatants were assessed by enzyme-linked immunosorbent assay (ELISA). The finding revealed both sPfAg and HZ could activate monocytes to express BAFF on surface and release sBAFF in the supernatant within 72h of stimulation. The B cells responded to specific activation, indicated by BAFF-R expression on the surface within 72h, marked proliferation on day 7, and final production of total and specific IgG during days 7-12. Comparing to sPfAg, HZ stimulated monocyte and B cell co-culture to express higher levels of BAFF and sBAFF during 24-48h, more BAFF-R on HZ activated B cells within 24h and induced marked proliferation of B cells with higher Pf specific IgG level. However, stimulation with sPfAg showed a more significant correlation between BAFF expression on the activated monocytes at 72h and the Pf specific IgG level on day 12 (r=0.961, p=0.039, Pearson Correlation). In conclusion, it is possible that both sPfAg and HZ stimulated B cells to produce specific IgG with BAFF involvement. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. The presence of B-cell activating factor (BAFF) in umbilical cord blood in both healthy and pre-eclamptic pregnancies and in human breast milk.

    Science.gov (United States)

    Bienertova-Vasku, Julie; Zlamal, Filip; Tomandl, Josef; Hodicka, Zuzana; Novak, Jan; Splichal, Zbynek; Ventruba, Pavel; Thon, Vojtech; Vasku, Anna

    2015-06-01

    B-cell activating factor (BAFF) is an important immune regulator that was recently reported to be secreted by placenta. The aim of the study was to investigate the presence of BAFF in umbilical cord blood, maternal serum, and breast milk in normal and in pre-eclamptic pregnancies. Pairs of maternal serum/umbilical cord blood were obtained from 12 pre-eclamptic and 34 physiological pregnancies. Another cohort of 10 healthy lactating women was established that was followed up for 6 months following delivery to investigate BAFF levels in breast milk. BAFF levels in maternal peripheral blood were significantly higher in physiological pregnancies than in pre-eclamptic pregnancies (p BAFF in breast milk during the 6-month post-partum period of breastfeeding. In this study, we demonstrate that BAFF levels are significantly lower in maternal peripheral blood in pre-eclamptic pregnancies. We also report the consistent presence of BAFF in breast milk in healthy women. More research into the role of BAFF in pregnancy, and during breastfeeding, is imperative. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Soluble BAFF Level Is Not Correlated to Mycobacterium avium Subspecies Paratuberculosis Antibodies and Increases After Interferon-β Therapy in Multiple Sclerosis Patients.

    Science.gov (United States)

    Mameli, Giuseppe; Cossu, Davide; Caggiu, Elisa; Arru, Giannina; Niegowska, Magdalena; Cocco, Eleonora; Frau, Jessica; Marrosu, Maria Giovanna; Sechi, Leonardo A

    2016-09-01

    B cells are being recognized as one of the major players in the pathogenesis of multiple sclerosis (MS). The B cell activating factor (BAFF) system plays an essential role in B cell homeostasis and function in the periphery. Mycobacterium avium subspecies paratuberculosis (MAP) has been previously associated to MS in Sardinia. Antibodies against a MAP surface protein, MAP_2694, have been found significantly associated to MS patients, and this response was modified by interferon-β therapy. Increased BAFF levels following IFN-β therapy have been also described in MS patients. In this study, we evaluated whether soluble BAFF levels are comparable in men and women affected by MS and performed a correlation of the reported BAFF increase in MS patients under IFN-β therapy with changes of humoral response against MAP_2694. For these reasons, we investigated 44 MS patients before and after IFN-β therapy. A significant difference of BAFF levels was found between men and women with MS; moreover, we confirmed that IFN-β therapy strongly induces BAFF serum levels, but this was not related to the modification of immunological response against MAP_2694. In conclusion, our study highlights that IFN-β therapy induces the potent B cell survival factor BAFF without alterations of the humoral immune response against MAP.

  15. Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus.

    Science.gov (United States)

    Salazar-Camarena, D C; Ortiz-Lazareno, P C; Cruz, A; Oregon-Romero, E; Machado-Contreras, J R; Muñoz-Valle, J F; Orozco-López, M; Marín-Rosales, M; Palafox-Sánchez, C A

    2016-05-01

    B-cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) signaling pathways regulate B-cell survival through interactions with their receptors BAFF-R, TACI and BCMA. We evaluated the association of these ligands/receptors on B-cell subsets according to clinical manifestations of systemic lupus erythematosus (SLE). BAFF and APRIL serum concentrations were measured in 30 SLE patients by enzyme-linked immunosorbent assay. The BAFF-R, TACI and BCMA expression was analyzed on each B cell subset (CD19 + CD27-CD38-/ + naïve; CD19 + CD27 + CD38-/ + memory; CD19 + CD27-CD38 + + immature and CD19 + CD27 + CD38 + + plasma cells) by flow cytometry, and compared among patients with different clinical manifestations as well as healthy controls (HCs). Serum BAFF and APRIL levels were high in SLE patients and correlated with the Mex-SLEDAI disease activity index (r = 0.584; p = 0.001 and r = 0.456; p = 0.011, respectively). The SLE patients showed an increased proportion of memory and plasma B cells (p < 0.05). BAFF-R, TACI and BCMA expression in SLE patients was decreased in almost all B cell subsets compared to HCs (p < 0.05). A lower BCMA expression was associated with severe disease activity, glomerulonephritis, serositis and hemolytic anemia (p < 0.01). BCMA expression showed a negative correlation with Mex-SLEDAI score (r = -0.494, p = 0.006). Decreased BCMA expression on peripheral B cells according to severe disease activity suggests that BCMA plays an important regulating role in B-cell hyperactivity and immune tolerance homeostasis in SLE patients. © The Author(s) 2015.

  16. Increased levels of BAFF and APRIL related to human active pulmonary tuberculosis.

    Directory of Open Access Journals (Sweden)

    Kai Liu

    Full Text Available BACKGROUND: Despite great efforts to improve diagnosis and treatment, tuberculosis (TB remains a major health problem worldwide, especially in developing countries. Lack of concrete immune markers is still the obstacle to properly evaluate active TB. Therefore, identification of more validated biomarkers and phenotypic signatures is imperative. In particular, T cell-related biomarkers are more significant. METHODOLOGY: To understand the nature of CD4(+ T cell-derived signatures involved in infection and disease development, we examined and analyzed whole genome expression profiles of purified CD4(+ T cells from healthy individuals (HD, two distinct populations with latent infection (with low or high IFN-γ levels, LTB(L/LTB(H and untreated TB patients. Following, we validated the expression profiles of genes in the peripheral CD4(+ T cells from each group and examined secretion levels of distinct cytokines in serum and pleural effusion. PRINCIPAL FINDINGS: Our bio-informatic analyses indicate that the two latent populations and clinical TB patients possess distinct CD4(+ T cell gene expression profiles. Furthermore, The mRNA and protein expression levels of B cell activating factor (BAFF, which belongs to the TNF family, and a proliferation-inducing ligand (APRIL were markedly up-regulated at the disease stage. In particular, the dramatic enhancement of BAFF and APRIL in the pleural effusion of patients with tuberculosis pleurisy suggests that these proteins may present disease status. In addition, we found that the BAFF/APRIL system was closely related to the Th1 immune response. Our study delineates previously unreported roles of BAFF and APRIL in the development of tuberculosis, and these findings have implications for the diagnosis of the disease. Our study also identifies a number of transcriptional signatures in CD4(+ T cells that have the potential to be utilized as diagnostic and prognostic tools to combat the tuberculosis epidemic.

  17. High expression levels of BLyS/BAFF by blood dendritic cells and granulocytes are associated with B-cell dysregulation in SIV-infected rhesus macaques.

    Science.gov (United States)

    Poudrier, Johanne; Soulas, Caroline; Chagnon-Choquet, Josiane; Burdo, Tricia; Autissier, Patrick; Oskar, Kathryn; Williams, Kenneth C; Roger, Michel

    2015-01-01

    Dendritic cells (DCs) modulate B-cell survival and differentiation, mainly through production of growth factors such as B lymphocyte stimulator (BLyS/BAFF). In recent longitudinal studies involving HIV-1-infected individuals with different rates of disease progression, we have shown that DCs were altered in number and phenotype in the context of HIV-1 disease progression and B-cell dysregulations were associated with increased BLyS/BAFF expression in plasma and by blood myeloid DCs (mDCs) in rapid and classic progressors but not in HIV-1-elite controllers (EC). Suggesting that the extent to which HIV-1 disease progression is controlled may be linked to BLyS/BAFF expression status and the capacity to orchestrate B-cell responses. Herein, longitudinal analyses of simian immunodeficiency virus (SIV)-infected rhesus macaques also revealed increased expression of BLyS/BAFF by blood mDCs as soon as day 8 and throughout infection. Strikingly, granulocytes presented the highest BLyS/BAFF expression profile in the blood of SIV-infected macaques. BLyS/BAFF levels were also increased in plasma and correlated with viral loads. Consequently, these SIV-infected animals had plasma hyperglobulinemia and reduced blood B-cell numbers with altered population frequencies. These data underscore that BLyS/BAFF is associated with immune dysregulation in SIV-infected rhesus macaques and suggest that BLyS/BAFF is a key regulator of immune activation that is highly conserved among primates. These findings emphasize the potential importance of this SIV-infected primate model to test whether blocking excess BLyS/BAFF has an effect on the overall inflammatory burden and immune restoration.

  18. High expression levels of BLyS/BAFF by blood dendritic cells and granulocytes are associated with B-cell dysregulation in SIV-infected rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Johanne Poudrier

    Full Text Available Dendritic cells (DCs modulate B-cell survival and differentiation, mainly through production of growth factors such as B lymphocyte stimulator (BLyS/BAFF. In recent longitudinal studies involving HIV-1-infected individuals with different rates of disease progression, we have shown that DCs were altered in number and phenotype in the context of HIV-1 disease progression and B-cell dysregulations were associated with increased BLyS/BAFF expression in plasma and by blood myeloid DCs (mDCs in rapid and classic progressors but not in HIV-1-elite controllers (EC. Suggesting that the extent to which HIV-1 disease progression is controlled may be linked to BLyS/BAFF expression status and the capacity to orchestrate B-cell responses. Herein, longitudinal analyses of simian immunodeficiency virus (SIV-infected rhesus macaques also revealed increased expression of BLyS/BAFF by blood mDCs as soon as day 8 and throughout infection. Strikingly, granulocytes presented the highest BLyS/BAFF expression profile in the blood of SIV-infected macaques. BLyS/BAFF levels were also increased in plasma and correlated with viral loads. Consequently, these SIV-infected animals had plasma hyperglobulinemia and reduced blood B-cell numbers with altered population frequencies. These data underscore that BLyS/BAFF is associated with immune dysregulation in SIV-infected rhesus macaques and suggest that BLyS/BAFF is a key regulator of immune activation that is highly conserved among primates. These findings emphasize the potential importance of this SIV-infected primate model to test whether blocking excess BLyS/BAFF has an effect on the overall inflammatory burden and immune restoration.

  19. VAV1 and BAFF, via NFκB pathway, are genetic risk factors for myasthenia gravis

    DEFF Research Database (Denmark)

    Avidan, Nili; Le Panse, Rozen; Harbo, Hanne F

    2014-01-01

    confirmation loci were genotyped in 1177 EOMG patients and 814 controls, from nine European centres. RESULTS: ALLELE FREQUENCY DIFFERENCES WERE FOUND IN FOUR NOVEL LOCI: CD86, AKAP12, VAV1, B-cell activating factor (BAFF), and tumor necrosis factor-alpha (TNF-α), and these differences were consistent in all...... are novel and of interest as VAV1 is a key signal transducer essential for T- and B-cell activation, and BAFF is a cytokine that plays important roles in the proliferation and differentiation of B-cells. Moreover, we noted striking epistasis between the predisposing VAV1 and BAFF haplotypes; they conferred...

  20. Relationship between Circulating BAFF Serum Levels with Proliferating Markers in Patients with Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Michael G. Alexandrakis

    2013-01-01

    Full Text Available In multiple myeloma, there are many factors influencing the growth of the malignant clone in direct and indirect manners. BAFF is a growth factor for myeloma cells. The aim of the study was to measure its circulating levels in 54 pretreatment patients, along with serum levels of other proliferation markers, such as interleukins-6, -10, and -15, CRP, and beta-2 microglobulin, as well as bone marrow plasma cell infiltration and expression of Ki-67 PI, in various stages of the disease and after effective treatment in 28 of them. Serum levels of the previously mentioned factors were measured by ELISA, whereas bone marrow plasma cell infiltration and Ki-67 expression were estimated immunohistochemically. All measured parameters were higher in pretreated myeloma patients compared to healthy population and were also increasing with the progression of the disease. They all also decreased after effective therapy. Furthermore, all pretreatment values correlated to each other. BAFF seems to be an important growth factor for myeloma plasma cells. Measuring its serum levels, along with the previously mentioned cytokines, may provide important information regarding the degree of myeloma cells’ proliferation. Therefore, they all could be used as markers of proliferation and disease activity.

  1. Characteristics of BAFF and APRIL factor expression in multiple myeloma and clinical significance.

    Science.gov (United States)

    Pan, Jing; Sun, Yuanyuan; Zhang, Ning; Li, Jianming; Ta, Fangxin; Wei, Wei; Yu, Shanshan; Ai, Limei

    2017-09-01

    The characteristics of the proliferation of B-cell activating factor (BAFF) and the proliferation-inducing ligand (APRIL) mRNA expression in mononuclear cell in multiple myeloma patients were detected, and the correlation was analyzed between the BAFF and APRIL concentrations in plasma and tumor burden parameters of multiple myeloma. Bone marrow samples from 60 patients with multiple myeloma and 20 healthy persons taken as controls, were collected. Bone marrow mononuclear cells (BMMCs) were harvested, and plasma was extracted. BAFF and APRIL mRNA expression was quantified using real-time fluorescent quantitative PCR in the BMMCs. ELISA was used to detect the characteristics of gene and protein expression of BAFF and APRIL in KM3 cell line. The BAFF and APRIL mRNA expression in initial treatment group, remission group and non-remission group were markedly higher than that in control group (PBAFF concentration in multiple myeloma (P=0.0027). In conclusion, for the gene and protein expression of BAFF and APRIL in patients with multiple myeloma, the initial treatment group and non-remission are higher than control and remission group. The higher the stage was, the more the factors were expressed. Characteristics of expression of BAFF and APRIL may be used as a new index to evaluate the prognosis of multiple myeloma.

  2. Expression of BAFF and BAFF-R in Follicular Lymphoma: Correlation with Clinicopathologic Characteristics and Survival Outcomes

    OpenAIRE

    Li, Ya-Jun; Jiang, Wen-Qi; Rao, Hui-Lan; Huang, Jia-Jia; Xia, Yi; Huang, Hui-Qiang; Lin, Tong-Yu; Xia, Zhong-Jun; Li, Su; Li, Zhi-Ming

    2012-01-01

    BACKGROUND: B-cell activation factor (BAFF) and BAFF-receptor (BAFF-R) play crucial roles in the viability and proliferation of malignant lymphoma cells. Limited information exists regarding expression profiles and the prognostic role of BAFF and BAFF-R in follicular lymphoma (FL). We sought to determine the expression profiles of BAFF and BAFF-R in FL and to evaluate the correlation of BAFF and BAFF-R expression with clinicopathologic characteristics and outcome of FL. Correlation between ex...

  3. Molecular characterization and evolutionary analysis of horse BAFF-R, a tumor necrosis factor receptor related to B-cell survival.

    Science.gov (United States)

    Wu, Haitao; Chen, Shanshan; Liu, Meng; Xu, Xingzhou; Ji, Xuemei; Gao, Kai; Tian, Aiying; Ke, Zhen; Zhang, Jianrong; Zhao, Bo; Zhang, Shuangquan

    2014-01-01

    B-cell survival depends on signals induced by B-cell activating factor (BAFF) that binds to the BAFF receptor (BAFF-R). Herein, a BAFF-R homolog was identified in a horse (Equus caballus). The horse BAFF-R gene, located on chromosome 28, spans 1444 base pairs and encodes a 183-amino acid protein. The protein is structurally conserved, in which the DxL motif plays an important role in binding to BAFF. Furthermore, the horse BAFF-R extracellular domain was expressed and purified, which specifically bound to His6-sBAFF and had the capability of blocking the function of His6-sBAFF in vitro. Finally, evolutionary analyses indicated that some codon sites of BAFF-R evolve with positive selection and that the genetic relationship among a horse, Chiroptera, and Caniformia are the closest. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. The role of BAFF in the progression of rheumatoid arthritis.

    Science.gov (United States)

    Wei, Fang; Chang, Yan; Wei, Wei

    2015-12-01

    Rheumatoid arthritis (RA) is a common autoimmune disease that is marked by a systemic inflammatory reaction and joint erosions. Elevated levels of B cell activating factor (BAFF) have been detected in the serum and synovial fluid of RA patients. Moreover, the levels of BAFF increase in cases of autoimmune disease and are correlated with the level of disease activity. As an innate cytokine mediator, BAFF affects the immune response of the synovial microenvironment. In this review, we consider recent observations of BAFF and its receptors in RA progression, as well as the effects of BAFF on the cell-cell interactions network. We also summarize the clinical development of BAFF antagonists for the treatment of RA. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Serum BAFF and thyroid autoantibodies in autoimmune thyroid disease.

    Science.gov (United States)

    Lin, Jiunn-Diann; Wang, Yuan-Hung; Fang, Wen-Fang; Hsiao, Chia-Jung; Chagnaadorj, Amarzaya; Lin, Yuh-Feng; Tang, Kam-Tsun; Cheng, Chao-Wen

    2016-11-01

    This study investigated the association of serum B-lymphocyte activating factor (BAFF) levels with autoimmune thyroid disease (AITD) in a Chinese population. We enrolled 221 patients with AITD [170 patients with Graves' disease (GD), 51 patients with Hashimoto's thyroiditis (HT)], and 124 healthy controls. Serum BAFF levels, thyroid function and thyroid autoantibody (TAb) levels, including of thyroid-stimulating hormone receptor antibody (TSHRAb), anti-thyroid peroxidase antibody (Anti-TPO Ab), and antithyroglobulin antibody (ATA), were measured at baseline. Serum BAFF levels were higher in the GD, HT, and AITD groups than in the control group. Significant correlations were observed between BAFF and TSHRAb levels (r=0.238, p=0.018), between BAFF and Anti-TPO Ab levels (p=0.038), and between BAFF and ATA titers (p=0.025) in women but not in men. In addition, serum BAFF levels were significantly associated with free thyroxine (r=0.430, p=0.004) and TSHRAb (r=0.495, p=0.001) levels in women with active GD but not in those with inactive GD. Serum BAFF levels are increased in GD, HT, and AITD. The correlation between serum BAFF and TAb levels exhibits a dimorphic pattern, particularly in active GD. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. CsBAFF, a Teleost B Cell Activating Factor, Promotes Pathogen-Induced Innate Immunity and Vaccine-Induced Adaptive Immunity.

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    Yun Sun

    Full Text Available B cell activating factor (BAFF is a member of the tumor necrosis factor family that is known to play an important role in B cell activation, proliferation, and differentiation in mammals. However, studies of BAFF in teleosts are very limited and its function, in particular that under in vivo conditions, is essentially unknown. In this study, we conducted in vivo as well as in vitro functional analyses of a BAFF homologue (CsBAFF from the teleost fish tongue sole (Cynoglossus semilaevis. CsBAFF is composed of 261 residues and shares moderate sequence identities with known BAFFs of other teleosts. CsBAFF expression was most abundant in immune organs and was upregulated during bacterial infection. Purified recombinant CsBAFF (rCsBAFF bound to tongue sole lymphocytes and promoted cellular proliferation and survival. The results of an in vivo study showed that CsBAFF overexpression in tongue sole significantly enhanced macrophage activation and reduced bacterial infection in fish tissues, whereas knockdown of CsBAFF expression resulted in increased bacterial dissemination and colonization in fish tissues. Furthermore, vaccination studies showed that CsBAFF enhanced the immunoprotection of a DNA vaccine and augmented the production of specific serum antibodies. Taken together, these results provide the first in vivo evidence to indicate that teleost BAFF is an immunostimulator that significantly contributes to the innate antibacterial immune response and vaccine-induced adaptive immune response.

  7. Gingival crevicular fluid and serum levels of APRIL, BAFF and TNF-alpha in rheumatoid arthritis and osteoporosis patients with periodontal disease.

    Science.gov (United States)

    Gümüş, Pinar; Buduneli, Eralp; Biyikoğlu, Başak; Aksu, Kenan; Saraç, Fulden; Buduneli, Nurcan; Lappin, David F

    2013-10-01

    This study was performed to evaluate gingival crevicular fluid (GCF) and serum levels of a proliferation inducing ligand (APRIL) and B cell activating factor (BAFF) and compare this to differences between TNF-alpha levels in rheumatoid arthritis (RA), osteoporosis (OPR) and systemically healthy women with periodontal disease (SH). Gingival crevicular fluid (GCF) and serum samples were obtained before any periodontal intervention from 17 RA, 19 OPR patients and 13 SH women with periodontitis. Full-mouth clinical periodontal measurements were recorded. APRIL, BAFF and TNF-α levels were determined by ELISA. Statistical analysis was performed using multivariate analysis, ANOVA and Spearman correlation. Pocket depths differed in site-specific comparisons, but otherwise clinical measurements were similar in the three study groups. Multivariate least squares regression ANOVA adjusted for age and for plaque index indicated that total amounts of TNF-α and concentrations of TNF-α, BAFF and APRIL were significantly greater in the RA patients than in the SH group (p<0.05), and GCF concentrations of BAFF were greater in OPR patients than in SH. Serum TNF-α and BAFF were significantly higher in the RA group compared to SH (p<0.05) and serum TNF-α was greater in RA than in OPR (p<0.05). APRIL and BAFF correlated with RANKL levels in GCF and serum (p<0.05). Despite long-term usage of anti-inflammatory drugs in the RA and OPR patients, increased TNF-family cytokines, might suggest that these patients have a propensity to overproduce these inflammatory mediators but whether this results from greater disease activity or contribute to greater disease activity remains moot. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. B cell activating factor (BAFF) selects IL-10-B cells over IL-10+B cells during inflammatory responses.

    Science.gov (United States)

    Ma, Ning; Zhang, Yu; Liu, Qilin; Wang, Zhiding; Liu, Xiaoling; Zhu, Gaizhi; Yu, Dandan; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Wang, Tianxiao; Ma, Yuanfang; Shen, Beifen; Li, Yan; Xiao, He; Wang, Renxi

    2017-05-01

    B cell activating factor (BAFF) regulates B cell maturation, survival, function, and plays a critical pathogenic role in autoimmune diseases. It remains unclear how BAFF affects IL-10 - B cells versus regulatory B cells (Bregs) in inflammatory responses. In this study, we found that IL-10-expressing Bregs decreased in lupus-prone MRL/lpr mice and experimental allergic encephalomyelitis (EAE) mice. On blockade of the effects of BAFF with TACI-IgG, IL-10 + Bregs were upregulated in MRL/lpr and EAE mice. In addition, BAFF expanded IL-10 + B cells over IL-10 - B cells under noninflammatory conditions in vitro, whereas it expanded IL-10 - B cells over IL-10 + B cells during inflammatory responses, such as stimulation with autoantigen and LPS. Finally, the selection of IL-10 - B cells over IL-10 + B cells by BAFF was dependent on BAFF receptors (BAFFR, TACI, and BCMA) that were upregulated by inflammatory responses. This study suggests that BAFF selects IL-10 - B cells over IL-10 + regulatory B cells via BAFF receptors in inflammatory responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Expression of BAFF and BR3 in patients with systemic lupus erythematosus

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    J.H. Duan

    2016-03-01

    Full Text Available The objective of this study was to examine the relationship between the expression of B cell activating factor (BAFF and BAFF receptor in patients with disease activity of systemic lupus erythematosus (SLE. Real-time RT-PCR was used to examine BAFF mRNA expression in peripheral blood monocytes of active and stable SLE patients and healthy controls. The percentage of BAFF receptor 3 (BR3 on B lymphocytes was measured by flow cytometry. Soluble BAFF levels in serum were assayed by ELISA. Microalbumin levels were assayed by an automatic immune analysis machine. BAFF mRNA and soluble BAFF levels were highest in the active SLE group, followed by the stable SLE group, and controls (P<0.01. The percentage of BR3 on B lymphocytes was downregulated in the active SLE group compared with the stable SLE group and controls (P<0.01. BAFF mRNA levels and soluble BAFF levels were higher in patients who were positive for proteinuria than in those who were negative (P<0.01. The percentage of BR3 on B lymphocytes was lower in patients who were positive for proteinuria than in those who were negative (P<0.01. The BAFF/BR3 axis may be over-activated in SLE patients. BAFF and BR3 levels may be useful parameters for evaluating treatment.

  10. BAFF promotes proliferation of human mesangial cells through interaction with BAFF-R

    OpenAIRE

    Zheng, Nuoyan; Wang, Donxian; Ming, Hongyan; Zhang, Haiqing; Yu, Xueqing

    2015-01-01

    Background B cell activating factor belonging to the TNF family (BAFF) is vital for B cell survival, proliferation and activation. Evidence indicates that BAFF is systemically or locally increased in glomerulonephritis (e.g. lupus nephritis, IgA nephropathy). However, the effect of BAFF on human mesangial cells is not known. Methods The impact of BAFF on the proliferation of a human mesangial cell line in vitro was investigated. The expression of BAFF receptor (BAFF-R) and downstream signal t...

  11. Targeting BAFF and APRIL in systemic lupus erythematosus and other antibody-associated diseases.

    Science.gov (United States)

    Samy, Eileen; Wax, Stephen; Huard, Bertrand; Hess, Henry; Schneider, Pascal

    2017-01-02

    The B cell-stimulating molecules, BAFF (B cell activating factor) and APRIL (a proliferation-inducing ligand), are critical factors in the maintenance of the B cell pool and humoral immunity. In addition, BAFF and APRIL are involved in the pathogenesis of a number of human autoimmune diseases, with elevated levels of these cytokines detected in the sera of patients with systemic lupus erythematosus (SLE), IgA nephropathy, Sjögren's syndrome, and rheumatoid arthritis. As such, both molecules are rational targets for new therapies in B cell-driven autoimmune diseases, and several inhibitors of BAFF or BAFF and APRIL together have been investigated in clinical trials. These include the BAFF/APRIL dual inhibitor, atacicept, and the BAFF inhibitor, belimumab, which is approved as an add-on therapy for patients with active SLE. Post hoc analyses of these trials indicate that baseline serum levels of BAFF and BAFF/APRIL correlate with treatment response to belimumab and atacicept, respectively, suggesting a role for the two molecules as predictive biomarkers. It will, however, be important to refine future testing to identify active forms of BAFF and APRIL in the circulation, as well as to distinguish between homotrimer and heteromer configurations. In this review, we discuss the rationale for dual BAFF/APRIL inhibition versus single BAFF inhibition in autoimmune disease, by focusing on the similarities and differences between the physiological and pathogenic roles of the two molecules. A summary of the preclinical and clinical data currently available is also presented.

  12. Therapeutic Effects of PADRE-BAFF Autovaccine on Rat Adjuvant Arthritis

    Directory of Open Access Journals (Sweden)

    Guo-dong Feng

    2014-01-01

    Full Text Available B cell activating factor (BAFF is a cytokine of tumor necrosis factor family mainly produced by monocytes and dendritic cells. BAFF can regulate the proliferation, differentiation, and survival of B lymphocytes by binding with BAFF-R on B cell membrane. Accumulating evidences showed that BAFF played crucial roles and was overexpressed in various autoimmune diseases such as systemic lupus erythematous (SLE and rheumatoid arthritis (RA. This suggests that BAFF may be a therapeutic target for these diseases. In the present study, we developed a BAFF therapeutic vaccine by coupling a T helper cell epitope AKFVAAWTLKAA (PADRE to the N terminus of BAFF extracellular domains (PADRE-BAFF and expressed this fusion protein in Escherichia coli. The purified vaccine can induce high titer of neutralizing BAFF antibodies and ameliorate the syndrome of complete Freund’s adjuvant (CFA induced rheumatoid arthritis in rats. Our data indicated that the BAFF autovaccine may be a useful candidate for the treatment of some autoimmune diseases associated with high level of BAFF.

  13. BAFF and BAFF receptor levels correlate with B cell subset activation and redistribution in controlled human malaria infection

    NARCIS (Netherlands)

    Scholzen, A.; Teirlinck, A.C.; Bijker, E.M.; Roestenberg, M.; Hermsen, C.C.; Hoffman, S.L.; Sauerwein, R.W.

    2014-01-01

    Characteristic features of Plasmodium falciparum malaria are polyclonal B cell activation and an altered composition of the blood B cell compartment, including expansion of CD21(-)CD27(-) atypical memory B cells. BAFF is a key cytokine in B cell homeostasis, but its potential contribution to the

  14. BAFF promotes proliferation of human mesangial cells through interaction with BAFF-R.

    Science.gov (United States)

    Zheng, Nuoyan; Wang, Donxian; Ming, Hongyan; Zhang, Haiqing; Yu, Xueqing

    2015-05-15

    B cell activating factor belonging to the TNF family (BAFF) is vital for B cell survival, proliferation and activation. Evidence indicates that BAFF is systemically or locally increased in glomerulonephritis (e.g. lupus nephritis, IgA nephropathy). However, the effect of BAFF on human mesangial cells is not known. The impact of BAFF on the proliferation of a human mesangial cell line in vitro was investigated. The expression of BAFF receptor (BAFF-R) and downstream signal transduction were explored. The influence of BAFF on the expression of related genes was also studied. Our data indicated that BAFF had a proliferative effect on human mesangial cells, as supported by the results of cell proliferation assays and the inhibited expression of the pro-apoptotic gene Bim. BAFF-R was expressed on the cell membrane of human mesangial cells and blockade of BAFF/BAFF-R binding abrogated the proliferative effect of BAFF on human mesangial cells. BAFF stimulation led to rapid phosphorylation of NF-κBp65, Akt and MAPK p38 kinase in human mesangial cells, whereas it had no effect on the expression of NF-κB p100 and phosphorylation of Erk. The phosphorylation of Akt was very sensitive to blockade of BAFF/BAFF-R ligation, although activation of MAPK p38 and NF-κBp65 was not. BAFF treatment resulted in decreased expression of BAFF-R, which implied negative feedback regulation after its binding. BAFF promoted proliferation of human mesangial cells, which was mediated via BAFF-R. The BAFF/BAFF-R interaction triggered Akt, p65 and p38 activation, with Akt phosphorylation being tightly dependent on BAFF/BAFF-R interaction.

  15. BAFF and its receptors involved in the inflammation progress in adjuvant induced arthritis rats.

    Science.gov (United States)

    Wei, Fang; Xu, Shu; Jia, Xiaoyi; Sun, Xiaojing; Yang, Xuezhi; Wei, Wei; Chang, Yan

    2016-02-01

    This study is in order to clear the roles of BAFF and its receptors in the inflammation course of autoimmune arthritis. We used a T cell-mediated experimental autoimmune model adjuvant-induced arthritis (AA) rat to study the profiles of BAFF and its receptors in spleen during the inflammation arthritis induction and the effects of BAFF on DCs functions. In vivo, the levels of BAFF and the expression of BAFF-R, TACI were increased in spleen from very early stage of AA. The lesions of spleen were definite correlated with increased levels of BAFF in homogenization. The mature of DCs and increased number in spleen were mainly at early stage of arthritis. In addition, the levels of Interleukin (IL)-12 were found highest and IL-10 were found lowest at this time too. In vitro recombinant BAFF promoted maturation of DCs and inhibited the phagocytosis of DCs. Under stimulation of BAFF on DCs, the levels of tumor necrosis factor (TNF)-α, IL-6, IL-12 were increased, IL-10 and transforming growth factor (TGF)-β1 were decreased. Moreover, BAFF-treated DCs induced proliferation of CD4(+) T cell. These findings support the crucial pathogenic role of DCs, BAFF, and its receptors in the development of experimental arthritis. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Accelerated Central Nervous System Autoimmunity in BAFF-Receptor-Deficient Mice

    OpenAIRE

    Kim, Susan S.; Richman, David P.; Zamvil, Scott S.; Agius, Mark A.

    2011-01-01

    B cell activating factor (BAFF) is critical for B cell survival, a function that is mediated by BAFF receptor, (BAFF-R). The role of BAFF (or BAFF-R) in the multiple sclerosis model, experimental autoimmune encephalomyelitis (EAE), was examined using BAFF-R-deficient mice. BAFF-R deficiency resulted in paradoxically increased severity of EAE induced by myelin-oligodendrocyte glycoprotein (MOG) peptide 35-55. Inflammatory foci in BAFF-R-deficient mice comprised increased numbers of activated m...

  17. Role of BAFF in pulmonary autoantibody responses induced by chronic cigarette smoke exposure in mice.

    Science.gov (United States)

    Morissette, Mathieu C; Gao, Yang; Shen, Pamela; Thayaparan, Danya; Bérubé, Jean-Christophe; Paré, Peter D; Brandsma, Corry-Anke; Hao, Ke; Bossé, Yohan; Ettinger, Rachel; Herbst, Ronald; Humbles, Alison A; Kolbeck, Roland; Zhong, Nanshan; Chen, Rongchang; Stämpfli, Martin R

    2016-12-01

    Emerging evidence suggests that autoimmune processes are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). In this study, we assessed the expression of B-cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary antinuclear antibodies (ANA) and tertiary lymphoid tissues (TLTs) using a preclinical mouse model. We observed that BAFF levels were elevated in smokers and mice exposed to cigarette smoke. In mice, BAFF expression was rapidly induced in the lungs following 4 days of cigarette smoke exposure and remained elevated following 8 and 24 weeks of exposure. Alveolar macrophages were the major source of BAFF Blockade of BAFF using a BAFF receptor-Fc (BAFFR-Fc) construct prevented pulmonary ANA and TLT formation when delivered concurrent with cigarette smoke exposure. Under these conditions, no impact on lung inflammation was observed. However, administration of BAFFR-Fc following smoking cessation markedly reduced the number of TLTs and ANA levels and, of note, reduced pulmonary neutrophilia. Altogether, this study shows for the first time a central role of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary ANA and suggests that BAFF blockade following smoking cessation could have beneficial effects on persistent inflammatory processes.In this study, we assessed the expression of B-cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and maintenance of cigarette smoke-induced pulmonary antinuclear antibodies (ANA) and tertiary lymphoid tissues (TLTs) using a preclinical mouse model. Data presented show that BAFF plays a central role in the induction and maintenance of cigarette smoke-induced pulmonary ANA and suggest a therapeutic potential for BAFF blockade in limiting autoimmune processes associated with smoking. © 2016 The Authors. Physiological

  18. Expression of BAFF and BR3 in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Duan, J H; Jiang, Y; Mu, H; Tang, Z Q

    2016-03-01

    The objective of this study was to examine the relationship between the expression of B cell activating factor (BAFF) and BAFF receptor in patients with disease activity of systemic lupus erythematosus (SLE). Real-time RT-PCR was used to examine BAFF mRNA expression in peripheral blood monocytes of active and stable SLE patients and healthy controls. The percentage of BAFF receptor 3 (BR3) on B lymphocytes was measured by flow cytometry. Soluble BAFF levels in serum were assayed by ELISA. Microalbumin levels were assayed by an automatic immune analysis machine. BAFF mRNA and soluble BAFF levels were highest in the active SLE group, followed by the stable SLE group, and controls (PBAFF mRNA levels and soluble BAFF levels were higher in patients who were positive for proteinuria than in those who were negative (PBAFF/BR3 axis may be over-activated in SLE patients. BAFF and BR3 levels may be useful parameters for evaluating treatment.

  19. Effect of glucocorticoid treatment on BAFF and APRIL expression in patients with immune thrombocytopenia (ITP).

    Science.gov (United States)

    Kamhieh-Milz, Julian; Ghosoun, Nuha; Sterzer, Viktor; Salama, Abdulgabar

    2018-03-01

    Immune thrombocytopenic purpura (ITP) is an idiopathic bleeding disorder. B cell activating factor (BAFF) and 'A proliferation-inducing ligand' (APRIL) have regulatory effects on B and T cells and may represent relevant factors in the pathogenesis of ITP. Serum levels and gene expression were investigated in ITP patients. Both BAFF and APRIL serum levels were significantly elevated in active ITP. However, gene expression analysis revealed both factors to have a tendency toward downregulation. Glucocorticoid treatment significantly reduced BAFF but not APRIL serum levels, which may be mediated by differences in transcription factor binding sites. The glucocorticoid receptor binding site is present in the BAFF promotor region, but not in the APRIL promotor region. Prednisolone in combination with vitamin D3 may be effective in reducing APRIL serum levels. In conclusion, glucocorticoid treatment exerts different regulatory effects on both BAFF and APRIL, whereas antioxidant supplementation may also be beneficial in reducing serum levels. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. The Role of BAFF System Molecules in Host Response to Pathogens.

    Science.gov (United States)

    Sakai, Jiro; Akkoyunlu, Mustafa

    2017-10-01

    The two ligands B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) and the three receptors BAFF receptor (BAFF-R), transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI), and B cell maturation antigen (BCMA) are members of the "BAFF system molecules." BAFF system molecules are primarily involved in B cell homeostasis. The relevance of BAFF system molecules in host responses to microbial assaults has been investigated in clinical studies and in mice deficient for each of these molecules. Many microbial products modulate the expression of these molecules. Data from clinical studies suggest a correlation between increased expression levels of BAFF system molecules and elevated B cell responses. Depending on the pathogen, heightened B cell responses may strengthen the host response or promote susceptibility. Whereas pathogen-mediated increases in the expression levels of the ligands and/or the receptors appear to promote microbial clearance, certain pathogens have evolved to ablate B cell responses by suppressing the expression of TACI and/or BAFF-R on B cells. Other than its well-established role in B cell responses, the TACI-mediated activation of macrophages is also implicated in resistance to intracellular pathogens. An improved understanding of the role that BAFF system molecules play in infection may assist in devising novel strategies for vaccine development. Copyright © 2017 American Society for Microbiology.

  1. BAFF controls neural cell survival through BAFF receptor.

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    Satoru Tada

    Full Text Available Various neuroprotective factors have been shown to help prevention of neuronal cell death, which is responsible for the progression of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS. However, most of these therapeutic potentials have been tested by administration of recombinant proteins, transgenic expression or virus vector-mediated gene transfer. Therefore, it remains to be clarified whether any endogenous factors has advantage for neuroprotection in a pathological nervous system. Here we show the role of BAFF-R signaling pathway in the control of neural cell survival. Both B cell-activating factor (BAFF and its receptor (BAFF-R are expressed in mouse neurons and BAFF-R deficiency reduces the survival of primary cultured neurons. Although many studies have so far addressed the functional role of BAFF-R on the differentiation of B cells, impaired BAFF-R signaling resulted in accelerated disease progression in an animal model of inherited ALS. We further demonstrate that BAFF-R deficient bone marrow cells or genetic depletion of B cells does not affect the disease progression, indicating that BAFF-mediated signals on neurons, not on B cells, support neural cell survival. These findings suggest opportunities to improve therapeutic outcome for patients with neurodegenerative diseases by synthesized BAFF treatment.

  2. Expression profile of BAFF in peripheral blood from patients of IgA nephropathy: Correlation with clinical features and Streptococcus pyogenes infection.

    Science.gov (United States)

    Zheng, Nuoyan; Fan, Jinjin; Wang, Bing; Wang, Dongxian; Feng, Pinning; Yang, Qiongqiong; Yu, Xueqing

    2017-04-01

    B cells are critically important for the pathogenesis of IgA nephropathy (IgAN). The present study aimed to investigate the abundance of B cell activating factor (BAFF), which belongs to the tumor necrosis factor superfamily, in the peripheral blood of patients with IgAN. The different forms of BAFF in peripheral blood and its association with clinical features and immunological factors were analyzed. mRNA levels of BAFF and other associated genes in the peripheral blood mononuclear cells (PBMCs) of patients with IgAN and controls were analyzed by quantitative polymerase chain reaction. Cellular BAFF proteins in PBMCs and plasma soluble BAFF proteins were measured by western blot analysis and ELISA, respectively. PBMCs from patients were stimulated with Streptococcus pyogenes (S. pyogenes) ex vivo for the BAFF secretion assay. The data demonstrated that, although mRNA levels of BAFF in PBMC were not significantly increased in patients with IgAN, they were positively associated with those of a proliferation inducing ligand (APRIL), Toll‑like receptor (TLR)2, TLR4 and TLR7. The cellular BAFF protein in PBMCs was not upregulated. Plasma BAFF protein levels in patients with IgAN (n=76) were significantly decreased compared with controls. However, plasma BAFF levels were positively associated with serum creatinine, proteinuria, uric acid and group A Streptococcus infection index in patients with IgAN. In patients with IgAN, plasma BAFF concentrations were markedly higher in those with more severe renal tubular atrophy/interstitial fibrosis and global glomerulosclerosis. Furthermore, BAFF production in PBMCs of patients with IgAN was increased following S. pyogenes stimulation ex vivo. In conclusion, plasma BAFF levels in patients with IgAN were associated with renal function and disease activity. S. pyogenes infection was closely associated with BAFF production in patients with IgAN.

  3. Association of variants in BAFF (rs9514828 and rs1041569) and BAFF-R (rs61756766) genes with the risk of chronic lymphocytic leukemia.

    Science.gov (United States)

    Jasek, Monika; Bojarska-Junak, Agnieszka; Wagner, Marta; Sobczyński, Maciej; Wołowiec, Dariusz; Roliński, Jacek; Karabon, Lidia; Kuśnierczyk, Piotr

    2016-10-01

    The B-cell activator factor (BAFF)/BAFF receptor (BAFF-R) axis seems to play an important role in the development and progression of chronic lymphocytic leukemia (CLL). Here, we investigated the association of eight single nucleotide polymorphisms (SNPs) in the BAFF (TNFSF13B) and BAFF-R (TNFRSF13C) genes with risk of sporadic CLL in a group of 439 CLL patients and 477 controls. We also examined the correlation between selected SNPs and CLL clinical parameters as well as BAFF plasma levels and intracellular BAFF expression. Our results point to a possible association between the rs9514828 (CT vs. CC + TT; OR = 0.74; CI 95 % = 0.57; 0.97; p = 0.022) and rs1041569 (AT vs. AA + TT; OR = 0.72; CI 95 % = 0.54; 0.95; p = 0.021) of BAFF gene and rs61756766 (CC vs. CT; OR = 2.03; CI 95 % = 1.03; 3.99; p = 0.03) of BAFF-R gene and CLL risk. Additionally, we observed that homozygotes rs1041569 AA and TT had a slightly higher risk (HR = 1.12) for the need of treatment in comparison to AT heterozygotes. In conclusion, our results indicate that SNPs in BAFF and BAFF-R genes may be considered as potential CLL risk factors.

  4. B-Cell-Activating Factor and Autoimmune Myasthenia Gravis

    Directory of Open Access Journals (Sweden)

    Samia Ragheb

    2011-01-01

    Full Text Available BAFF is a potent B-cell survival factor, and it plays an essential role in B-cell homeostasis and B-cell function in the periphery. Both normal and autoreactive B cells are BAFF dependent; however, excess BAFF promotes the survival, growth, and maturation of autoreactive B cells. When overexpressed, BAFF protects B cells from apoptosis, thereby contributing to autoimmunity. Three independent studies have shown higher BAFF levels in the circulation of MG patients. BAFF may play an important role in the pathogenesis of MG. BAFF antagonists may well provide new treatment options for MG patients, particularly those patients with thymic lymphoid follicular hyperplasia.

  5. Significance of BAFF/APRIL Expression and Their Receptors in Pediatric Patients With Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Sun, Baolan; Li, Lin; Xu, Meiyu; Wang, Xudong; Wang, Feng; Ni, Hongbing

    2016-04-01

    In this study, we investigated the mRNA expression and protein levels of B-cell activating factor (BAFF)/a proliferation-inducing ligand (APRIL) and their receptors in acute lymphoblastic leukemia (ALL) cell lines and pediatric patients with ALL using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting. The location and level of the BAFF/APRIL proteins in ALL cell lines were also detected by immunofluorescence cytochemistry and flow cytometry. Correlations between plasma protein levels of BAFF/APRIL and primary clinical parameters were analyzed. We found that BAFF/APRIL was highly expressed in pediatric ALL patients and ALL cell lines. The BAFF/APRIL proteins were located on the cell membrane, and the proportion of positive cells and mean fluorescence intensity were significantly higher than in the healthy control group (PBAFF/APRIL and their receptors in untreated ALL children were significantly higher than in healthy controls (PBAFF/APRIL were positively correlated with the white blood cell count, lactate dehydrogenase, and serum ferritin. Abnormal levels of BAFF/APRIL in pediatric ALL suggest that BAFF/APRIL are associated with the development and progression of ALL in children and may provide information for the development of BAFF-based and APRIL-based targeted therapies.

  6. Potential role of serum BAFF as a biomarker in HIV infection.

    Science.gov (United States)

    Carbone, Javier; Calahorra, Leticia; Navarro, Joaquin; Sarmiento, Elizabeth

    2015-04-01

    We evaluated the potential role of serum B-cell activating factor (BAFF) as a biomarker in HIV infection and analyzed the relationship between BAFF concentration and the immunophenotypic activation status of T-cells. We tested the hypothesis that higher serum BAFF concentrations are associated with risk for development of AIDS in HIV positive individuals. Forty-one HIV patients (CDC category A 17, category B 24) were evaluated retrospectively. Serum BAFF concentrations were assessed using a commercial enzyme-linked immunosorbent assay. Cox regression was used to estimate the probability for development of AIDS. Patients with higher BAFF concentrations (> 2100 pg/mL) were at greater risk of developing AIDS (relative hazard 5.69; p = 0.0033). BAFF levels were independently associated with risk of AIDS after adjustment by clinical risk factors. Serum BAFF was correlated with activated T-cell subsets and with neopterin levels. BAFF is a good candidate for further evaluation as a nonspecific surrogate marker in HIV infection.

  7. IFN type I and II induce BAFF secretion from human decidual stromal cells.

    Science.gov (United States)

    Lundell, Anna-Carin; Nordström, Inger; Andersson, Kerstin; Lundqvist, Christina; Telemo, Esbjörn; Nava, Silvia; Kaipe, Helen; Rudin, Anna

    2017-01-06

    B cell activating factor (BAFF) is a critical cytokine for maturation of immature B cells. In murine lymph nodes, BAFF is mainly produced by podoplanin-expressing stromal cells. We have previously shown that circulating BAFF levels are maximal at birth, and that farmers' children exhibit higher BAFF levels in cord blood than non-farmers' children. Here, we sought to investigate whether maternal-derived decidual stromal cells from placenta secrete BAFF and examine what factors could stimulate this production. We found that podoplanin is expressed in decidua basalis and in the underlying villous tissue as well as on isolated maternal-derived decidual stromal cells. Decidual stromal cells produced BAFF when stimulated with IFN-γ and IFN-α, and NK cells and NK-T-like cells competent of IFN-γ production were isolated from the decidua. Finally, B cells at different maturational stages are present in decidua and all expressed BAFF-R, while stromal cells did not. These findings suggest that decidual stromal cells are a cellular source of BAFF for B cells present in decidua during pregnancy.

  8. Inhibition of B cell activating factor (BAFF) in the management of systemic lupus erythematosus (SLE).

    Science.gov (United States)

    Stohl, William

    2017-06-01

    The anti-BAFF monoclonal antibody, belimumab, was approved 5+ years ago by the US Food and Drug Administration for the treatment of adult SLE patients. Although BAFF is now a proven therapeutic target in SLE, the limited clinical efficacy both in the clinical trials setting and in 'real-life' experience begs for further therapeutic improvement. Areas covered: In addition to belimumab, three other BAFF antagonists (atacicept, blisibimod, tabalumab) that biologically differ from belimumab are being or have been evaluated in SLE late-stage clinical trials. Literature search was performed using the search words/phrases, 'BAFF', 'BLyS', 'APRIL', 'BCMA', 'TACI', 'BR3', 'belimumab', 'atacicept', 'blisibimod', 'tabalumab', 'lupus clinical trial' along with papers from the author's personal library. Expert commentary: The reasons underlying current lack of enthusiasm among clinicians for BAFF antagonism are discussed, and speculation if offered regarding the use of a BAFF antagonist as part of sequential therapy and regarding the utility of individual or pairs of BAFF receptors as therapeutic targets.

  9. Cigarette smoke inhibits BAFF expression and mucosal immunoglobulin A responses in the lung during influenza virus infection.

    Science.gov (United States)

    Wang, Jianmiao; Li, Qinghai; Xie, Jungang; Xu, Yongjian

    2015-03-14

    It is incompletely understood how cigarette smoke (CS) exposure affects lung mucosal immune responses during viral respiratory infections. B cell activating factor belonging to the tumor necrosis factor family (BAFF) plays an important role in the induction of secretory immunoglobulin A (S-IgA) which is the main effector of the mucosal immune system. We therefore investigated the effects of CS exposure on BAFF expression and S-IgA responses in the lung during influenza virus infection. Mice were exposed to CS and/or infected with influenza virus. Bronchoalveolar lavage fluid and lung compartments were analyzed for BAFF expression, influenza-specific S-IgA level and histological changes. Lung B cells were isolated and the activation-induced cytidine deaminase (Aicda) expression was determined. BEAS-2B cells were treated with CS extract (CSE), influenza virus, interferon beta or N-acetylcysteine and BAFF expression was measured. CS inhibited BAFF expression in the lung, particularly after long-term exposure. BAFF and S-IgA levels were increased during influenza virus infection. Three-month CS exposure prior to influenza virus infection resulted in reduced BAFF and S-IgA levels in the lung as well as augmented pulmonary inflammation on day 7 after infection. Prior CS exposure also caused decreased Aicda expression in lung B cells during infection. Neutralization of BAFF in the lung resulted in reduced S-IgA levels during influenza virus infection. CSE inhibited virus-mediated BAFF induction in a dose-dependent manner in BEAS-2B cells, while this inhibition of BAFF by CSE was prevented by pretreatment with the antioxidant N-acetylcysteine. Our findings indicate that CS may hinder early mucosal IgA responses in the lung during influenza virus infection through oxidative inhibition of BAFF, which might contribute to the increased incidence and severity of viral infections in smokers.

  10. BAFF-R Specific Activation of TRAF6 and the PI3K-Pathway in Lymphoma B Cells

    OpenAIRE

    Secreto, Frank; Manske, Michelle; Price-Troska, Tammy; Ziesmer, Steven; Hodge, Lucy S.; Ansell, Stephen M.; Cerhan, James R.; Novak, Anne J.

    2014-01-01

    BAFF-R is the primary BAFF receptor that is responsible for promoting B-cell development and survival. Malignant B-cells exploit the BAFF/BAFF receptor system and high serum BAFF levels or genetic alterations in BAFF receptors have been found in B-cell cancers. BAFF signaling impacts pro-survival pathways, however, other than NF-κB2, little is known about the specific pathways activated by individual BAFF receptors. Using a novel BAFF-R expression model we now demonstrate that activation of B...

  11. HIV-1-triggered release of type I IFN by plasmacytoid dendritic cells induces BAFF production in monocytes.

    Science.gov (United States)

    Gomez, Alejandro M; Ouellet, Michel; Tremblay, Michel J

    2015-03-01

    HIV-1 infection leads to numerous B cell abnormalities, including hypergammaglobulinemia, nonspecific B cell activation, nonspecific class switching, increased cell turnover, breakage of tolerance, increased immature/transitional B cells, B cell malignancies, as well as a loss of capacity to generate and maintain memory, all of which contribute to a global impairment of the immune humoral compartment. Several cytokines and soluble factors, which are increased in sera of HIV-1-infected individuals, have been suggested to directly or indirectly contribute to these B cell dysfunctions, and one of these is the B cell-activating factor (BAFF). We report in this study that HIV-1 (X4- and R5-tropic) upregulates BAFF expression and secretion by human monocytes. Moreover, we show that the virus-mediated production of BAFF by monocytes relies on a type I IFN response by a small percentage of plasmacytoid dendritic cells (pDCs) present in the monocyte cultures. HIV-1-induced type I IFN by pDCs triggers BAFF production in both classical and intermediate monocytes, but not in nonclassical monocytes, which nonetheless display a very strong basal BAFF production. We report also that basal BAFF secretion was higher in monocytes obtained from females compared with those from male donors. This study provides a novel mechanistic explanation for the increased BAFF levels observed during HIV-1 infection and highlights the importance of pDC/monocyte crosstalk to drive BAFF secretion. Copyright © 2015 by The American Association of Immunologists, Inc.

  12. B cell activating factor (BAFF) and a proliferation inducing ligand (APRIL) mediate CD40-independent help by memory CD4 T cells.

    Science.gov (United States)

    Gorbacheva, V; Ayasoufi, K; Fan, R; Baldwin, W M; Valujskikh, A

    2015-02-01

    Donor-reactive memory T cells undermine organ transplant survival and are poorly controlled by immunosuppression or costimulatory blockade. Memory CD4 T cells provide CD40-independent help for the generation of donor-reactive effector CD8 T cells and alloantibodies (alloAbs) that rapidly mediate allograft rejection. The goal of this study was to investigate the role of B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in alloresponses driven by memory CD4 T cells. The short-term neutralization of BAFF alone or BAFF plus APRIL synergized with anti-CD154 mAb to prolong heart allograft survival in recipients containing donor-reactive memory CD4 T cells. The prolongation was associated with reduction in antidonor alloAb responses and with inhibited reactivation and helper functions of memory CD4 T cells. Additional depletion of CD8 T cells did not enhance the prolonged allograft survival suggesting that donor-reactive alloAbs mediate late graft rejection in these recipients. This is the first report that targeting the BAFF cytokine network inhibits both humoral and cellular immune responses induced by memory CD4 T cells. Our results suggest that reagents neutralizing BAFF and APRIL may be used to enhance the efficacy of CD40/CD154 costimulatory blockade and improve allograft survival in T cell-sensitized recipients. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

  13. BAFF and APRIL expression as an autoimmune signature of membranous nephropathy.

    Science.gov (United States)

    Han, Seung Seok; Yang, Seung Hee; Jo, Hyung Ah; Oh, Yun Jung; Park, Minkyoung; Kim, Joo Young; Lee, Hajeong; Lee, Jung Pyo; Lee, Sang-Ho; Joo, Kwon Wook; Lim, Chun Soo; Kim, Yon Su; Kim, Dong Ki

    2018-01-09

    Based on the fact that B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) have a regulatory role in B cell biology, excessive levels of these cytokines can promote autoimmune pathogenesis. However, the expression and implication remain unresolved in cases of membranous nephropathy (MN). The plasma BAFF levels of the primary MN patients were higher than those of healthy controls but lower than those of secondary MN patients, whereas the APRIL levels were similar between the MN patients and healthy controls. The BAFF levels were higher in relapse cases, whereas the APRIL levels were higher in the patients who did not experience remission compared with the counterpart patients. The ectopic expression of BAFF and APRIL was observed in the glomeruli or circulating B cells of MN patients, and this high expression trend was similar to that of lupus patients. Expression profile of BAFF and APRIL in MN is similar to that of other autoimmune disease, which affects the kidney outcomes. Plasma BAFF and APRIL levels were measured upon kidney biopsy in patients with primary ( n = 89) and secondary MN ( n = 13), and the results were compared with the levels in healthy controls ( n = 111). The kidney outcomes (e.g., remission and relapse) were traced for the median of 3 years. Aberrant expression of the cytokines was evaluated in the kidney and circulating B cells using immunohistochemistry and flow cytometry analyses, respectively.

  14. Dual functional BAFF receptor aptamers inhibit ligand-induced proliferation and deliver siRNAs to NHL cells

    Science.gov (United States)

    Zhou, Jiehua; Tiemann, Katrin; Chomchan, Pritsana; Alluin, Jessica; Swiderski, Piotr; Burnett, John; Zhang, Xizhe; Forman, Stephen; Chen, Robert; Rossi, John

    2013-01-01

    The B-cell–activating factor (BAFF)-receptor (BAFF-R) is restrictedly expressed on B-cells and is often overexpressed in B-cell malignancies, such as non-Hodgkin’s lymphoma. On binding to its ligand BAFF, proliferation and cell survival are increased, enabling cancer cells to proliferate faster than normal B-cells. Nucleic acid aptamers can bind to target ligands with high specificity and affinity and may offer therapeutic advantages over antibody-based approaches. In this study, we isolated several 2′-F–modified RNA aptamers targeting the B-cell–specific BAFF-R with nanomolar affinity using in vitro SELEX technology. The aptamers efficiently bound to BAFF-R on the surface of B-cells, blocked BAFF-mediated B-cell proliferation and were internalized into B-cells. Furthermore, chimeric molecules between the BAFF-R aptamer and small interfering RNAs (siRNAs) were specifically delivered to BAFF-R expressing cells with a similar efficiency as the aptamer alone. We demonstrate that a signal transducer and activator of transcription 3 (STAT3) siRNA delivered by the BAFF-R aptamer was processed by Dicer and efficiently reduced levels of target mRNA and protein in Jeko-1 and Z138 human B-cell lines. Collectively, our results demonstrate that the dual-functional BAFF-R aptamer–siRNA conjugates are able to deliver siRNAs and block ligand mediated processes, suggesting it might be a promising combinatorial therapeutic agent for B-cell malignancies. PMID:23470998

  15. BAFF/APRIL system in pediatric OMS: relation to severity, neuroinflammation, and immunotherapy.

    Science.gov (United States)

    Pranzatelli, Michael R; Tate, Elizabeth D; McGee, Nathan R; Travelstead, Anna L; Colliver, Jerry A; Ness, Jayne M; Ransohoff, Richard M

    2013-01-16

    B-cell dysregulation has been implicated but not fully characterized in pediatric opsoclonus-myoclonus syndrome (OMS), a neuroblastoma-associated neuroinflammatory disorder. To assess the role of B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), two critical B cell-modulating cytokines, as potential biomarkers of disease activity and treatment biomarkers in OMS. Soluble BAFF and APRIL were measured in cerebrospinal fluid (CSF) and serum by ELISA in 433 children (296 OMS, 109 controls, 28 other inflammatory neurological disorders (OIND)). BAFF-R receptors on circulating CD19+ B cells were measured by flow cytometry. A blinded scorer rated motor severity on the OMS Evaluation Scale. Immunotherapies were evaluated cross-sectionally and longitudinally. The mean CSF BAFF concentration, which was elevated in untreated OMS and OIND, correlated with OMS severity category (P = 0.006), and reduction by adrenocorticotropic hormone or corticotropin (ACTH) (-61%) or corticosteroids (-38%) was seen at each level of severity. In contrast, CSF APRIL was normal in OMS and OIND and unaffected by immunotherapy. When the entire OMS dataset was dichotomized into 'high' versus 'normal' CSF BAFF concentration, the phenotype of the high group included greater motor severity and number of CSF oligoclonal bands, and a higher concentration of inflammatory chemokines CXCL13 and CXCL10 in CSF and CXCL9 and CCL21 in serum. Serum APRIL was 6.7-fold higher in the intravenous immunoglobulins (IVIg) group, whereas serum BAFF was 2.6-fold higher in the rituximab group. The frequency of B cell BAFF-R expression was similar in untreated and treated OMS. Longitudinal studies of CSF BAFF revealed a significant decline in ACTH-treated patients (with or without rituximab) (P OMS displayed heterogeneity in CSF BAFF expression, which met many but not all criteria as a potential biomarker of disease activity. We speculate that CSF BAFF may have more utility in a biomarker panel

  16. Involvement of BAFF and APRIL in Resistance to Apoptosis of Acute Myeloid Leukemia.

    Science.gov (United States)

    Bolkun, Lukasz; Grubczak, Kamil; Schneider, Gabriela; Zembko, Paula; Radzikowska, Urszula; Singh, Paulina; Kloczko, Janusz; Ratajczak, Mariusz Z; Moniuszko, Marcin; Eljaszewicz, Andrzej

    2016-01-01

    B-cell activation factor of the TNF family (BAFF), and a proliferation-inducing ligand (APRIL), two members of the tumour necrosis factor (TNF) superfamily, beyond playing a significant role in normal B-cell development, promote survival and proliferation of malignant B cells. Both ligands interact with 3 receptors: BAFF-R, specific to BAFF, and TACI and BCMA which are shared by both BAFF and APRIL. Here we wished to investigate the potential role of these proteins in resistance of acute myeloid leukaemia (AML) blasts to apoptosis. We found that the levels of both mRNA and proteins of APRIL, BAFF and their receptors were expressed in leukaemic cells of 24 newly diagnosed, untreated AML patients. We also demonstrated that patients who did not further respond to induction therapy (NR) presented with significantly higher baseline APRIL and BAFF expression on AML blasts as compared to these subjects who, after induction, achieved complete remission (CR) following induction therapy. Moreover, we observed striking differences in baseline levels of BCMA between CR and NR patients as we did not find detectable expression of this receptor in the latter group of patients. Interestingly, we found that AML blasts collected at baseline from NR patients cultured in presence of exogenous BAFF and APRIL were significantly more resistant to spontaneous or drug-induced apoptosis as compared with cells derived from CR patients. Altogether, our data confirm that BAFF and APRIL signaling play important role in AML pathogenesis and susceptibility to cytotoxic therapy while measuring of BCMA expression on AML cells can become a novel prognostic factor for chemotherapy response.

  17. Mice overexpressing BAFF develop a commensal flora–dependent, IgA-associated nephropathy

    Science.gov (United States)

    McCarthy, Douglas D.; Kujawa, Julie; Wilson, Cheryl; Papandile, Adrian; Poreci, Urjana; Porfilio, Elisa A.; Ward, Lesley; Lawson, Melissa A.E.; Macpherson, Andrew J.; McCoy, Kathy D.; Pei, York; Novak, Lea; Lee, Jeannette Y.; Julian, Bruce A.; Novak, Jan; Ranger, Ann; Gommerman, Jennifer L.; Browning, Jeffrey L.

    2011-01-01

    B cell activation factor of the TNF family (BAFF) is a potent B cell survival factor. BAFF overexpressing transgenic mice (BAFF-Tg mice) exhibit features of autoimmune disease, including B cell hyperplasia and hypergammaglobulinemia, and develop fatal nephritis with age. However, basal serum IgA levels are also elevated, suggesting that the pathology in these mice may be more complex than initially appreciated. Consistent with this, we demonstrate here that BAFF-Tg mice have mesangial deposits of IgA along with high circulating levels of polymeric IgA that is aberrantly glycosylated. Renal disease in BAFF-Tg mice was associated with IgA, because serum IgA was highly elevated in nephritic mice and BAFF-Tg mice with genetic deletion of IgA exhibited less renal pathology. The presence of commensal flora was essential for the elevated serum IgA phenotype, and, unexpectedly, commensal bacteria–reactive IgA antibodies were found in the blood. These data illustrate how excess B cell survival signaling perturbs the normal balance with the microbiota, leading to a breach in the normal mucosal-peripheral compartmentalization. Such breaches may predispose the nonmucosal system to certain immune diseases. Indeed, we found that a subset of patients with IgA nephropathy had elevated serum levels of a proliferation inducing ligand (APRIL), a cytokine related to BAFF. These parallels between BAFF-Tg mice and human IgA nephropathy may provide a new framework to explore connections between mucosal environments and renal pathology. PMID:21881212

  18. A loop region of BAFF controls B cell survival and regulates recognition by different inhibitors.

    Science.gov (United States)

    Vigolo, Michele; Chambers, Melissa G; Willen, Laure; Chevalley, Dehlia; Maskos, Klaus; Lammens, Alfred; Tardivel, Aubry; Das, Dolon; Kowalczyk-Quintas, Christine; Schuepbach-Mallepell, Sonia; Smulski, Cristian R; Eslami, Mahya; Rolink, Antonius; Hummler, Edith; Samy, Eileen; Fomekong Nanfack, Yves; Mackay, Fabienne; Liao, Maofu; Hess, Henry; Jiang, Xuliang; Schneider, Pascal

    2018-03-23

    The B cell survival factor (TNFSF13B/BAFF) is often elevated in autoimmune diseases and is targeted in the clinic for the treatment of systemic lupus erythematosus. BAFF contains a loop region designated the flap, which is dispensable for receptor binding. Here we show that the flap of BAFF has two functions. In addition to facilitating the formation of a highly active BAFF 60-mer as shown previously, it also converts binding of BAFF to TNFRSF13C (BAFFR) into a signaling event via oligomerization of individual BAFF-BAFFR complexes. Binding and activation of BAFFR can therefore be targeted independently to inhibit or activate the function of BAFF. Moreover, structural analyses suggest that the flap of BAFF 60-mer temporarily prevents binding of an anti-BAFF antibody (belimumab) but not of a decoy receptor (atacicept). The observed differences in profiles of BAFF inhibition may confer distinct biological and clinical efficacies to these therapeutically relevant inhibitors.

  19. Comparative genomic of the BAFF and BAFF-like genes and immune response to bacteria of miiuy croaker (Miichthys miiuy).

    Science.gov (United States)

    Meng, Fanqiang; Sun, Yuena; Xu, Tianjun

    2015-03-01

    As a member of the tumor necrosis factor (TNF) family, B cell activating factor (BAFF), also known as TNF ligand superfamily member 13B (TNF13B), playing a critical role in enhancing immune responses. BAFF is a central cytokine for B-cell survival, proliferation, maturation and immunoglobulin secretion. In the present study, we describe the identification of the miiuy croaker BAFF (designed MmBAFF) and BAFF-like (designed MmBAFF-like) genes. The cDNA of MmBAFF contains an open reading frame (ORF) of 795 nucleotides that are translated into a predicted 264 amino acids. The ORF of MmBAFF-like consists of 705 bases encoding 234 amino acids. Amino acid sequence comparison indicated that MmBAFF and MmBAFF-like possessed the TNF signatures, a predicted transmembrane domain, three conserved cysteine residues and a putative furin protease cleavage site, which were the typical characteristics of TNF gene in mammals and birds. The predicted three-dimensional (3D) structure of the MmBAFF and MmBAFF-like monomer analyzed by comparative protein modeling revealed that they were very similar to human counterpart. Comparative genomic analysis revealed that the locations of MmBAFF and MmBAFF-like genes are conserved among the bony fish. Phylogenetic analysis shows the MmBAFF is most closely related to other teleost BAFFs with the highest similarity to Epinephelus awoara. And BAFF-like cluster get together first to BAFF cluster than three closely related TNF superfamily (TNFSF) members. Real-time quantitative PCR analysis shows the MmBAFF and MmBAFF-like transcripts are expressed in a wide range of tissues with the highest expression in skin and lymphoid tissue spleen. Upon induction by Vibrio anguillarum, their expressions are significantly upregulated in liver, spleen and kidney as compared to phosphate-buffered saline injected control fish. The association of increased BAFF expression after bacterial infection suggests that it plays a potentially important role in immune system

  20. Increased BAFF expression in nasal polyps is associated with local IgE production, Th2 response and concomitant asthma.

    Science.gov (United States)

    Dilidaer; Zheng, Yan; Liu, Zhuofu; Hu, Xianting; Zhang, Jia; Hu, Li; Han, Miaomiao; Wang, Dehui; Li, Huabin

    2017-04-01

    B-cell activating factor of the TNF family is critical for the survival and maturation of B cells and play a role in the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP). In this study, nasal tissues were enrolled from 25 CRSwNP patients (asthmatic, 16; non-asthmatic, 9), 12 CRSsNP patients and ten control subjects, respectively. The immunoreactivity of BAFF, CD20 and CD138 were examined using immunohistochemistry staining. The mRNA expression of BAFF, CD20, εGLT, AID, GATA3 and CRTH2 were examined using real-time RT-PCR. The protein levels of BAFF, IL-5 and IgE were measured using ELISA assays and the Unicap system, respectively. We found the numbers of BAFF+ cells, CD20+ cells (B cells) and CD138+ cells (plasma cells) were significantly increased in polyp tissues compared with control groups. The concentrations of BAFF, IgE and IL-5 in tissue homogenates were also significantly increased in polyp tissues compared with control groups, and the BAFF protein level in the polyp homogenates was significantly associated with the IgE and IL-5 levels and with concomitant asthma in CRSwNP patients. Our findings indicate that BAFF expression is significantly increased in CRSwNP patients and may orchestrate inflammatory load in polyp tissues by regulating T and B cell-mediated response.

  1. Deleting the BAFF receptor TACI protects against systemic lupus erythematosus without extensive reduction of B cell numbers.

    Science.gov (United States)

    Figgett, William A; Deliyanti, Devy; Fairfax, Kirsten A; Quah, Pin Shie; Wilkinson-Berka, Jennifer L; Mackay, Fabienne

    2015-07-01

    B cell-activating factor of the TNF family (BAFF) is an essential B cell survival factor. However, high levels of BAFF promote systemic lupus erythematosus (SLE) in mice and humans. Belimumab (anti-human BAFF) limits B cell survival and is approved for use in patients with SLE. Surprisingly, the efficacy of rituximab (anti-human CD20) in SLE remains controversial, despite depleting B cells more potently than belimumab. This raises the question of whether B cell depletion is really the mechanism of action of belimumab. In BAFF transgenic mice, SLE development is T cell-independent but relies on innate activation of B cells via TLRs, and TLR expression is modulated by the BAFF receptor TACI. Here, we show that loss of TACI on B cells protected against BAFF-mediated autoimmune manifestations while preserving B cells, suggesting that loss of BAFF signaling through TACI rather than loss of B cells may underpin the effect of belimumab in the clinic. Therefore, B cell-sparing blockade of TACI may offer a more specific and safer therapeutic alternative to broad B cell depletion in SLE. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Specific forms of BAFF favor BAFF receptor-mediated epithelial cell survival.

    Science.gov (United States)

    Lahiri, Ayan; Varin, Marie-Michèle; Le Pottier, Laëtitia; Pochard, Pierre; Bendaoud, Boutahar; Youinou, Pierre; Pers, Jacques-Olivier

    2014-06-01

    Although B cell activating factor (BAFF) and its receptor BR3 are produced and expressed by many cells, their role has been restricted to the lymphocyte lineage. Using various techniques (RT-PCR, indirect immunofluorescence, flow cytometry analysis), we observed the expression of BR3 and the production of BAFF by the human salivary gland cell line, by epithelial cells from biopsies of Sjögren's syndrome patients and their controls, but also by salivary gland epithelial cells in culture. To decipher the role of BAFF and BR3 on epithelial cells, BAFF and BR3 were neutralized by blocking antibodies or RNA specific inhibitor (siBR3) and epithelial cell survival was analyzed. Blocking BR3 promotes epithelial cell apoptosis in vitro. This apoptosis resulted in the nuclear translocation of PKCδ. BAFF neutralization by various anti-BAFF antibodies leads to different effects depending on the antibody used suggesting that only some forms of BAFF are required for epithelial cell survival. Our study demonstrates that BR3 is involved in the survival of cultured epithelial cells due to an autocrine effect of BAFF. It also suggests that epithelial cells produce different forms of BAFF and that only some of them are responsible for this effect. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Expression of the B cell differentiation factor BAFF and chemokine CXCL13 in a murine model of Respiratory Syncytial Virus infection.

    Science.gov (United States)

    Alturaiki, Wael; McFarlane, Amanda J; Rose, Katie; Corkhill, Rachel; McNamara, Paul S; Schwarze, Jürgen; Flanagan, Brian F

    2018-01-26

    Innate immune responses are known to influence the subsequent development of adaptive immunity. We have previously shown that RSV infection of human airway epithelial cells results in production of the B cell growth factor, BAFF. To better understand how the airway responds to RSV infection by production of this and other factors to support or enhance local B cell responses to infection, we analysed the lung expression of BAFF and B cell homeostatic chemokines CXCL12, CXCL13, CCL19 and CCL21 in a murine model of RSV infection. Following infection with A2 strain RSV, the highest RSV N gene expression was observed at day 4 after challenge with virus. In contrast, two peaks of elevated BAFF expression at days 2 and 7 were observed. CXCL13 was significantly elevated at days 1, 2 and 7. CXCL12, CCL19 and CCL21 were expressed within lung tissue from control and RSV challenged animals but no significant difference in expression was found. Immunofluorescence showed BAFF to be present throughout the tissue however CXCL13 expression was localized to cell rich areas probably constituting lymphoid aggregates. Our results define the kinetics of B cell chemoattractant and growth factor expression during RSV infection and indicate an important role for these cytokines in the airway response to RSV infection. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. BAFF- and TACI-Dependent Processing of BAFFR by ADAM Proteases Regulates the Survival of B Cells.

    Science.gov (United States)

    Smulski, Cristian R; Kury, Patrick; Seidel, Lea M; Staiger, Hannah S; Edinger, Anna K; Willen, Laure; Seidl, Maximilan; Hess, Henry; Salzer, Ulrich; Rolink, Antonius G; Rizzi, Marta; Schneider, Pascal; Eibel, Hermann

    2017-02-28

    B cell activating factor (BAFF) provides B cells with essential survival signals. It binds to three receptors: BAFFR, TACI, and BCMA that are differentially expressed by B cell subsets. BAFFR is early expressed in circulating B cells and provides key signals for further maturation. Here, we report that highly regulated BAFFR processing events modulate BAFF responses. BAFFR processing is triggered by BAFF binding in B cells co-expressing TACI and it is executed by the metalloproteases ADAM10 and ADAM17. The degree of BAFF oligomerization, the expression of ADAM proteins in different B cell subsets, and the activation status of the cell determine the proteases involved in BAFFR processing. Inhibition of ADAM10 augments BAFF-dependent survival of primary human B cells, whereas inhibition of ADAM17 increases BAFFR expression levels on germinal center B cells. Therefore, BAFF-induced processing of BAFFR regulates BAFF-mediated B cell responses in a TACI-dependent manner. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  5. BAFF overexpression increases lymphocytic infiltration in Sjögren's target tissue, but only inefficiently promotes ectopic B-cell differentiation.

    Science.gov (United States)

    Ding, Jian; Zhang, Wei; Haskett, Scott; Pellerin, Alex; Xu, Shanqin; Petersen, Britta; Jandreski, Luke; Hamann, Stefan; Reynolds, Taylor L; Zheng, Timothy S; Mingueneau, Michael

    2016-08-01

    B-cell activating factor (BAFF) levels are increased in rheumatoid arthritis, lupus and primary Sjögren's syndrome (pSS). However, BAFF contribution to pathogenesis is not completely understood. In pSS, immune infiltration of the salivary and lacrimal glands leads to xerostomia and xerophtalmia. Glandular B cell hyperactivation, differentiation into germinal center (GC)-like structures and plasma cell accumulation are histopathological hallmarks that were attributed to increased BAFF. Here, we experimentally tested this hypothesis by overexpressing BAFF in a mouse model of pSS. BAFF overexpression enhanced lymphocytic infiltration and MHCII expression on B cells. Increased BAFF also induced B cell differentiation into GC B cells within the autoimmune target tissue. However, even in these conditions, GC B cells only accounted for BAFF is not efficiently promoting ectopic GC formation in pSS and warranting further investigation of therapeutics targeting both BAFF and the related TNF-family member APRIL. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Investigations of a rabbit (Oryctolagus cuniculus model of systemic lupus erythematosus (SLE, BAFF and its receptors.

    Directory of Open Access Journals (Sweden)

    Jiahui Yang

    2009-12-01

    Full Text Available B-cell activation factor belonging to the tumor necrosis factor family (BAFF is a major contributor to survival of B lymphocytes during development and maturation. A relationship between circulating BAFF levels and disease activity has been reported in patients with the autoimmune disease Systemic Lupus Erythematosus (SLE. Clinical trials targeting BAFF or its receptors are currently in progress. In order to further characterize a rabbit (Oryctolagus cuniculus model of SLE, we investigated the expression of BAFF and its receptors in non-inbred, pedigreed rabbits derived from breeding and selection based on autoantibody responses. We immunized rabbits related to previous groups that developed autoantibodies and inflammatory responses after immunizations with peptides synthesized on multiple antigen-branched polylysine backbones. Blood and sera collected before immunization and after boosts were used for health monitoring, analyses of serum autoantibody responses by ELISA and immunofluorescence. Peripheral blood mononuclear cells (PBMC were studied by flow cytometry and were the source of mRNA for quantitative PCR analyses. We hypothesized that BAFF mRNA expression and serum BAFF levels measured indirectly through BAFF receptor binding might increase in autoantibody-producing rabbits. Immunized rabbits developed elevated levels of leucocyte populations, anti-nuclear, anti-dsDNA and other autoantibodies. BR3 mRNA levels in total PBMC decreased and BAFF levels remained low and unchanged in most immunized rabbits. By flow cytometry, percentages of BAFF positive cells decreased. Percentages of transmembrane activator and CAML interactor (TACI decreased in most rabbits from all the immunized groups. The rabbit is an important model for human autoimmune and infectious diseases, and a high quality draft rabbit genome assembly was recently completed. Human disease models developed in non-inbred pedigreed animals are better able to reflect the complexities

  7. Alteration of B cell subsets and the receptor for B cell activating factor (BAFF) in paediatric patients with type 1 diabetes.

    Science.gov (United States)

    Parackova, Zuzana; Klocperk, Adam; Rataj, Michal; Kayserova, Jana; Zentsova, Irena; Sumnik, Zdenek; Kolouskova, Stanislava; Sklenarova, Jana; Pruhova, Stepanka; Obermannova, Barbora; Petruzelkova, Lenka; Lebl, Jan; Kalina, Tomas; Sediva, Anna

    2017-09-01

    Lately, mounting evidence has shown that B cells play an important role in the pathogenesis of type 1 diabetes (T1D). Here, we present alterations in B cell subsets including BAFF receptor (BAFFR) expression in cohorts of patients with type 1 diabetes (T1D) and their relatives. B cells were studied in 438 patients with T1D (158 at disease onset and 280 with long-term disease), 136 first-degree relatives and 53 healthy controls. The B cell panel included transitional, naïve, MZ-like, switched memory B cells and plasmablasts. We also measured serum BAFF levels as well as BAFFR expression on both B and T cells. Moreover, the effect of BAFF on T and B lymphocytes was analysed in vitro. We observed a significant decrease in the proportion of transitional B cells in the patients with T1D, accompanied by an increased proportion of plasmablasts, especially in recent-onset patients and their relatives. While the BAFF serum levels did not differ in the patients with T1D, BAFFR-expressing B and especially T cell numbers were reduced in the T1D cohort, with the exception of patients with recent-onset disease who exhibited a significant increase in the number of BAFFR-expressing T cells. T cell activation and B cell proliferation were more pronounced after activation with BAFF in the T1D cohort compared to controls. The B cell panel in patients with T1D is characterized by significantly reduced populations of B cells in their early stages of development with a shift towards plasma cells. The dynamics of BAFFR-expressing B and T cells and the more pronounced responsiveness of the T1D T cells to BAFF point to the role of BAFF and T and B cell cooperation in the development of T1D. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  8. Fingolimod induces BAFF and expands circulating transitional B cells without activating memory B cells and plasma cells in multiple sclerosis.

    Science.gov (United States)

    Miyazaki, Yusei; Niino, Masaaki; Takahashi, Eri; Suzuki, Masako; Mizuno, Masanori; Hisahara, Shin; Fukazawa, Toshiyuki; Amino, Itaru; Nakano, Fumihito; Nakamura, Masakazu; Akimoto, Sachiko; Minami, Naoya; Fujiki, Naoto; Doi, Shizuki; Shimohama, Shun; Terayama, Yasuo; Kikuchi, Seiji

    2018-02-01

    Patients with multiple sclerosis (MS) who are treated with fingolimod have an increased proportion of transitional B cells in the circulation, but the underlying mechanism is not known. We hypothesized that B cell-activating factor of the tumor necrosis factor family (BAFF) is involved in the process. Compared with healthy controls and untreated MS patients, fingolimod-treated MS patients had significantly higher serum concentrations of BAFF, which positively correlated with the proportions and the absolute numbers of transitional B cells in blood. Despite the elevated concentrations of BAFF in fingolimod-treated MS patients, serum levels of soluble transmembrane activator and calcium-modulating cyclophilin ligand interactor, and B cell maturation antigen were not elevated. Our results show that fingolimod induces BAFF in the circulation and expands transitional B cells, but does not activate memory B cells or plasma cells in MS, which is favorable for the treatment of this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Association of BAFF with PI3K/Akt/mTOR signaling in lupus nephritis.

    Science.gov (United States)

    Ge, Fengmei; Wang, Fangfang; Yan, Xiuqing; Li, Zhao; Wang, Xuebin

    2017-11-01

    Systemic lupus erythematosus is a connective tissue disease characterized by autoimmune inflammation, which leads to specific and nonspecific immune disorders with the formation of various autoantibodies by activated B cells. B‑cell‑activating factor (BAFF) is secreted by macrophages and activated T cells, and is responsible for the proliferation, maturation and differentiation of B cells. However, the mechanism of BAFF involvement in lupus nephritis (LN) remains unclear. The aim of the present study was to investigate the association between BAFF and phosphoinositide 3‑kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling in order to elucidate the pathogenesis of LN. In the present study, 18 patients with LN and 20 controls were included. The clinical data were analyzed and plasma levels of BAFF were measured using an ELISA. The mRNA and protein levels of BAFF, phosphorylated (p)‑PI3K, p‑Akt and p‑mTOR in kidney tissues were measured using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting. Plasma BAFF levels were significantly increased in patients with LN compared with the controls (PBAFF, p‑PI3K, p‑Akt and p‑mTOR in kidney tissue were significantly increased in patients with LN compared with the controls (all PBAFF in the kidney tissues of patients with LN were positively correlated with the levels of p‑PI3K, p‑Akt and p‑mTOR. The results of the present study revealed a correlation between BAFF and the PI3K/Akt/mTOR signaling pathway, and it is hypothesized that they are involved in the pathogenesis of LN.

  10. Active chronic sarcoidosis is characterized by increased transitional blood B cells, increased IL-10-producing regulatory B cells and high BAFF levels.

    Directory of Open Access Journals (Sweden)

    Anne Saussine

    Full Text Available BACKGROUND: Sarcoidosis is a multisystemic disease of unknown etiology characterized by a disproportionate Th1 granulomatous immune response in the organs involved. Plasmatic hypergammaglobulinemia and B cell accumulation in granulomatous lesions suggest the possible role of humoral immune responses in the pathogenesis of sarcoidosis. The purpose of this study is to describe B cell peripheral compartment in sarcoidosis. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed blood B cell subsets and BAFF levels in 33 patients with chronic sarcoidosis (active sarcoidosis n = 18; inactive sarcoidosis n = 15 and 18 healthy donors. Active chronic sarcoidosis patients had significantly less circulating memory B cells (p<0.01, more transitional (p<0.01 and increased numbers of IL-10-producing regulatory B cells (p<0.05 compared with healthy donors and patients with inactive sarcoidosis. BAFF serum levels were significantly higher in patients with active sarcoidosis (p<0.01 versus healthy donors and inactive sarcoidosis patients and strongly correlated with serum hypergammaglobulinemia (r = 0.53, p<0.01 and angiotensin converting enzyme levels (r = 0.61, p = <0.01. CONCLUSIONS/SIGNIFICANCE: These data show that there is an altered B cell homeostasis in active sarcoidosis and suggest BAFF antagonist drugs as potential new treatments of this disease.

  11. Targeting the splicing of mRNA in autoimmune diseases: BAFF inhibition in Sjögren's syndrome as a proof of concept

    NARCIS (Netherlands)

    Roescher, N.; Vosters, J. L.; Alsaleh, G.; Dreyfus, P.; Jacques, S.; Chiocchia, G.; Sibilia, J.; Tak, P. P.; Chiorini, J. A.; Mariette, X.; Gottenberg, Jacques-Eric

    2014-01-01

    BAFF (B-cell-activating factor of the tumor necrosis factor family), a pivotal cytokine for B-cell activation, is overexpressed by salivary gland (SG) epithelial cells in primary Sjogren's syndrome (pSS). ΔBAFF, a physiological inhibitor of BAFF, is a minor alternative splice variant of BAFF. A U7

  12. BAFF-R Specific Activation of TRAF6 and the PI3K-Pathway in Lymphoma B Cells

    Science.gov (United States)

    Secreto, Frank; Manske, Michelle; Price-Troska, Tammy; Ziesmer, Steven; Hodge, Lucy S.; Ansell, Stephen M.; Cerhan, James R.; Novak, Anne J.

    2014-01-01

    BAFF-R is the primary BAFF receptor that is responsible for promoting B-cell development and survival. Malignant B-cells exploit the BAFF/BAFF receptor system and high serum BAFF levels or genetic alterations in BAFF receptors have been found in B-cell cancers. BAFF signaling impacts pro-survival pathways, however, other than NF-κB2, little is known about the specific pathways activated by individual BAFF receptors. Using a novel BAFF-R expression model we now demonstrate that activation of BAFF-R, independent of TACI and BCMA, can induce phosphorylation of Akt and GSK3β. Expression of an activated form of BAFF-R also enhanced a pro-survival gene expression pattern, including the novel BAFF-regulated gene Pin1, whose expression was PI3K-dependent. Additionally, we show that TRAF6 is essential for mediating BAFF-R-dependent activation of Akt. Together these data describe a novel role for TRAF6 in BAFF-R-specific activation of the PI3K pathway and provide evidence suggesting a new role for Pin1 in BAFF-R signaling. PMID:24206092

  13. BAFF knockout improves systemic inflammation via regulating adipose tissue distribution in high-fat diet-induced obesity.

    Science.gov (United States)

    Kim, Do-Hwan; Do, Myoung-Sool

    2015-01-16

    Obesity is recognized as a chronic low-grade inflammatory state due to adipose tissue expansion being accompanied by an increase in the production of proinflammatory adipokines. Our group is the first to report that B-cell-activating factor (BAFF) is produced from adipocytes and functions as a proinflammatory adipokine. Here, we investigated how loss of BAFF influenced diet-induced obesity in mice by challenging BAFF(-/-) mice with a high-fat diet for 10 weeks. The results demonstrated that weight gain in BAFF(-/-) mice was >30% than in control mice, with a specific increase in the fat mass of the subcutaneous region rather than the abdominal region. Expression of lipogenic genes was examined by quantitative real-time PCR, and increased lipogenesis was observed in the subcutaneous adipose tissue (SAT), whereas lipogenesis in the epididymal adipose tissue (EAT) was reduced. A significant decrease in EAT mass resulted in the downregulation of inflammatory gene expression in EAT, and more importantly, overall levels of inflammatory cytokines in the circulation were reduced in obese BAFF(-/-) mice. We also observed that the macrophages recruited in the enlarged SAT were predominantly M2 macrophages. 3T3-L1 adipocytes were cultured with adipose tissue conditioned media (ATCM), demonstrating that EAT ATCM from BAFF(-/-) mice contains antilipogenic and anti-inflammatory properties. Taken together, BAFF(-/-) improved systemic inflammation by redistributing adipose tissue into subcutaneous regions. Understanding the mechanisms by which BAFF regulates obesity in a tissue-specific manner would provide therapeutic opportunities to target obesity-related chronic diseases.

  14. Serum BAFF in Indian patients with IIM: a retrospective study reveals novel clinico-phenotypic associations in children and adults.

    Science.gov (United States)

    Gupta, Latika; Chaurasia, Smriti; Srivastava, Puja; Dwivedi, Sanjay; Lawrence, Able; Misra, Ramnath

    2018-03-07

    We studied the serum levels of B cell survival factors BAFF and APRIL in patients with idiopathic inflammatory myositis (IIM) and their relation with clinical and autoantibodies. Seventy-five patients (51 females and 24 males) with IIM (Bohan and Peter's criteria 1975) and 25 healthy adults were analyzed for BAFF, APRIL and IL-17 by ELISA, and myositis-specific and associated antibodies (MSA and MAA) using line immunoblot assay. Of the 75 patients, 59 were adults, 42 had Dermatomyositis (DM), and 17 had Polymyositis. Median disease duration was 5 (3-12) months. BAFF levels were higher in IIM than healthy controls [p = 0.001], and in children with jDM than adults [p = 0.026]. BAFF levels were higher in adults with arthritis [p = 0.018], weight loss [p = 0.007], and PAH [p = 0.004]. Among the various MSAs, lowest levels were seen in those with anti-SRP [p = 0.043]. Median follow-up duration was 145 patient years. Twelve patients relapsed, while nine were in drug-free remission. BAFF were similar between these groups. Serum APRIL levels were elevated in limited number of patients with myositis, and the levels did not differ amongst the clinico-serologic phenotypes. IL-17 levels were higher in individuals positive for anti-SRP [p = 0.028]. Serum BAFF levels are elevated in IIM, more so in children. BAFF levels may be useful as biomarker for PAH and arthritis. Anti-SRP positivity is associated with elevated IL-17 levels suggesting role in pathogenesis.

  15. Molecular structure, distribution, and immunology function of TNFSF13B (BAFF) in Nile tilapia (Oreochromis niloticus).

    Science.gov (United States)

    Liu, Hongzhen; Zhang, Jiaxin; Li, Jianfeng; Song, Jinyun; Zhang, Shuangquan

    2016-04-01

    B cell-activating factor (BAFF)is a member of the tumor necrosis factor (TNF) family and plays roles in B cell survival and maturation. In this study, the full-length cDNA of Nile tilapia (Oreochromis niloticus) BAFF (tBAFF) was amplified from the spleen by reverse transcription PCR (RT-PCR). The open reading frame of this cDNA encodes a protein of 261 amino acids containing a predicted transmembrane domain and a furin protease cleavage site, similar to mammalian, avian, and reptile BAFF. Real-time quantitative PCR (qPCR) analysis revealed that tBAFF is present in various tissues and is predominantly expressed in the spleen. The predicted three-dimensional (3D) structure of the Nile tilapia (Oreochromis niloticus) soluble BAFF (tsBAFF) monomer was determined by (3D) structure modeling monomeranalyzed by (3D) structure mouse counterpart. Both tsBAFF and EGFP/tsBAFF were efficiently expressed in Escherichia coli BL21 (DE3), as confirmed by SDS-PAGE and Western blot analysis. After purification, the EGFP/tsBAFF fusion protein showed a fluorescence spectrum similar to that of EGFP. Laser scanning confocal microscopy showed that EGFP/tsBAFF bound to its receptor. In vitro, tsBAFF promoted the proliferation of Nile tilapia and mouse splenic B cells together with/without a priming agent (Staphylococcus aureus Cowan 1, SAC) or anti-mouse IgM. Furthermore, tsBAFF showed a similar proliferation-stimulating effect on mouse B cells compared to msBAFF. These findings indicate that tsBAFF plays an important role in the proliferation of Nile tilapia B cells and has functional cross-reactivity among Nile tilapia and mammals. Therefore, BAFF may represent a useful factor for enhancing immunological efficacy in animals. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. A Pathway Switch Directs BAFF Signaling to Distinct NFκB Transcription Factors in Maturing and Proliferating B Cells

    Directory of Open Access Journals (Sweden)

    Jonathan V. Almaden

    2014-12-01

    Full Text Available BAFF, an activator of the noncanonical NFκB pathway, provides critical survival signals during B cell maturation and contributes to B cell proliferation. We found that the NFκB family member RelB is required ex vivo for B cell maturation, but cRel is required for proliferation. Combined molecular network modeling and experimentation revealed Nfkb2 p100 as a pathway switch; at moderate p100 synthesis rates in maturing B cells, BAFF fully utilizes p100 to generate the RelB:p52 dimer, whereas at high synthesis rates, p100 assembles into multimeric IκBsome complexes, which BAFF neutralizes in order to potentiate cRel activity and B cell expansion. Indeed, moderation of p100 expression or disruption of IκBsome assembly circumvented the BAFF requirement for full B cell expansion. Our studies emphasize the importance of p100 in determining distinct NFκB network states during B cell biology, which causes BAFF to have context-dependent functional consequences.

  17. A pathway switch directs BAFF signaling to distinct NFκB transcription factors in maturing and proliferating B cells.

    Science.gov (United States)

    Almaden, Jonathan V; Tsui, Rachel; Liu, Yi C; Birnbaum, Harry; Shokhirev, Maxim N; Ngo, Kim A; Davis-Turak, Jeremy C; Otero, Dennis; Basak, Soumen; Rickert, Robert C; Hoffmann, Alexander

    2014-12-24

    BAFF, an activator of the noncanonical NFκB pathway, provides critical survival signals during B cell maturation and contributes to B cell proliferation. We found that the NFκB family member RelB is required ex vivo for B cell maturation, but cRel is required for proliferation. Combined molecular network modeling and experimentation revealed Nfkb2 p100 as a pathway switch; at moderate p100 synthesis rates in maturing B cells, BAFF fully utilizes p100 to generate the RelB:p52 dimer, whereas at high synthesis rates, p100 assembles into multimeric IκBsome complexes, which BAFF neutralizes in order to potentiate cRel activity and B cell expansion. Indeed, moderation of p100 expression or disruption of IκBsome assembly circumvented the BAFF requirement for full B cell expansion. Our studies emphasize the importance of p100 in determining distinct NFκB network states during B cell biology, which causes BAFF to have context-dependent functional consequences. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  18. B cell activating factor is central to bleomycin- and IL-17-mediated experimental pulmonary fibrosis.

    Science.gov (United States)

    François, Antoine; Gombault, Aurélie; Villeret, Bérengère; Alsaleh, Ghada; Fanny, Manoussa; Gasse, Paméla; Adam, Sylvain Marchand; Crestani, Bruno; Sibilia, Jean; Schneider, Pascal; Bahram, Seiamak; Quesniaux, Valérie; Ryffel, Bernhard; Wachsmann, Dominique; Gottenberg, Jacques-Eric; Couillin, Isabelle

    2015-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive devastating, yet untreatable fibrotic disease of unknown origin. We investigated the contribution of the B-cell activating factor (BAFF), a TNF family member recently implicated in the regulation of pathogenic IL-17-producing cells in autoimmune diseases. The contribution of BAFF was assessed in a murine model of lung fibrosis induced by airway administered bleomycin. We show that murine BAFF levels were strongly increased in the bronchoalveolar space and lungs after bleomycin exposure. We identified Gr1(+) neutrophils as an important source of BAFF upon BLM-induced lung inflammation and fibrosis. Genetic ablation of BAFF or BAFF neutralization by a soluble receptor significantly attenuated pulmonary fibrosis and IL-1β levels. We further demonstrate that bleomycin-induced BAFF expression and lung fibrosis were IL-1β and IL-17A dependent. BAFF was required for rIL-17A-induced lung fibrosis and augmented IL-17A production by CD3(+) T cells from murine fibrotic lungs ex vivo. Finally we report elevated levels of BAFF in bronchoalveolar lavages from IPF patients. Our data therefore support a role for BAFF in the establishment of pulmonary fibrosis and a crosstalk between IL-1β, BAFF and IL-17A. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Profile of BAFF and its receptors' expression in lupus nephritis is associated with pathological classes.

    Science.gov (United States)

    Suso, J P; Posso-Osorio, I; Jiménez, C A; Naranjo-Escobar, J; Ospina, F E; Sánchez, A; Cañas, C A; Tobón, G J

    2018-04-01

    Background/Objective B-cell activating factor (BAFF) plays an important role in the pathogenesis of systemic lupus erythematosus. However, the role of BAFF in lupus nephritis (LN) is not understood. Our aim was to evaluate the expression of BAFF and its three receptors in renal biopsy samples from patients with LN and investigate a relationship with pathological class. Methods We conducted a prospective descriptive study (2011-2014) on 52 kidney biopsy samples from patients with LN. Immunohistochemistry for BAFF, its receptors (transmembrane activator and calcium modulator and cyclophilin ligand interaction (TACI), protein maturation of B cells (BCMA), and BAFF-receptor (BAFF-R)), and CD20 expression was performed. Samples were scored according to the percentage of cells with positive expression. Results In class II LN, BAFF-R and TACI were not expressed, whereas BCMA and BAFF were lowly expressed in the interstitial inflammatory infiltrates. Proliferative class III/IV had elevated BAFF expression in the glomeruli, and TACI was expressed in interstitial inflammatory infiltrates and the glomeruli. Interestingly, the class IV cases with vasculopathy ( n = 4) had endothelial BAFF expression, which was not visible in thrombotic microangiopathy ( n = 4). Class V was characterized by low BAFF expression in interstitial inflammatory infiltrates and by BAFF, TACI, and BCMA expression in the glomeruli. BAFF expression was associated with inflammatory scores and CD20 positive infiltrates, mainly in class IV. Conclusions Expression patterns of BAFF and its receptors differ according to LN class. Our study provides evidence that BAFF could be used as a routine marker in LN biopsies and to determine which patients will benefit from anti-BAFF therapy.

  20. Stoichiometry of Heteromeric BAFF and APRIL Cytokines Dictates Their Receptor Binding and Signaling Properties*

    Science.gov (United States)

    Schuepbach-Mallepell, Sonia; Das, Dolon; Willen, Laure; Vigolo, Michele; Tardivel, Aubry; Lebon, Luc; Kowalczyk-Quintas, Christine; Nys, Josquin; Smulski, Cristian; Zheng, Timothy S.; Maskos, Klaus; Lammens, Alfred; Jiang, Xuliang; Hess, Henry; Tan, Seng-Lai; Schneider, Pascal

    2015-01-01

    The closely related TNF family ligands B cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) serve in the generation and maintenance of mature B-lymphocytes. Both BAFF and APRIL assemble as homotrimers that bind and activate several receptors that they partially share. However, heteromers of BAFF and APRIL that occur in patients with autoimmune diseases are incompletely characterized. The N and C termini of adjacent BAFF or APRIL monomers are spatially close and can be linked to create single-chain homo- or hetero-ligands of defined stoichiometry. Similar to APRIL, heteromers consisting of one BAFF and two APRILs (BAA) bind to the receptors B cell maturation antigen (BCMA), transmembrane activator and CAML interactor (TACI) but not to the BAFF receptor (BAFFR). Heteromers consisting of one APRIL and two BAFF (ABB) bind to TACI and BCMA and weakly to BAFFR in accordance with the analysis of the receptor interaction sites in the crystallographic structure of ABB. Receptor binding correlated with activity in reporter cell line assays specific for BAFFR, TACI, or BCMA. Single-chain BAFF (BBB) and to a lesser extent single-chain ABB, but not APRIL or single-chain BAA, rescued BAFFR-dependent B cell maturation in BAFF-deficient mice. In conclusion, BAFF-APRIL heteromers of different stoichiometries have distinct receptor-binding properties and activities. Based on the observation that heteromers are less active than BAFF, we speculate that their physiological role might be to down-regulate BAFF activity. PMID:25953898

  1. A Pathway Switch Directs BAFF Signaling to Distinct NFκB Transcription Factors in Maturing and Proliferating B Cells

    OpenAIRE

    Jonathan V. Almaden; Rachel Tsui; Yi C. Liu; Harry Birnbaum; Maxim N. Shokhirev; Kim A. Ngo; Jeremy C. Davis-Turak; Dennis Otero; Soumen Basak; Robert C. Rickert; Alexander Hoffmann

    2014-01-01

    SUMMARY BAFF, an activator of the noncanonical NF?B pathway, provides critical survival signals during B cell maturation and contributes to B cell proliferation. We found that the NF?B family member RelB is required ex vivo for B cell maturation, but cRel is required for proliferation. Combined molecular network modeling and experimentation revealed Nfkb2 p100 as a pathway switch; at moderate p100 synthesis rates in maturing B cells, BAFF fully utilizes p100 to generate the RelB:p52 dimer, wh...

  2. Increased B cell-activating factor promotes tumor invasion and metastasis in human pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Mitsuhito Koizumi

    Full Text Available B cell-activating factor (BAFF is a cytokine belonging to the tumor necrosis factor (TNF superfamily. It has been reported that BAFF is elevated in patients with autoimmune pancreatitis and contributes to the malignant potential of blood cancers and solid tumors. In this study, clinical evidence of increased BAFF levels in patients with pancreatic ductal adenocarcinoma (PDAC was obtained, and the roles and mechanisms of BAFF in PDAC were clarified in human tissues of PDAC and from in vitro data of PDAC cell lines. Serum levels of BAFF in patients with PDAC were significantly higher than in healthy subjects (p = 0.0121. Patients with UICC stage IV PDAC (T1-4, N0-1, M1 had significantly higher levels of serum BAFF compared to patients with PDAC (p = 0.0182. BAFF was remarkably expressed in infiltrating B lymphocytes surrounding pancreatic cancer in human pancreatic tissues, suggesting that BAFF may play a role in progression of pancreatic cancer. PDAC cell lines were cultured with human recombinant BAFF, and morphology and gene expression were analyzed; pancreatic cancer cells changed to a fibroblast-like morphology, and showed altered gene expression of E-cadherin, vimentin and Snail. These BAFF-induced changes reflect enhanced cell motility and invasion. BAFF-R-overexpressing cell clones confirmed the association between these BAFF-induced changes and epithelial-mesenchymal transition (EMT-related genes. BAFF was elevated in patients with metastatic advanced PDAC and induced alterations in PDAC cells via regulation of EMT-related genes. Elucidation of the precise role and mechanism of control of BAFF may lead to new therapeutic approaches with the aim of improving pancreatic cancer survival.

  3. Increased B Cell-Activating Factor Promotes Tumor Invasion and Metastasis in Human Pancreatic Cancer

    Science.gov (United States)

    Koizumi, Mitsuhito; Hiasa, Yoichi; Kumagi, Teru; Yamanishi, Hirofumi; Azemoto, Nobuaki; Kobata, Tetsuji; Matsuura, Bunzo; Abe, Masanori; Onji, Morikazu

    2013-01-01

    B cell-activating factor (BAFF) is a cytokine belonging to the tumor necrosis factor (TNF) superfamily. It has been reported that BAFF is elevated in patients with autoimmune pancreatitis and contributes to the malignant potential of blood cancers and solid tumors. In this study, clinical evidence of increased BAFF levels in patients with pancreatic ductal adenocarcinoma (PDAC) was obtained, and the roles and mechanisms of BAFF in PDAC were clarified in human tissues of PDAC and from in vitro data of PDAC cell lines. Serum levels of BAFF in patients with PDAC were significantly higher than in healthy subjects (p = 0.0121). Patients with UICC stage IV PDAC (T1-4, N0-1, M1) had significantly higher levels of serum BAFF compared to patients with PDAC (p = 0.0182). BAFF was remarkably expressed in infiltrating B lymphocytes surrounding pancreatic cancer in human pancreatic tissues, suggesting that BAFF may play a role in progression of pancreatic cancer. PDAC cell lines were cultured with human recombinant BAFF, and morphology and gene expression were analyzed; pancreatic cancer cells changed to a fibroblast-like morphology, and showed altered gene expression of E-cadherin, vimentin and Snail. These BAFF-induced changes reflect enhanced cell motility and invasion. BAFF-R-overexpressing cell clones confirmed the association between these BAFF-induced changes and epithelial-mesenchymal transition (EMT)-related genes. BAFF was elevated in patients with metastatic advanced PDAC and induced alterations in PDAC cells via regulation of EMT-related genes. Elucidation of the precise role and mechanism of control of BAFF may lead to new therapeutic approaches with the aim of improving pancreatic cancer survival. PMID:23940742

  4. Serum BAFF and APRIL Levels, T-Lymphocyte Subsets, and Immunoglobulins after B-Cell Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Myalgic Encephalopathy/Chronic Fatigue Syndrome

    Science.gov (United States)

    Lunde, Sigrid; Kristoffersen, Einar K.; Sapkota, Dipak; Risa, Kristin; Dahl, Olav; Bruland, Ove; Mella, Olav; Fluge, Øystein

    2016-01-01

    Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is a disease of unknown etiology. We have previously suggested clinical benefit from B-cell depletion using the monoclonal anti-CD20 antibody rituximab in a randomized and placebo-controlled study. Prolonged responses were then demonstrated in an open-label phase-II study with maintenance rituximab treatment. Using blood samples from patients in the previous two clinical trials, we investigated quantitative changes in T-lymphocyte subsets, in immunoglobulins, and in serum levels of two B-cell regulating cytokines during follow-up. B-lymphocyte activating factor of the tumor necrosis family (BAFF) in baseline serum samples was elevated in 70 ME/CFS patients as compared to 56 healthy controls (p = 0.011). There were no significant differences in baseline serum BAFF levels between patients with mild, moderate, or severe ME/CFS, or between responders and non-responders to rituximab. A proliferation-inducing ligand (APRIL) serum levels were not significantly different in ME/CFS patients compared to healthy controls at baseline, and no changes in serum levels were seen during follow-up. Immunophenotyping of peripheral blood T-lymphocyte subsets and T-cell activation markers at multiple time points during follow-up showed no significant differences over time, between rituximab and placebo groups, or between responders and non-responders to rituximab. Baseline serum IgG levels were significantly lower in patients with subsequent response after rituximab therapy compared to non-responders (p = 0.03). In the maintenance study, slight but significant reductions in mean serum immunoglobulin levels were observed at 24 months compared to baseline; IgG 10.6–9.5 g/L, IgA 1.8–1.5 g/L, and IgM 0.97–0.70 g/L. Although no functional assays were performed, the lack of significant associations of T- and NK-cell subset numbers with B-cell depletion, as well as the lack of associations to clinical responses, suggest that B

  5. Exploring BAFF: its expression, receptors and contribution to the immunopathogenesis of Sjögren's syndrome.

    Science.gov (United States)

    Thompson, Nicolyn; Isenberg, David A; Jury, Elizabeth C; Ciurtin, Coziana

    2016-09-01

    SS is an autoimmune condition characterized by exocrine gland destruction, autoantibody production, immune complex deposition and systemic complications associated with lymphocytic infiltration of many organs. Genetic, environmental and viral factors play a role in disease aetiology, however, the exact mechanisms driving the immunopathogenesis of SS remain uncertain. Here we discuss a role for B cell activating factor (BAFF), whereby B cell hyperactivity and increased BAFF secretion observed in patients and animal models of the disease can be explained by the altered expression of cell-specific BAFF/BAFF receptor (BAFF-R) variants in several immune cell types. Understanding the role of BAFF/BAFF-R heterogeneity in SS pathogenesis could help to facilitate new treatment strategies for patients. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. BAFF-driven autoimmunity requires CD19 expression.

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    Fairfax, Kirsten A; Tsantikos, Evelyn; Figgett, William A; Vincent, Fabien B; Quah, Pin Shie; LePage, Mélanie; Hibbs, Margaret L; Mackay, Fabienne

    2015-08-01

    B cell activating factor of the tumor necrosis factor family (BAFF or BLyS) is a critical factor for B cell survival and maturation. BAFF-transgenic (BAFF-Tg) mice develop autoimmunity that resembles systemic lupus erythematosus (SLE) in a T cell-independent but MyD88-dependent manner, implicating toll-like receptor (TLR) signaling. The specific B cell subtypes that make pro-inflammatory autoantibodies in BAFF-Tg mice are TLR-activated innate B cells known as marginal zone (MZ) and B1 B cells. These cells infiltrate the salivary glands and kidneys of diseased BAFF-Tg mice. However, loss of B1a or MZ B cells does not protect BAFF-Tg mice against disease, suggesting that B1b B cells might be the important pathogenic B cell subset. To test this hypothesis, we have generated BAFF-Tg mice that retained follicular B cells, but are deficient in B1a, B1b and MZ B cells, by crossing BAFF-Tg mice to CD19-deficient mice (BTg-CD19(-/-)). The BTg-CD19(-/-) mice did not produce autoantibodies and were protected from splenomegaly, kidney pathology and all signs of autoimmunity. This work suggests that B1b B cells, rather than MZ or B1a B cells, are sufficient and possibly required for the development of autoimmunity. Loss of the majority of innate-like B cells was able to protect BAFF-Tg mice from developing disease, so we can now conclude that autoimmunity induced by excessive BAFF production requires B1b B cells and CD19 signaling. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. HIV-1-Mediated BAFF Secretion in Macrophages Does Not Require Endosomal TLRs, Type-I IFN, and Nef, but Depends on the Cellular Phenotype Status.

    Science.gov (United States)

    Gomez, Alejandro M; Ouellet, Michel; Deshiere, Alexandre; Breton, Yann; Tremblay, Michel J

    2016-05-01

    HIV-1 infection is characterized by persistent viral replication, chronic immune activation, and CD4(+) T cell depletion. Moreover, several immune dysfunctions are observed in cells that are not targeted by the virus, such as B cells. Some B cell abnormalities include hypergammaglobulinemia, nonspecific B cell activation, class switching, increased cell turnover, breakage of tolerance, and a loss of the capacity to generate and maintain memory. Several cytokines and growth factors that are increased in the serum of HIV-1-infected individuals have been suggested to directly or indirectly trigger B cell activation, and one of these is BAFF. In this study, we investigate the ability of fully competent (R5-tropic) HIV-1 to induce BAFF production by monocyte-derived macrophages (MDMs). We demonstrate here that HIV-1 drives BAFF production in MDMs in a type-I IFN- and TLR-independent manner. Moreover, we determine that HIV-1 Nef accessory protein is dispensable in BAFF upregulation as a nef-deleted HIV-1 strain is still able to increase BAFF at levels similar to the wild type strain. Finally, we show that the macrophage phenotype status affects HIV-1 replication and BAFF induction, as both were abrogated in MDMs displaying a M1 phenotype. This study provides new useful information about the increased levels of BAFF observed during HIV-1 infection and highlights the importance of macrophages as a source of BAFF, a phenomenon that might contribute to B cell dysfunctions at inflammatory tissue sites in infected individuals. Copyright © 2016 by The American Association of Immunologists, Inc.

  8. BAFF inhibition: a new class of drugs for the treatment of autoimmunity

    Science.gov (United States)

    Liu, Zheng; Davidson, Anne

    2011-01-01

    BAFF (BLyS) and APRIL are TNF-like cytokines that support survival and differentiation of B cells. Recent studies have discovered a role for BAFF in augmenting both innate and adaptive immune responses as well as in collaborating with other inflammatory cytokines to promote the activation and differentiation of effector immune cells. BAFF is an important pathogenic factor in lupus mouse models and BAFF inhibition successfully delays disease onset in these mice, although the responsiveness to BAFF inhibition varies among different strains. These results have led to the development of inhibitors targeting BAFF and APRIL in humans. An anti-BAFF antibody has shown significant but modest efficacy in two Phase III clinical trials for moderately active SLE and other inhibitors are being developed or at early stages of clinical testing. PMID:21333645

  9. The BAFF/APRIL system: emerging functions beyond B cell biology and autoimmunity.

    Science.gov (United States)

    Vincent, Fabien B; Saulep-Easton, Damien; Figgett, William A; Fairfax, Kirsten A; Mackay, Fabienne

    2013-06-01

    The BAFF system plays a key role in the development of autoimmunity, especially in systemic lupus erythematosus (SLE). This often leads to the assumption that BAFF is mostly a B cell factor with a specific role in autoimmunity. Focus on BAFF and autoimmunity, driven by pharmaceutical successes with the recent approval of a novel targeted therapy Belimumab, has relegated other potential roles of BAFF to the background. Far from being SLE-specific, the BAFF system has a much broader relevance in infection, cancer and allergy. In this review, we provide the latest views on additional roles of the BAFF system in health and diseases, as well as an update on BAFF and autoimmunity, with particular focus on current clinical trials. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Characterization of Lamprey BAFF-like Gene: Evolutionary Implications.

    Science.gov (United States)

    Das, Sabyasachi; Sutoh, Yoichi; Hirano, Masayuki; Han, Qifeng; Li, Jianxu; Cooper, Max D; Herrin, Brantley R

    2016-10-01

    BAFF (TNF superfamily [TNFSF] 13B/Blys) and APRIL (TNFSF13) are important regulatory factors for lymphocyte activation and survival in mammals. A BAFF/APRIL-like relative called BAFF- and APRIL-like molecule (BALM) has also been identified in cartilaginous and bony fishes, and we report in this study a BAFF-like gene in lampreys. Our phylogenetic analysis of these genes and a related TNFSF12 gene called TNF-like weak inducer of apoptosis (TWEAK) suggest that, whereas an ancestral homolog of BAFF and APRIL was already present in a common ancestor of jawed and jawless vertebrates, TWEAK evolved early on in the jawed vertebrate lineage. Like mammalian BAFF and APRIL, the lamprey BAFF-like gene is expressed in T-like, B-like, and innate immune cells. The predicted protein encoded by this BAFF-like gene in lampreys exhibits higher sequence similarity with mammalian BAFF than APRIL. Correspondingly, we find BAFF orthologs in all of the jawed vertebrate representatives that we examined, although APRIL and/or BALM orthologs are not identifiable in certain jawed vertebrates. For example, BALM is not identifiable in tetrapods, and APRIL is not identifiable in several bony fishes or in birds, the latter of which also lack a TWEAK-like gene. Our analysis further suggests that a hybrid molecule called TWE-PRIL, which is a product of an in-genomic fusion between APRIL and TWEAK genes evolved early in mammalian evolution. Copyright © 2016 by The American Association of Immunologists, Inc.

  11. BAFF mediates splenic B cell response and antibody production in experimental Chagas disease.

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    Daniela A Bermejo

    Full Text Available BACKGROUND: B cells and antibodies are involved not only in controlling the spread of blood circulating Trypanosoma cruzi, but also in the autoreactive manifestations observed in Chagas disease. Acute infection results in polyclonal B cell activation associated with hypergammaglobulinemia, delayed specific humoral immunity and high levels of non-parasite specific antibodies. Since TNF superfamily B lymphocyte Stimulator (BAFF mediates polyclonal B cell response in vitro triggered by T. cruzi antigens, and BAFF-Tg mice show similar signs to T. cruzi infected mice, we hypothesized that BAFF can mediate polyclonal B cell response in experimental Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: BAFF is produced early and persists throughout the infection. To analyze BAFF role in experimental Chagas disease, Balb/c infected mice were injected with BR3:Fc, a soluble receptor of BAFF, to block BAFF activity. By BAFF blockade we observed that this cytokine mediates the mature B cell response and the production of non-parasite specific IgM and IgG. BAFF also influences the development of antinuclear IgG and parasite-specific IgM response, not affecting T. cruzi-specific IgG and parasitemia. Interestingly, BAFF inhibition favors the parasitism in heart. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate, for the first time, an active role for BAFF in shaping the mature B cell repertoire in a parasite infection.

  12. Gender-Specific Mechanisms Underlying the Amelioration of High-Fat Diet-Induced Glucose Intolerance in B-Cell-Activating Factor Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Bobae Kim

    Full Text Available It has recently been found that B cell activating factor (BAFF plays an important role in the regulation of energy homeostasis. We also have previously reported that BAFF deficiency reverses high-fat (HF diet-induced glucose intolerance by potentiating adipose tissue function. In the present study, we found that BAFF deficient (BAFF-/- mice exhibit gender-specific differences in protection against diet-induced glucose intolerance, and aimed to characterize the gender-dependent molecular alterations in energy metabolism. Under HF feeding conditions, serum BAFF level of female wild-type (WT mice was considerably higher than that of male mice. Despite increased body weight gain, both male and female BAFF-/- mice showed significantly improved glucose tolerance compared to their WT counterparts. Expressions of genes involved in glucose transport, thermogenesis and lipid oxidation were up-regulated in brown adipose tissues of both male and female BAFF-/- mice. Interestingly, the expression of thermogenic genes in subcutaneous adipose tissue was significantly enhanced in female BAFF-/- compared to WT mice, but the difference was not observed between male BAFF-/- and WT mice. The enhanced thermogenic program was confirmed by higher protein levels of UCP1 and irisin in female BAFF-/- than in WT mice. Additionally, adiponectin production in white adipose tissues and AMPK phosphorylation in subcutaneous adipose tissue were also significantly elevated in female BAFF-/- compared to WT mice, but not in male BAFF-/- mice. Our findings define a comprehensive scenario for the enhancing effect of BAFF depletion on glucose tolerance wherein the underlying mechanism is, at least in part, gender-specific, and suggest that gender difference should be considered as an important factor in the use of BAFF blockade as a therapeutic approach for the prevention and treatment of type 2 diabetes.

  13. Aiolos Overexpression in Systemic Lupus Erythematosus B Cell Subtypes and BAFF-Induced Memory B Cell Differentiation Are Reduced by CC-220 Modulation of Cereblon Activity.

    Science.gov (United States)

    Nakayama, Yumi; Kosek, Jolanta; Capone, Lori; Hur, Eun Mi; Schafer, Peter H; Ringheim, Garth E

    2017-10-01

    BAFF is a B cell survival and maturation factor implicated in the pathogenesis of systemic lupus erythematosus (SLE). In this in vitro study, we describe that soluble BAFF in combination with IL-2 and IL-21 is a T cell contact-independent inducer of human B cell proliferation, plasmablast differentiation, and IgG secretion from circulating CD27 + memory and memory-like CD27 - IgD - double-negative (DN) B cells, but not CD27 - IgD + naive B cells. In contrast, soluble CD40L in combination with IL-2 and IL-21 induces these activities in both memory and naive B cells. Blood from healthy donors and SLE patients have similar circulating levels of IL-2, whereas SLE patients exhibit elevated BAFF and DN B cells and reduced IL-21. B cell differentiation transcription factors in memory, DN, and naive B cells in SLE show elevated levels of Aiolos, whereas Ikaros levels are unchanged. Treatment with CC-220, a modulator of the cullin ring ligase 4-cereblon E3 ubiquitin ligase complex, reduces Aiolos and Ikaros protein levels and BAFF- and CD40L-induced proliferation, plasmablast differentiation, and IgG secretion. The observation that the soluble factors BAFF, IL-2, and IL-21 induce memory and DN B cell activation and differentiation has implications for extrafollicular plasmablast development within inflamed tissue. Inhibition of B cell plasmablast differentiation by reduction of Aiolos and Ikaros may have utility in the treatment of SLE, where elevated levels of BAFF and Aiolos may prime CD27 + memory and DN memory-like B cells to become Ab-producing plasmablasts in the presence of BAFF and proinflammatory cytokines. Copyright © 2017 by The American Association of Immunologists, Inc.

  14. BAFF is decreased in the cerebrospinal fluid of multiple sclerosis at clinical onset.

    Science.gov (United States)

    Puthenparampil, M; Miante, S; Federle, L; Zanetta, C; Toffanin, E; Ruggero, S; Rinaldi, F; Gallo, P

    2016-08-15

    B-cells are thought to play a relevant role in multiple sclerosis (MS) pathology. BAFF (B cell activating factor of the TNF family) is a B-cell survival factor constitutively produced inside the CNS by astrocytes. We studied the intrathecal synthesis of BAFF in MS at clinical onset. Paired serum and cerebrospinal fluid (CSF) specimens from 40 clinically isolated syndromes (CIS) suggestive of MS or early relapse-onset MS (eRRMS) and from 18 healthy controls (HC) were analysed. Patients were classified based on the detection of oligoclonal IgG bands in the CSF (IgGOB+ and IgGOB-). BAFF was detected by highly sensitive ELISA and its ratio (CSF-BAFF/serum-BAFF, QBAFF) and Index (QBAFF/QAlb, BAFF-Index) were calculated. IgGOB+ presented lower CSF concentrations of BAFF compared to both HC and IgGOB- (pBAFF Index was significantly lower in IgGOB+ compared to both HC and IgGOB- (pBAFF index and IgGIF (r: -0.4, pBAFF in IgGOB+ at clinical onset suggest the absorption of this factor by intrathecally recruited B cells since the early disease phases. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. BAFF activation of the ERK5 MAP kinase pathway regulates B cell survival.

    Science.gov (United States)

    Jacque, Emilie; Schweighoffer, Edina; Tybulewicz, Victor L J; Ley, Steven C

    2015-06-01

    B cell activating factor (BAFF) stimulation of the BAFF receptor (BAFF-R) is essential for the homeostatic survival of mature B cells. Earlier in vitro experiments with inhibitors that block MEK 1 and 2 suggested that activation of ERK 1 and 2 MAP kinases is required for BAFF-R to promote B cell survival. However, these inhibitors are now known to also inhibit MEK5, which activates the related MAP kinase ERK5. In the present study, we demonstrated that BAFF-induced B cell survival was actually independent of ERK1/2 activation but required ERK5 activation. Consistent with this, we showed that conditional deletion of ERK5 in B cells led to a pronounced global reduction in mature B2 B cell numbers, which correlated with impaired survival of ERK5-deficient B cells after BAFF stimulation. ERK5 was required for optimal BAFF up-regulation of Mcl1 and Bcl2a1, which are prosurvival members of the Bcl-2 family. However, ERK5 deficiency did not alter BAFF activation of the PI3-kinase-Akt or NF-κB signaling pathways, which are also important for BAFF to promote mature B cell survival. Our study reveals a critical role for the MEK5-ERK5 MAP kinase signaling pathway in BAFF-induced mature B cell survival and homeostatic maintenance of B2 cell numbers. © 2015 Jacque et al.

  16. Current and emerging treatment options for ANCA-associated vasculitis: potential role of belimumab and other BAFF/APRIL targeting agents

    Science.gov (United States)

    Lenert, Aleksander; Lenert, Petar

    2015-01-01

    Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises several clinical entities with diverse clinical presentations, outcomes, and nonunifying pathogenesis. AAV has a clear potential for relapses, and shows unpredictable response to treatment. Cyclophosphamide-based therapies have remained the hallmark of induction therapy protocols for more than four decades. Recently, B-cell depleting therapy with the anti-CD20 antibody rituximab has proved beneficial in AAV, leading to Food and Drug Administration approval of rituximab in combination with corticosteroids for the treatment of AAV in adults. Rituximab for ANCA-associated vasculitis and other clinical trials provided clear evidence that rituximab was not inferior to cyclophosphamide for remission induction, and rituximab appeared even more beneficial in patients with relapsing disease. This raised hopes that other B-cell-targeted therapies directed either against CD19, CD20, CD22, or B-cell survival factors, B-cell activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand could also be beneficial for the management of AAV. BAFF neutralization with the fully humanized monoclonal antibody belimumab has already shown success in human systemic lupus erythematosus and, along with another anti-BAFF reagent blisibimod, is currently undergoing Phase II and III clinical trials in AAV. Local production of BAFF in granulomatous lesions and elevated levels of serum BAFF in AAV provide a rationale for BAFF-targeted therapies not only in AAV but also in other forms of vasculitis such as Behcet’s disease, large-vessel vasculitis, or cryoglobulinemic vasculitis secondary to chronic hepatitis C infection. BAFF-targeted therapies have a very solid safety profile, and may have an additional benefit of preferentially targeting newly arising autoreactive B cells over non-self-reactive B cells. PMID:25609919

  17. The function of BAFF on T helper cells in autoimmunity.

    Science.gov (United States)

    Chen, Maogen; Lin, Xiaohong; Liu, Ya; Li, Qiang; Deng, Yiling; Liu, Zhongmin; Brand, David; Guo, Zhiyong; He, Xiaoshun; Ryffel, Bernhard; Zheng, Song Guo

    2014-06-01

    B cell-activating factor belonging to the TNF family (BAFF) exerts its pathogenic role in supporting the survival and proliferation of B cells, regulating class switch recombination as well as the selection of autoreactive B cells. Overexpression of BAFF induces a dramatic expansion of activated B cells, particularly marginal zone B cells, as well as hypergammaglobulinemia, autoantibody production and immune complex deposition. However, in addition to its effect on B cells, recent work has also demonstrated that BAFF can promote T cell activation, proliferation and differentiation. In this review, we have discussed the recent progress on the function and role of BAFF on T cells and T cell-mediated diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. The function of BAFF on T helper cells in autoimmunity

    Science.gov (United States)

    Chen, Maogen; Lin, Xiaohong; Liu, Ya; Li, Qiang; Deng, Yiling; Liu, Zhongmin; Brand, David; Guo, Zhiyong; He, Xiaoshun; Ryffel, Bernhard; Zheng, Song Guo

    2014-01-01

    Summary B cell-activating factor belonging to the TNF family (BAFF) exerts its pathogenic role in supporting the survival and proliferation of B cells, regulating class switch recombination as well as the selection of autoreactive B cells. Overexpression of BAFF induces a dramatic expansion of activated B cells, particularly marginal zone B cells, as well as hypergammaglobulinemia, autoantibody production and immune complex deposition. However, in addition to its effect on B cells, recent work has also demonstrated that BAFF can promote T cell activation, proliferation and differentiation. In this review, we have discussed the recent progress on the function and role of BAFF on T cells and T cell-mediated diseases. PMID:24411564

  19. IL-2, IL-4, IFN-γ or TNF-α enhances BAFF-stimulated cell viability and survival by activating Erk1/2 and S6K1 pathways in neoplastic B-lymphoid cells.

    Science.gov (United States)

    Gui, Lin; Zeng, Qingyu; Xu, Zhigang; Zhang, Hai; Qin, Shanshan; Liu, Chunxiao; Xu, Chong; Qian, Zhou; Zhang, Shuangquan; Huang, Shile; Chen, Long

    2016-08-01

    B-cell activating factor of the TNF family (BAFF) has been documented to act as a critical factor in the development of aggressive B lymphocytes and autoimmune diseases. However, the effect of various cytokines on BAFF-elicited neoplastic B-lymphoid cells is not known. In this study, we exhibited that administration of human soluble BAFF (hsBAFF), IL-2, IL-4, IFN-γ, or TNF-α alone increased cell viability and survival in Raji cells concentration-dependently, yet a more robust viability/survival was seen in the cells co-treatment of IL-2, IL-4, IFN-γ, or TNF-α with hsBAFF, respectively. Further research revealed that both Erk1/2 and S6K1 signaling pathways were essential for IL-2, IL-4, IFN-γ, or TNF-α enhancement of the viability/survival in the hsBAFF-stimulated cells, as inhibition of Erk1/2 with U0126 or down-regulation of Erk1/2, or blockage of S6K1 with rapamycin or silencing S6K1, or silencing S6K1/Erk1/2, respectively, reduced the cell viability/survival in the cells treated with/without hsBAFF±IL-2, IL-4, IFN-γ, or TNF-α. These findings indicate that IL-2, IL-4, IFN-γ or TNF-α enhances BAFF-stimulated cell viability/survival by activating Erk1/2 and S6K1 signaling in neoplastic B-lymphoid cells. Our data suggest that modulation of IL-2, IL-4, IFN-γ and/or TNF-α levels, or inhibitors of Erk1/2 or S6K1 may be a new approach to prevent BAFF-induced aggressive B-cell malignancies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. BAFF upregulates CD28/B7 and CD40/CD154 expression and promotes mouse T and B cell interaction in vitro via BAFF receptor.

    Science.gov (United States)

    Zhang, Feng; Song, Shan-Shan; Shu, Jin-Ling; Li, Ying; Wu, Yu-Jing; Wang, Qing-Tong; Chen, Jing-Yu; Chang, Yan; Wu, Hua-Xun; Zhang, Ling-Ling; Wei, Wei

    2016-08-01

    B cell-activating factor belonging to the TNF family (BAFF) is a member of TNF family and required for peripheral B cell survival and homeostasis. BAFF has been shown to promote the proliferation of T and B cells. In this study we examined whether and how BAFF mediated the interaction between mouse T and B cells in vitro. BAFF-stimulated B or T cells were co-cultured with T or B cells. The interactions between T and B cells were analyzed by measuring the expression of co-stimulatory molecules (CD28/CD80 or CD40/CD154), the proliferation and secretion of T and B cells and other factors. Two siRNAs against the transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and BAFF receptor (BAFF-R) were used to identify the receptors responsible for the actions of BAFF. BAFF-stimulated B cells significantly promoted the proliferation and activity of co-cultured T cells, and increased the percentages of CD4(+)CD28(+) and CD4(+)CD154(+) T cells. Similarly, BAFF-stimulated T cells significantly promoted the proliferation and activity of co-cultured B cells, and increased CD19(+)CD80(+) and CD19(+)CD40(+)B cell subpopulations. BAFF-R siRNA-silenced B cells showed significantly lower expression of CD40 and CD80 than the control B cells. When the BAFF-R siRNA-silenced B cells were stimulated with BAFF, then co-cultured with T cells, the expression of CD28 and CD154 on T cells was not increased. TACI siRNA-silenced B cells exhibited higher expression of CD40 and CD80 than the control B cells. When the TACI siRNA-silenced B cells were stimulated with BAFF, then co-cultured with T cells, the expression of CD28 and CD154 on T cells was significantly increased. BAFF upregulates CD28/B7 and CD40/CD154 expression, and promotes the interactions between T and B cells in a BAFF-R-dependent manner.

  1. Stoichiometry of Heteromeric BAFF and APRIL Cytokines Dictates Their Receptor Binding and Signaling Properties.

    Science.gov (United States)

    Schuepbach-Mallepell, Sonia; Das, Dolon; Willen, Laure; Vigolo, Michele; Tardivel, Aubry; Lebon, Luc; Kowalczyk-Quintas, Christine; Nys, Josquin; Smulski, Cristian; Zheng, Timothy S; Maskos, Klaus; Lammens, Alfred; Jiang, Xuliang; Hess, Henry; Tan, Seng-Lai; Schneider, Pascal

    2015-06-26

    The closely related TNF family ligands B cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) serve in the generation and maintenance of mature B-lymphocytes. Both BAFF and APRIL assemble as homotrimers that bind and activate several receptors that they partially share. However, heteromers of BAFF and APRIL that occur in patients with autoimmune diseases are incompletely characterized. The N and C termini of adjacent BAFF or APRIL monomers are spatially close and can be linked to create single-chain homo- or hetero-ligands of defined stoichiometry. Similar to APRIL, heteromers consisting of one BAFF and two APRILs (BAA) bind to the receptors B cell maturation antigen (BCMA), transmembrane activator and CAML interactor (TACI) but not to the BAFF receptor (BAFFR). Heteromers consisting of one APRIL and two BAFF (ABB) bind to TACI and BCMA and weakly to BAFFR in accordance with the analysis of the receptor interaction sites in the crystallographic structure of ABB. Receptor binding correlated with activity in reporter cell line assays specific for BAFFR, TACI, or BCMA. Single-chain BAFF (BBB) and to a lesser extent single-chain ABB, but not APRIL or single-chain BAA, rescued BAFFR-dependent B cell maturation in BAFF-deficient mice. In conclusion, BAFF-APRIL heteromers of different stoichiometries have distinct receptor-binding properties and activities. Based on the observation that heteromers are less active than BAFF, we speculate that their physiological role might be to down-regulate BAFF activity. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Overexpression of the Cytokine BAFF and Autoimmunity Risk.

    Science.gov (United States)

    Steri, Maristella; Orrù, Valeria; Idda, M Laura; Pitzalis, Maristella; Pala, Mauro; Zara, Ilenia; Sidore, Carlo; Faà, Valeria; Floris, Matteo; Deiana, Manila; Asunis, Isadora; Porcu, Eleonora; Mulas, Antonella; Piras, Maria G; Lobina, Monia; Lai, Sandra; Marongiu, Mara; Serra, Valentina; Marongiu, Michele; Sole, Gabriella; Busonero, Fabio; Maschio, Andrea; Cusano, Roberto; Cuccuru, Gianmauro; Deidda, Francesca; Poddie, Fausto; Farina, Gabriele; Dei, Mariano; Virdis, Francesca; Olla, Stefania; Satta, Maria A; Pani, Mario; Delitala, Alessandro; Cocco, Eleonora; Frau, Jessica; Coghe, Giancarlo; Lorefice, Lorena; Fenu, Giuseppe; Ferrigno, Paola; Ban, Maria; Barizzone, Nadia; Leone, Maurizio; Guerini, Franca R; Piga, Matteo; Firinu, Davide; Kockum, Ingrid; Lima Bomfim, Izaura; Olsson, Tomas; Alfredsson, Lars; Suarez, Ana; Carreira, Patricia E; Castillo-Palma, Maria J; Marcus, Joseph H; Congia, Mauro; Angius, Andrea; Melis, Maurizio; Gonzalez, Antonio; Alarcón Riquelme, Marta E; da Silva, Berta M; Marchini, Maurizio; Danieli, Maria G; Del Giacco, Stefano; Mathieu, Alessandro; Pani, Antonello; Montgomery, Stephen B; Rosati, Giulio; Hillert, Jan; Sawcer, Stephen; D'Alfonso, Sandra; Todd, John A; Novembre, John; Abecasis, Gonçalo R; Whalen, Michael B; Marrosu, Maria G; Meloni, Alessandra; Sanna, Serena; Gorospe, Myriam; Schlessinger, David; Fiorillo, Edoardo; Zoledziewska, Magdalena; Cucca, Francesco

    2017-04-27

    Genomewide association studies of autoimmune diseases have mapped hundreds of susceptibility regions in the genome. However, only for a few association signals has the causal gene been identified, and for even fewer have the causal variant and underlying mechanism been defined. Coincident associations of DNA variants affecting both the risk of autoimmune disease and quantitative immune variables provide an informative route to explore disease mechanisms and drug-targetable pathways. Using case-control samples from Sardinia, Italy, we performed a genomewide association study in multiple sclerosis followed by TNFSF13B locus-specific association testing in systemic lupus erythematosus (SLE). Extensive phenotyping of quantitative immune variables, sequence-based fine mapping, cross-population and cross-phenotype analyses, and gene-expression studies were used to identify the causal variant and elucidate its mechanism of action. Signatures of positive selection were also investigated. A variant in TNFSF13B, encoding the cytokine and drug target B-cell activating factor (BAFF), was associated with multiple sclerosis as well as SLE. The disease-risk allele was also associated with up-regulated humoral immunity through increased levels of soluble BAFF, B lymphocytes, and immunoglobulins. The causal variant was identified: an insertion-deletion variant, GCTGT→A (in which A is the risk allele), yielded a shorter transcript that escaped microRNA inhibition and increased production of soluble BAFF, which in turn up-regulated humoral immunity. Population genetic signatures indicated that this autoimmunity variant has been evolutionarily advantageous, most likely by augmenting resistance to malaria. A TNFSF13B variant was associated with multiple sclerosis and SLE, and its effects were clarified at the population, cellular, and molecular levels. (Funded by the Italian Foundation for Multiple Sclerosis and others.).

  3. Orbital fibroblasts of Graves' orbitopathy stimulated with proinflammatory cytokines promote B cell survival by secreting BAFF.

    Science.gov (United States)

    Tang, Fen; Chen, Xiaoqing; Mao, Yuxiang; Wan, Shangtao; Ai, Siming; Yang, Huasheng; Liu, Guangming; Zou, Yusha; Lin, Miaoli; Dan, Liang

    2017-05-05

    The success of rituximab for the treatment of active Graves' orbitopathy (GO) suggests that B cells play a critical role in intraorbital inflammation. B cell activating factor (BAFF) and its homolog a proliferation-inducing ligand (APRIL) are critical for B cell survival. However, the contribution of BAFF/APRIL to GO remains unclear. We sought to determine the role of BAFF/APRIL in the orbits of GO, and found that BAFF was markedly upregulated, while APRIL was not. Additionally, cultured GO orbital fibroblasts (GO-OFs) 2 expressing BAFF were induced to produce a large amount of BAFF. In contrast, a weak APRIL expression was detected in the OFs, and they exhibited a slight response to stimulation. Notably, pretreated GO-OFs promoted B cell survival, and this effect was significantly inhibited by a BAFF-R neutralizing antibody. This study indicates that OFs from GO can express BAFF and mediate the intraorbital survival of B cells via BAFF mechanism. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. CLINICAL VALUE OF BAFF AND APRIL CONCENTRATIONS IN SYSTEMIC LUPUS ERYTHEMATOSUS

    Directory of Open Access Journals (Sweden)

    T. A. Panafidina

    2016-01-01

    Full Text Available Systemic lupus erythematosus (SLE is characterized by the pathological activation and differentiation of B lymphocytes. The B-lymphocyte stimulator (BLyS, also known as B cell-activating factor of the tumor necrosis factor family (BAFF, and its homologue, a proliferation-inducing ligand (APRIL, belong to the ligands of the tumor necrosis factor (TNF family and play a key role in B-lymphocyte selection and survival.Objective: to determine serum BAFF and APRIL concentrations in patients with SLE and a relationship of the clinical and laboratory parameters of the disease to the level of these cytokines.Subjects and methods. The investigation enrolled 73 patients (62 women and 11 men; median age, 30.0 [28.0; 46.0] years with SLE (disease duration, 5.0 [1.5; 11.0] years and its high activity (the median SLEDAI-2K scores of 8 [2; 13].Involvement of the kidneys and joints were found in 40 and 36% of cases, respectively; there were hematologic disorders in 38%, antinuclear factor (ANF in 94.5%, and anti-double stranded DNA antibodies in 77%. The concurrent antiphospholipid syndrome was detected in 15% of the patients. 66% of the patients took glucocorticoids (GCs (the median dose was 10 [0; 15] mg/day, calculated with reference to prednisolone, 42% received cytotoxic drugs (cyclophosphamide, mycophenolate mofetil, azathioprine; 12% used biological agents (BAs; 31.5% received no therapy at enrolment in the investigation. Serum BAFF and APRIL concentrations were estimated using an enzyme immunoassay.Results and discussion. The concentrations of BAFF and APRIL did not differ essentially in the patients with SLE and in the controls: the median level of BAFF was 0.02 [0.01; 0.64] and 0.02 [0.01; 0.03] ng/ml; that of APRIL was 2.09 [0.01; 3.80] and 0.01 [0.01; 4.16] ng/ml, respectively. The elevated concentration of BAFF (>0.82 ng/ml was revealed in 5.5% of the patients with SLE and that of APRIL (>5.96 ng/ml in 4.1%. There was a positive correlation between

  5. Up-regulated BAFF and BAFF receptor expression in patients with intractable temporal lobe epilepsy and a pilocarpine-induced epilepsy rat model.

    Science.gov (United States)

    Ma, Limin; Li, Ruohan; Huang, Hao; Yuan, Jinxian; Ou, Shu; Xu, Tao; Yu, Xinyuan; Liu, Xi; Chen, Yangmei

    2017-05-01

    Some studies have suggested that BAFF and BAFFR are highly expressed in the central nervous system (CNS) and participate in inflammatory and immune associated diseases. However, whether BAFF and BAFFR are involved in the pathogenesis of epilepsy remains unknown. This study aimed to investigate the expression of BAFF and BAFFR proteins in the brains of patients with temporal lobe epilepsy (TLE) and in a pilocarpine-induced rat model of TLE to identify possible roles of the BAFF-BAFFR signaling pathway in epileptogenesis. Real-time quantitative polymerase chain reaction (RT-qPCR), western blot, immunohistochemistry, and double-immunofluorescence were performed in this study. The results showed that BAFF and BAFFR expression levels were markedly up-regulated in intractable TLE patients and TLE rats. Moreover, BAFF and BAFFR proteins mainly highly expressed in the membranes and cytoplasms of the dendritic marker MAP2 in the cortex and hippocampus. Therefore, the significant increased in BAFF and BAFFR protein expression in both TLE patients and rats suggest that BAFF and BAFFR may play important roles in regulating the pathogenesis of epilepsy. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  6. Role of BAFF in pulmonary autoantibody responses induced by chronic cigarette smoke exposure in mice

    NARCIS (Netherlands)

    Morissette, Mathieu C; Gao, Yang; Shen, Pamela; Thayaparan, Danya; Bérubé, Jean-Christophe; Paré, Peter D; Brandsma, Corry-Anke; Hao, Ke; Bossé, Yohan; Ettinger, Rachel; Herbst, Ronald; Humbles, Alison A; Kolbeck, Roland; Zhong, Nanshan; Chen, Rongchang; Stämpfli, Martin R

    2016-01-01

    Emerging evidence suggests that autoimmune processes are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). In this study, we assessed the expression of B-cell activating factor (BAFF) in smokers, and investigated the functional importance of BAFF in the induction and

  7. Role of BAFF in pediatric patients with allergic rhinitis during sublingual immunotherapy.

    Science.gov (United States)

    Luo, Renzhong; Liu, Wenlong; Wang, Jie; Chen, Yanqiu; Sun, Changzhi; Zhou, Lifeng; Li, Yan; Deng, Li

    2014-08-01

    Sublingual immunotherapy (SLIT) is the only therapeutic option for allergic rhinitis (AR) that modifies the immunological process to an allergen, rather than treating symptoms simply. However, its regulatory mechanisms are largely unknown. B-cell-activating factor of the TNF family (BAFF) plays very important roles in the development, differentiation, and proliferation of B cells and T cells. The aim of this study was to identify the role of BAFF during SLIT in pediatric patients with AR. Seventy-two house dust mite (HDM)-sensitized pediatric patients with AR were enrolled in this study. Thirty-six pediatric patients received HDM allergen extract for SLIT and 36 pediatric patients received placebo. Serum and nasal aspirate of different time points during treatment was collected and used for enzyme-linked immunosorbent assay (ELISA) of BAFF and related cytokines, respectively. Peripheral blood mononuclear cells were collected and stimulated by HDM allergen with or without rhBAFF after 12 months of treatment. Our results showed that the expression of BAFF protein decreased during the SLIT treatment compared with that in the placebo group after 6 months of therapy, and this trend lasted for 12 months. The decreased BAFF expression was positively related to Th2 cytokines and increased IL-10 expression. BAFF was also related to local production of IgA. In vitro experiments showed that BAFF can promote Th2 cytokines and inhibit IL-10 expression by PBMCs. During SLIT, BAFF expression was decreased and related to low Th2 cytokine expression and enhanced IL-10 expression. Besides, BAFF may contribute to local production of IgA. Our results suggested that BAFF may be an important biomarker during SLIT. Authors' summary. Sublingual immunotherapy (SLIT) is the only therapeutic option for allergic rhinitis (AR) that modifies the immunological process to an allergen, rather than simply treating symptoms. However, its regulatory mechanisms are largely unknown. B

  8. BAFF is involved in macrophage-induced bortezomib resistance in myeloma.

    Science.gov (United States)

    Chen, Jing; He, Donghua; Chen, Qingxiao; Guo, Xing; Yang, Li; Lin, Xuanru; Li, Yi; Wu, Wenjun; Yang, Yang; He, Jingsong; Zhang, Enfan; Yi, Qing; Cai, Zhen

    2017-11-02

    We aimed to characterize the role of B-cell activating factor (BAFF) in macrophage-mediated resistance of multiple myeloma (MM) cells to bortezomib (bort), and to further understand the molecular mechanisms involved in the process. First, we detected BAFF and its three receptors on myeloma cells and macrophages using the quantitative reverse transcriptase-polymerase chain reaction and flow cytometry. The secretion of BAFF was tested in patients with MM, MM cell lines, and macrophages. The ability of macrophages to protect MM cells from bort-induced apoptosis was significantly attenuated using BAFF-neutralizing antibody in the co-culture system or knocking down the expression of BAFF in macrophages with small interfering RNA. We also showed that the MM-macrophage interaction through BAFF and its receptors was primarily mediated by the activation of Src, Erk1/2, Akt, and nuclear factor kappa B signaling and the suppression of caspase activation induced by bort. Our data demonstrated that BAFF played a functional role in the macrophage-mediated resistance of MM cells to bort, suggesting that targeting BAFF may provide a basis for the molecular- and immune-targeted therapeutic approach.

  9. BAFF promotes autoantibody production via TACI-dependent activation of transitional B cells

    Science.gov (United States)

    Jacobs, Holly M.; Thouvenel, Christopher D.; Leach, Sarah; Arkatkar, Tanvi; Metzler, Genita; Scharping, Nicole E.; Kolhatkar, Nikita S.; Rawlings, David J.; Jackson, Shaun W.

    2016-01-01

    Mice overexpressing B cell activating factor of the TNF family (BAFF) develop systemic autoimmunity characterized by class-switched anti-nuclear antibodies. Transmembrane activator and CAML interactor (TACI) signals are critical for BAFF-mediated autoimmunity, but the B cell developmental subsets undergoing TACI-dependent activation in settings of excess BAFF remains unclear. We now report that, whereas surface TACI expression is usually limited to mature B cells, excess BAFF promotes the expansion of TACI-expressing transitional B cells. TACIhi transitional cells from BAFF-Tg mice are characterized by an activated, cycling phenotype; and the TACIhi cell subset is specifically enriched for autoreactivity, expresses activation-induced cytidine deaminase (AID) and T-bet and exhibits evidence of somatic hypermutation. Consistent with a potential contribution to BAFF-mediated humoral autoimmunity, TACIhi transitional B cells from BAFF-Tg mice spontaneously produce class-switched autoantibodies ex vivo. These combined findings highlight a novel mechanism whereby BAFF promotes humoral autoimmunity via direct, TACI-dependent activation of transitional B cells. PMID:27022196

  10. Cutting Edge: BAFF Promotes Autoantibody Production via TACI-Dependent Activation of Transitional B Cells.

    Science.gov (United States)

    Jacobs, Holly M; Thouvenel, Christopher D; Leach, Sarah; Arkatkar, Tanvi; Metzler, Genita; Scharping, Nicole E; Kolhatkar, Nikita S; Rawlings, David J; Jackson, Shaun W

    2016-05-01

    Mice overexpressing B cell activating factor of the TNF family (BAFF) develop systemic autoimmunity characterized by class-switched anti-nuclear Abs. Transmembrane activator and CAML interactor (TACI) signals are critical for BAFF-mediated autoimmunity, but the B cell developmental subsets undergoing TACI-dependent activation in settings of excess BAFF remain unclear. We report that, although surface TACI expression is usually limited to mature B cells, excess BAFF promotes the expansion of TACI-expressing transitional B cells. TACI(+) transitional cells from BAFF-transgenic mice are characterized by an activated, cycling phenotype, and the TACI(+) cell subset is specifically enriched for autoreactivity, expresses activation-induced cytidine deaminase and T-bet, and exhibits evidence of somatic hypermutation. Consistent with a potential contribution to BAFF-mediated humoral autoimmunity, TACI(+) transitional B cells from BAFF-transgenic mice spontaneously produce class-switched autoantibodies ex vivo. These combined findings highlight a novel mechanism through which BAFF promotes humoral autoimmunity via direct, TACI-dependent activation of transitional B cells. Copyright © 2016 by The American Association of Immunologists, Inc.

  11. Chicoric acid suppresses BAFF expression in B lymphocytes by inhibiting NF-κB activity.

    Science.gov (United States)

    Chen, Lingxi; Huang, Gang; Gao, Min; Shen, Xiaodong; Gong, Wei; Xu, Zhizhen; Zeng, Yijun; He, Fengtian

    2017-03-01

    B cell activating factor belonging to the TNF family (BAFF) plays a critical role in the pathogenesis of autoimmune diseases. The inhibition of BAFF expression is an emerging therapeutic approach for these disorders. Chicoric acid (CA), a bioactive phytochemical found in several widely used traditional medicinal plants, has significant anti-inflammatory activity and anti-arthritic effects. However, the role of CA in modulation of BAFF expression remains unknown. In this study, we demonstrated that CA reduced BAFF expression in human B lymphocyte cell lines and decreased the DNA-binding activity of nuclear factor-κB (NF-κB) in the BAFF promoter region. Furthermore, CA inhibited both the nuclear translocation of p65 (the subunit of NF-κB) and the phosphorylation of IκBα (inhibitor of NF-κB). These results suggest that CA suppresses BAFF expression by inhibiting NF-κB activity, and CA may serve as a novel therapeutic agent to down-regulate excessive BAFF expression in autoimmune diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. BAFF promotes regulatory T-cell apoptosis and blocks cytokine production by activating B cells in primary biliary cirrhosis

    Directory of Open Access Journals (Sweden)

    Bo Zhang

    2013-10-01

    Full Text Available Primary biliary cirrhosis (PBC is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology. A number of questions regarding its etiology are unclear. CD4+CD25+ regulatory T cells (Tregs play a critical role in self-tolerance and, for unknown reasons, their relative number is reduced in PBC patients. B-cell-activating factor (BAFF is a key survival factor during B-cell maturation and its concentration is increased in peripheral blood of PBC patients. It has been reported that activated B cells inhibit Treg cell proliferation and there are no BAFF receptors on Tregs. Therefore, we speculated that excessive BAFF may result in Treg reduction via B cells. To prove our hypothesis, we isolated Tregs and B cells from PBC and healthy donors. BAFF and IgM concentrations were then analyzed by ELISA and CD40, CD80, CD86, IL-10, and TGF-β expression in B cells and Tregs were measured by flow cytometry. BAFF up-regulated CD40, CD80, CD86, and IgM expression in B cells. However, BAFF had no direct effect on Treg cell apoptosis and cytokine secretion. Nonetheless, we observed that BAFF-activated B cells could induce Treg cell apoptosis and reduce IL-10 and TGF-β expression. We also showed that BAFF-activated CD4+ T cells had no effect on Treg apoptosis. Furthermore, we verified that bezafibrate, a hypolipidemic drug, can inhibit BAFF-induced Treg cell apoptosis. In conclusion, BAFF promotes Treg cell apoptosis and inhibits cytokine production by activating B cells in PBC patients. The results of this study suggest that inhibition of BAFF activation is a strategy for PBC treatment.

  13. BAFF promotes regulatory T-cell apoptosis and blocks cytokine production by activating B cells in primary biliary cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Bo; Hu, Mintao [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China); Zhang, Peng [Nanjing Medical University, Nanjing, Jiangsu (China); Cao, Hong [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China); Wang, Yongzhen [The Second Hospital of Nanjing, Nanjing, Jiangsu (China); Wang, Zheng; Su, Tingting [Department of Hepatology, Wuxi Infectious Diseases Hospital, Wuxi, Jiangsu (China)

    2013-05-10

    Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology. A number of questions regarding its etiology are unclear. CD4+CD25+ regulatory T cells (Tregs) play a critical role in self-tolerance and, for unknown reasons, their relative number is reduced in PBC patients. B-cell-activating factor (BAFF) is a key survival factor during B-cell maturation and its concentration is increased in peripheral blood of PBC patients. It has been reported that activated B cells inhibit Treg cell proliferation and there are no BAFF receptors on Tregs. Therefore, we speculated that excessive BAFF may result in Treg reduction via B cells. To prove our hypothesis, we isolated Tregs and B cells from PBC and healthy donors. BAFF and IgM concentrations were then analyzed by ELISA and CD40, CD80, CD86, IL-10, and TGF-β expression in B cells and Tregs were measured by flow cytometry. BAFF up-regulated CD40, CD80, CD86, and IgM expression in B cells. However, BAFF had no direct effect on Treg cell apoptosis and cytokine secretion. Nonetheless, we observed that BAFF-activated B cells could induce Treg cell apoptosis and reduce IL-10 and TGF-β expression. We also showed that BAFF-activated CD4+ T cells had no effect on Treg apoptosis. Furthermore, we verified that bezafibrate, a hypolipidemic drug, can inhibit BAFF-induced Treg cell apoptosis. In conclusion, BAFF promotes Treg cell apoptosis and inhibits cytokine production by activating B cells in PBC patients. The results of this study suggest that inhibition of BAFF activation is a strategy for PBC treatment.

  14. Transgenic overexpression of BAFF regulates the expression of immune-related genes in zebrafish, Danio rerio.

    Science.gov (United States)

    Zhang, Li; Liu, Chao; Zhou, Xin; Xie, Ying; Su, Libo; Geng, Qi; Liu, Binghui; Liu, Shufeng

    2016-12-01

    The B-cell activating factor (BAFF) is a member of tumour necrosis factor (TNF) superfamily that specifically regulates B lymphocyte proliferation and survival. Excess BAFF leads to overproduction of antibodies for secretion, anti-dsDNA antibodies and a lupus-like syndrome in mice. To investigate whether transgenic overexpression of the zebrafish BAFF leads to immunoglobulin changes and/or early maturing of the immune system, a Tol2-GFP-2A-BAFF/His recombinant plasmid was constructed by inserting a 2A peptide between the green fluorescent protein (GFP) and BAFF sequences. Functional GFP and BAFF proteins were expressed separately and confirmed in HeLa cells. The relative expression of immune-related genes (IgLC-1, IgLC-2, IgLC-3, IgD, IgM and IL-4), early lymphoid markers (Ikaros, Rag-1 and TCRAC), and the protooncogene Bcl-2 were evaluated by quantitative polymerase chain reaction (PCR) in F0 founder of transgenic zebrafish juveniles and adults. Ectopic expression of BAFF in adults was confirmed using Western blots and was shown to upregulate IgLC-1, IgLC-2, IgD, IgM, IgZ/T, Ikaros, Rag-1, TCRAC, IL-4 and Bcl-2 expression in juveniles on day 21 and IgLC-1, IgLC-2, IgD, IgM,IgZ/T, Rag-1, TCRAC and Bcl-2 expression in zebrafish three months postfertilization. The relative titers of specific IgM against Edwardsiella tarda WED were assessed using modified enzyme-linked immunosorbent assay (ELISA) with the whole body homogenate of zebrafish and demonstrated a significant increase in BAFF-transgenic group. Therefore, our findings provided novel insight into further exploration of modulating adaptive immunity and studying autoimmune diseases caused by regulating BAFF.

  15. Current and emerging treatment options for ANCA-associated vasculitis: potential role of belimumab and other BAFF/APRIL targeting agents

    Directory of Open Access Journals (Sweden)

    Lenert A

    2015-01-01

    Full Text Available Aleksander Lenert,1 Petar Lenert21Division of Rheumatology, University of Kentucky, Kentucky Clinic, Lexington, KY, USA; 2Division of Immunology, Department of Internal Medicine, The University of Iowa, Iowa City, IA, USAAbstract: Antineutrophil cytoplasmic antibody (ANCA-associated vasculitis (AAV comprises several clinical entities with diverse clinical presentations, outcomes, and nonunifying pathogenesis. AAV has a clear potential for relapses, and shows unpredictable response to treatment. Cyclophosphamide-based therapies have remained the hallmark of induction therapy protocols for more than four decades. Recently, B-cell depleting therapy with the anti-CD20 antibody rituximab has proved beneficial in AAV, leading to Food and Drug Administration approval of rituximab in combination with corticosteroids for the treatment of AAV in adults. Rituximab for ANCA-associated vasculitis and other clinical trials provided clear evidence that rituximab was not inferior to cyclophosphamide for remission induction, and rituximab appeared even more beneficial in patients with relapsing disease. This raised hopes that other B-cell-targeted therapies directed either against CD19, CD20, CD22, or B-cell survival factors, B-cell activating factor of the tumor necrosis factor family (BAFF and a proliferation-inducing ligand could also be beneficial for the management of AAV. BAFF neutralization with the fully humanized monoclonal antibody belimumab has already shown success in human systemic lupus erythematosus and, along with another anti-BAFF reagent blisibimod, is currently undergoing Phase II and III clinical trials in AAV. Local production of BAFF in granulomatous lesions and elevated levels of serum BAFF in AAV provide a rationale for BAFF-targeted therapies not only in AAV but also in other forms of vasculitis such as Behcet’s disease, large-vessel vasculitis, or cryoglobulinemic vasculitis secondary to chronic hepatitis C infection. BAFF

  16. Transgenic overexpression of BAFF regulates the expression of ...

    Indian Academy of Sciences (India)

    GFP-2A-BAFF/His recombinant plasmid was constructed by inserting a 2A peptide between the green fluorescent protein (GFP) and BAFF sequences. Functional GFP and BAFF proteins were expressed separately and confirmed in HeLa cells.

  17. Roles of TRAFs in NF-κB signaling pathways mediated by BAFF.

    Science.gov (United States)

    Tang, Xiaoyu; Zhang, Lingling; Wei, Wei

    2018-04-01

    B cell activating factor (BAFF) is an important cytokine for the maintenance of B cell development, survival and homeostasis. BAFF/BAFF-R could directly activate nuclear factor kappa B (NF-κB) pathway. Tumour necrosis factor receptor-associated factors (TRAFs) are key regulatory proteins in NF-κB signaling pathways. TRAF1 enhances the activation of tumor necrosis factor receptor 2 (TNF-R2) induced by NF-κB. TRAF2 and TRAF3 signal adapters act cooperatively to control the maturation and survival signals mediated by BAFF receptor. TRAF5 is most homologous to TRAF3, as well as most functionally similar to TRAF2. TRAF6 is also required for the BAFF-mediated activation of NF-κB signal pathway. TRAF7 is involved in signal transduction pathways that lead either to activation or repression of NF-κB transcription factor. In this article, we reviewed the roles of TRAFs in NF-κB signaling pathway mediated by BAFF. Copyright © 2018 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  18. BAFF induces spleen CD4{sup +} T cell proliferation by down-regulating phosphorylation of FOXO3A and activates cyclin D2 and D3 expression

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Fang; Chen, Rongjing [Department of Orthodontics, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai (China); Liu, Baojun [Laboratory of Lung, Inflammation and Cancers, Huashan Hospital, Fudan University, Shanghai (China); Zhang, Xiaoping [Department of Nuclear Medicine, Shanghai 10th People' s Hospital, Tongji University School of Medicine, Shanghai 200072 (China); Han, Junli; Wang, Haining [Department of General Dentistry, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai (China); Shen, Gang [Department of Orthodontics, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai (China); Tao, Jiang, E-mail: taojiang2012@yahoo.cn [Department of General Dentistry, Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai (China)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer Firstly analyze the mechanism of BAFF and anti-CD3 co-stimulation on purified mouse splenic CD4{sup +} T cells. Black-Right-Pointing-Pointer Carrying out siRNA technology to study FOXO3A protein function. Black-Right-Pointing-Pointer Helpful to understand the T cell especially CD4{sup +} T cell's role in immunological reaction. -- Abstract: The TNF ligand family member 'B cell-activating factor belonging to the TNF family' (BAFF, also called BLyS, TALL-1, zTNF-4, and THANK) is an important survival factor for B and T cells. In this study, we show that BAFF is able to induce CD4{sup +} spleen T cell proliferation when co-stimulated with anti-CD3. Expression of phosphorylated FOXO3A was notably down-regulated and cyclins D2 and D3 were up-regulated and higher in the CD4{sup +} T cells when treated with BAFF and anti-CD3, as assessed by Western blotting. Furthermore, after FOXO3A was knocked down, expression of cyclin D1 was unchanged, compared with control group levels, but the expression of cyclins D2 and D3 increased, compared with the control group. In conclusion, our results suggest that BAFF induced CD4{sup +} spleen T cell proliferation by down-regulating the phosphorylation of FOXO3A and then activating cyclin D2 and D3 expression, leading to CD4{sup +} T cell proliferation.

  19. BAFF Expression is Modulated by Female Hormones in Human Immune Cells.

    Science.gov (United States)

    Drehmer, Manuela N; Suterio, Dalila G; Muniz, Yara C N; de Souza, Iliada R; Löfgren, Sara E

    2016-10-01

    Among several autoimmune diseases, one of the main risk factors is the female gender, and much consideration has been given to the involvement of female hormones in their etiology. B-cell activating factor (BAFF) is a key factor in survival and maturation of B cells and is overexpressed in several autoimmune patients although the mechanism behind this feature is unclear. In murine models, BAFF expression could be upregulated by exogenous estrogen treatment in splenocytes; however, no evidence of this relationship was available in humans. Here, leukocytes from healthy male and female individuals were collected and cultivated in the presence or absence of estrogen or progesterone. BAFF gene expression was accessed by quantitative PCR and compared between treated and untreated group of cells. In the presence of estrogen, BAFF expression was upregulated by more than 5 times in both genders. When exposed to progesterone, the female-originated cells showed increased expression, while the cells of male origin a significant downregulation of BAFF. Our results suggest that female hormones can modulate the expression of BAFF, a key cytokine in autoimmune pathways, in human immune cells. These data might contribute to the understanding of the etiology as well as the gender bias featured by several autoimmune disorders.

  20. Enhanced anti-tumor therapeutic efficacy of DNA vaccine by fusing the E7 gene to BAFF in treating human papillomavirus-associated cancer.

    Science.gov (United States)

    Wu, Chao-Chih; Wu, Fang-Cih; Hsu, Yun-Tin; Hsiao, Yu-Chia; Yang, Yuh-Cheng; Chang, C Allen; Chang, Chih-Long

    2017-05-16

    B-cell-activating factor (BAFF) belongs to the tumor necrosis factor family that not only stimulates B and T cells but also counteracts immune tolerance. BAFF is also a type II membrane protein, which is secreted through the endoplasmic reticulum (ER)-Golgi apparatus pathway. Fusing an antigen to BAFF might enhance the presentation of major histocompatibility complex class I molecules. These characteristics represent an opportunity to enhance the antitumor effects of DNA vaccines. Therefore, we fused BAFF to human papillomavirus type 16 E7 as a DNA vaccine and evaluated its antitumor effects. We found that this vaccine increased E7-specific CD8+ T-cell immune responses, engendered major antitumor effects against E7-expressing tumors, and prolonged the survival of the immunized mice. Interestingly, vaccinating B-cell-deficient mice with BAFF-E7 revealed considerable E7-specific CD8+ T-cell immune responses, suggesting that B cells do not contribute to this immune response. Image analysis through confocal fluorescence microscopy revealed that fusing BAFF to E7 targeted the protein to the ER, but not BAFF lacking 128 N-terminal residues that generated a lower number of E7-specific CD8+ T cells in the vaccinated mice. Our data indicated that the ER-targeting characteristic of BAFF is the main factor improving the potency of DNA vaccines.

  1. VNAR single-domain antibodies specific for BAFF inhibit B cell development by molecular mimicry.

    Science.gov (United States)

    Häsler, Julien; Flajnik, Martin F; Williams, Gareth; Walsh, Frank S; Rutkowski, J Lynn

    2016-07-01

    B cell-activating factor (BAFF) plays a dominant role in the B cell homeostasis. However, excessive BAFF promotes the development of autoreactive B-cells and several antibodies have been developed to block its activity. Bispecific antibodies with added functionality represent the next wave of biologics that may be more effective in the treatment of complex autoimmune disease. The single variable domain from the immunoglobulin new antigen receptor (VNAR) is one of the smallest antibody recognition units that could be combined with monospecific antibodies to develop bispecific agents. We isolated a panel of BAFF-binding VNARs with low nM potency from a semi-synthetic phage display library and examined their functional activity. The anti-BAFF VNARs blocked the binding of BAFF to all three of its receptors (BR3, TACI and BCMA) and the presence of the conserved DXL receptor motif found in the CDR3 regions suggests molecular mimicry as the mechanism of antagonism. One clone was formatted as an Fc fusion for functional testing and it was found to inhibit both mouse and human BAFF with equal potency ex vivo in a splenocyte proliferation assay. In mice, subchronic administration reduced the number of immature and transitional intermediates B cells and mature B cell subsets. These results indicate that VNAR single domain antibodies function as selective B-cell inhibitors and offer an alternative molecular format for targeting B-cell disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Microglia-mediated BAFF-BAFFR ligation promotes neuronal survival in brain ischemia injury.

    Science.gov (United States)

    Li, Kai; Yu, Wei; Cao, Rangjuan; Zhu, Zhihua; Zhao, Guoqing

    2017-11-05

    The innate immune responses of brain to vascular occlusion are primarily orchestrated by activated microglia. However, the roles of microglia in inflammatory responses to brain ischemic injuries are controversial. Here, we report a new mechanism by which microglia confer protective effects on ischemic neuronal cells. We found that under ischemic condition, the B-cell-activating factor (BAFF) was vastly upregulated in microglia and this upregulation could at least be attributed to JAK-STAT signaling pathway activated by IFN-γ and IL-10, which were spatio-temporally enriched in I/R-injured brain as well. Meanwhile, the expression of BAFFR, one member of BAFF receptors, was also upregulated on neurons after I/R injury. More importantly, recombinant BAFF treatment not only promoted neuronal survival under ischemic stresses in vitro but also attenuated infarct volume and neural deficit caused by middle cerebral artery occlusion (MCAO) in vivo. Furthermore, blocking BAFF-BAFFR ligation with TACI-Ig abrogated these therapeutic benefits. Taken together, these results indicate that the BAFF-BAFFR ligation bridged between microglia and neurons could play a critical neuroprotective role in I/R injury. Thus, augmenting BAFF-BAFFR signaling might represent a potential target for clinical stroke therapy. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. Generation and characterization of tabalumab, a human monoclonal antibody that neutralizes both soluble and membrane-bound B-cell activating factor

    Science.gov (United States)

    Manetta, Joseph; Bina, Holly; Ryan, Paul; Fox, Niles; Witcher, Derrick R; Kikly, Kristine

    2014-01-01

    B-cell activating factor (BAFF) is a B-cell survival factor with a key role in B-cell homeostasis and tolerance. Dysregulated BAFF expression may contribute to autoimmune diseases or B-cell malignancies via effects on abnormal B-lymphocyte activation, proliferation, survival, and immunoglobulin secretion. Monoclonal antibodies were generated against human BAFF, characterized for species specificity and affinity, and screened for the ability to neutralize both membrane-bound and soluble BAFF. In addition, studies were undertaken to determine the relative potency of membrane-bound and soluble BAFF. Tabalumab has a high affinity for human, cynomolgus monkey, and rabbit BAFF. No binding to mouse BAFF was detected. Tabalumab was able to neutralize soluble human, cynomolgus monkey, or rabbit BAFF with equal potency. Our data demonstrate that membrane-bound BAFF can be a more potent stimulus for B-cells than soluble BAFF, and tabalumab also neutralized membrane-bound BAFF. Tabalumab prevented BAFF from binding to BAFF receptors and demonstrated pharmacodynamic effects in human BAFF transgenic mice. Tabalumab is a high-affinity human antibody with neutralizing activity against membrane-bound and soluble BAFF. Given our findings that membrane-bound BAFF can have greater in vitro potency than soluble BAFF, neutralization of both forms of BAFF is likely to be important for optimal therapeutic effect. PMID:25258549

  4. Generation and characterization of tabalumab, a human monoclonal antibody that neutralizes both soluble and membrane-bound B-cell activating factor.

    Science.gov (United States)

    Manetta, Joseph; Bina, Holly; Ryan, Paul; Fox, Niles; Witcher, Derrick R; Kikly, Kristine

    2014-01-01

    B-cell activating factor (BAFF) is a B-cell survival factor with a key role in B-cell homeostasis and tolerance. Dysregulated BAFF expression may contribute to autoimmune diseases or B-cell malignancies via effects on abnormal B-lymphocyte activation, proliferation, survival, and immunoglobulin secretion. Monoclonal antibodies were generated against human BAFF, characterized for species specificity and affinity, and screened for the ability to neutralize both membrane-bound and soluble BAFF. In addition, studies were undertaken to determine the relative potency of membrane-bound and soluble BAFF. Tabalumab has a high affinity for human, cynomolgus monkey, and rabbit BAFF. No binding to mouse BAFF was detected. Tabalumab was able to neutralize soluble human, cynomolgus monkey, or rabbit BAFF with equal potency. Our data demonstrate that membrane-bound BAFF can be a more potent stimulus for B-cells than soluble BAFF, and tabalumab also neutralized membrane-bound BAFF. Tabalumab prevented BAFF from binding to BAFF receptors and demonstrated pharmacodynamic effects in human BAFF transgenic mice. Tabalumab is a high-affinity human antibody with neutralizing activity against membrane-bound and soluble BAFF. Given our findings that membrane-bound BAFF can have greater in vitro potency than soluble BAFF, neutralization of both forms of BAFF is likely to be important for optimal therapeutic effect.

  5. ΔBAFF, an Alternate Splice Isoform That Regulates Receptor Binding and Biopresentation of the B Cell Survival Cytokine, BAFF*

    OpenAIRE

    Gavin, Amanda L; Aït-Azzouzene, Djemel; Ware, Carl F.; Nemazee, David

    2003-01-01

    The tumor necrosis family member BAFF is limiting for the survival of follicular B lymphocytes, but excessive BAFF signaling can lead to autoimmunity, suggesting that its activity must be tightly regulated. We have identified a conserved alternate splice isoform of BAFF, called ΔBAFF, which lacks 57 nt encoding the A–A1 loop and is co-expressed with BAFF in many mouse and human myeloid cells. Mouse ΔBAFF appears on the plasma membrane, but unlike BAFF it is inefficiently released by proteolys...

  6. Renal tubular epithelial cell-derived BAFF expression mediates kidney damage and correlates with activity of proliferative lupus nephritis in mouse and men.

    Science.gov (United States)

    Schwarting, A; Relle, M; Meineck, M; Föhr, B; Triantafyllias, K; Weinmann, A; Roth, W; Weinmann-Menke, J

    2018-02-01

    B-cell activating factor of the tumour necrosis factor family (BAFF) is a cytokine, mainly produced by hematopoietic cells (e.g. monocytes/macrophages, dendritic cells), indispensable for B-cell maturation. The BLISS studies have demonstrated that blocking BAFF by the human monoclonal antibody belimumab is a valuable therapeutic approach in patients with clinically and serologically active systemic lupus erythematosus (SLE). However, the defined sources of BAFF, which contributes to SLE, are still unclear. Recent findings show that BAFF expression is not restricted to myeloid cells. Since lupus nephritis is the main cause of morbidity and mortality for SLE patients, the aim of this study was to investigate whether renal tubular epithelial cells (TEC) are an important source of BAFF and thus may contribute to the pathogenesis and progression of SLE. We found BAFF expression both in cultured murine and human TEC. These results could be verified with in situ data from the kidney. Moreover, BAFF expression in the kidneys of lupus-prone MRL- Fas lpr mice correlated with disease activity, and BAFF expression on TEC in biopsies of patients with diffuse proliferative lupus nephritis showed a correlation with the histopathological activity index. In vitro functional assays revealed an autocrine loop of BAFF with its binding receptors on TEC, resulting in a strong induction of colony stimulating factor-1. Finally, we identified divergent effects of BAFF on TEC depending on the surrounding milieu ('inflammatory versus non-inflammatory'). Taken together, our findings indicate that renal-derived BAFF may play an important role in the pathophysiology of the systemic autoimmune disease SLE.

  7. SYK inhibition thwarts the BAFF - B-cell receptor crosstalk and thereby antagonizes Mcl-1 in chronic lymphocytic leukemia.

    Science.gov (United States)

    Paiva, Cody; Rowland, Taylor A; Sreekantham, Bhargava; Godbersen, Claire; Best, Scott R; Kaur, Prabhjot; Loriaux, Marc M; Spurgeon, Stephen E F; Danilova, Olga V; Danilov, Alexey V

    2017-11-01

    Although small molecule inhibitors of B-cell receptor-associated kinases have revolutionized therapy in chronic lymphocytic leukemia (CLL), responses are incomplete. Pro-survival signaling emanating from the microenvironment may foster therapeutic resistance of the malignant B cells resident in the protective lymphoid niches. B-cell activating factor (BAFF) is critical to the survival of both healthy and neoplastic B cells. However, the pro-survival pathways triggered by BAFF have not been fully characterized. Here we show that BAFF elicited resistance to spontaneous and drug-induced apoptosis in stromal co-cultures, induced activation of both canonical and non-canonical NFκB signaling pathways, and triggered B-cell receptor signaling in CLL cells, independently of IGHV mutational status. SYK, a proximal kinase in the B-cell receptor signaling cascade, acted via STAT3 to bolster transcription of the anti-apoptotic protein Mcl-1, thereby contributing to apoptosis resistance in BAFF-stimulated cells. SYK inhibitor entospletinib downregulated Mcl-1, abrogating BAFF-mediated cell survival. BAFF-B-cell receptor crosstalk in neoplastic B cells was mediated by SYK interaction with TRAF2/TRAF3 complex. Thus, SYK inhibition is a promising therapeutic strategy uniquely poised to antagonize crosstalk between BAFF and B-cell receptor, thereby disrupting the pro-survival microenvironment signaling in chronic lymphocytic leukemia. Copyright© Ferrata Storti Foundation.

  8. A BAFF receptor His159Tyr mutation in Sjögren's syndrome-related lymphoproliferation.

    Science.gov (United States)

    Papageorgiou, Aristea; Mavragani, Clio P; Nezos, Andrianos; Zintzaras, Elias; Quartuccio, Luca; De Vita, Salvatore; Koutsilieris, Michael; Tzioufas, Athanasios G; Moutsopoulos, Haralampos M; Voulgarelis, Michael

    2015-10-01

    To study the prevalence, clinical associations, and functional implications of the His159Tyr mutation of the BAFF receptor (BAFF-R) in patients with Sjögren's syndrome (SS). The BAFF-R His159Tyr mutation was evaluated using polymerase chain reaction (PCR)-based assays in 247 patients with SS (of whom 70 had SS complicated by lymphoma [SS-lymphoma]), 145 with systemic lupus erythematosus (SLE), and 101 with rheumatoid arthritis (RA), as well as 180 healthy controls. Real-time PCR and Western blotting were performed for the quantification of both NF-κB1 and NF-κB2 messenger RNA (mRNA) transcript and protein levels in isolated B cells from patients with SS-lymphoma carrying the mutation (SS-lymphoma-BAFF-RHis159Tyr -derived B cells) compared to B cells from patients with SS-lymphoma who were not carriers of the mutation and healthy controls. Both the SS-lymphoma and SS-nonlymphoma patient subgroups exhibited significantly higher frequencies of the His159Tyr BAFF-R mutation compared to healthy controls (8.6% of SS-lymphoma patients and 6.2% of SS-nonlymphoma patients versus 1.7% of healthy controls; P = 0.02 and P = 0.04, respectively). The corresponding frequencies of the His159Tyr BAFF-R mutation in SLE and RA patients were 3.5% and 3%, respectively. Of interest, 71.4% of the SS patients with mucosa-associated lymphoid tissue (MALT) lymphoma who were between the ages of 31 and 40 years at disease onset were mutation carriers. The generalized odds ratio for the development of SS-related MALT lymphoma in the younger age at onset (age BAFF-R mutation was 6.1 (95% confidence interval 2.0-18.7) (P BAFF-RHis159Tyr -derived B cells. This study identifies an increased prevalence of the BAFF-R His159Tyr mutation in patients with SS, particularly in those with SS complicated by MALT lymphoma whose disease onset occurred at a younger age. BAFF-RHis159Tyr -mediated activation of the alternate NF-κB pathway might contribute to the pathogenesis of SS

  9. Development of a Novel BAFF Responsive Cell Line Suitable for Detecting Bioactive BAFF and Neutralizing Antibodies against BAFF-Pathway Inhibiting Therapeutics

    OpenAIRE

    Hu, Jenny; Yu, Yanbin; Han, Hong; Civoli, Francesca; Zhuang, Yao; Thomas, John; Swanson, Steve; Jing, Shuqian; Gupta, Shalini

    2014-01-01

    BAFF has a critical role in B-cell survival, maturation and function, which makes its pathway a prime therapeutic target for various autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis and Sjögren’s syndrome. A cell-based assay that measures the functional activity of BAFF is required for many high throughput purposes, such as lead target screening and BAFF quantification. We report here the development of a sensitive BAFF responsive cell line via stable tra...

  10. Vibration Induces BAFF Overexpression and Aberrant O-Glycosylation of IgA1 in Cultured Human Tonsillar Mononuclear Cells in IgA Nephropathy

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    Muyao Ye

    2016-01-01

    Full Text Available Objective. To investigate the influence of in vitro vibratory stimulation of human tonsillar mononuclear cells (TMCs. Methods. Fourteen IgA nephropathy (IgAN patients with chronic tonsillitis (CT and 12 CT patients with no renal pathology were enrolled. Group A TMCs were collected after 24 hours of culture and used to determine baseline levels. TMCs in groups B, C, D, E, and F were exposed to vibratory stimulation (60 Hz for 0 (as the control group, 1, 3, 5, and 10 minutes, respectively. Results. Baseline concentrations of B-cell-activation factor (BAFF and IgA1, BAFF mRNA expression, and aberrant O-glycosylation IgA1 level were higher in the IgAN group as compared to that in the CT group, and all increased after vibratory stimulation. Baseline mRNA expressions of core β1,3-galactosyltransferase (C1GALT1 and core β1,3GalT-specific molecular chaperone (Cosmc were lower in the IgAN group; the levels decreased further after vibratory stimulation. Conclusion. In patients with IgAN, vibratory stimulation of TMCs appears to induce IgA1 secretion through activation of BAFF release and to aberrant O-glycosylation IgA1 by suppressing C1GALT1 and Cosmc expression. In vitro vibratory stimulation of human TMCs mimics the vibratory simulation of palatine tonsils produced by vocal cords during phonation.

  11. Increase of Intracellular BAFF in B Cells of Sjögren’s Patients Is Not Affected by Decrease of BAFFR

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    Jan Krejsek

    2015-07-01

    Full Text Available The presence of a broad spectrum of autoantibodies in Sjögren’s syndrome (SjS patients is the result of abnormal B-cell regulation that can be at least partially explained by abnormal BAFF/BAFFR regulation. The objective of this study was to determine both membrane and intracellular expression of BAFF/BAFFR in monocytes and B-cells in peripheral blood of 19 primary Sjögren’s syndrome patients and 20 healthy controls using flow cytometry. We also measured sBAFF in serum. Compared to healthy controls, both surface and intracellular expression of BAFF was significantly increased in monocytes and B-cells of SjS patients. Also serum sBAFF level was elevated. Expression of BAFFR on B-cells of SjS patients was surprisingly decreased, but there was no clear increase or decrease within monocytes. Our results indicate that activated monocytes communicate with B-cells via BAFF and BAFFR, so that B-cells are stimulated, but BAFF is also produced to stimulate cells in autocrine way. The decrease of BAFFR expression in SjS patients suggests that there is the mechanism that attempts to take over in order to balance the high level of BAFF.

  12. Reduced Number of Transitional and Naive B Cells in Addition to Decreased BAFF Levels in Response to the T Cell Independent Immunogen Pneumovax®23.

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    Alena Roth

    Full Text Available Protective immunity against T cell independent (TI antigens such as Streptococcus pneumoniae is characterized by antibody production of B cells induced by the combined activation of T cell independent type 1 and type 2 antigens in the absence of direct T cell help. In mice, the main players in TI immune responses have been well defined as marginal zone (MZ B cells and B-1 cells. However, the existence of human equivalents to these B cell subsets and the nature of the human B cell compartment involved in the immune reaction remain elusive. We therefore analyzed the effect of a TI antigen on the B cell compartment through immunization of healthy individuals with the pneumococcal polysaccharide (PnPS-based vaccine Pneumovax®23, and subsequent characterization of B cell subpopulations. Our data demonstrates a transient decrease of transitional and naïve B cells, with a concomitant increase of IgA+ but not IgM+ or IgG+ memory B cells and a predominant generation of PnPS-specific IgA+ producing plasma cells. No alterations could be detected in T cells, or proposed human B-1 and MZ B cell equivalents. Consistent with the idea of a TI immune response, antigen-specific memory responses could not be observed. Finally, BAFF, which is supposed to drive class switching to IgA, was unexpectedly found to be decreased in serum in response to Pneumovax®23. Our results demonstrate that a characteristic TI response induced by Pneumovax®23 is associated with distinct phenotypical and functional changes within the B cell compartment. Those modulations occur in the absence of any modulations of T cells and without the development of a specific memory response.

  13. BAFF regulates activation of self-reactive T cells through B-cell dependent mechanisms and mediates protection in NOD mice.

    Science.gov (United States)

    Mariño, Eliana; Walters, Stacey N; Villanueva, Jeanette E; Richards, James L; Mackay, Charles R; Grey, Shane T

    2014-04-01

    Targeting the BAFF/APRIL system has shown to be effective in preventing T-cell dependent autoimmune disease in the NOD mouse, a spontaneous model of type 1 diabetes. In this study we generated BAFF-deficient NOD mice to examine how BAFF availability would influence T-cell responses in vivo and the development of spontaneous diabetes. BAFF-deficient NOD mice which lack mature B cells, were protected from diabetes and showed delayed rejection of an allogeneic islet graft. Diabetes protection correlated with a failure to expand pathogenic IGRP-reactive CD8(+) T cells, which were maintained in the periphery at correspondingly low levels. Adoptive transfer of IGRP-reactive CD8(+) T cells with B cells into BAFF-deficient NOD mice enhanced IGRP-reactive CD8(+) T-cell expansion. Furthermore, when provoked with cyclophosphamide, or transferred to a secondary lymphopenic host, the latent pool of self-reactive T cells resident in BAFF-deficient NOD mice could elicit beta cell destruction. We conclude that lack of BAFF prevents the procurement of B-cell-dependent help necessary for the emergence of destructive diabetes. Indeed, treatment of NOD mice with the BAFF-blocking compound, BR3-Fc, resulted in a delayed onset and reduced incidence of diabetes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. CP-25 attenuates the inflammatory response of fibroblast-like synoviocytes co-cultured with BAFF-activated CD4(+) T cells.

    Science.gov (United States)

    Jia, Xiaoyi; Wei, Fang; Sun, Xiaojing; Chang, Yan; Xu, Shu; Yang, Xuezhi; Wang, Chun; Wei, Wei

    2016-08-02

    Total glucosides of paeony (TGP) is the first anti-inflammatory immune regulatory drug approved for the treatment of rheumatoid arthritis in China. A novel compound, paeoniflorin-6'-O-benzene sulfonate (code CP-25), comes from the structural modification of paeoniflorin (Pae), which is the effective active ingredient of TGP. The aim of the present study is to investigate the effect of CP-25 on adjuvant arthritis (AA) fibroblast-like synoviocytes (FLS) co-cultured with BAFF-activated CD4(+) T cells and the expression of BAFF-R in CD4(+) T cells. The mRNA expression of BAFF and its receptors was assessed by qPCR. The expression of BAFF receptors in CD4(+) T cells was analyzed by flow cytometry. The effect of CP-25 on AA rats was evaluated by their joint histopathology. The cell culture growth of thymocytes and FLS was detected by cell counting kit (CCK-8). The concentrations of IL-1β, TNF-α, and IL-6 were measured by Enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of BAFF and BAFF-R were enhanced in the mesenteric lymph nodes of AA rats, TACI expression was reduced, and BCMA had no change. The expression of BAFF-R in CD4(+) T cells was also enhanced. CP-25 alleviated the joint histopathology and decreased the expression of BAFF-R in CD4(+) T cells from AA rats in vivo. In vitro, CP-25 inhibited the abnormal cell culture growth of BAFF-stimulated thymocytes and FLS. In the co-culture system, IL-1β, IL-6 and TNF-α production was enhanced by FLS co-cultured with BAFF-activated CD4(+) T cells. Moreover, BAFF-stimulated CD4(+) T cells promoted the cell culture growth of FLS. The addition of CP-25 decreased the expression of BAFF-R in CD4(+) T cells and inhibited the cell culture growth and cytokine secretion ability of FLS co-cultured with BAFF-activated CD4(+) T cells. The present study indicates that CP-25 may repress the cell culture growth and cytokine secretion ability of FLS, and its inhibitory effects might be associated with its ability

  15. MiR-30a-3p negatively regulates BAFF synthesis in systemic sclerosis and rheumatoid arthritis fibroblasts.

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    Ghada Alsaleh

    Full Text Available We evaluated micro (mi RNA-mediated regulation of BAFF expression in fibroblasts using two concomitant models: (i synovial fibroblasts (FLS isolated from healthy controls (N or Rheumatoid Arthritis (RA patients; (ii human dermal fibroblasts (HDF isolated from healthy controls (N or Systemic Sclerosis (SSc patients. Using RT-qPCR and ELISA, we first showed that SScHDF synthesized and released BAFF in response to Poly(I:C or IFN-γ treatment, as previously observed in RAFLS, whereas NHDF released BAFF preferentially in response to IFN-γ. Next, we demonstrated that miR-30a-3p expression was down regulated in RAFLS and SScHDF stimulated with Poly(I:C or IFN-γ. Moreover, we demonstrated that transfecting miR-30a-3p mimic in Poly(I:C- and IFN-γ-activated RAFLS and SScHDF showed a strong decrease on BAFF synthesis and release and thus B cells survival in our model. Interestingly, FLS and HDF isolated from healthy subjects express higher levels of miR-30a-3p and lower levels of BAFF than RAFLS and SScHDF. Transfection of miR-30a-3p antisense in Poly(I:C- and IFN-γ-activated NFLS and NHDF upregulated BAFF secretion, confirming that this microRNA is a basal repressors of BAFF expression in cells from healthy donors. Our data suggest a critical role of miR-30a-3p in the regulation of BAFF expression, which could have a major impact in the regulation of the autoimmune responses occurring in RA and SSc.

  16. Context-Specific BAFF-R Signaling by the NF-κB and PI3K Pathways

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    Julia Jellusova

    2013-11-01

    Full Text Available BAFF is a soluble factor required for B cell maturation and survival. BAFF-R signals via the noncanonical NF-κB pathway regulated by the TRAF3/NIK/IKK1 axis. We show that deletion of Ikk1 during early B cell development causes a partial impairment in B cell maturation and BAFF-dependent survival, but inactivation of Ikk1 in mature B cells does not affect survival. We further show that BAFF-R employs CD19 to promote survival via phosphatidylinositol 3-kinase (PI3K, and that coinactivation of Cd19 and Ikk1 causes a profound block in B cell maturation at the transitional stage. Consistent with a role for PI3K in BAFF-R function, inactivation of PTEN mediates a partial rescue of B cell maturation and function in Baff−/− animals. Elevated PI3K signaling also circumvents BAFF-dependent survival in a spontaneous B cell lymphoma model. These findings indicate that the combined activities of PI3K and IKK1 drive peripheral B cell differentiation and survival in a context-dependent manner.

  17. Context-specific BAFF-R signaling by the NF-κB and PI3K pathways

    Science.gov (United States)

    Jellusova, Julia; Miletic, Ana V.; Cato, Matthew H.; Lin, Wai-Wai; Hu, Yinling; Bishop, Gail A.; Shlomchik, Mark J.; Rickert, Robert C.

    2014-01-01

    Summary BAFF is a soluble factor required for B cell maturation and survival. BAFF-R signals via the non-canonical NF-κB pathway regulated by the TRAF3/NIK/IKK1 axis. We show that deletion of Ikk1 during early B cell development causes a partial impairment in B cell maturation and BAFF-dependent survival, but inactivation of Ikk1 in mature B cells does not affect survival. We further show that BAFF-R employs CD19 to promote survival via PI3K, and that co-inactivation of Cd19 and Ikk1 causes a profound block in B cell maturation at the transitional stage. Consistent with a role for PI3K in BAFF-R function, inactivation of PTEN mediates a partial rescue of B cell maturation and function in Baff−/− animals. Elevated PI3K signaling also circumvents BAFF-dependent survival in a spontaneous B cell lymphoma model. These findings indicate that the combined activities of PI3K and IKK1 drive peripheral B cell differentiation and survival in a context-dependent manner. PMID:24239354

  18. BAFF promotes Th17 cells and aggravates experimental autoimmune encephalomyelitis.

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    Xiaohui Zhou

    Full Text Available BAFF, in addition to promoting B cell survival and differentiation, may affect T cells. The objective of this study was to determine the effect of BAFF on Th17 cell generation and its ramifications for the Th17 cell-driven disease, EAE.Th17 cells were increased in BAFF-Tg B6 (B6.BTg mice and decreased in B6.Baff(-/- mice. Th17 cells in B6.Baff(-/- mice bearing a BAFF Tg (B6.Baff(-/-.BTg mice were identical to those in B6.BTg mice, indicating that membrane BAFF is dispensable for Th17 cell generation as long as soluble BAFF is plentiful. In T + non-T cell criss-cross co-cultures, Th17 cell generation was greatest in cultures containing B6.BTg T cells and lowest in cultures containing B6.Baff(-/- T cells, regardless of the source of non-T cells. In cultures containing only T cells, Th17 cell generation followed an identical pattern. CD4(+ cell expression of CD126 (IL-6R α chain was increased in B6.BTg mice and decreased in B6.Baff(-/- mice, and activation of STAT3 following stimulation with IL-6 + TGF-β was also greatest in B6.BTg cells and lowest in B6.Baff(-/- cells. EAE was clinically and pathologically most severe in B6.BTg mice and least severe in B6.Baff(-/- mice and correlated with MOG(35-55 peptide-induced Th17 cell responses.Collectively, these findings document a contribution of BAFF to pathogenic Th17 cell responses and suggest that BAFF antagonism may be efficacious in Th17 cell-driven diseases.

  19. Precursor B Cells Increase in the Lung during Airway Allergic Inflammation: A Role for B Cell-Activating Factor.

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    Konstantinos Samitas

    Full Text Available B cells, key cells in allergic inflammation, differentiate in the bone marrow and their precursors include pro-B, pre-B and immature B cells. Eosinophil progenitor cells increase in the lung after allergen exposure. However, the existence and possible role of B cell precursors in the lung during allergic inflammation remains elusive.A BALB/c mouse model of allergic airway inflammation was utilized to perform phenotypic and quantification analyses of pro-B and pre-B cells in the lung by flow cytometry. B cell maturation factors IL-7 and B cell-activating factor (BAFF and their receptors (CD127 and BAFFR, BCMA, TACI, respectively were also evaluated in the lung and serum. The effect of anti-BAFF treatment was investigated both in vivo (i.p. administration of BAFF-R-Ig fusion protein and in vitro (colony forming cell assay. Finally, BAFF levels were examined in the bronchoalveolar lavage (BAL of asthmatic patients and healthy controls.Precursor pro and pre-B cells increase in the lung after allergen exposure, proliferate in the lung tissue in vivo, express markers of chemotaxis (CCR10 and CXCR4 and co-stimulation (CD40, CD86 and are resistant to apoptosis (Bax. Precursor B cells express receptors for BAFF at baseline, while after allergen challenge both their ligand BAFF and the BCMA receptor expression increases in B cell precursors. Blocking BAFFR in the lung in vivo decreases eosinophils and proliferating precursor B cells. Blocking BAFFR in bone marrow cultures in vitro reduces pre-B colony formation units. BAFF is increased in the BAL of severe asthmatics.Our data support the concept of a BAFF-mediated role for B cell precursors in allergic airway inflammation.

  20. The BAFF receptor TACI controls IL-10 production by regulatory B cells and CLL B cells

    Science.gov (United States)

    Saulep-Easton, Damien; Vincent, Fabien B.; Quah, Pin Shie; Wei, Andrew; Ting, Stephen B.; Croce, Carlo M.; Tam, Constantine; Mackay, Fabienne

    2015-01-01

    Interleukin (IL)-10-producing B cells (B10 cells) have emerged as important regulatory players with immunosuppressive roles. Chronic lymphocytic leukemia (CLL) B cells also secrete IL-10 and share features of B10 cells, suggesting a possible contribution of CLL B cells to immunosuppression in CLL patients. Factors controlling the emergence of B10 cells are not known. B cell-activating factor of the tumour necrosis factor (TNF) family (BAFF) is critical for B cell maturation and survival, and is implicated in the development and progression of CLL. We sought to investigate the role of BAFF in the emergence of IL-10-producing B regulatory cells in healthy donors and CLL patients. Here, we report that BAFF signaling promotes IL-10 production by CLL B cells in a mouse model of CLL and in CLL patients. Moreover, BAFF-mediated IL-10 production by normal and CLL B cells is mediated via its receptor TACI. Our work uncovered a major targetable pathway important for the generation of regulatory B cells that is detrimental to immunity in CLL. PMID:26139429

  1. Transcriptional and post-transcriptional mechanisms of BAFF-receptor dysregulation in human B lineage malignancies

    OpenAIRE

    Mihalcik, Stephen A; Tschumper, Renee C; Jelinek, Diane F

    2010-01-01

    Together, circulating BAFF and dominant receptor BAFF-R homeostatically regulate the humoral immune system. Consistently aberrant BAFF-R expression in leukemic cells reveals an intimate connection of these cells' malignant physiology to the BAFF/BAFF-R axis and also provides an additional survival mechanism to the expressing cells. In this study, we used primary cells and cell lines to interrogate the mechanisms underlying aberrant BAFF-R expression in precursor B acute lymphoblastic leukemia...

  2. Generation and characterization of tabalumab, a human monoclonal antibody that neutralizes both soluble and membrane-bound B-cell activating factor

    Directory of Open Access Journals (Sweden)

    Manetta J

    2014-08-01

    Full Text Available Joseph Manetta, Holly Bina, Paul Ryan, Niles Fox, Derrick R Witcher, Kristine Kikly Biotechnology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA Abstract: B-cell activating factor (BAFF is a B-cell survival factor with a key role in B-cell homeostasis and tolerance. Dysregulated BAFF expression may contribute to autoimmune diseases or B-cell malignancies via effects on abnormal B-lymphocyte activation, proliferation, survival, and immunoglobulin secretion. Monoclonal antibodies were generated against human BAFF, characterized for species specificity and affinity, and screened for the ability to neutralize both membrane-bound and soluble BAFF. In addition, studies were undertaken to determine the relative potency of membrane-bound and soluble BAFF. Tabalumab has a high affinity for human, cynomolgus monkey, and rabbit BAFF. No binding to mouse BAFF was detected. Tabalumab was able to neutralize soluble human, cynomolgus monkey, or rabbit BAFF with equal potency. Our data demonstrate that membrane-bound BAFF can be a more potent stimulus for B-cells than soluble BAFF, and tabalumab also neutralized membrane-bound BAFF. Tabalumab prevented BAFF from binding to BAFF receptors and demonstrated pharmacodynamic effects in human BAFF transgenic mice. Tabalumab is a high-affinity human antibody with neutralizing activity against membrane-bound and soluble BAFF. Given our findings that membrane-bound BAFF can have greater in vitro potency than soluble BAFF, neutralization of both forms of BAFF is likely to be important for optimal therapeutic effect. Keywords: autoimmunity, B-cell malignancies, B-cell survival factor, BAFF

  3. Reduction of CD19 autoimmunity marker on B cells of paediatric SLE patients through repressing PU.1/TNF-α/BAFF axis pathway by miR-155.

    Science.gov (United States)

    Aboelenein, H R; Hamza, M T; Marzouk, H; Youness, R A; Rahmoon, M; Salah, S; Abdelaziz, A I

    2017-06-01

    microRNA-155 (miR-155) is implicated in regulating B-cell activation and survival that is important in systemic lupus erythematosus (SLE) pathogenesis. PU.1, a target for miR-155, is a crucial regulator of B-cell development and enhances Tumour-Necrosis-factor-alpha (TNF-α) expression. TNF-α induces the expression of B-cell-activating-factor (BAFF). BAFF is reported to increase the expression of the autoimmunity marker; CD19. This study aimed to investigate the regulation of expression of PU.1 in pediatric-systemic-lupus-erythematosus (pSLE) patients by miR-155, and hence evaluate its impact on TNF-α/BAFF/CD19 signalling pathway. Screening revealed that PU.1 is upregulated in PBMCs and B-cells of pSLE patients. PU.1 expression directly correlated with systemic-lupus-erythematosus disease-activity-index-2 K SLEDAI-2K. Ectopic expression of miR-155 and knockdown of PU.1 suppressed PU.1, TNF-α and BAFF. Finally, miR-155 decreased the proportion of BAFF-expressing-B-cells and CD19 protein expression. These findings suggest that miR-155 suppresses autoimmunity through transcriptional repression of PU.1 and TNF-α, which in turn suppresses BAFF and CD19 protein expression.

  4. Increased Serum B Cell Activating Factor and a Proliferation-inducing Ligand Are Associated with Interstitial Lung Disease in Patients with Juvenile Dermatomyositis.

    Science.gov (United States)

    Kobayashi, Norimoto; Kobayashi, Ichiro; Mori, Masaaki; Sato, Shinji; Iwata, Naomi; Shigemura, Tomonari; Agematsu, Kazunaga; Yokota, Shumpei; Koike, Kenichi

    2015-12-01

    Rapidly progressive interstitial lung disease (RP-ILD) is an intractable and fatal complication of juvenile dermatomyositis (JDM). This study evaluated serum levels of B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in JDM patients with complicating ILD, and their association with ILD phenotypes, clinical variables, and anti-melanoma differentiation-associated gene 5 (MDA5). We measured the levels of BAFF, APRIL, and anti-MDA5 in the sera of 23 JDM patients with ILD [8 in the RP-ILD group and 15 in the chronic ILD (C-ILD) group], 17 JDM patients without ILD (non-ILD group), and 10 age-matched controls, using the ELISA method. ILD was identified by high-resolution computed tomography. Serum BAFF titers were significantly higher in the JDM patients with RP-ILD versus those with C-ILD (p = 0.011) and in healthy controls (p = 0.0004). The C-ILD group had significantly higher levels of BAFF versus controls (p ≤ 0.0001). Serum APRIL was markedly elevated in the RP-ILD group as compared with the C-ILD group (p = 0.003) and controls (p = 0.006). In patients with ILD, both BAFF and APRIL levels were correlated with serum Krebs von den Lungen-6 and interleukin 18. Subjects with high titer anti-MDA5 (> 200 U) had higher levels of BAFF and APRIL than those with low titer anti-MDA5 (< 100 U; p = 0.019 and p = 0.0029, respectively), which may have been due to a relationship between RP-ILD and high anti-MDA5 titer. Our findings of markedly elevated levels of BAFF and APRIL in patients with RP-ILD JDM suggest the potential importance of these cytokines in the diagnosis and treatment of RP-ILD accompanying JDM.

  5. Data for the crystal structure of APRIL–BAFF–BAFF heterotrimer

    Directory of Open Access Journals (Sweden)

    Klaus Maskos

    2016-03-01

    Full Text Available The TNF family ligands B cell activation factor (BAFF and a proliferation-inducing ligand (APRIL modulate B cell function by forming homotrimers and heterotrimers. To determine the structure of a heterotrimer of BAFF and APRIL, these ligands were expressed as a single chain protein in HEK 293 cells, purified by affinity and size exclusion chromatographies, and crystallized. Crystals belonging to the orthorhombic crystal system with a space group of C2221 diffracted to 2.43 Å. Initial structural solution was obtained by the molecular replacement method, and the structure was further refined to an R factor of 0.179 and free R factor of 0.234. The atomic coordinates and structure factors have been deposited into the Protein Data Bank (accession code 4ZCH.

  6. The Unknown Aspect of BAFF: Inducing IL-35 Production by a CD5+CD1dhiFcγRIIbhiRegulatory B-Cell Subset in Lupus.

    Science.gov (United States)

    Zhang, Yamin; Li, Jun; Zhou, Nuoya; Zhang, Yi; Wu, Min; Xu, Jian; Shen, Chen; An, Xiangjie; Shen, Guanxin; Yang, Ming; Zhang, Chun; Tao, Juan

    2017-12-01

    IL-35 is a critical immunosuppressive cytokine that plays an important role in various autoimmune diseases. The purpose of this study was to determine whether BAFF, a key pathogenic factor in systemic lupus erythematosus, also a dichotomous regulator for B-cell immune responses, has an effect on IL-35-producing regulatory B cells and their underlying mechanisms in lupus. We found that exogenous BAFF could induce IL-35 production by splenic B cells from MRL-Fas lpr/lpr mice. BAFF-induced IL-35-producing B cells were mainly from the marginal zone B-cell subset and exhibited a CD5 + CD1d hi FcγRIIb hi phenotype. These IL-35-producing regulatory B-cell subsets exhibited regulatory effects on both CD4 + CD25 - T cells and CD4 + CD25 + regulatory T cells. We further identified that BAFF-TACI interaction could induce the production of IL-35 through the classical NF-κB1 pathway. In vivo study also showed that BAFF could facilitate IL-35 secretion in marginal zone B cells, whereas anti-BAFF treatment could decrease the frequency of IL-35-producing CD5 + CD1d hi FcγRIIb hi B cells in MRL-Fas lpr/lpr mice. We showed that BAFF could induce IL-35 production by a unique CD5 + CD1d hi FcγRIIb hi regulatory B-cell subset mainly through TACI activation in lupus, providing an advanced understanding of the regulatory effect of BAFF in autoimmune diseases. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. The interplay of IL-21 and BAFF in the formation and maintenance of human B cell memory

    Directory of Open Access Journals (Sweden)

    Jodi eKarnell

    2012-01-01

    Full Text Available To date, IL-21 stands out as the most influential cytokine for human B cell activation and differentiation. Indeed, when compared to other important B cell-tropic cytokines such as IL-2, IL-4, IL-6 and IL-10, IL-21 is clearly the most potent in terms of its ability to influence humoral immune responses in humans. IL-21 has wide reaching actions in determining how B cells will respond to co-stimulation ranging from induction of cell death upon BCR cross-linking to potent induction of class switch recombination and plasma cell differentiation when CD40 molecules are co-engaged. Another crucial B cell factor, exemplified in recent clinical trials, is BAFF/BLys. BAFF plays a critical role in the survival of human B cells and plasma blasts and influences B cell expansion and migration. Recent evidence has shown that IL-21 and BAFF can work in concert to promote and perhaps maintain humoral immunity in humans. Notably, BAFF has the unique ability to substitute for CD40L activities in regard to IL-21-costimulation and differentiation of a specific B cell subpopulation located in the human splenic marginal zone. However, and perhaps surprisingly, BAFF signals do not have the capability to override IL-21-driven cell death events when BCR is engaged. In stark contrast, anti-CD40 ligation of B cells co-activated with IL-21 and anti-IgM not only reverses this aforementioned activation-induced cell death, but transforms this death signal into one that drives plasma cell differentiation. Here we will discuss these two critical B cell factors, IL-21 and BAFF, and their distinct and complimentary effects on human B cell responses.

  8. Immune complexes induce TNF-α and BAFF production from U937 cells by HMGB1 and RAGE.

    Science.gov (United States)

    Gao, X-J; Qu, Y-Y; Liu, X-W; Zhu, M; Ma, C-Y; Jiao, Y-L; Cui, B; Chen, Z-J; Zhao, Y-R

    2017-04-01

    This study investigated the effects of immune complexes (ICs) on tumor necrosis factor α (TNF-α) and B cell-activating factor (BAFF) production from U937 cells and further explored the mechanism. U937 cells were incubated with necrosis supernatant or systemic lupus erythematosus (SLE) sera alone, or their combination. The expression of TNF-α and BAFF was determined by Real-time polymerase chain reaction and enzyme-linked immunosorbent assay. High mobility group box protein 1(HMGB1) A-box was produced by gene recombination. HMGB1 A-box and anti-receptor for advanced glycation end products (RAGE) antibody were adopted in the blocking experiments. The importance of DNA for cytokine induction was investigated by DNase treatment. The combination of necrosis supernatant and SLE sera induced the expression of TNF-α and BAFF significantly increased compared to necrosis supernatant or SLE sera alone. Recombinant HMGB1 A-box protein was purified, and TNF-α and BAFF production, which were induced by this combination, was blocked via HMGB1 A-box and anti-RAGE antibody. Moreover, we found that DNA component is important for the immunostimulatory activity of this combination. ICs containing DNA can promote TNF-α and BAFF production in U937 cells, and this process can be mediated by HMGB1 and RAGE. One possible mechanism of increasing BAFF production in SLE is proposed in this study whereby B cell activation, antibody production and ICs stimulated monocytes may create a vicious cycle that leads to B cell hyperactivity, which can be of importance for SLE etiopathogenesis.

  9. B cell phenotypes in patients with rheumatoid arthritis relapsing after rituximab: expression of B cell-activating factor-binding receptors on B cell subsets.

    Science.gov (United States)

    Becerra, E; De La Torre, I; Leandro, M J; Cambridge, G

    2017-12-01

    Serum levels of B cell-activating factor (BAFF) rise following rituximab (RTX) therapy in patients with rheumatoid arthritis (RA). Initiation of naive B cell return to the periphery and autoreactive B cell expansion leading to relapse after RTX may therefore be linked to interactions between BAFF and BAFF-binding receptors (BBR). Relationships between serum BAFF and BBR expression [(BAFFR, calcium signal modulating cyclophilic ligand interactor (TACI) and B cell maturation antigen (BCMA)] were determined on B cell subsets, defined using immunoglobulin (Ig)D/CD38. Twenty pre-RTX and 18 RA patients relapsing after B cell depletion were included. Results were analysed with respect to timing of relapse up to 7 months after peripheral B cell return (≥ 5 B cells/μl) and to serum BAFF levels. After B cell return, B cell populations from relapsing patients had significantly lower BAFFR + expression compared to HC and pre-RTX patients. The percentage of BAFFR + B cells increased with time after B cell return and was correlated inversely with serum BAFF levels. BAFFR expression remained reduced. The percentage of TACI + memory B cells were lower in RA patients after RTX compared with healthy controls (HC). BCMA expression (% and expression) did not differ between patients and HC. Relapse following B cell return appeared largely independent of the percentage of BAFFR + or percentage of BCMA + B cells or serum BAFF levels. The lower percentage of TACI + memory B cells may reduce inhibitory signalling for B cell differentiation. In patients relapsing at longer periods after B cell return, recovery of the B cell pool was more complete, suggesting that selection or expansion of autoreactive B cells may be needed to precipitate relapse. © 2017 British Society for Immunology.

  10. Protein microarray analysis reveals BAFF-binding autoantibodies in systemic lupus erythematosus

    Science.gov (United States)

    Price, Jordan V.; Haddon, David J.; Kemmer, Dodge; Delepine, Guillaume; Mandelbaum, Gil; Jarrell, Justin A.; Gupta, Rohit; Balboni, Imelda; Chakravarty, Eliza F.; Sokolove, Jeremy; Shum, Anthony K.; Anderson, Mark S.; Cheng, Mickie H.; Robinson, William H.; Browne, Sarah K.; Holland, Steven M.; Baechler, Emily C.; Utz, Paul J.

    2013-01-01

    Autoantibodies against cytokines, chemokines, and growth factors inhibit normal immunity and are implicated in inflammatory autoimmune disease and diseases of immune deficiency. In an effort to evaluate serum from autoimmune and immunodeficient patients for Abs against cytokines, chemokines, and growth factors in a high-throughput and unbiased manner, we constructed a multiplex protein microarray for detection of serum factor–binding Abs and used the microarray to detect autoantibody targets in SLE. We designed a nitrocellulose-surface microarray containing human cytokines, chemokines, and other circulating proteins and demonstrated that the array permitted specific detection of serum factor–binding probes. We used the arrays to detect previously described autoantibodies against cytokines in samples from individuals with autoimmune polyendocrine syndrome type 1 and chronic mycobacterial infection. Serum profiling from individuals with SLE revealed that among several targets, elevated IgG autoantibody reactivity to B cell–activating factor (BAFF) was associated with SLE compared with control samples. BAFF reactivity correlated with the severity of disease-associated features, including IFN-α–driven SLE pathology. Our results showed that serum factor protein microarrays facilitate detection of autoantibody reactivity to serum factors in human samples and that BAFF-reactive autoantibodies may be associated with an elevated inflammatory disease state within the spectrum of SLE. PMID:24270423

  11. The BAFF / APRIL axis plays an important role in virus-induced peritoneal responses in rainbow trout.

    Science.gov (United States)

    Soleto, Irene; Abós, Beatriz; Castro, Rosario; González, Lucia; Tafalla, Carolina; Granja, Aitor G

    2017-05-01

    IgM + B cells have been recently demonstrated to be key regulators of peritoneal inflammation in teleost, as a large number of them occupy the peritoneal cavity after 48 h of antigenic stimulation. Despite this, the number of studies addressing the mechanism through which this cell population expands and differentiates in response to stimuli has been scarcely addressed. Because the BAFF/APRIL axis is known to play a major role in B cell survival and differentiation in mammals, we hypothesized that it could be affected in the peritoneal cavity in response to an inflammatory stimulus. To verify this hypothesis, we studied how BAFF, APRIL and the fish-specific related cytokine BALM as well as their putative receptors are regulated in rainbow trout after intraperitoneal (i.p.) injection of viral hemorrhagic septicemia virus (VHSV). When the transcriptional analysis was performed in total cells from the peritoneum, we observed that VHSV provoked an up-regulation of both BAFF and BAFF receptor (BAFF-R) mRNA levels. However, when we examined how isolated peritoneal IgM + B cells were transcriptionally affected by VHSV i.p. injection, we found that APRIL, BALM and the transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) were also up-regulated in response to the virus. IgM - cells, on the other hand, only up-regulated BALM transcription in response to VHSV. Finally, to gain further insight on the role that these cytokines play in the peritoneum, we have studied their effect on the survival of peritoneal IgM + B cells. This work demonstrates a key role for the BAFF/APRIL axis in the peritoneal inflammatory response and contributes to further understanding how IgM + B cells are regulated at this specific peripheral site. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Different IgM+B cell subpopulations residing within the peritoneal cavity of vaccinated rainbow trout are differently regulated by BAFF.

    Science.gov (United States)

    Granja, Aitor G; Tafalla, Carolina

    2017-10-05

    In teleost fish, IgM + B cells are one of the main responders against inflammatory stimuli in the peritoneal cavity, as IgM + B cells dominate the peritoneum after intraperitoneal stimulation, also increasing the levels of secreted IgM. BAFF, a cytokine known to play a major role in B cell biology, has been shown to be up-regulated along with its receptors in the peritoneum of rainbow trout upon antigenic exposure, however, the regulatory mechanisms underneath this response remain unclear. In this study, we have identified two different IgM + B cell types residing in the peritoneal cavity of previously vaccinated rainbow trout (Oncorhynchus mykiss): IgD + IgM hi MHCII hi cells, resembling naïve B cells, and IgD - IgM lo MHCII lo cells, resembling antibody-secreting cells. Based on their membrane IgM levels, these cell types were named IgM hi and IgM lo B cells, respectively. As each of these B cell populations showed a distinct expression pattern for the different BAFF receptors, we studied the effect of BAFF individually on each cell subset. Recombinant BAFF promoted the survival of IgM lo but not IgM hi B cells in vitro, resulting in increased levels of IgM-secreting cells. In contrast, BAFF increased the levels of membrane MHC II only on IgM hi B cells, suggesting different functions on these B cell subsets. Moreover, we also showed that peritoneal IgM hi B cells expressed BAFF at levels comparable to those seen on myeloid cells. These results point to BAFF as a main regulator of B cell homeostasis in the peritoneal cavity, suggesting that this cytokine can trigger different signals on different peritoneal B cell subsets in a specific manner. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. The effects of Jieduquyuzishen prescription-treated rat serum on the BAFF/BAFF-R signal pathway.

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    De-Hong Wu

    Full Text Available Systemic lupus erythematosus (SLE is a chronic inflammatory disease mainly characterized by B cell hyperactivity. Glucocorticoid (GC is widely used in SLE for its potent anti-inflammatory and immunosuppressive effects. Despite its important clinical efficacy, high-dose or long-term use of GC can cause severe side effects, such as osteoporosis, osteonecrosis, cataracts, hyperglycemia, coronary heart disease and cognitive impairment. Our early clinical studies have shown that Jieduquyuzishen prescription (JP can effectively reduce the adverse effects and improve the curative effect of GC in the treatment of SLE. The BAFF/BAFF-R signaling pathway plays an important role in the development of SLE and has been regarded as a potential target for the therapy of SLE. In this study, we attempt to investigate the effect of JP on the BAFF/BAFF-R signaling pathway to explore the mechanism of JP in reducing the toxicity and enhancing the efficacy of GC. YAC-1 cells, isolated rat peripheral blood lymphocytes, polymorphonuclear neutrophils and spleen lymphocytes were treated with drug-containing serum. The results of RT-PCR, Western blot and dual-luciferase reporter gene assays indicate that either JP or GC can inhibit the mBAFF-induced up-regulation of BAFF, BAFF-R, Bcl-2, IL-10 and NF-κB in YAC-1 cells and WEHI-231 cells. Furthermore, MTS, flow cytometry and CFSE results reveal that the proliferation and survival of lymphocytes activated by mBAFF are suppressed by JP, GC and their combination. Contrary to GC, JP can reduce the apoptosis and raise the survival of polymorphonuclear neutrophils and can't increase the apoptosis of the peripheral blood lymphocytes and spleen lymphocytes. Therefore, it is possible that JP can down-regulate the BAFF/BAFF-R signaling pathway as effectively as GC, which may result in the dosage reduction of GC, thus decreasing the toxicity and improving the efficacy of GC-based treatment of SLE.

  14. Evaluation of biochemical parameters and local and systemic levels of osteoactive and B-cell stimulatory factors in gestational diabetes in the presence or absence of gingivitis.

    Science.gov (United States)

    Gümüş, Pınar; Özçaka, Özgün; Ceyhan-Öztürk, Banu; Akcali, Aliye; Lappin, David F; Buduneli, Nurcan

    2015-03-01

    Gestational diabetes mellitus (GDM) is defined as varying glucose intolerance, with first onset or recognition in pregnancy. This study evaluates clinical and biochemical parameters in a possible association between GDM and gingivitis. A total of 167 pregnant females was included in the study. There were 101 females with GDM and 66 females without GDM. Subgroups were created according to the presence or absence of gingival inflammation. Plaque index, bleeding on probing, and probing depth were recorded at four sites per tooth. Serum, saliva, and gingival crevicular fluid (GCF) levels of interleukin (IL)-6, IL-8, soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), osteoprotegerin (OPG), B-cell activating factor (BAFF), and a proliferation-inducing ligand (APRIL) were determined by enzyme-linked immunosorbent assay. Data were analyzed by Kruskal-Wallis and Mann-Whitney U tests and Spearman correlation analysis. Age and anthropometric indices were higher in the GDM than non-GDM group (P gingivitis group than non-GDM with gingivitis group (P = 0.044). Serum and GCF BAFF (P gingivitis group than GDM without gingivitis group. The inflammatory response seems to be more pronounced in females with GDM. The observed increase in both local and systemic levels of inflammatory cytokines may suggest an interaction between gingivitis and GDM.

  15. BAFF-neutralizing interaction of belimumab related to its therapeutic efficacy for treating systemic lupus erythematosus.

    Science.gov (United States)

    Shin, Woori; Lee, Hyun Tae; Lim, Heejin; Lee, Sang Hyung; Son, Ji Young; Lee, Jee Un; Yoo, Ki-Young; Ryu, Seong Eon; Rhie, Jaejun; Lee, Ju Yeon; Heo, Yong-Seok

    2018-03-23

    BAFF, a member of the TNF superfamily, has been recognized as a good target for autoimmune diseases. Belimumab, an anti-BAFF monoclonal antibody, was approved by the FDA for use in treating systemic lupus erythematosus. However, the molecular basis of BAFF neutralization by belimumab remains unclear. Here our crystal structure of the BAFF-belimumab Fab complex shows the precise epitope and the BAFF-neutralizing mechanism of belimumab, and demonstrates that the therapeutic activity of belimumab involves not only antagonizing the BAFF-receptor interaction, but also disrupting the formation of the more active BAFF 60-mer to favor the induction of the less active BAFF trimer through interaction with the flap region of BAFF. In addition, the belimumab HCDR3 loop mimics the DxL(V/L) motif of BAFF receptors, thereby binding to BAFF in a similar manner as endogenous BAFF receptors. Our data thus provides insights for the design of new drugs targeting BAFF for the treatment of autoimmune diseases.

  16. Transgenic overexpression of BAFF regulates the expression of ...

    Indian Academy of Sciences (India)

    LI ZHANG

    GFP-2A-BAFF/His recombinant plasmid was constructed by ... vided novel insight into further exploration of modulating adaptive immunity and studying autoimmune diseases caused by ... major role in the survival, proliferation and differentiation.

  17. Expression of TNF-superfamily members BAFF and APRIL in breast cancer: Immunohistochemical study in 52 invasive ductal breast carcinomas

    Directory of Open Access Journals (Sweden)

    Stathopoulos Efstathios N

    2008-03-01

    Full Text Available Abstract Background Recent studies suggest an association between chronic inflammation, modulating the tissue microenvironment, and tumor biology. Tumor environment consists of tumor, stromal and endothelial cells and infiltrating macrophages, T lymphocytes, and dendritic cells, producing an array of cytokines, chemokines and growth factors, accounting for a complex cell interaction and regulation of differentiation, activation, function and survival of tumor and surrounding cells, responsible for tumor progression and spreading or induction of antitumor immune responses and rejection. Tumor Necrosis Factor (TNF family members (19 ligands and 29 receptors represent a pleiotropic family of agents, related to a plethora of cellular events from proliferation and differentiation to apoptosis and tumor reduction. Among these members, BAFF and APRIL (CD257 and CD256 respectively gained an increased interest, in view of their role in cell protection, differentiation and growth, in a number of lymphocyte, epithelial and mesenchymal structures. Methods We have assayed by immunohistochemistry 52 human breast cancer biopsies for the expression of BAFF and APRIL and correlated our findings with clinicopathological data and the evolution of the disease. Results BAFF was ubiquitely expressed in breast carcinoma cells, DCIS, normal-appearing glands and ducts and peritumoral adipocytes. In contrast, APRIL immunoreactive expression was higher in non-malignant as compared to malignant breast structures. APRIL but not BAFF immunoreactivity was higher in N+ tumors, and was inversely related with the grade of the tumors. Neither parameter was related to DFS or the OS of patients. Conclusion Our data show, for the first time, an autocrine secretion of BAFF and APRIL from breast cancer cells, offering new perspectives for their role in neoplastic and normal breast cell biology and offering new perspectives for possible selective intervention in breast cancer.

  18. BAFF Promotes Th17 Cells and Aggravates Experimental Autoimmune Encephalomyelitis

    Science.gov (United States)

    Lan, Qin; Wang, Julie; Su, Wenru; Han, Yuan-Ping; Fan, Huimin; Liu, Zhongmin; Stohl, William; Zheng, Song Guo

    2011-01-01

    Background BAFF, in addition to promoting B cell survival and differentiation, may affect T cells. The objective of this study was to determine the effect of BAFF on Th17 cell generation and its ramifications for the Th17 cell-driven disease, EAE. Methodology/Principal Findings Th17 cells were increased in BAFF-Tg B6 (B6.BTg) mice and decreased in B6.Baff−/− mice. Th17 cells in B6.Baff−/− mice bearing a BAFF Tg (B6.Baff−/−.BTg mice) were identical to those in B6.BTg mice, indicating that membrane BAFF is dispensable for Th17 cell generation as long as soluble BAFF is plentiful. In T + non-T cell criss-cross co-cultures, Th17 cell generation was greatest in cultures containing B6.BTg T cells and lowest in cultures containing B6.Baff−/− T cells, regardless of the source of non-T cells. In cultures containing only T cells, Th17 cell generation followed an identical pattern. CD4+ cell expression of CD126 (IL-6R α chain) was increased in B6.BTg mice and decreased in B6.Baff−/− mice, and activation of STAT3 following stimulation with IL-6 + TGF-β was also greatest in B6.BTg cells and lowest in B6.Baff−/− cells. EAE was clinically and pathologically most severe in B6.BTg mice and least severe in B6.Baff−/− mice and correlated with MOG35–55 peptide-induced Th17 cell responses. Conclusions/Significance Collectively, these findings document a contribution of BAFF to pathogenic Th17 cell responses and suggest that BAFF antagonism may be efficacious in Th17 cell-driven diseases. PMID:21897850

  19. Interleukin 21 blockade modulates activated T- and B-cell homeostasis via B-cell activating factor pathway-mediated inhibition in a murine model of acute graft-versus-host disease.

    Science.gov (United States)

    Lim, Jung-Yeon; Park, Min-Jung; Im, Keon-Il; Kim, Nayoun; Park, Hyun-Sil; Lee, Sung-Hee; Kim, Eun-Kung; Nam, Young-Sun; Lee, Eun-Sol; Cho, Mi-La; Cho, Seok-Goo

    2015-01-01

    Interleukin (IL) 21 plays a key role in the development of acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation. Therapeutic manipulation of IL-21 activity may improve acute GVHD during the early-posttransplant period. We investigated the mechanisms regulating T- and B-cells during IL-21 blockade in acute GVHD. Interleukin 21 blockade enhanced regulatory T and T helper (Th) 2 cell differentiation and inhibited Th1- and Th17-derived transcription factors and cytokines as a modulator of activated T-cells. Interleukin 21(-/-) cell recipients showed increased mature B- and marginal-zone B-cells, but decreased memory B-cells, germinal center formation, and plasma cells that did not lead to immunoglobulin production. B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are involved in the induction and maintenance of T- and B-cell responses. We observed decreased levels of only BAFF during acute GVHD and confirmed that mammalian target of rapamycin complex 1 was reduced by the BAFF/BAFF-receptor pathway. Therefore, this study suggests that IL-21 blockade modulates activated T- and B-cell homeostasis via BAFF-pathway-mediated inhibition in acute GVHD following murine allogeneic bone marrow transplantation. Copyright © 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  20. Pathway of Toll-like receptor 7/B cell activating factor/B cell activating factor receptor plays a role in immune thrombocytopenia in vivo.

    Directory of Open Access Journals (Sweden)

    Qing Yang

    Full Text Available Immune thrombocytopenia (ITP is an autoimmune disorder characterized by anti-platelet autoantibody-mediated platelet destruction. Antigen-presenting cell (APC dysfunction is considered to play crucial roles in ITP. However, how APC affects autoreactive B cells in ITP is still unknown. Using a mouse model of immune thrombocytopenia, we demonstrated an increase in levels of TLR7 in splenic mononuclear cells (SMCs. Using both TLR7 agonist and TLR7 silencing lentivirus, we found stimulation of TLR7 decreased platelet counts and increased levels of platelet-associated IgG (PAIgG in ITP mice, which correlates TLR7 with platelet destruction by autoantibodies. Levels of serum BAFF increased significantly in ITP mice and stimulation of TLR7 promoted secretion of BAFF. Among the three BAFF receptors, only BAFF receptor (BAFF-R increased in ITP mice. However, activation of TLR7 showed no effect on the expression of BAFF receptors. These findings indicate that upregulation of TLR7 may augment BAFF secretion by APC and through ligation of BAFF-R promote autoreactive B cell survival and thus anti-platelet autoantibody production. The pathway of TLR7/BAFF/BAFF-R provides us with an explanation of how activation of APC affects autoantibody production by B cells in ITP and thus might provide a reasonable therapeutic strategy for ITP.

  1. Analysis of Associations of Human BAFF Gene Polymorphisms with Autoimmune Thyroid Diseases.

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    Jiunn-Diann Lin

    Full Text Available The B-lymphocyte-activating factor (BAFF is associated with B-cell functions, and gene polymorphisms of the BAFF have been linked to autoimmune diseases (AIDs. In this study, we explored possible associations of two BAFF single-nucleotide polymorphisms (SNPs, rs1041569 and rs2893321, with autoimmune thyroid diseases (AITDs in an ethnic Chinese population.In total, 319 Graves' disease (GD, 83 Hashimoto's thyroiditis (HT patients, and 369 healthy controls were enrolled. Polymerase chain reaction-restriction fragment length polymorphism and direct sequencing were used to genotype rs2893321 and rs1041569.There was a significant difference in frequencies of the G allele and AG+GG genotype of rs2893321 between the GD and control groups (p = 0.013, odds ratio (OR = 0.76, and p = 0.017, OR = 0.68, respectively and between the AITD and control groups (p = 0.009, OR = 0.76, and, p = 0.014, OR = 0.69, respectively. The AA genotype of rs2893321 was associated with low titers of the thyroid-stimulating hormone receptor antibody (TSHRAb (p = 0.015 in males but not in females. The AA genotype of rs2893321 was associated with the presence of two different types of thyroid autoantibody (TAb (TSHRAb and Hashimoto's autoantibody (anti-thyroglobulin or anti-microsomal antibody in females and with that of one type in males.rs2893321 may be a susceptible genetic variant for the development of GD and AITDs. Associations of rs2893321 with susceptibility to GD and AITDs and the correlation between rs2893321 and TAb exhibit a dimorphic pattern. Additional studies with larger sample sizes are required to confirm our findings.

  2. B-Cell-Activating Factor Affects the Occurrence of Thyroid Autoimmunity in Chronic Hepatitis C Patients Treated with Interferon Alpha

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    Yusuke Kajiyama

    2012-01-01

    Full Text Available Chronic hepatitis C (CHC patients frequently suffer from thyroid disorders during interferon therapy. However, the mechanism remains unclear. In this study, we investigated the association between serum B-cell-activating factor belonging to the TNF family (BAFF levels and the presence of antithyroid peroxidase antibody (anti-TPO in CHC patients treated with pegylated interferon alpha and ribavirin combination therapy. Six months after the therapy, anti-TPO antibody was detected in 10 (males, 1; females, 9 of 50 patients. The mean age of these patients was higher than that of the anti-TPO-negative patients (61 yr versus 55 yr. Before treatment, the serum BAFF levels of the anti-TPO-positive patients were higher than those of the anti-TPO-negative patients. After starting therapy, the serum BAFF levels of both the anti-TPO-positive and -negative patient groups were elevated. Our findings suggest that the serum BAFF concentration before therapy can predict the risk of thyroid autoimmunity in elderly female patients with CHC.

  3. Detection of The TNFSF Members BAFF, APRIL, TWEAK and Their Receptors in Normal Kidney and Renal Cell Carcinomas

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    Vassiliki Pelekanou

    2011-01-01

    Full Text Available In advanced renal cell carcinoma (RCC, surgery combined with systemic chemotherapy and immunotherapy have had limited effectiveness. Therapeutic modalities targeting VEGF, PDGF, and c-kit using tyrosine kinase inhibitors and m-TOR using specific biologic factors are in development. Therapeutic approaches targeting TNF-alpha have shown limited efficacy, while anti-TRAIL (TNFSF10 antibodies have shown enhanced activity. The presence and potential significance of other members of the TNFSF has not been investigated. Here, we assayed the TNFSF members APRIL, BAFF, TWEAK and their receptors (BCMA, TACI, BAFFR, Fn14 in 86 conventional type clear cell RCC, using immunohistochemistry and correlated our findings with histological data and, in a limited series, follow-up of patients. We observed a differential expression of these TNFSF ligands and receptors in cancerous and non-cancerous structures. BAFF was found in all RCC; APRIL expression is associated with an aggressive phenotype, correlating negatively with patients' disease-free survival, while TWEAK and its receptor Fn14 are heterogeneously expressed, correlating negatively with the grade and survival of RCC patients. This is the first study, presenting together the TNFSF members APRIL, BAFF, TWEAK and their receptors in different areas of normal renal tissue and RCC, suggesting a potential role of these TNFSF members in renal tumor biology.

  4. Chemokine/cytokine profiling after rituximab: reciprocal expression of BCA-1/CXCL13 and BAFF in childhood OMS.

    Science.gov (United States)

    Pranzatelli, Michael R; Tate, Elizabeth D; Travelstead, Anna L; Verhulst, Steven J

    2011-03-01

    The aim of the study was to test the hypothesis that B-cell repopulation following rituximab (anti-CD20) therapy is orchestrated by chemokines and non-chemokine cytokines. Twenty-five children with opsoclonus-myoclonus syndrome (OMS) received rituximab with or without conventional agents. A comprehensive panel of 40 chemokines and other cytokines were measured in serum by ELISA and multiplexed fluorescent bead-based immunoassay. Serum BAFF concentration changed dramatically (even after first infusion) and inversely with B-cell depletion/repopulation and CXCL13 concentration at 1, 3, and 6 months. Negative correlations were found for BAFF concentration vs blood B cell percentage and serum CXCL13 concentration; positive correlations with serum rituximab concentrations. Six months after initiation of therapy, no significant difference in the levels of APRIL, CXCL10, IL-6, or 17 other cytokines/chemokines were detected. These data reveal a major role for BAFF in peripheral B cell repopulation following rituximab-induced B-cell depletion, and novel changes in CXCL13. ClinicalTrials.gov NCT0024436. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Characterization of BAFF and APRIL subfamily receptors in rainbow trout (Oncorhynchus mykiss). Potential role of the BAFF / APRIL axis in the pathogenesis of proliferative kidney disease.

    Science.gov (United States)

    Granja, Aitor G; Holland, Jason W; Pignatelli, Jaime; Secombes, Christopher J; Tafalla, Carolina

    2017-01-01

    Proliferative kidney disease (PKD) is a parasitic infection of salmonid fish characterized by hyper-secretion of immunoglobulins in response to the presence of the myxozoan parasite, Tetracapsuloides bryosalmonae. In this context, we hypothesized that the BAFF/APRIL axis, known to play a major role in B cell differentiation and survival in mammals, could be affected by the parasite and consequently be involved in the apparent shift in normal B cell activity. To regulate B cell activity, BAFF and APRIL bind to transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA), whereas BAFF also binds to BAFF receptor (BAFF-R). In teleost fish, although some BAFF and APRIL sequences have been reported, their receptors have not been identified. Thus, as a first step in the current work, we have identified homologues to mammalian TACI, BCMA and BAFF-R in rainbow trout (Oncorhynchus mykiss), that constitute the first report of BAFF and APRIL receptor sequences in fish. Subsequently we studied the transcriptional modulation of BAFF, APRIL, and the fish-specific related cytokine, BALM and their putative receptors in fish naturally exposed to T. bryosalmonae. Finally, to gain further insights on the functional role that these cytokines play during the course of PKD, we have studied their effect on the survival of kidney IgM+ B cells and on immunoglobulin transcription. Our results support the premise that the BAFF / APRIL axis could play an important role during PKD, which may open the possibility of new therapeutic treatments against the disease.

  6. Characterization of BAFF and APRIL subfamily receptors in rainbow trout (Oncorhynchus mykiss. Potential role of the BAFF / APRIL axis in the pathogenesis of proliferative kidney disease.

    Directory of Open Access Journals (Sweden)

    Aitor G Granja

    Full Text Available Proliferative kidney disease (PKD is a parasitic infection of salmonid fish characterized by hyper-secretion of immunoglobulins in response to the presence of the myxozoan parasite, Tetracapsuloides bryosalmonae. In this context, we hypothesized that the BAFF/APRIL axis, known to play a major role in B cell differentiation and survival in mammals, could be affected by the parasite and consequently be involved in the apparent shift in normal B cell activity. To regulate B cell activity, BAFF and APRIL bind to transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI and B cell maturation antigen (BCMA, whereas BAFF also binds to BAFF receptor (BAFF-R. In teleost fish, although some BAFF and APRIL sequences have been reported, their receptors have not been identified. Thus, as a first step in the current work, we have identified homologues to mammalian TACI, BCMA and BAFF-R in rainbow trout (Oncorhynchus mykiss, that constitute the first report of BAFF and APRIL receptor sequences in fish. Subsequently we studied the transcriptional modulation of BAFF, APRIL, and the fish-specific related cytokine, BALM and their putative receptors in fish naturally exposed to T. bryosalmonae. Finally, to gain further insights on the functional role that these cytokines play during the course of PKD, we have studied their effect on the survival of kidney IgM+ B cells and on immunoglobulin transcription. Our results support the premise that the BAFF / APRIL axis could play an important role during PKD, which may open the possibility of new therapeutic treatments against the disease.

  7. CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agents

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    2017-12-01

    Full Text Available Paeoniflorin-6′-O-benzene sulfonate (code: CP-25 was the chemistry structural modifications of Paeoniflorin (Pae. CP-25 inhibited B cells proliferation stimulated by B cell activating factor belonging to the TNF family (BAFF or Tumor necrosis factor alpha (TNF-alpha. CP-25, Rituximab and Etanercept reduced the percentage and numbers of CD19+ B cells, CD19+CD20+ B cells, CD19+CD27+ B cells and CD19+CD20+CD27+ B cells induced by BAFF or TNF-alpha. There was significant difference between CP-25 and Rituximab or CP-25 and Etanercept. CP-25 down-regulated the high expression of BAFFR, BCMA, and TACI stimulated by BAFF or TNF-alpha. The effects of Rituximab and Etanercept on BAFFR or BCMA were stronger than that of CP-25. CP-25, Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated the expression of MKK3, P-p38, P-p65, TRAF2, and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha. These results suggest that CP-25 regulated moderately activated B cells function by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway. This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.

  8. CP-25, a Novel Anti-inflammatory and Immunomodulatory Drug, Inhibits the Functions of Activated Human B Cells through Regulating BAFF and TNF-alpha Signaling and Comparative Efficacy with Biological Agents.

    Science.gov (United States)

    Zhang, Feng; Shu, Jin-Ling; Li, Ying; Wu, Yu-Jing; Zhang, Xian-Zheng; Han, Le; Tang, Xiao-Yu; Wang, Chen; Wang, Qing-Tong; Chen, Jing-Yu; Chang, Yan; Wu, Hua-Xun; Zhang, Ling-Ling; Wei, Wei

    2017-01-01

    Paeoniflorin-6'- O -benzene sulfonate (code: CP-25) was the chemistry structural modifications of Paeoniflorin (Pae). CP-25 inhibited B cells proliferation stimulated by B cell activating factor belonging to the TNF family (BAFF) or Tumor necrosis factor alpha (TNF-alpha). CP-25, Rituximab and Etanercept reduced the percentage and numbers of CD19 + B cells, CD19 + CD20 + B cells, CD19 + CD27 + B cells and CD19 + CD20 + CD27 + B cells induced by BAFF or TNF-alpha. There was significant difference between CP-25 and Rituximab or CP-25 and Etanercept. CP-25 down-regulated the high expression of BAFFR, BCMA, and TACI stimulated by BAFF or TNF-alpha. The effects of Rituximab and Etanercept on BAFFR or BCMA were stronger than that of CP-25. CP-25, Rituximab and Etanercept down-regulated significantly the expression of TNFR1 and TNFR2 on B cell stimulated by BAFF or TNF-alpha. CP-25, Rituximab and Etanercept down-regulated the expression of MKK3, P-p38, P-p65, TRAF2, and p52 in B cells stimulated by BAFF and the expression of TRAF2 and P-p65 in B cells stimulated by TNF-alpha. These results suggest that CP-25 regulated moderately activated B cells function by regulating the classical and alternative NF-κB signaling pathway mediated by BAFF and TNF-alpha-TRAF2-NF-κB signaling pathway. This study suggests that CP-25 may be a promising anti-inflammatory immune and soft regulation drug.

  9. B cell-independent contribution of BAFF to murine autoimmune disease.

    Science.gov (United States)

    Stohl, William; Banfalvi, Agnes

    2016-11-01

    BAFF blockade is efficacious in murine and human SLE. Whereas the attendant reduction in B cells contributes to the efficacy, it remains unresolved whether a B cell-independent component also contributes. Since accurate assessment of a B cell-independent component can only be made in a B cell-independent autoimmune disease, we investigated MOG 35-55 -induced EAE in C57BL/6 mice. Neither pharmacologic neutralization nor genetic elimination of BAFF affected disease, nor did elimination of APRIL (with or without elimination of BAFF) or constitutive over-expression of BAFF. Eliminating BAFF had no effect on disease even in mice that were genetically manipulated to maintain greater-than-normal numbers of B cells. However, elimination of BAFF in B cell-deficient mice dramatically reduced disease, thereby unmasking a B cell-independent contribution of BAFF to an autoimmune disease. Our findings raise the plausibility that BAFF contributes to SLE not only through effects on B cells but through B cell-independent pathways as well. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. DNA vaccine molecular adjuvants SP-D-BAFF and SP-D-APRIL enhance anti-gp120 immune response and increase HIV-1 neutralizing antibody titers.

    Science.gov (United States)

    Gupta, Sachin; Clark, Emily S; Termini, James M; Boucher, Justin; Kanagavelu, Saravana; LeBranche, Celia C; Abraham, Sakhi; Montefiori, David C; Khan, Wasif N; Stone, Geoffrey W

    2015-04-01

    Broadly neutralizing antibodies (bNAbs) specific for conserved epitopes on the HIV-1 envelope (Env) are believed to be essential for protection against multiple HIV-1 clades. However, vaccines capable of stimulating the production of bNAbs remain a major challenge. Given that polyreactivity and autoreactivity are considered important characteristics of anti-HIV bNAbs, we designed an HIV vaccine incorporating the molecular adjuvants BAFF (B cell activating factor) and APRIL (a proliferation-inducing ligand) with the potential to facilitate the maturation of polyreactive and autoreactive B cells as well as to enhance the affinity and/or avidity of Env-specific antibodies. We designed recombinant DNA plasmids encoding soluble multitrimers of BAFF and APRIL using surfactant protein D as a scaffold, and we vaccinated mice with these molecular adjuvants using DNA and DNA-protein vaccination strategies. We found that immunization of mice with a DNA vaccine encoding BAFF or APRIL multitrimers, together with interleukin 12 (IL-12) and membrane-bound HIV-1 Env gp140, induced neutralizing antibodies against tier 1 and tier 2 (vaccine strain) viruses. The APRIL-containing vaccine was particularly effective at generating tier 2 neutralizing antibodies following a protein boost. These BAFF and APRIL effects coincided with an enhanced germinal center (GC) reaction, increased anti-gp120 antibody-secreting cells, and increased anti-gp120 functional avidity. Notably, BAFF and APRIL did not cause indiscriminate B cell expansion or an increase in total IgG. We propose that BAFF and APRIL multitrimers are promising molecular adjuvants for vaccines designed to induce bNAbs against HIV-1. Recent identification of antibodies that neutralize most HIV-1 strains has revived hopes and efforts to create novel vaccines that can effectively stimulate HIV-1 neutralizing antibodies. However, the multiple immune evasion properties of HIV have hampered these efforts. These include the instability of

  11. Cutting Edge: BAFF Overexpression Reduces Atherosclerosis via TACI-Dependent B Cell Activation.

    Science.gov (United States)

    Jackson, Shaun W; Scharping, Nicole E; Jacobs, Holly M; Wang, Shari; Chait, Alan; Rawlings, David J

    2016-12-15

    Patients with systemic lupus erythematosus exhibit accelerated atherosclerosis, a chronic inflammatory disease of the arterial wall. The impact of B cells in atherosclerosis is controversial, with both protective and pathogenic roles described. For example, natural IgM binding conserved oxidized lipid epitopes protect against atherosclerosis, whereas anti-oxidized low-density lipoprotein (oxLDL) IgG likely promotes disease. Because BAFF promotes B cell class-switch recombination and humoral autoimmunity, we hypothesized that excess BAFF would accelerate atherosclerosis. In contrast, BAFF overexpression markedly reduced hypercholesterolemia and atherosclerosis in hyperlipidemic mice. BAFF-mediated atheroprotection required B cells and was associated with increased protective anti-oxLDL IgM. Surprisingly, high-titer anti-oxLDL IgM production and reduced atherosclerosis was dependent on the BAFF family receptor transmembrane activator and CAML interactor. In summary, we identified a novel role for B cell-specific, BAFF-dependent transmembrane activator and CAML interactor signals in atherosclerosis pathogenesis, of particular relevance to the use of BAFF-targeted therapies in systemic lupus erythematosus. Copyright © 2016 by The American Association of Immunologists, Inc.

  12. Aberrant Expression of Functional BAFF-System Receptors by Malignant B-Cell Precursors Impacts Leukemia Cell Survival

    Science.gov (United States)

    Maia, Sara; Pelletier, Marc; Ding, Jixin; Hsu, Yen-Ming; Sallan, Stephen E.; Rao, Sambasiva P.; Nadler, Lee M.; Cardoso, Angelo A.

    2011-01-01

    Despite exhibiting oncogenic events, patient's leukemia cells are responsive and dependent on signals from their malignant bone marrow (BM) microenvironment, which modulate their survival, cell cycle progression, trafficking and resistance to chemotherapy. Identification of the signaling pathways mediating this leukemia/microenvironment interplay is critical for the development of novel molecular targeted therapies. We observed that primary leukemia B-cell precursors aberrantly express receptors of the BAFF-system, BAFF-R, BCMA, and TACI. These receptors are functional as their ligation triggers activation of NF-κB, MAPK/JNK, and Akt signaling. Leukemia cells express surface BAFF and APRIL ligands, and soluble BAFF is significantly higher in leukemia patients in comparison to age-matched controls. Interestingly, leukemia cells also express surface APRIL, which seems to be encoded by APRIL-δ, a novel isoform that lacks the furin convertase domain. Importantly, we observed BM microenvironmental cells express the ligands BAFF and APRIL, including surface and secreted BAFF by BM endothelial cells. Functional studies showed that signals through BAFF-system receptors impact the survival and basal proliferation of leukemia B-cell precursors, and support the involvement of both homotypic and heterotypic mechanisms. This study shows an unforeseen role for the BAFF-system in the biology of precursor B-cell leukemia, and suggests that the target disruption of BAFF signals may constitute a valid strategy for the treatment of this cancer. PMID:21687682

  13. Aberrant expression of functional BAFF-system receptors by malignant B-cell precursors impacts leukemia cell survival.

    Directory of Open Access Journals (Sweden)

    Sara Maia

    Full Text Available Despite exhibiting oncogenic events, patient's leukemia cells are responsive and dependent on signals from their malignant bone marrow (BM microenvironment, which modulate their survival, cell cycle progression, trafficking and resistance to chemotherapy. Identification of the signaling pathways mediating this leukemia/microenvironment interplay is critical for the development of novel molecular targeted therapies.We observed that primary leukemia B-cell precursors aberrantly express receptors of the BAFF-system, BAFF-R, BCMA, and TACI. These receptors are functional as their ligation triggers activation of NF-κB, MAPK/JNK, and Akt signaling. Leukemia cells express surface BAFF and APRIL ligands, and soluble BAFF is significantly higher in leukemia patients in comparison to age-matched controls. Interestingly, leukemia cells also express surface APRIL, which seems to be encoded by APRIL-δ, a novel isoform that lacks the furin convertase domain. Importantly, we observed BM microenvironmental cells express the ligands BAFF and APRIL, including surface and secreted BAFF by BM endothelial cells. Functional studies showed that signals through BAFF-system receptors impact the survival and basal proliferation of leukemia B-cell precursors, and support the involvement of both homotypic and heterotypic mechanisms.This study shows an unforeseen role for the BAFF-system in the biology of precursor B-cell leukemia, and suggests that the target disruption of BAFF signals may constitute a valid strategy for the treatment of this cancer.

  14. BAFF, stimulatory DNA and IL-15 stimulates IgA(+) memory B cells and provides a novel approach for analysis of memory responses to mucosal vaccines.

    Science.gov (United States)

    Tengvall, Sara; Lundgren, Anna; Quiding-Järbrink, Marianne; Svennerholm, Ann-Mari

    2010-07-26

    Assessment of immune responses induced by mucosal vaccines is to a large extent based on measurement of IgA levels in mucosal secretions and detection of short-lived effector IgA-secreting cells circulating in peripheral blood. Since these immunological parameters poorly reflect long-term IgA-mediated responses, we sought to investigate novel approaches that would enable detection of vaccine specific IgA memory B cells. We demonstrate that stimulation of human peripheral blood mononuclear cells in vitro with immunostimulatory DNA in combination with B cell-activating factor (BAFF) and IL-15 promotes differentiation of IgA memory B cells to IgA-secreting cells. By using the inactivated oral cholera vaccine Dukoral we demonstrate that vaccine specific IgA memory B cells are induced by oral immunization and are circulating for at least 9 months after vaccination. We also show that stimulated IgA memory B cells do not secrete IgA unless they reencounter the specific antigen. Copyright 2010 Elsevier Ltd. All rights reserved.

  15. A Novel VHH Antibody Targeting the B Cell-Activating Factor for B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Wen Wu

    2014-05-01

    Full Text Available Objective: To construct an immune alpaca phage display library, in order to obtain a single domain anti-BAFF (B cell-activating factor antibody. Methods: Using phage display technology, we constructed an immune alpaca phage display library, selected anti-BAFF single domain antibodies (sdAbs, cloned three anti-BAFF single-domain antibody genes into expression vector pSJF2, and expressed them efficiently in Escherichia coli. The affinity of different anti-BAFF sdAbs were measured by Bio layer interferometry. The in vitro biological function of three sdAbs was investigated by cell counting kit-8 (CCK-8 assay and a competitive enzyme-linked immunosorbent assay (ELISA. Results: We obtained three anti-BAFF single domain antibodies (anti-BAFF64, anti-BAFF52 and anti-BAFFG3, which were produced in high yield in Escherichia coli and inhibited tumor cell proliferation in vitro. Conclusion: The selected anti-BAFF antibodies could be candidates for B-cell lymphoma therapies.

  16. CREDIT LEVEL INFLUENCING FACTORS AT HUNGARIAN FARMS

    Directory of Open Access Journals (Sweden)

    Toth Jozsef

    2012-12-01

    Full Text Available In this paper we estimate the impact of different factors on creditability of agricultural farms. According to the literature the collateral (tangible assets, the farm size, productivity, and subsidies should have significant effects on farm loans. We use data from the Hungarian Farm Accountancy Data Network to test our two hypotheses and theoretical assumptions for the period 2001-2010. Because of using panel data, we do our estimations using fixed effects econometrics model to test our assumptions. The results indicate that the chosen factors have significant influence on total liabilities and short- and long-term loans as well. With specially interest of subsidies the growing level of supports decrease the need of other financial tools. At output factors (inclusive farm size have significant and positive effect, same as collateral (tangible assets.

  17. Dietary factors and fluctuating levels of melatonin

    Directory of Open Access Journals (Sweden)

    Katri Peuhkuri

    2012-07-01

    Full Text Available Melatonin is secreted principally by the pineal gland and mainly at nighttime. The primary physiological function is to convey information of the daily cycle of light and darkness to the body. In addition, it may have other health-related functions. Melatonin is synthesized from tryptophan, an essential dietary amino acid. It has been demonstrated that some nutritional factors, such as intake of vegetables, caffeine, and some vitamins and minerals, could modify melatonin production but with less intensity than light, the most dominant synchronizer of melatonin production. This review will focus on the nutritional factors apart from the intake of tryptophan that affect melatonin levels in humans. Overall, foods containing melatonin or promoting the synthesis of it by impacting the availability of tryptophan, as well those containing vitamins and minerals which are needed as co-factors and activators in the synthesis of melatonin, may modulate the levels of melatonin. Even so, the influence of daytime diet on the synthesis of nocturnal melatonin is limited, however, the influence of the diet seems to be more obvious on the daytime levels.

  18. The effect of BAFF inhibition on autoreactive B cell selection in murine SLE.

    Science.gov (United States)

    Boneparth, Alexis; Woods, Megan; Huang, Weiqing; Akerman, Meredith; Lesser, Martin; Davidson, Anne

    2016-02-12

    The goal of this study was to determine how BAFF availability influences selection of the autoreactive B cell repertoire in NZB/W and NZW/BXSB lupus prone mice bearing the site-directed heavy chain transgene 3H9 that encodes for anti-dsDNA and anti-CL autoantibodies. We used a bone marrow chimera system in which autoreactive 3H9 transgenic B cells were allowed to mature in competition with wild type cells and could be identified by GFP fluorescence. The light chain repertoire associated with the 3H9 heavy chain in naïve and antigen-activated B cell subsets was assessed using single cell PCR. We found that deletion of autoreactive transgenic B cells occurred in the bone marrow of both strains regardless of BAFF availability and there were only modest and physiologically non-relevant effects on the naïve B cell repertoire. BAFF inhibition had different effects on selection of the germinal center repertoire in the two strains. In the NZW/BXSB strain, BAFF inhibition phenocopied the loss of one TLR7 allele in that it influenced the selection of 3H9 encoded autoreactive B cells in the germinal center but did not prevent somatic mutation. In the NZB/W strain BAFF inhibition did not alter the selection of 3H9 encoded B cells in the germinal center but it influenced selection of a subset of germinal center cells into the plasma cell compartment. Our data underscore the complexity of regulation of the autoreactive B cell repertoire by BAFF and may help to explain the heterogeneity of responses observed after BAFF inhibition in humans.

  19. Socioeconomic factors that affect international caries levels.

    Science.gov (United States)

    Diehnelt, D E; Kiyak, H A

    2001-06-01

    Health policy makers have examined the impact of economic policies and a nation's social development on the health of its population. The purpose of this research was to investigate the association between health care expenditures, socioeconomic factors, and caries levels in 109 countries representing an array of social and economic conditions, and to determine how such factors are related to caries experience at different levels of economic development. Countries were divided into established market economies and three groups of developing nations, based on their GNP (high, medium, low income). Total health expenditures as percent GDP and as US dollars per capita, public expenditures and aid flow as percent of total health expenditures, dentists per 100,000 population, per capita sugar consumption, and urbanization of the population were compared among these countries. Correlations between these variables, and decayed, missing and filled teeth (DMFT) of 12-year-olds in these countries were assessed. The highest correlations were found between DMFT and public expenditures, sugar consumption, and urbanization. Highly significant differences emerged across nation groups by stages of development on several variables. The findings suggest that it is important to consider the stage of development of a given country when planning caries prevention policies and programs. Such a contextual approach is more likely to be successful in reducing caries levels.

  20. Scalable group level probabilistic sparse factor analysis

    DEFF Research Database (Denmark)

    Hinrich, Jesper Løve; Nielsen, Søren Føns Vind; Riis, Nicolai Andre Brogaard

    2017-01-01

    Many data-driven approaches exist to extract neural representations of functional magnetic resonance imaging (fMRI) data, but most of them lack a proper probabilistic formulation. We propose a scalable group level probabilistic sparse factor analysis (psFA) allowing spatially sparse maps, component...... pruning using automatic relevance determination (ARD) and subject specific heteroscedastic spatial noise modeling. For task-based and resting state fMRI, we show that the sparsity constraint gives rise to components similar to those obtained by group independent component analysis. The noise modeling...

  1. IgG-immune complexes promote B cell memory by inducing BAFF1

    Science.gov (United States)

    Kang, SunAh; Keener, Amanda B.; Jones, Shannon Z.; Benschop, Robert J.; Caro-Maldonado, Alfredo; Rathmell, Jeffrey C.; Clarke, Stephen H.; Matsushima, Glenn K.; Whitmire, Jason K.; Vilen, Barbara J.

    2015-01-01

    Memory B cell responses are vital for protection against infections, but must also be regulated to prevent autoimmunity. Cognate T cell help, somatic hypermutation, and affinity maturation within germinal centers (GCs) are required for high affinity memory B cell formation; however, the signals that commit GC B cells to the memory pool remain unclear. In this study, we identify a role for IgG immune complexes (ICs), FcγRs, and BAFF during the formation of memory B cells in mice. We found that early secretion of IgG in response to immunization with a T-dependent antigen leads to IC-FcγR interactions that induce DCs to secrete BAFF which acts at or upstream of Bcl-6 in activated B cells. Loss of CD16, hematopoietic cell-derived BAFF, or blocking IC:FcγR regions in vivo diminished the expression of Bcl-6, the frequency of GC and memory B cells, and secondary antibody responses. BAFF also contributed to the maintenance and/or expansion of the Tfh population, although it was dispensable for their formation. Thus, early antibody responses contribute to the optimal formation of B cell memory through IgG-ICs and BAFF. Our work defines a new role for FcγRs in GC and memory B cell responses. PMID:26621863

  2. Ectopic expression of CXCL13, BAFF, APRIL and LT-β is associated with artery tertiary lymphoid organs in giant cell arteritis.

    Science.gov (United States)

    Ciccia, Francesco; Rizzo, Aroldo; Maugeri, Rosario; Alessandro, Riccardo; Croci, Stefania; Guggino, Giuliana; Cavazza, Alberto; Raimondo, Stefania; Cannizzaro, Alessandra; Iacopino, Domenico Gerardo; Salvarani, Carlo; Triolo, Giovanni

    2017-01-01

    To investigate whether artery tertiary lymphoid organs (ATLOs) are present in giant cell arteritis (GCA) and that their formation is associated with the ectopic expression of constitutive lymphoid tissue-homing chemokines. Reverse transcriptase PCR, immunohistochemical and immunofluorescence analysis were used to determine the presence of ectopic ATLOs in GCA and the expression of chemokines/chemokine receptors and cytokines involved in lymphoneogenesis in the temporal artery samples obtained from 50 patients with GCA and 30 controls. The presence of lymphatic conduits, of follicular dendritic cells (FDCs) precursors and lymphoid tissue inducer cells was also investigated. Finally, expression of CXCL13, B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and CCL21 by isolated myofibroblasts was evaluated before and after stimulation with Toll-like receptors (TLRs) agonists and cytokines. ATLOs were observed in the media layer of 60% of patients with GCA in close proximity to high endothelial venules and independently by the age of patients and the presence of atherosclerosis. ATLO formation was also accompanied by the expression of CXCL13, BAFF, a proliferation-inducing ligand (APRIL), lymphotoxin (LT)-β, interleukin (IL)-17 and IL-7, the presence of FDC precursors and of lymphoid conduits. Stimulation of myofibroblasts with TLR agonists and cytokines resulted in the upregulation of BAFF and CXCL13. ATLOs occur in the inflamed arteries of patients with GCA possibly representing the immune sites where immune responses towards unknown arterial wall-derived antigens may be organised. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  3. Coagulation Factors Level in Fresh Frozen Plasma in Rwanda ...

    African Journals Online (AJOL)

    Coagulation Factors Level in Fresh Frozen Plasma in Rwanda. ... Factor X, Von Willbrand Factor, Protein C and Antithrombin decreased from baseline up to three months and then Factor VIII, Factor IX, Factor XI, Factor XII and Protein S, remained constant from baseline up to one month and decreased up to three months.

  4. New Level-3 BLAS Kernels for Cholesky Factorization

    DEFF Research Database (Denmark)

    Gustavson, Fred G.; Wasniewski, Jerzy; Herrero, José R.

    2012-01-01

    Some Linear Algebra Libraries use Level-2 routines during the factorization part of any Level-3 block factorization algorithm. We discuss four Level-3 routines called DPOTF3, a new type of BLAS, for the factorization part of a block Cholesky factorization algorithm for use by LAPACK routine DPOTRF...

  5. Impairment of mature B-cell maintenance upon combined deletion of the alternative NF-?B transcription factors RELB and NF-?B2 in B cells$

    OpenAIRE

    De Silva, Nilushi S.; Silva, Kathryn; Anderson, Michael M.; Bhagat, Govind; Klein, Ulf

    2016-01-01

    B-cell activating factor (BAFF) is critical for the survival and maturation of mature B-cells. BAFF, via the BAFF receptor (BAFFR), activates multiple signaling pathways in B-cells, including the alternative nuclear factor-?B (NF-?B) pathway. The transcription factors RELB and NF-?B2 (p100/p52) are the downstream mediators of the alternative pathway; however, the B-cell-intrinsic functions of these NF-?B subunits have not been studied in vivo using conditional alleles, either individually or ...

  6. Selective Binding BAFF/APRIL by the In and Outside Conservative Region of BCMA.

    Science.gov (United States)

    Zheng, Chang; Zhang, Xiaojuan; Zhao, Zhen; Hao, Xiaofei; Wei, Jing; Sun, Jian

    2017-01-01

    BAFF and APRIL are members of TNF superfamily. They play vital roles in the pathogenesis of autoimmune diseases. BCMA, a receptor, shows higher affinity for APRIL than for BAFF. Previous studies found that ligand binding specificity of BCMA may be determined by sequence outside DxL motif. Investigate the contribution of a segment outside the DxL motif of BCMA for binding with ligands. In this study, the conservative region of BCMA was divided into two segments: BCMA1 (NEYFDSLLHACIPC), a segment of the DXL motif and BCMA2 (QLRCSSNTPPLT), a segment outside of the DXL motif. Two peptides corresponding to the two segments were synthesized and their contribution to the ligands binding were detected by competitive ELISA. BCMA1-Fc fusion protein was also constructed, purified and analyzed by indirect and competitive ELISA. BCMA2 had no inhibiting effect on the interaction of BCMA-Fc and BCMA1-Fc with BAFF, but, it inhibited 22.5% and 15.2% of the interaction of BCMA-Fc and BCMA1-Fc with mAPRIL respectively. The binding rates of BCMA1-Fc for BAFF were 91.7%, but 80.6% for mAPRIL, suggesting that BCMA1-Fc without BCMA2, bound BAFF well and less efficiently to mAPRIL. These results suggest that BCMA2 outside of the conservative DxL motif of BCMA may play an important role in the binding selectivity to its ligands. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Plasma placenta growth factor levels in midtrimester pregnancies

    NARCIS (Netherlands)

    Tjoa, M. L.; van Vugt, J. M.; Mulders, M. A.; Schutgens, R. B.; Oudejans, C. B.; van Wijk, I. J.

    2001-01-01

    Previous studies have shown decreased levels of placenta growth factor in serum of pregnant women with preeclampsia. The aim of this study was to investigate whether levels of placenta growth factor are decreased before the clinical onset of preeclampsia, and whether placenta growth factor levels

  8. Understanding the Institutional-Level Factors of Urban School Quality

    Science.gov (United States)

    Gottfried, Michael A.

    2012-01-01

    Background/Context: This article addresses which school-level factors contribute to school quality. Previous research has focused on assessing the effects of school-level variables on student-level quality (e.g., achievement). However, the field has been limited in not evaluating the effects of school-level factors directly on measured…

  9. Signals from activation of B-cell receptor with anti-IgD can override the stimulatory effects of excess BAFF on mature B cells in vivo.

    Science.gov (United States)

    Nguyen, Tue G; Morris, Jonathan M

    2014-09-01

    The selection and maturation of B-cell clones are critically determined by tonic signals from activated B cell receptors (BCR) and survival signals from BAFF cytokine. These finely tuned and coordinated signals provide a net positive signal that can promote the selection, maturation, proliferation and differentiation of a developing B cell. Stimulation with an anti-IgD antibody can also activate BCR but can lead to depletion and an arrest of mature B-cell development in vivo. It is not known whether survival signals from excess BAFF can override the suppressive effects of treatment with anti-IgD on mature B cells in vivo. Herein, we examined the effects of co-treatment of BAFF and anti-IgD on the mature B-cell compartment and antibody production in vivo by treating mice with either 1mg/kg BAFF or anti-IgD alone or in combination for 3 consecutive days. We found that co-treatment with anti-IgD significantly abrogated these stimulatory effects of BAFF treatment on splenic CD19+ B cells as well as mature CD19+IgD(hi)IgM+ B cells in vivo. Anti-IgD down-regulated the expression of the BCR complex (mIgM, mIgD and CD19) and the BAFF receptor TACI without regard to the presence of BAFF. Anti-IgD treatment also significantly negated BAFF-induced IgM production in vivo. Both BAFF and anti-IgD could individually stimulate IL-10 synthesis in B cells but did not affect one another. Taken together, our data suggest that activation of BCR with an anti-IgD antibody can override the stimulatory effects from excess BAFF on B cell proliferation and antibody production by down-regulating the expression of BCR complex and BAFF receptors. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. BAFF and APRIL from Activin A-Treated Dendritic Cells Upregulate the Antitumor Efficacy of Dendritic Cells In Vivo.

    Science.gov (United States)

    Shurin, Michael R; Ma, Yang; Keskinov, Anton A; Zhao, Ruijing; Lokshin, Anna; Agassandian, Marianna; Shurin, Galina V

    2016-09-01

    The members of the TGFβ superfamily play a key role in regulating developmental and homeostasis programs by controlling differentiation, proliferation, polarization, and survival of different cell types. Although the role of TGFβ1 in inflammation and immunity is well evident, the contribution of other TGFβ family cytokines in the modulation of the antitumor immune response remains less documented. Here we show that activin A triggers SMAD2 and ERK1/2 pathways in dendritic cells (DC) expressing type I and II activin receptors, and upregulates production of the TNFα family cytokines BAFF (TALL-1, TNFSF13B) and APRIL (TALL-2, TNFSF13A), which is blocked by SMAD2 and ERK1/2 inhibitors, respectively. BAFF and APRIL derived from activin A-treated DCs upregulate proliferation and survival of T cells expressing the corresponding receptors, BAFF-R and TACI. In vivo, activin A-stimulated DCs demonstrate a significantly increased ability to induce tumor-specific CTLs and inhibit the growth of melanoma and lung carcinoma, which relies on DC-derived BAFF and APRIL, as knockdown of the BAFF and APRIL gene expression in activin A-treated DCs blocks augmentation of their antitumor potential. Although systemic administration of activin A, BAFF, or APRIL for the therapeutic purposes is not likely due to the pluripotent effects on malignant and nonmalignant cells, our data open a novel opportunity for improving the efficacy of DC vaccines. In fact, a significant augmentation of the antitumor activity of DC pretreated with activin A and the proven role of DC-derived BAFF and APRIL in the induction of antitumor immunity in vivo support this direction. Cancer Res; 76(17); 4959-69. ©2016 AACR. ©2016 American Association for Cancer Research.

  11. Sea level rise and the geoid: factor analysis approach

    Directory of Open Access Journals (Sweden)

    Alexey Sadovski

    2013-08-01

    Full Text Available Sea levels are rising around the world, and this is a particular concern along most of the coasts of the United States. A 1989 EPA report shows that sea levels rose 5-6 inches more than the global average along the Mid-Atlantic and Gulf Coasts in the last century. The main reason for this is coastal land subsidence. This sea level rise is considered more as relative sea level rise than global sea level rise. Thus, instead of studying sea level rise globally, this paper describes a statistical approach by using factor analysis of regional sea level rates of change. Unlike physical models and semi-empirical models that attempt to approach how much and how fast sea levels are changing, this methodology allows for a discussion of the factor(s that statistically affects sea level rates of change, and seeks patterns to explain spatial correlations.

  12. COAGULATION FACTORS LEVEL IN FRESH FROZEN PLASMA IN RWANDA.

    Science.gov (United States)

    Uwamungu, S; Nyamache, A K; Masaisa, F; Njoki, S K; Abdalah, F; Saibu, K; Ndahiriwe, O; Agwata, D

    2014-02-01

    Objectives: To determine the level of coagulation factors and inherited inhibitors in Fresh Frozen Plasma (FFP) and to evaluate Prothrombin Time and activated partial thrombin time in fresh frozen plasma. Cross-sectional study. Jomo Kenyatta University of Agriculture and Technology in Medical Laboratory Sciences. Eighteen blood bags collected from voluntary blood donors. Coagulation factors and inhibitors levels, Prothrombin Time (PT) and Activated Partial thrombin Time (APTT) remained within the reference range requested by quality assurance regulations after three months of storage. APTT and PT show an increase from baseline to one month then remain constant up to three months, while, Fibrinogen, Factor II, Factor V, Factor VII, Factor X, Von Willbrand Factor, Protein C and Antithrombin decreased from baseline up to three months and then Factor VIII, Factor IX, Factor XI, Factor XII and Protein S, remained constant from baseline up to one month and decreased up to three months. There is good retention of all coagulation factors and inhibitors in plasma produced from whole blood within eight hours of collection, stored at minus 18 degrees C for three months.

  13. Raised Interleukin 6 Levels: A Risk Factor for Cardiovascular ...

    African Journals Online (AJOL)

    Raised Interleukin 6 Levels: A Risk Factor for Cardiovascular Associated Complications in HIV Positive Zambians before Initiation of Antiretroviral Therapy. P Nhhoma, T Kaile, G Kwenda, M Sinkala, F Mwaba, H. Mantina ...

  14. No evidence that soluble TACI induces signalling via membrane-expressed BAFF and APRIL in myeloid cells.

    Directory of Open Access Journals (Sweden)

    Josquin Nys

    Full Text Available Myeloid cells express the TNF family ligands BAFF/BLyS and APRIL, which exert their effects on B cells at different stages of differentiation via the receptors BAFFR, TACI (Transmembrane Activator and CAML-Interactor and/or BCMA (B Cell Maturation Antigen. BAFF and APRIL are proteins expressed at the cell membrane, with both extracellular and intracellular domains. Therefore, receptor/ligand engagement may also result in signals in ligand-expressing cells via so-called "reverse signalling". In order to understand how TACI-Fc (atacicept technically may mediate immune stimulation instead of suppression, we investigated its potential to activate reverse signalling through BAFF and APRIL. BAFFR-Fc and TACI-Fc, but not Fn14-Fc, reproducibly stimulated the ERK and other signalling pathways in bone marrow-derived mouse macrophages. However, these effects were independent of BAFF or APRIL since the same activation profile was observed with BAFF- or APRIL-deficient cells. Instead, cell activation correlated with the presence of high molecular mass forms of BAFFR-Fc and TACI-Fc and was strongly impaired in macrophages deficient for Fc receptor gamma chain. Moreover, a TACI-Fc defective for Fc receptor binding elicited no detectable signal. Although these results do not formally rule out the existence of BAFF or APRIL reverse signalling (via pathways not tested in this study, they provide no evidence in support of reverse signalling and point to the importance of using appropriate specificity controls when working with Fc receptor-expressing myeloid cells.

  15. Factors Associated With Plasma IL-6 Levels During HIV Infection

    DEFF Research Database (Denmark)

    Borges, Álvaro H; O'Connor, Jemma L; Phillips, Andrew N

    2015-01-01

    BACKGROUND: Elevated interleukin 6 (IL-6) levels have been linked to cardiovascular disease, cancer and death. Persons with human immunodeficiency virus (HIV) infection receiving treatment have higher IL-6 levels, but few data are available on factors associated with circulating IL-6. METHODS......: Participants in 3 trials with IL-6 measured at baseline were included (N = 9864). Factors associated with IL-6 were identified by linear regression. Demographic and HIV variables (nadir/entry CD4(+) cell count, HIV RNA level, antiretroviral therapy regimen) were investigated in all 3 trials. In the SMART...... education, whereas black race was associated with lower IL-6. Higher HIV RNA levels were associated with higher IL-6 levels, and higher nadir CD4(+) cell counts with lower IL-6 levels. Compared with efavirenz, protease inhibitors were associated with higher and nevirapine with lower IL-6 levels. Smoking...

  16. What Factors Determine the Uptake of A-level Physics?

    OpenAIRE

    Gill, Timothy; Bell, John F

    2011-01-01

    Abstract There has been much concern recently in the UK about the decline in the number of students studying physics beyond age 16. To investigate why this might be we used data from a national database of student qualifications and a multilevel modelling technique to investigate which factors had the greatest impact on the uptake of physics at Advanced Level (A-level) in a particular year. Each factor of interest was entered into a separate model, whilst accounting for prior attai...

  17. Methylene tetrahydrofolate reductase, transforming growth factor-β1 and lymphotoxin-α genes polymorphisms and susceptibility to rheumatoid arthritis.

    Science.gov (United States)

    Shaker, Olfat G; Alnoury, Amina M; Hegazy, Gehan A; El Haddad, Hemmat E; Sayed, Safaa; Hamdy, Ahmed

    Rheumatoid arthritis is a widely prevalent autoimmune disorder with suggested genetic predisposition. The aim of this study is to detect the pattern of genetic polymorphism of methylene tetrahydrofolate reductase (MTHFR C677 T and A1298 C), transforming growth factor-β1 (TGF-β1 T869 C) and lymphotoxin-α (LT-α A252G) in patients having rheumatoid arthritis and correlate these patterns to disease activity and serum levels of tumor necrosis factor-alpha (TNF-α), B-Cell Activating Factor (BAFF), and osteopontin. A total of 194 subjects, 90 controls and 104 patients with rheumatoid arthritis were genotyped for MTHFR C677 T and A1298 C, TGF-β1 T869 C and LT-α A252G polymorphisms using a methodology based on PCR-RFLP. Also serum levels of TNF-α, osteopontin and BAFF were measured by ELISA kits. The CT genotype and T allele of MTHFR C677 T and GG genotype and G allele of LT-α A252G are associated with the risk of RA and with higher levels of the pro-inflammatory cytokine, TNF-α in patients with rheumatoid arthritis. Our findings suggest that there is association between MTHFR C677 T and LT-α A252G genes polymorphisms and increased risk of RA in this sample of Egyptian population. Copyright © 2016. Published by Elsevier Editora Ltda.

  18. Factors associated with high cholesterol levels in Lusaka, Zambia: a ...

    African Journals Online (AJOL)

    Background: High cholesterol level is a risk factor for cardiovascular disease. The objective of the study was to estimate the prevalence and correlates for high cholesterol levels in Lusaka district, Zambia. Methods: A modified World Health Organization STEPwise approach to surveillance method was used to collect data ...

  19. Factors Influencing Exemplary Science Teachers' Levels of Computer Use

    Science.gov (United States)

    Hakverdi, Meral; Dana, Thomas M.; Swain, Colleen

    2011-01-01

    The purpose of this study was to examine exemplary science teachers' use of technology in science instruction, factors influencing their level of computer use, their level of knowledge/skills in using specific computer applications for science instruction, their use of computer-related applications/tools during their instruction, and their…

  20. Food choices, physical activity levels and other factors associated

    African Journals Online (AJOL)

    user

    Food choices (healthy vs. unhealthy), PA levels, and health knowledge ... physical activity; South Africa. Food choices, physical activity levels and other factors associated with weight gain in primary school educators. 83 ...... educators that reflect fast-food intake (take-outs, pies, sausage rolls, samosas, fried foods and.

  1. Factors affecting radon levels in homes in British Columbia, Canada

    International Nuclear Information System (INIS)

    Morley, D.R.; Phillips, B.G.; Van Netten, C.

    1992-01-01

    British Columbia, Canada's most westerly province, has diverse geologic and climatic characteristics, making it a region where predicting radon gas level is quite complex. Data recently obtained for eleven (11) communities confirm an association between background terrestrial gamma radiation measurements and indoor radon levels in homes. Direct links between radon levels and other factors such as home design/construction features and heating/ventilation systems were observed in data for some communities, but not necessarily from the overall data. (author)

  2. Evaluation of factors associated with elevated newborn 17-hydroxyprogesterone levels.

    Science.gov (United States)

    Anandi, V Shobi; Shaila, Bhattacharyya

    2017-05-24

    Measurement of 17-hydroxyprogesterone (17-OHP) in dried blood spots has been widely used as a newborn screening tool for congenital adrenal hyperplasia (CAH). Various maternal and neonatal factors can result in falsely high values of 17-OHP. There is a paucity of Indian studies in this regard because routine evaluation of newborn 17-OHP levels as a screening program is not widely practiced in India. Hence, this study was undertaken to evaluate the influence of various maternal and neonatal factors on newborn 17-OHP levels. The aim of the study was to determine the effect of various maternal and neonatal factors on the newborn 17-OHP values. Retrospective data related to a total of 3080 newborn 17-OHP values and clinical characteristics were collected for 3 years (2013-2015). The data were analyzed to determine the influence of various factors on 17-OHP values. The mean value of 17-OHP in our study was 5.486±3.96 ng/mL. Gender and mode of delivery did not significantly affect the 17-OHP levels. The levels were significantly higher in preterm and low birth weight babies as compared to term babies and babies with normal birth weight. Stress factors like pregnancy induced hypertension (PIH), early onset sepsis (EOS), neonatal seizures and birth asphyxia significantly increase the neonatal 17-OHP levels. The levels of 17-OHP in newborns was measured around day 3 of life are very sensitive to the influence of gestational age, birth weight and presence of stress factors like maternal PIH, birth asphyxia, neonatal sepsis and neonatal seizures and should be interpreted cautiously.

  3. An Exploratory Study of Factors Affecting Stress Levels Among ...

    African Journals Online (AJOL)

    for work quality; unmanageable number of projects; more work than can be done in one day; and having no time for a break. Implications for these findings are discussed in detail in this paper. Keywords: stress levels, teachers, factors, experience, coping strategies, Zimbabwe Nigerian Journal of Guidance and Counselling ...

  4. coagulation factors level in fresh frozen plasma in rwanda

    African Journals Online (AJOL)

    2014-02-02

    Feb 2, 2014 ... National Centre for Blood Transfusion Division/Kigali-Rwanda, D. Agwata, BSc, MSc, Medical Laboratory Sciences,. Jomo Kenyatta University Of Agriculture and Technology. COAGULATION FACTORS LEVEL IN FRESH FROZEN PLASMA IN RWANDA. S. UWAMUNGU, A. K. NYAMACHE, F. MASAISA, ...

  5. Humoral Immunological Factors and Nitric Oxide Levels in HIV ...

    African Journals Online (AJOL)

    Methods: The plasma levels of Complement regulators (C3 activator and C1 inhibitor), Complement factors (C3c and C4), immunoglobulin classes (IgG, A and M) were estimated using immunoplates in controls, HIV patients with <200 CD4+ T lymphocytes per microliter of blood and HIV patients with 200–499 CD4+ T ...

  6. Analysis of Factors Affecting Decisions to Participate and Levels of ...

    African Journals Online (AJOL)

    Structured questionnaire administered to the 158 respondents were used to collect cross-sectional data on factors influencing the market participation ... credit, education, cooperative society membership and minituber yam, in order to significantly increase the decision to participate in selling minituber yam and the level of ...

  7. What Factors Determine the Uptake of A-level Physics?

    Science.gov (United States)

    Gill, Tim; Bell, John F.

    2013-03-01

    There has been much concern recently in the UK about the decline in the number of students studying physics beyond age 16. To investigate why this might be we used data from a national database of student qualifications and a multilevel modelling technique to investigate which factors had the greatest impact on the uptake of physics at Advanced Level (A-level) in a particular year. Each factor of interest was entered into a separate model, while accounting for prior attainment and gender (both well-known predictors of A-level uptake). We found that factors associated with greater probability of uptake included better attainment in physics (or combined science) and maths qualifications at age 16 in comparison to other subjects, and (for girls only) attending an independent or grammar school. While it is difficult to address these factors directly, the results imply that more needs to be done to improve relative performance at General Certificate of Secondary Education, perhaps by increasing the supply of specialist physics teachers at this level and to overcome the perception (especially among girls) that physics is a particularly difficult subject.

  8. High level expression of human basic fibroblast growth factor in ...

    African Journals Online (AJOL)

    High level expression of human basic fibroblast growth factor in Escherichia coli : Evaluating the effect of the GC content and rare codons within the first 13 codons. ... Nterminally modified genes were PCR amplified and cloned into the expression vector, pET-22b. Meanwhile, wild-type gene remarkably expressed in all the ...

  9. Determination of risk factors and level of awareness of caprine ...

    African Journals Online (AJOL)

    In Oju, goats are the major livestock kept and there is a well established goat market held every five days. This study was aimed at determining the risk factors associated with caprine brucellosis and assessing level of awareness amongst goat owners in Oju Local Government Area (LGA) of Benue State using a structured ...

  10. [Factors associated with low levels of aerobic fitness among adolescents].

    Science.gov (United States)

    Gonçalves, Eliane Cristina de Andrade; Silva, Diego Augusto Santos

    2016-06-01

    To evaluate the prevalence of low aerobic fitness levels and to analyze the association with sociodemographic factors, lifestyle and excess body fatness among adolescents of southern Brazil. The study included 879 adolescents aged 14 to 19 years the city of São José/SC, Brazil. The aerobic fitness was assessed by Canadian modified test of aerobic fitness. Sociodemographic variables (skin color, age, sex, study turn, economic level), sexual maturation and lifestyle (eating habits, screen time, physical activity, consumption of alcohol and tobacco) were assessed by a self-administered questionnaire. Excess body fatness was evaluated by sum of skinfolds triceps and subscapular. We used logistic regression to estimate odds ratios and 95% confidence intervals. Prevalence of low aerobic fitness level was 87.5%. The girls who spent two hours or more in front screen, consumed less than one glass of milk by day, did not smoke and had an excess of body fatness had a higher chance of having lower levels of aerobic fitness. White boys with low physical activity had had a higher chance of having lower levels of aerobic fitness. Eight out of ten adolescents were with low fitness levels aerobic. Modifiable lifestyle factors were associated with low levels of aerobic fitness. Interventions that emphasize behavior change are needed. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  11. B Cell-Activating Factor Regulates Different Aspects of B Cell Functionality and Is Produced by a Subset of Splenic B Cells in Teleost Fish

    Science.gov (United States)

    Tafalla, Carolina; González, Lucia; Castro, Rosario; Granja, Aitor G.

    2017-01-01

    In mammals, B cell functionality is greatly influenced by cytokines released by innate cells, such as macrophages or dendritic cells, upon the early recognition of common pathogen patterns through invariant receptors. B cell-activating factor (BAFF) is one of these innate B cell-helper signals and plays a key role in the survival and differentiation of B cells. Although, evolutionarily, teleost fish constitute the first animal group in which adaptive immunity based on Ig receptors is present, fish still rely greatly on innate responses. In this context, we hypothesized that BAFF would play a key role in the control of B cell responses in fish. Supporting this, our results show that teleost BAFF recapitulates mammalian BAFF stimulating actions on B cells, upregulating the expression of membrane MHC II, improving the survival of fish naïve B cells and antibody-secreting cells, and increasing the secretion of IgM. Surprisingly, we also demonstrate that BAFF is not only produced in fish by myeloid cells but is also produced by a subset of splenic B cells. Thus, if this B cell-produced BAFF proves to be actively regulating this same B cell subset, our findings point to an ancient mechanism to control B cell differentiation and survival in lower vertebrates, which has been silenced in mammals in physiological conditions, but reemerges under pathological conditions, such as B cell lymphomas and autoimmune diseases. PMID:28360916

  12. Base level Investigation in various buildings and corresponding effective factors

    Directory of Open Access Journals (Sweden)

    Mohsen Tehranizadeh

    2017-07-01

    Full Text Available Base level is one of the important parameters in determining the seismic force and preliminary design of structural sections. Base level, According to 2800 seismic regulations, in cases which the basement perimeter is executed with reinforced concrete walls integrated by structure, in addition with surrounding dense soil; set top of basement walls. The critical issue involved in determining base level is horizontal motion of the land. Usually horizontal movement of the Earth is transferred by shear and friction between the edges of the basement walls and foundation, also this process is completed by soil friction between underside of slabs and shallow. Different conditions such as non-same elevated foundations, soil type around building, soil-structure interaction and type of foundation are impressive on location of base level. Other factors including retaining wall openings in basement, basement floors and soil characteristics around the base structures affect base level coordination. As regards there is cleared definition for base level in different regulation all around the world, sometimes engineers cannot comprehend main purpose correctly, or concepts occasionally are interpreted inaccurately. When structure conditions little different from what normally there is, for example, buildings on slope, or structures on deep foundation such as piles, often experts are conflicted by finding location of base level in this status. In this paper investigations about base level in the past years expressed and studied, also, important issues around them are discussed.

  13. Serum IL-6 level and associated factors: hemodialysis patients

    Directory of Open Access Journals (Sweden)

    Seifi S, Mokhtari A

    2008-07-01

    Full Text Available "nBackground: The annual amount of mortality in ESRD exceeds the expectation and represents the recent evidences of the inflammation as its etiology. The etiology of inflammation is not clearly known. Chronic inflammation is a dominant occurrence of ESRD which increases the risk of atherosclerosis, malnutrition and peripheral vascular disease. Inflammatory responses are orchestrated by cytokines. Some of the proinflammatory cytokines like IL-6 have a crucial role in this phenomenon. The IL-6 and its receptor activity is up regulated in ESRD patients and the increased level of IL-6 predicts cardiovascular mortality and morbidity in normal and CRF patients. This study devotes itself to determining the serum level of IL-6 and factors affecting it in patients undergoing chronic hemodialysis in Imam Khomeini Hospital which can represent the Iranian Society. By identifying factors affecting the serum level of IL-6 and high-risk patients we can provide treatment possibilities, a decrease in mortality and an improvement in its prognosis. "n"nMethods: In this study 42 patients in Imam Dialysis Center were chosen and their serum IL-6 levels were measured at 2 times at three month interval and at the same time blood sample analysis were done for the following: Alb CPR, Ca, P, PTH, TIBC, Ferritin, TG, Chol, LDL, HDL, Uric Acid, Hb, WBC and urea."n"nResults: The mean serum level of IL-6 in hemodialysis patients was 6.35±4.47pg/ml (minimum: 0.55, maximum: 18.25 with the normal range of 1.3±3.2pg/ml."n"nConclusions: The IL-6 level was higher than normal range in the 52% of the patients. The serum IL-6 level had a significant correlations with CPR, Ferritin, TIBC, WBC and their serum IL-6 level was significantly higher in patients with hypertension, but no significant correlation was observed between other parameters and IL-6

  14. Exposure level of ergonomic risk factors in hotel industries

    Science.gov (United States)

    Nasrull Abdol Rahman, Mohd; Syahir Muhamad Jaffar, Mohd; Fahrul Hassan, Mohd; Zamani Ngali, Mohd; Pauline, Ong

    2017-08-01

    Ergonomic Risk Factors (ERFs) which contribute to Musculoskeletal Disorders (MSDs) among room attendants were considered as a problem or trouble since these ERFs would affect their work performance for hotel industries. The purpose of this study was to examine the exposure level of ERFs among room attendants in hotel industries. 65 of respondents were obtained from selected hotels in Peninsular Malaysia. Data were collected by direct observation via Workplace Ergonomic Risk Assessment (WERA) and Quick Exposure Checklist (QEC). There were 36 males and 29 females room attendants involved throughout the research. Most of room attendants experienced high exposure level for back, leg, forceful and vibration based on the exposure level evaluation through WERA while QEC results showed that all room attendants were found to have moderate exposure level for risk factors including back for movement use, shoulders/arms, wrists/hands and neck. All the results obtained showed that the related ERFs for MSDs were associated and essential ergonomic interventions are needed in order to eliminate risk of exposures to MSDs among room attendants in hotel industries.

  15. Environmental factors associated with blood lead levels in Venezuelan children.

    Science.gov (United States)

    Rojas, M; Squillante, G; Medina, E; de Rojas, O; Sarmiento, A

    2000-06-01

    A preliminary study explored the relative contribution of residential sources of lead exposure on mentally challenged children who attend "special education" institutions (GI) compared to a group of age and sex matched school children (G2). We captured descriptive information and analyzed demographic variables, personal and household information, medical effects, environmental exposure factors, and children habits. Home paint, dust, soil, and water sampling was conducted and blood lead (BPb) levels determined. Eighteen G1 and 20 G2 children were studied. The mean G1 BPb was 16.9 +/- 7.9 microg/dl and was significantly higher than that in G2. Fifty percent of G1 children had PbB >20 microg/dl and 72.2% were >10 microg/dl. Low muscular strength, decreased osteotendinose reflexes, fine and gross motricity, deficient equilibrium, and hipotonic muscular tone coincided with >18 microg/dl BPb levels. In 61.1% of G1 homes paint lead levels were higher than permissible levels and 33.3% had dust lead exceeding that level. The high BPb levels in G1 probably resulted from ingestion of household paint, dust, and soil via "hand-to-mouth" activity. Environmental exposure to lead can be an important source of lead intake by infants and children and could affect neurological development. This study provides new insights currently unavailable for these children in Venezuela.

  16. Dietary factors and fibroblast growth factor-23 levels in young adults with African ancestry.

    Science.gov (United States)

    Kosk, Dominique; Kramer, Holly; Luke, Amy; Camacho, Pauline; Bovet, Pascal; Rhule, Jacob Plange; Forrester, Terrence; Wolf, Myles; Sempos, Chris; Melamed, Michal L; Dugas, Lara R; Cooper, Richard; Durazo-Arvizu, Ramon

    2017-11-01

    Fibroblast growth factor-23 (FGF23), a phosphaturic hormone secreted mainly by osteocytes, maintains serum phosphate levels within a tight range by promoting phosphaturia. Previous studies have mainly focused on the link between FGF23 levels and dietary intake of phosphate, but other dietary factors may also influence FGF23 levels. This cross-sectional study pooled three populations of young adults with African ancestry (452 in Chicago, IL, USA; 477 in Victoria, Seychelles; and 482 in Kumasi, Ghana) with estimated glomerular filtration rate >80 ml/min/1.73 m 2 to examine the association of dietary factors based on two 24-h recalls with FGF23 levels measured using a C-terminal assay. Linear regression was used to examine the association between log-transformed FGF23 levels and quartiles of calorie-adjusted dietary factors with adjustment for covariates. In the pooled sample of 1411 study participants, the mean age was 35.2 (6.2) years and 45.3% were male. Median plasma C-terminal FGF23 values in relative units (RU)/ml were 59.5 [interquartile range (IQR) 44.1, 85.3] in the USA, 43.2 (IQR 33.1, 57.9) in Seychelles, and 34.0 (IQR 25.2, 50.4) in Ghana. With adjustment for covariates, increasing quartiles of calcium and animal protein and decreasing quartiles of vegetable protein, fiber, and magnesium intake were associated with significantly higher FGF23 levels compared to the lowest quartile. After further adjustment for dietary factors, significant trends in FGF23 levels were noted only for quartiles of calcium, fiber, and magnesium intake (P < 0.001). Dietary factors other than phosphate are associated with FGF23 levels in young adults.

  17. Sequential plasma angiogenic factors levels in women with suspected preeclampsia.

    Science.gov (United States)

    Baltajian, Kedak; Bajracharya, Surichhya; Salahuddin, Saira; Berg, Anders H; Geahchan, Carl; Wenger, Julia B; Thadhani, Ravi; Karumanchi, S Ananth; Rana, Sarosh

    2016-07-01

    Alterations in circulating angiogenic factors are associated with the diagnosis of preeclampsia and correlate with adverse perinatal outcomes during the third trimester. Analysis of the sequential levels of plasma angiogenic factors among patients admitted for evaluation of preeclampsia. We performed an observational study among women with singleton pregnancies admitted to Beth Israel Deaconess Medical Center, Boston, Massachusetts, for evaluation of preeclampsia at less than 37 weeks of gestation. Plasma samples were collected on admission and daily for the first 3 days and then weekly until delivery. Doppler ultrasound was performed on admission (within 48 hours) and then weekly (within 24 hours of blood collection) to evaluate uteroplacental and umbilical blood flows. Maternal demographics, hospital course, mode of delivery, diagnosis of hypertensive disorder, adverse maternal outcomes (elevated liver function enzymes, low platelet count, pulmonary edema, cerebral hemorrhage, convulsion, acute renal insufficiency, or maternal death), and adverse fetal/neonatal outcomes (small for gestational age, abnormal umbilical artery Doppler, fetal death, and neonatal death) were recorded. Circulating angiogenic factors (soluble fms-like tyrosine kinase and placental growth factor were measured on automated platform in a single batch after delivery and in a blinded fashion. Data are presented as median (25th to 75th centile), mean, or proportions as appropriate. During the study period, data from 100 women were analyzed for the study, and 43 had adverse outcomes. Women with adverse outcomes had lower gestational age of delivery, higher systolic and diastolic blood pressures during hospitalization, and lower birthweight and placental weight (all P preeclampsia, women at risk for adverse pregnancy outcomes have higher soluble fms-like tyrosine kinase/placental growth factor ratio on admission, which continued to rise until delivery. Women with high soluble fms-like tyrosine

  18. The global distribution of risk factors by poverty level.

    Science.gov (United States)

    Blakely, Tony; Hales, Simon; Kieft, Charlotte; Wilson, Nick; Woodward, Alistair

    2005-02-01

    To estimate the individual-level association of income poverty with being underweight, using tobacco, drinking alcohol, having access only to unsafe water and sanitation, being exposed to indoor air pollution and being obese. Using survey data for as many countries as possible, we estimated the relative risk association between income or assets and risk factors at the individual level within 11 medium- and low-income subregions of WHO. WHO and The World Bank data on the prevalence of risk factors and income poverty (defined as living on US$ 2.00 per day) were analysed to impute the association between poverty and risk factors for each subregion. The possible effect of poverty reduction on the prevalence of risk factors was estimated using population-attributable risk percentages. There were strong associations between poverty and malnutrition among children, having access only to unsafe water and sanitation, and being exposed to indoor air pollution within each subregion (relative risks were twofold to threefold greater for those living on US$ 2.00 per day). Associations between poverty and obesity, tobacco use and alcohol use varied across subregions. If everyone living on US$ 2.00 per day, 51% of exposures to unimproved water and sanitation could be avoided as could 37% of malnutrition among children and 38% of exposure to indoor air pollution. The more realistic, but still challenging, Millennium Development Goal of halving the number of people living on global health requires both poverty eradication and public health action. The methods used in this study may be useful for monitoring pro-equity progress towards Millennium Development Goals.

  19. Area-Level and Individual-Level Factors for Teenage Motherhood: A Multilevel Analysis in Japan.

    Science.gov (United States)

    Baba, Sachiko; Iso, Hiroyasu; Fujiwara, Takeo

    2016-01-01

    Teenage motherhood is strongly associated with a range of disadvantages for both the mother and the child. No epidemiological studies have examined related factors for teenage motherhood at both area and individual levels among Japanese women. Therefore, we performed a multilevel analysis of nationwide data in Japan to explore the association of area- and individual-level factors with teenage motherhood. The study population comprised 21,177 mothers living in 47 prefectures who had their first, singleton baby between 10 and 17 January or between 10 and 17 July, 2001. Information on the prefecture in which the mothers resided was linked to prefecture-level variables. Primary outcomes were area-level characteristics (single-mother households, three-generation households, college enrollment, abortions, juvenile crime, and per capita income) and individual-level characteristics, and divided into tertiles or quintiles based on their variable distributions. Multilevel logistic regression analysis was then performed. There were 440 teenage mothers (2.1%) in this study. In addition to individual low level of education [adjusted odds ratio (OR), 7.40; 95% confidence interval (CI), 5.59-9.78], low income [4.23 (2.95-6.08)], and smoking [1.65 (1.31-2.07)], high proportions of single-mother households [1.72 (1.05-2.80)] and three-generation household [1.81 (1.17-2.78)], and per capita income [2.19 (1.06-3.81)] at an area level were positively associated, and high level of college enrollment [0.46 (0.25-0.83)] and lower crime rate [0.62 (0.40-0.98)] at area level were inversely associated with teenage motherhood compared with the corresponding women living in prefectures with the lowest levels of these variables. Our findings suggest that encouraging the completion of higher education and reducing the number of single-mother household at an area level may be important public health strategies to reduce teenage motherhood.

  20. B-Cell-Activating Factor and the B-Cell Compartment in HIV/SIV Infection

    Science.gov (United States)

    Borhis, Gwenoline; Trovato, Maria; Chaoul, Nada; Ibrahim, Hany M.; Richard, Yolande

    2017-01-01

    With the goal to design effective HIV vaccines, intensive studies focused on broadly neutralizing antibodies, which arise in a fraction of HIV-infected people. Apart from identifying new vulnerability sites in the viral envelope proteins, these studies have shown that a fraction of these antibodies are produced by self/poly-reactive B-cells. These findings prompted us to revisit the B-cell differentiation and selection process during HIV/SIV infection and to consider B-cells as active players possibly shaping the helper T-cell program within germinal centers (GCs). In this context, we paid a particular attention to B-cell-activating factor (BAFF), a key cytokine in B-cell development and immune response that is overproduced during HIV/SIV infection. As it does in autoimmune diseases, BAFF excess might contribute to the abnormal rescue of self-reactive B-cells at several checkpoints of the B-cell development and impair memory B-cell generation and functions. In this review, we first point out what is known about the functions of BAFF/a proliferation-inducing ligand and their receptors [B-cell maturation, transmembrane activator and CAML interactor (TACI), and BAFF-R], in physiological and pathophysiological settings, in mice and humans. In particular, we highlight recent results on the previously underappreciated regulatory functions of TACI and on the highly regulated production of soluble TACI and BAFF-R that act as decoy receptors. In light of recent data on BAFF, TACI, and BAFF-R, we then revisit the altered phenotypes and functions of B-cell subsets during the acute and chronic phase of HIV/SIV infection. Given the atypical phenotype and reduced functions of memory B-cells in HIV/SIV infection, we particularly discuss the GC reaction, a key checkpoint where self-reactive B-cells are eliminated and pathogen-specific memory B-cells and plasmablasts/cells are generated in physiological settings. Through its capacity to differentially bind and process BAFF-R and

  1. Factors influencing exemplary science teachers' levels of computer use

    Science.gov (United States)

    Hakverdi, Meral

    This study examines exemplary science teachers' use of technology in science instruction, factors influencing their level of computer use, their level of knowledge/skills in using specific computer applications for science instruction, their use of computer-related applications/tools during their instruction, and their students' use of computer applications/tools in or for their science class. After a relevant review of the literature certain variables were selected for analysis. These variables included personal self-efficacy in teaching with computers, outcome expectancy, pupil-control ideology, level of computer use, age, gender, teaching experience, personal computer use, professional computer use and science teachers' level of knowledge/skills in using specific computer applications for science instruction. The sample for this study includes middle and high school science teachers who received the Presidential Award for Excellence in Science Teaching Award (sponsored by the White House and the National Science Foundation) between the years 1997 and 2003 from all 50 states and U.S. territories. Award-winning science teachers were contacted about the survey via e-mail or letter with an enclosed return envelope. Of the 334 award-winning science teachers, usable responses were received from 92 science teachers, which made a response rate of 27.5%. Analysis of the survey responses indicated that exemplary science teachers have a variety of knowledge/skills in using computer related applications/tools. The most commonly used computer applications/tools are information retrieval via the Internet, presentation tools, online communication, digital cameras, and data collection probes. Results of the study revealed that students' use of technology in their science classroom is highly correlated with the frequency of their science teachers' use of computer applications/tools. The results of the multiple regression analysis revealed that personal self-efficacy related to

  2. Aging and ABO blood type influence von Willebrand factor and factor VIII levels through interrelated mechanisms.

    Science.gov (United States)

    Albánez, S; Ogiwara, K; Michels, A; Hopman, W; Grabell, J; James, P; Lillicrap, D

    2016-05-01

    Essentials von Willebrand factor (VWF) and factor VIII (FVIII) levels are modulated by age and ABO status. The effect of aging and ABO blood type on VWF and FVIII was assessed in 207 normal individuals. Aging and ABO blood type showed combined and bidirectional influences on VWF and FVIII levels. Aging and ABO blood type influence VWF levels through both secretion and clearance mechanisms. Background The effect of aging and ABO blood type on plasma levels of von Willebrand factor (VWF) and factor VIII (FVIII) have been widely reported; however, a comprehensive analysis of their combined effect has not been performed and the mechanisms responsible for the age-related changes have not been determined. Objectives To assess the influence of aging and ABO blood type on VWF and FVIII levels, and to evaluate the contribution of VWF secretion and clearance to the age-related changes. Methods A cross-sectional observational study was performed in a cohort of 207 normal individuals, whose levels of VWF, FVIII, VWF propeptide (VWFpp), VWFpp/VWF:Ag ratio and blood type A antigen content on VWF (A-VWF) were quantified. Results Aging and ABO blood type exerted interrelated effects on VWF and FVIII plasma levels, because the age-related increase in both proteins was significantly higher in type non-O individuals (β = 0.011 vs. 0.005). This increase with age in non-O subjects drove the differences between blood types in VWF levels, as the mean difference increased from 0.13 U/mL in the young to 0.57 U/mL in the old. Moreover, A-VWF was associated with both VWF antigen (β = 0.29; 95% confidence interval [CI], 0.09, 0.50) and VWF clearance (β = -0.15; 95% CI, -0.25, -0.06). We also documented an effect of ABO blood type on VWF secretion with aging, as old individuals with blood type non-O showed higher levels of VWFpp (mean difference 0.29 U/mL). Conclusions Aging and ABO blood type have an interrelated effect on VWF and FVIII levels, where the effect of one is significantly

  3. Meteorological factors for PM10 concentration levels in Northern Spain

    Science.gov (United States)

    Santurtún, Ana; Mínguez, Roberto; Villar-Fernández, Alejandro; González Hidalgo, Juan Carlos; Zarrabeitia, María Teresa

    2013-04-01

    Atmospheric particulate matter (PM) is made up of a mixture of solid and aqueous species which enter the atmosphere by anthropogenic and natural pathways. The levels and composition of ambient air PM depend on the climatology and on the geography (topography, soil cover, proximity to arid zones or to the coast) of a given region. Spain has particular difficulties in achieving compliance with the limit values established by the European Union (based on recommendations from the World Health Organization) for particulate matter on the order of 10 micrometers of diameter or less (PM10), but not only antropogenical emissions are responsible for this: some studies show that PM10 concentrations originating from these kinds of sources are similar to what is found in other European countries, while some of the geographical features of the Iberian Peninsula (such as African mineral dust intrusion, soil aridity or rainfall) are proven to be a factor for higher PM concentrations. This work aims to describe PM10 concentration levels in Cantabria (Northern Spain) and their relationship with the following meteorological variables: rainfall, solar radiation, temperature, barometric pressure and wind speed. Data consists of daily series obtained from hourly data records for the 2000-2010 period, of PM10 concentrations from 4 different urban-background stations, and daily series of the meteorological variables provided by Spanish National Meteorology Agency. The method used for establishing the relationships between these variables consists of several steps: i) fitting a non-stationary probability density function for each variable accounting for long-term trends, seasonality during the year and possible seasonality during the week to distinguish between work and weekend days, ii) using the marginal distribution function obtained, transform the time series of historical values of each variable into a normalized Gaussian time series. This step allows using consistently time series

  4. The level satisfaction of teachers and motivational factors

    Directory of Open Access Journals (Sweden)

    Renata Červ

    2012-02-01

    Full Text Available RQ: Employee satisfaction is an area that is relevant in every organization and for this reason management has to pay special attention to this area. A satisfied worker brings better results and invests all their knowledge and abilities into their work. Otherwise they will invest only what is required of them that will not bring success to the organization in achieving their goals. Work satisfaction reflects an individual’s emotional experiences in theenvironment that they are working in. Many times management starts paying attention when it is too late. For this reason, measuring employee satisfaction should occur in each organization. This way appropriate actions and decisions can be made to improve current conditions.Purpose: To investigate employee satisfaction, determine the level of satisfaction or dissatisfaction and identify motivational factors. Furthermore, to examine how personal goals of individuals influence their work and to which degree money is a motivator for work.Methods: A descriptive approach was used to examine the the oretical content, interview. An interview was conducted with which data was obtained on employee satisfaction.Results: Employees are satisfied with their work and it gives them a personal challenge, offers satisfaction, a source of income and pleasure. They are motivated by pay, student satisfaction, and successful transference of knowledge to students. Possible dissatisfaction of employees would not influence their effectiveness and work results. They believe that fulfilling their personal goals can influence their satisfaction.Organization: The obtained data will be used by management for improvement. The obtained results will lead management in decision making to increase employee satisfaction.Society: Refresh knowledge from the area of creating employee satisfaction and motivational factors that influences people at work.Originality: The limited number of interview participants and personal acquaintance

  5. Exploring Serum Levels of Brain Derived Neurotrophic Factor and Nerve Growth Factor Across Glaucoma Stages.

    Directory of Open Access Journals (Sweden)

    Francesco Oddone

    Full Text Available To investigate the serum levels of Brain Derived Neurotrophic Factor (BDNF and Nerve Growth Factor (NGF in patients affected by primary open angle glaucoma with a wide spectrum of disease severity compared to healthy controls and to explore their relationship with morphological and functional glaucoma parameters.45 patients affected by glaucoma at different stages and 15 age-matched healthy control subjects underwent visual field testing, peripapillary retinal nerve fibre layer thickness measurement using Spectral Domain Optical Coherence Tomography and blood collection for both neurotrophins detection by Enzyme-Linked Immunosorbent Assay. Statistical analysis and association between biostrumental and biochemical data were investigated.Serum levels of BDNF in glaucoma patients were significantly lower than those measured in healthy controls (261.2±75.0 pg/ml vs 313.6±79.6 pg/ml, p = 0.03. Subgroups analysis showed that serum levels of BDNF were significantly lower in early (253.8±40.7 pg/ml, p = 0.019 and moderate glaucoma (231.3±54.3 pg/ml, p = 0.04 but not in advanced glaucoma (296.2±103.1 pg/ml, p = 0.06 compared to healthy controls. Serum levels of NGF in glaucoma patients were significantly lower than those measured in the healthy controls (4.1±1 pg/mL vs 5.5±1.2 pg/mL, p = 0.01. Subgroups analysis showed that serum levels of NGF were significantly lower in early (3.5±0.9 pg/mL, p = 0.0008 and moderate glaucoma (3.8±0.7 pg/ml, p<0.0001 but not in advanced glaucoma (5.0±0.7 pg/ml, p = 0.32 compared to healthy controls. BDNF serum levels were not related to age, visual field mean deviation or retinal nerve fibre layer thickness either in glaucoma or in controls while NGF levels were significantly related to visual field mean deviation in the glaucoma group (r2 = 0.26, p = 0.004.BDNF and NGF serum levels are reduced in the early and moderate glaucoma stages, suggesting the possibility that both factors could be further investigated

  6. Cacao in México: Restrictive factors and productivity levels

    Directory of Open Access Journals (Sweden)

    Julio Díaz-José

    2014-12-01

    Full Text Available Cacao (Theobroma cacao L. represents one of the most important agricultural crops of the humid Mexican tropics. In the last 10 yr, approximately 23.000 t of this grain were no longer produced per cycle. The objective of this study was to identify characteristics and factors that restrict production in the states of Tabasco and Chiapas. A survey was applied to obtain information about 184 producers and their plantations by two-stage sampling. Descriptive statistics were calculated and multilevel models were adjusted to analyze the information. Results show that there are differences (P < 0.05 in cacao yield between municipalities (380 kg ha-1 + u,o j is the estimated residual for each municipality. Crop productivity levels are higher in the state of Tabasco than in Chiapas (644 and 344 kg ha-1, respectively. Incidence of frosty pod rot of cacoa, also known as moniliasis, induced by Moniliophthora roreri [(Cif H.C. Evans, Stalpers, Samson & Benny 1978] is significantly greater (P < 0.05 in the state of Chiapas (60% than in Tabasco (48%.Producers who carry out more crop management practices increase yields and decrease the pathogen's impact on their plantations. Results suggest the need to apply differentiated public policies to promote production within each region or municipality.

  7. FACTORS IN OSCAR RATINGS OF SECONDARY LEVEL STUDENT-TEACHERS.

    Science.gov (United States)

    MERRIFIELD, PHILIP R.; AND OTHERS

    THIS FACTOR ANALYTIC STUDY OF OSCAR (OBSERVATION SCHEDULE AND RECORDS) SCORES FOR CLASSROOM BEHAVIOR EMPLOYED RATINGS BY SUPERVISING FACULTY MEMBERS OF THE CLASSROOM BEHAVIORS OF 115 STUDENT TEACHERS AND THEIR PUPILS ON THREE OCCASIONS APPROXIMATELY 1 MONTH APART. FIVE FACTORS WHICH COULD BE INTERPRETED AS INDEPENDENT ASPECTS OF TEACHER AND PUPIL…

  8. Fluctuating levels of reprogramming factor expression in cultured ...

    African Journals Online (AJOL)

    user

    Although human undifferentiated keratinocytes (HUKs) can be reprogrammed to become induced pluripotent stem cells (iPSCs) with high efficiency and rapid kinetics by transducing reprogramming factors (RFs), the endogenous expression of reprogramming factors in cultured HUKs is not clear at different stages. In this ...

  9. Human factors evaluation of level 2 and level 3 automated driving concepts : concepts of operation.

    Science.gov (United States)

    2014-07-01

    The Concepts of Operation document evaluates the functional framework of operations for Level 2 and Level 3 automated vehicle systems. This is done by defining the varying levels of automation, the operator vehicle interactions, and system components...

  10. Strength training and testosterone treatment have opposing effects on migration inhibitor factor levels in ageing men

    DEFF Research Database (Denmark)

    Glintborg, D.; Christensen, L. L.; Kvorning, T.

    2013-01-01

    Strength Training and Testosterone Treatment Have Opposing Effects on Migration Inhibitor Factor Levels in Ageing Men......Strength Training and Testosterone Treatment Have Opposing Effects on Migration Inhibitor Factor Levels in Ageing Men...

  11. B-cell activating factor in the pathophysiology of multiple myeloma: a target for therapy?

    NARCIS (Netherlands)

    Hengeveld, P. J.; Kersten, M. J.

    2015-01-01

    Multiple myeloma (MM) is a currently incurable malignancy of plasma cells. Malignant myeloma cells (MMCs) are heavily dependent upon the bone marrow (BM) microenvironment for their survival. One component of this tumor microenvironment, B-Cell Activating Factor (BAFF), has been implicated as a key

  12. Importance of high triglycerides levels between novel coronary risk factors

    Directory of Open Access Journals (Sweden)

    Valmore Bermúdez

    2017-11-01

    Full Text Available Introduction: The analysis of new cardiovascular risk factors is under an extensive debate in the cardiology and metabolic research fields. Objective: To determine the main factors that contribute to the classification of individuals with higher coronary risk in the adult population from Maracaibo, Venezuela. Methods: A descriptive, cross-sectional study with multistage random sampling in 1379 individuals belonging to the Maracaibo City Metabolic Syndrome Prevalence Study (MMSPS was performed. They were classified according to the coronary risk by Framingham-Wilson equation adapted to our population. The association between various risk factors was evaluated by ordinal logistic regression models. Results: 1,379 subjects (females 55.9%; n = 771 were evaluated, 66.2% (n = 913 were classified with low coronary risk. In univariate (χ2 = 112.35; p < 0.00001 and multivariate analysis [OR: 3.98 (2.39-6.63; p < 0.01], the main factors associated to be classified as the highest risk category were hypertriglyceridemia. Conclusion: There are several factors that should be included in predictive models use worldwide. The most important in our population were dyslipidemia such as hypertriglyceridemia, hyperlipoproteinemia (a and insulin resistance. Resumen: Introducción: El análisis de nuevos factores de riesgo cardiovascular constituye un tema de amplio debate en la investigación cardio-metabólica. Objetivo: Determinar los principales factores que contribuyen a la clasificación de sujetos en las categorías de mayor riesgo coronario en individuos adultos de la ciudad de Maracaibo, Venezuela. Métodos: Estudio descriptivo, trasversal con muestreo aleatorio multietapas en 1.379 individuos pertenecientes al Estudio de Prevalencia de Síndrome Metabólico de la Ciudad de Maracaibo (EPSMM. Estos fueron clasificaron de acuerdo con el riesgo coronario mediante la fórmula Framingham-Wilson adaptada para

  13. Grade Level Differences in Factors of Self-Esteem

    Science.gov (United States)

    Kokenes, Barbara

    1974-01-01

    Investigated the construct validity of the Coopersmith Self Esteem Inventory, using approximately 1500 elementary school students. Also investigated grade level differences in preadolescent and adolescent children. (Author/ED)

  14. Plasma transforming growth factor beta levels in breast cancer patients

    NARCIS (Netherlands)

    Sminia, P; Barten, AD; Van Waarde, MAWH; Vujaskovic, Z; Van Tienhoven, G

    1998-01-01

    We investigated whether the concentration of circulating transforming growth factor beta (TGF beta) yields diagnostic value in breast cancer. Blood was collected from twenty stage I and II breast cancer patients both prior to treatment and after surgical excision of the tumour. Both latent and

  15. Plasma transforming growth factor beta levels in breast cancer patients

    NARCIS (Netherlands)

    Sminia, P.; Barten, A. D.; van Waarde, M. A.; Vujaskovic, Z.; van Tienhoven, G.

    1998-01-01

    We investigated whether the concentration of circulating transforming growth factor beta (TGFbeta) yields diagnostic value in breast cancer. Blood was collected from twenty stage I and II breast cancer patients both prior to treatment and after surgical excision of the tumour. Both latent and active

  16. Cardiovascular Risk Factor Levels in Adults with Mental Retardation.

    Science.gov (United States)

    Rimmer, James H.; And Others

    1994-01-01

    Comparison of cardiovascular risk factors (blood lipids, obesity, and smoking) in 329 adults with mental retardation residing in various settings with subjects in the Framingham Offspring Study found that adults with mental retardation had cardiovascular risk profiles similar to those of individuals without mental retardation. (Author/DB)

  17. Psychopathy and Violence: The Importance of Factor Level Interactions

    Science.gov (United States)

    Walsh, Zach; Kosson, David S.

    2008-01-01

    The power of scales based on the Psychopathy Checklist (PCL; R. D. Hare, 1980) for prediction of violent behavior is well established. Although evidence suggests that this relationship is chiefly due to the impulsive and antisocial lifestyle component (Factor 2), the predictive power of psychopathy for violence may also reflect the multiplicative…

  18. Affective factors which relate to dance on secondary school level ...

    African Journals Online (AJOL)

    between dance achievement and motivation, anxiety or self-concept. Similarly, no significant differences could be identified between the affective factors in the different grades. Keywords: Motivation; Stress; Anxiety; Self-concept; Affective variables; Dance achievement. South African Journal for Research in Sport, Physical ...

  19. Serum levels of macrophage migration inhibitory factor in children ...

    African Journals Online (AJOL)

    Background: There is growing awareness of an immunological involvement in children with autistic disorder (AD). Studies suggest that innate rather than adaptive neuroimmune responses are associated with autism. Macrophage migration inhibitory factor (MIF), being an upstream regulator of innate and adaptive immunity, ...

  20. What Factors Determine the Uptake of A-Level Physics?

    Science.gov (United States)

    Gill, Tim; Bell, John F.

    2013-01-01

    There has been much concern recently in the UK about the decline in the number of students studying physics beyond age 16. To investigate why this might be we used data from a national database of student qualifications and a multilevel modelling technique to investigate which factors had the greatest impact on the uptake of physics at Advanced…

  1. BAFF, APRIL, TWEAK, BCMA, TACI and Fn14 proteins are related to human glioma tumor grade: immunohistochemistry and public microarray data meta-analysis.

    Directory of Open Access Journals (Sweden)

    Vassiliki Pelekanou

    Full Text Available Gliomas are common and lethal tumors of the central nervous system (CNS. Genetic alterations, inflammatory and angiogenic processes have been identified throughout tumor progression; however, treatment still remains palliative for most cases. Biological research on parameters influencing cell survival, invasion and tumor heterogeneity identified several cytokines interfering in CNS inflammation, oxidative stress and malignant transformation, including TNF-superfamily (TNFSF members. In this report we performed a meta-analysis of public gene-array data on the expression of a group of TNFSF ligands (BAFF, APRIL, TWEAK and their receptors (BAFF-R, TACI, BCMA, Fn14 in gliomas. In addition, we investigated by immunohistochemistry (IHC the tumor cells' expression of these ligands and receptors in a series of 56 gliomas of different grade. We show that in IHC, BAFF and APRIL as well as their cognate receptors (BCMA, TACI and Fn14 expression correlate with tumor grade. This result was not evidenced in micro-arrays meta-analysis. Finally, we detected for the first time Fn14, BAFF, BCMA and TACI in glioma-related vascular endothelium. Our data, combined with our previous report in glioma cell lines, suggest a role for these receptors and ligands in glioma biology and advance these molecules as potential markers for the classification of these tumors to the proliferative, angiogenic or stem-like molecular subtype.

  2. Food choices, physical activity levels and other factors associated ...

    African Journals Online (AJOL)

    The aim of the study was to evaluate educators' health behaviours regarding dietary intake and physical activity (PA). A survey was undertaken in 517 educators at 83 primary schools in the Western Cape. Food choices (healthy vs. unhealthy), PA levels, and health knowledge were measured by questionnaire. The six most ...

  3. Factors associated with high cholesterol levels among adults in ...

    African Journals Online (AJOL)

    Esem

    Conclusion: A series of surveys to determine changes in total and LDL cholesterol are needed to estimate changes in the health level of the residents in Lusaka. These results could be used in the formulation of an action plan to prevent and control high cholesterol and its consequences among Zambian urban residents.

  4. Math Anxiety--Contributing School and Individual Level Factors

    Science.gov (United States)

    Radišic, Jelena; Videnovic, Marina; Baucal, Aleksander

    2015-01-01

    PISA 2003 survey data indicate high levels of mathematics anxiety among students in Serbia. More than a half of Serbian students are concerned with whether they will have difficulties in a mathematics class or earn poor marks. At the same time, the achievement on the mathematical literacy scale is very poor. Building on control-value theory, the…

  5. Propagation & Level: Factors Influencing in the ICT Composite Index at the School Level

    Science.gov (United States)

    Aoki, Hiroyuki; Kim, JaMee; Lee, WonGyu

    2013-01-01

    Many nations are greatly affected by their education policies, and the educational level of different schools is relevant to a nation's ICT policy. In the area of ICT, Korea has achieved quite high levels of competency. This study analyzed the level of ICT competency of 4490 elementary and 2419 middle schools in Korea within the context of the…

  6. Toll-like receptor 9 activation enhances B cell activating factor and interleukin-21 induced anti-proteinase 3 autoantibody production in vitro

    NARCIS (Netherlands)

    Lepse, Nikola; Land, Judith; Rutgers, Abraham; Kallenberg, Cees G. M.; Stegeman, Coen A.; Abdulahad, Wayel H.; Heeringa, Peter

    Objectives. Granulomatosis with polyangiitis (GPA) is a relapsing small-vessel vasculitis characterized by circulating ANCA against PR3. The mechanisms that trigger PR3-ANCA production are unknown. The aim of this study was to determine whether endogenous factors [B cell activating factor (BAFF) and

  7. Global Sourcing, Technology, and Factor Intensity: Firm-level Relationships

    OpenAIRE

    TOMIURA Eiichi

    2007-01-01

    This paper empirically examines how technology and capital intensity are related with the firm's global sourcing decision. Firm-level data are derived from a survey covering all manufacturing industries in Japan without any firm-size threshold. Firms are disaggregated by their make-or-buy decision (in-house or outsourcing) and by their choice of sourcing location (offshore or domestic). Capital-intensive or R&D-intensive firms tend to source in-house from their FDI affiliates rather than outs...

  8. Systemic and intestinal levels of factor XIII-A

    DEFF Research Database (Denmark)

    Søndergaard, Christoffer; Kvist, Peter Helding; Seidelin, Jakob Benedict

    2016-01-01

    , indicating a reduction of the M2 phenotype with consequent loss of FXIII-A. No induction of iNOS positive macrophages was observed. Stimulation of naïve monocytes with physiological concentrations of pro-inflammatory mediators negatively affected the expression of FXIII-A. Measurements in plasma confirmed...... the loss of both FXIII antigen and activity during active disease. CONCLUSIONS: Intestinal inflammation in UC induces loss of M2 macrophages with subsequent loss of FXIII-A synthesis. The loss of cellular FXIII-A may impact migration and phagocytosis, and hence limit pathogen eradication in UC.......BACKGROUND: Subunit A of coagulation factor XIII (FXIII-A) is important for clot stability and acts in the subsequent wound healing process. Loss of plasma FXIII-A has been reported after surgery, sepsis, and inflammatory conditions. In the intestinal mucosa, FXIII-A is expressed by macrophages...

  9. Ecological factors affect the level and scaling of avian BMR.

    Science.gov (United States)

    McNab, Brian Keith

    2009-01-01

    The basal rate of metabolism (BMR) in 533 species of birds, when examined with ANCOVA, principally correlates with body mass, most of the residual variation correlating with food habits, climate, habitat, a volant or flightless condition, use or not of torpor, and a highland or lowland distribution. Avian BMR also correlates with migratory habits, if climate and a montane distribution is excluded from the analysis, and with an occurrence on small islands if a flightless condition and migration are excluded. Residual variation correlates with membership in avian orders and families principally because these groups are behaviorally and ecologically distinctive. However, the distinction between passerines and other birds remains a significant correlate of avian BMR, even after six ecological factors are included, with other birds having BMRs that averaged 74% of the passerine mean. This combination of factors accounts for 97.7% of the variation in avian BMR. Yet, migratory species that belong to Anseriformes, Charadriiformes, Pelecaniformes, and Procellariiformes and breed in temperate or polar environments have mass-independent basal rates equal to those found in passerines. In contrast, penguins belong to an order of polar, aquatic birds that have basal rates lower than passerines because their flightless condition depresses basal rate. Passerines dominate temperate, terrestrial environments and the four orders of aquatic birds dominate temperate and polar aquatic environments because their high BMRs facilitate reproduction and migration. The low BMRs of tropical passerines may reflect a sedentary lifestyle as much as a life in a tropical climate. Birds have BMRs that are 30-40% greater than mammals because of the commitment of birds to an expensive and expansive form of flight.

  10. Factors other than chloride level influencing rate of reinforcement

    Energy Technology Data Exchange (ETDEWEB)

    Castel, A.; Arliguie, G. [Paul Sabatier Univ., Toulouse (France); Francois, R. [Institut National Des Sciences Appliques, Toulouse (France)

    2000-07-01

    To evaluate the degree of corrosion a 14 year-old concrete member was completely bared and three meter-long beams were stored in three-point flexion in an aggressive environment by sequences of drying and wetting by a salt fog. Total chloride content was measured at the level of all reinforcements. Despite the small concrete cover of 10 mm at the stirrups and 16 mm for the longitudinal reinforcement, no evidence was found to relate corrosion to chloride content, since a large part of the reinforcement was not affected by corrosion. It was concluded that the steel-concrete interface had a major influence on being able to predict the onset of corrosion in relation to chloride content. Indeed, corrosion damage was only present when the steel-concrete interface was damaged. These results call into question the validity of the chloride threshold as the single determining criterion to forecast corrosion development. It is suggested that the nature of the interface between steel and concrete, which may be randomly distributed along the reinforcements, should also be considered. Experimental evidence shows that steel-concrete interface damage is linked to non-elastic behaviour of bond that occurs at a given level of mechanical loading. Therefore, corrosion damage is best considered as a deterministic phenomenon linked to a bonding damage. 25 refs., 2 tabs., 10 figs.

  11. Factors influencing the transport accessibility level - seniors point of view

    Energy Technology Data Exchange (ETDEWEB)

    Zakowska, L.; Pulawska-Obiedowska, S.

    2016-07-01

    The growing group of European older inhabitants, namely senior citizens (aged + 65) belong to the most vulnerable group to social exclusion. Transport accessibility is a concept, that can lead to enhancing life quality of seniors, which is shown based on the case study of Cracow, Poland as a European city. 100 seniors, that are living in different areas (urban, suburban), were asked for define different aspects that may influence their travel behaviour. Respondents were indicating their individual concerns connected with travelling, the existing barriers and expected solutions.The goal of the paper is to present the main outcomes of the conducted surveys, in order to present the concept of transport accessibility in the context of the most important factors influencing seniors life quality. The accessibility conditions and barriers, which can affect mobility possibilities and different activities of senior citizens in urban areas, are indicated in the paper. The identification of the crucial aspects of accessibility play an important role in development of sustainable transport system together with sustainable urban design, that will be friendly for all citizens in aging society. (Author)

  12. Impairment of mature B-cell maintenance upon combined deletion of the alternative NF-κB transcription factors RELB and NF-κB2 in B cells$

    Science.gov (United States)

    De Silva, Nilushi S.; Silva, Kathryn; Anderson, Michael M.; Bhagat, Govind; Klein, Ulf

    2016-01-01

    B-cell activating factor (BAFF) is critical for the survival and maturation of mature B-cells. BAFF, via the BAFF receptor (BAFFR), activates multiple signaling pathways in B-cells, including the alternative nuclear factor-κB (NF-κB) pathway. The transcription factors RELB and NF-κB2 (p100/p52) are the downstream mediators of the alternative pathway; however, the B-cell-intrinsic functions of these NF-κB subunits have not been studied in vivo using conditional alleles, either individually or in combination. We here report that B-cell-specific deletion of relb led to only a slight decrease in the fraction of mature splenic B cells, whereas deletion of nfkb2 caused a marked reduction. This phenotype was further exacerbated upon combined deletion of relb and nfkb2 and most dramatically affected the maintenance of marginal zone B-cells. BAFF-stimulation, in contrast to CD40-activation, was unable to rescue relb/nfkb2-deleted B-cells in vitro. RNA-sequencing analysis of BAFF-stimulated nfkb2-deleted vs. normal B-cells suggests that the alternative NF-κB pathway, in addition to its critical role in BAFF-mediated cell survival, may control the expression of genes involved in the positioning of B-cells within the lymphoid microenvironment and in the establishment of T-cell-B-cell interactions. Thus, by ablating the downstream transcription factors of the alternative NF-κB pathway specifically in B-cells, we here identify a critical role for the combined activity of the RELB and NF-κB2 subunits in B-cell homeostasis that cannot be compensated for by the canonical NF-κB pathway under physiological conditions. PMID:26851215

  13. Factor V antigen levels and venous thrombosis: Risk profile, interaction with factor V leiden, and relation with factor VII antigen levels

    NARCIS (Netherlands)

    Kamphuisen, P.W.; Rosendaal, F.R.; Eikenboom, J.C.J.; Bos, R.; Bertina, R.M.

    2000-01-01

    Clotting factor V has a dual function in coagulation: after activation, procoagulant factor V stimulates the formation of thrombin, whereas anticoagulant factor V acts as a cofactor for activated protein C (APC) in the degradation of factor VIII/VIIIa, thereby reducing thrombin formation. In the

  14. Low-risk factor profile, estrogen levels, and breast cancer risk among postmenopausal women

    DEFF Research Database (Denmark)

    Rod, Naja Hulvej; Hansen, Ase Marie; Nielsen, Jens

    2008-01-01

    Obesity, alcohol consumption, physical inactivity and postmenopausal hormone use are known modifiable risk factors for breast cancer. We aim to measure incidence rates of breast cancer for women with favorable levels on all 4 risk factors (BMI......Obesity, alcohol consumption, physical inactivity and postmenopausal hormone use are known modifiable risk factors for breast cancer. We aim to measure incidence rates of breast cancer for women with favorable levels on all 4 risk factors (BMI...

  15. HIV-1 adenoviral vector vaccines expressing multi-trimeric BAFF and 4-1BBL enhance T cell mediated anti-viral immunity.

    Directory of Open Access Journals (Sweden)

    Saravana Kanagavelu

    Full Text Available Adenoviral vectored vaccines have shown considerable promise but could be improved by molecular adjuvants. Ligands in the TNF superfamily (TNFSF are potential adjuvants for adenoviral vector (Ad5 vaccines based on their central role in adaptive immunity. Many TNFSF ligands require aggregation beyond the trimeric state (multi-trimerization for optimal biological function. Here we describe Ad5 vaccines for HIV-1 Gag antigen (Ad5-Gag adjuvanted with the TNFSF ligands 4-1BBL, BAFF, GITRL and CD27L constructed as soluble multi-trimeric proteins via fusion to Surfactant Protein D (SP-D as a multimerization scaffold. Mice were vaccinated with Ad5-Gag combined with Ad5 expressing one of the SP-D-TNFSF constructs or single-chain IL-12p70 as adjuvant. To evaluate vaccine-induced protection, mice were challenged with vaccinia virus expressing Gag (vaccinia-Gag which is known to target the female genital tract, a major route of sexually acquired HIV-1 infection. In this system, SP-D-4-1BBL or SP-D-BAFF led to significantly reduced vaccinia-Gag replication when compared to Ad5-Gag alone. In contrast, IL-12p70, SP-D-CD27L and SP-D-GITRL were not protective. Histological examination following vaccinia-Gag challenge showed a dramatic lymphocytic infiltration into the uterus and ovaries of SP-D-4-1BBL and SP-D-BAFF-treated animals. By day 5 post challenge, proinflammatory cytokines in the tissue were reduced, consistent with the enhanced control over viral replication. Splenocytes had no specific immune markers that correlated with protection induced by SP-D-4-1BBL and SP-D-BAFF versus other groups. IL-12p70, despite lack of anti-viral efficacy, increased the total numbers of splenic dextramer positive CD8+ T cells, effector memory T cells, and effector Gag-specific CD8+ T cells, suggesting that these markers are poor predictors of anti-viral immunity in this model. In conclusion, soluble multi-trimeric 4-1BBL and BAFF adjuvants led to strong protection from

  16. Alternative complement pathway and factor B activities in rats with altered blood levels of thyroid hormone

    International Nuclear Information System (INIS)

    Bitencourt, C.S.; Duarte, C.G.; Azzolini, A.E.C.S.; Assis-Pandochi, A.I.

    2012-01-01

    Evaluating the activity of the complement system under conditions of altered thyroid hormone levels might help elucidate the role of complement in triggering autoimmune processes. Here, we investigated alternative pathway (AP) activity in male Wistar rats (180 ± 10 g) after altering their thyroid hormone levels by treatment with triiodothyronine (T3), propylthiouracil (PTU) or thyroidectomy. T3 and thyroxine (T4) levels were determined by chemiluminescence assays. Hemolytic assays were performed to evaluate the lytic activity of the AP. Factor B activity was evaluated using factor B-deficient serum. An anti-human factor B antibody was used to measure factor B levels in serum by radial immunodiffusion. T3 measurements in thyroidectomized animals or animals treated with PTU demonstrated a significant reduction in hormone levels compared to control. The results showed a reduction in AP lytic activity in rats treated with increasing amounts of T3 (1, 10, or 50 µg). Factor B activity was also decreased in the sera of hyperthyroid rats treated with 1 to 50 µg T3. Additionally, treating rats with 25 µg T3 significantly increased factor B levels in their sera (P < 0.01). In contrast, increased factor B concentration and activity (32%) were observed in hypothyroid rats. We conclude that alterations in thyroid hormone levels affect the activity of the AP and factor B, which may in turn affect the roles of AP and factor B in antibody production

  17. Factor Structure and Specific Variance of the WPPSI Subtests at Six Age Levels.

    Science.gov (United States)

    Carlson, Les; Reynolds, Cecil R.

    1981-01-01

    The Wechsler Preschool and Primary Scale of Intelligence (WPPSI) was factor analyzed at each of six age levels between four and six-plus years through the method of principal factors. Results substantially support Wechsler's division of the WPPSI subtests into a Verbal and a Performance scale at all age levels. (Author)

  18. Partial Safety Factors and Target Reliability Level in Danish Structural Codes

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Hansen, J. O.; Nielsen, T. A.

    2001-01-01

    The partial safety factors in the newly revised Danish structural codes have been derived using a reliability-based calibration. The calibrated partial safety factors result in the same average reliability level as in the previous codes, but a much more uniform reliability level has been obtained...

  19. Multi-Level Model of Contextual Factors and Teachers' Assessment Practices: An Integrative Review of Research

    Science.gov (United States)

    Fulmer, Gavin W.; Lee, Iris C. H.; Tan, Kelvin H. K.

    2015-01-01

    We present a multi-level model of contextual factors that may influence teachers' assessment practices, and use this model in a selected review of existing literature on teachers' assessment knowledge, views and conceptions with respect to these contextual factors. Adapting Kozma's model, we distinguish three levels of influence on teachers'…

  20. Geographic factors related to site suitability of low-level waste disposal

    International Nuclear Information System (INIS)

    Zittel, H.E.

    1981-01-01

    A number of factors related to the site suitability of low-level waste disposal sites are discussed. The factors are a combination of those which might be considered environmental and those dealing with site criteria. Among the factors covered are: possible population criteria, alternative site selection, transportation criteria and community involvement considerations. All these factors are discussed in a manner based on the premise that the technology exists to carry out low-level waste disposal in a manner such that public health and safety can be insured. The conclusion of the discussion is that problems encountered in siting low-level waste facilities will be largely societal and political in nature

  1. Neonatal levels of neurotrophic factors and risk of autism spectrum disorders

    DEFF Research Database (Denmark)

    Abdallah, Morsi; Mortensen, E L; Greaves-Lord, K

    2013-01-01

    To examine levels of 3 neurotrophic factors (NTFs): Brain derived neurotrophic factor (BDNF), Neurotrophin-4 (NT-4), and transforming growth factor-β (TGF-β) in dried blood spot samples of neonates diagnosed with autism spectrum disorders (ASD) later in life and frequency-matched controls....

  2. Empirical Analysis Of Factors Influencing The Level Of Job Satisfaction Of Caucasian And Hispanic Accounting Professionals

    OpenAIRE

    Glen D. Moyes; Tammi C. Redd

    2011-01-01

    This study examines the effect of 78 work-related variables on the level of job satisfaction of Caucasian and Hispanic accounting professionals. Factor analysis with Varimax Rotation reduced the number of variables to 12 factor groups for the Caucasian accountants and 11 factor groups for the Hispanic accountants. Data were analyzed using multiple regression models using the level of job satisfaction perceived by the Caucasian or Hispanic accountants as the dependent variable. From the Caucas...

  3. Risk factors for unstable blood glucose level: integrative review of the risk factors related to the nursing diagnosis

    Directory of Open Access Journals (Sweden)

    Andressa Magalhães Teixeira

    Full Text Available ABSTRACT Objective: to identify evidence in the literature on the possible risk factors for the risk of unstable blood glucose diagnosis in individuals with type 2 diabetes mellitus, and to compare them with the risk factors described by NANDA International. Method: an integrative literature review guided by the question: what are the risk factors for unstable blood glucose level in people with type 2 diabetes mellitus? Primary studies were included whose outcomes were variations in glycemic levels, published in English, Portuguese or Spanish, in PubMed or CINAHL between 2010 and 2015. Results: altered levels of glycated hemoglobin, body mass index>31 kg/m2, previous history of hypoglycemia, cognitive deficit/dementia, autonomic cardiovascular neuropathy, comorbidities and weight loss corresponded to risk factors described in NANDA International. Other risk factors identified were: advanced age, black skin color, longer length of diabetes diagnosis, daytime sleepiness, macroalbuminuria, genetic polymorphisms, insulin therapy, use of oral antidiabetics, and use of metoclopramide, inadequate physical activity and low fasting glycemia. Conclusions: risk factors for the diagnosis, risk for unstable blood glucose level, for persons with type 2 diabetes mellitus were identified, and 42% of them corresponded to those of NANDA International. These findings may contribute to the practice of clinical nurses in preventing the deleterious effects of glycemic variation.

  4. Decreased levels of brain-derived neurotrophic factor in the remitted state of unipolar depressive disorder

    DEFF Research Database (Denmark)

    Hasselbalch, Jacob; Knorr, U; Bennike, B

    2012-01-01

    Decreased levels of peripheral brain-derived neurotrophic factor (BDNF) have been associated with depression. It is uncertain whether abnormally low levels of BDNF in blood are present beyond the depressive state and whether levels of BDNF are associated with the course of clinical illness....

  5. The effects of student-level and classroom-level factors on elementary students' science achievement in five countries

    Science.gov (United States)

    Kaya, Sibel

    The interest in raising levels of achievement in math and science has led to a focus on investigating the factors that shape achievement in these subjects (Lamb & Fullarton, 2002) as well as understanding how these factors operate across countries (Baker, Fabrega, Galindo, & Mishook, 2004). The current study examined the individual student factors and classroom factors on fourth grade science achievement within and across five countries. Guided by the previous school learning models, the elements of students' science learning were categorized as student-level and classroom-level factors. The student-level factors included gender, self-confidence in science, and home resources. The classroom-level factors included teacher characteristics, instructional variables and classroom composition. Results for the United States and four other countries, Singapore, Japan, Australia, and Scotland were reported. Multilevel effects of student and classroom variables were examined through Hierarchical Linear Modeling (HLM) using the Trends in International Mathematics and Science Study (TIMSS) 2003 fourth grade dataset. The outcome variable was the TIMSS 2003 science score. Overall, the results of this study showed that selected student background characteristics were consistently related to elementary science achievement in countries investigated. At the student-level, higher levels of home resources and self-confidence and at the classroom-level, higher levels of class mean home resources yielded higher science scores on the TIMSS 2003. In general, teacher and instructional variables were minimally related to science achievement. There was evidence of positive effects of teacher support in the U.S. and Singapore. The emphasis on science inquiry was positively related to science achievement in Singapore and negatively related in the U.S. and Australia. Experimental studies that investigate the impacts of teacher and instructional factors on elementary science achievement are

  6. Low levels of anti-secretory factor in placenta are associated with preterm birth and inflammation.

    Science.gov (United States)

    Gustafsson, Anna M; Fransson, Emma; Dubicke, Aurelija; Hjelmstedt, Anna K; Ekman-Ordeberg, Gunvor; Silfverdal, Sven-Arne; Lange, Stefan; Jennische, Eva; Bohlin, Kajsa

    2018-03-01

    Anti-secretory factor is a protein that regulates secretory and inflammatory processes and preterm birth is associated with inflammation. Therefore, our hypothesis was that anti-secretory factor might play a role in immune reactivity and homeostasis during pregnancy. Following spontaneous onset of labor and preterm or term delivery, placenta biopsies were collected. The levels of anti-secretory factor and markers of inflammation (CD68, CD163) and vascularization (CD34, smooth muscle actin) were analyzed by immunohistochemistry. The 61 placental biopsies included 31 preterm (preterm placentas exhibited lower levels of anti-secretory factor (p = 0.008) and larger numbers of CD68-positive cells (p Preterm placentas had blood vessel of smaller diameter (p = 0.036) indicative of immaturity. The level of interleukin-6 in cord blood was higher after very preterm than term birth, suggesting a fetal inflammatory response. The placenta level of anti-secretory factor was positively correlated to the length of gestation (p = 0.025) and negatively correlated to the levels of the inflammatory markers CD68 (p = 0.015) and CD163 (p = 0.028). Preterm delivery is associated with low levels of anti-secretory factor in placenta. Inflammation, a potential trigger of preterm birth, is more pronounced in the preterm placenta and inversely related to the placental level of anti-secretory factor, suggesting both a link and a potential target for intervention. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

  7. Is Surgical Menopause Associated With Future Levels of Cardiovascular Risk Factor Independent of Antecedent Levels? The CARDIA Study.

    Science.gov (United States)

    Appiah, Duke; Schreiner, Pamela J; Bower, Julie K; Sternfeld, Barbara; Lewis, Cora E; Wellons, Melissa F

    2015-12-15

    In the present study, we compared changes in risk factors for cardiovascular disease (CVD) before and after natural menopause (NM), hysterectomy with at least 1 ovary conserved (HOC), or hysterectomy with bilateral oophorectomy (HBSO). Data were obtained from women 18-30 years of age who were enrolled in the Coronary Artery Risk Development in Young Adults Study (1985-2011). Piecewise linear mixed models were used to examine changes in CVD risk factors from baseline to the index visit (the first visit after the date of NM or hysterectomy) and after index visit until the end of follow-up. During 25 years of follow-up, 1,045 women reached menopause (for NM, n = 588; for HOC, n = 304; and for HBSO, n = 153). At baseline, women with either type of hysterectomy had less favorable values for CVD risk factors. When comparing the annual rates of change of all CVD risk factors from baseline until the index visit to those from the index visit to the end of follow-up, we saw a small increase in rate of change for high-density lipoprotein cholesterol (β = 0.28 mg/dL; P = 0.002) and a decrease for triglycerides (β =-0.006 mg/dL; P = 0.027) for all groups. Hysterectomy was not associated with risk factors for CVD after accounting for baseline values. However, antecedent young-adult levels of CVD risk factors were strong predictors of levels of postmenopausal risk factors. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Levels of serum vascular endothelial growth factor in type 2 diabetics with retinopathy

    International Nuclear Information System (INIS)

    Parveen, N.; Rahman, S.; Khan, Q.

    2012-01-01

    Background: Ischemic retina in diabetic patients releases a number of chemical substances including vascular endothelial growth factor which leads to retinal vascular proliferation and blindness following rupture and bleeding of vessels. Strategies to control this action can considerably halt this process. Objectives: To determine the relationship of various stages of diabetic retinopathy with the levels vascular endothelial growth factor in the serum of type 2 diabetic patients. Study type, settings and duration: This cross sectional analytical study was done over one year (2010-2011) in three major public sector hospitals of Peshawar. Patients and Methods: Adult patients of either gender having type 2 diabetes mellitus with proliferative or non proliferative retinopathy and those without retinopathy were selected for the study. Retinopathy was diagnosed on fundoscopy. Non-diabetic patients without retinopathy were selected as controls. Serum levels of vascular endothelial growth factor were done in patients and controls using ELISA. Results: Serum vascular endothelial growth factor levels were significantly higher in all cases having retinopathy as compared to controls. These levels progressively increased with the grades of retinopathy. Levels were higher in females. Conclusions: Levels of vascular endothelial growth factor are raised in diabetic retinopathy and rising levels can alert the clinician in worsening of retinopathy so that preventive and therapeutic measures can be taken promptly. Policy message: Further larger scale studies are recommended on national level to pave way for the establishment of appropriate management paradigms for diabetic retinopathy through anti-VEGF treatment. (author)

  9. Organizational factors related to low levels of sickness absence in a representative set of Swedish companies.

    Science.gov (United States)

    Stoetzer, Ulrich; Bergman, Peter; Aborg, Carl; Johansson, Gun; Ahlberg, Gunnel; Parmsund, Marianne; Svartengren, Magnus

    2014-01-01

    The aim of this qualitative study was to identify manageable organizational factors that could explain why some companies have low levels of sickness absence. There may be factors at company level that can be managed to influence levels of sickness absence, and promote health and a prosperous organization. 38 representative Swedish companies. The study included a total of 204 semi-structured interviews at 38 representative Swedish companies. Qualitative thematic analysis was applied to the interviews, primarily with managers, to indicate the organizational factors that characterize companies with low levels of sickness absence. The factors that were found to characterize companies with low levels of sickness absence concerned strategies and procedures for managing leadership, employee development, communication, employee participation and involvement, corporate values and visions, and employee health. The results may be useful in finding strategies and procedures to reduce levels of sickness absence and promote health. There is research at individual level on the reasons for sickness absence. This study tries to elevate the issue to an organizational level. The findings suggest that explicit strategies for managing certain organizational factors can reduce sickness absence and help companies to develop more health-promoting strategies.

  10. Panel Data with Cross-Sectional Dependence Characterized by a Multi-Level Factor Structure

    DEFF Research Database (Denmark)

    Rodríguez-Caballero, Carlos Vladimir

    A panel data model with a multi-level cross-sectional dependence is proposed. The factor structure is driven by top-level common factors as well as non-pervasive factors. I propose a simple method to filter out the full factor structure that overcomes limitations in standard procedures which may...... mix up both levels of unobservable factors and may hamper the identification of the model. The model covers both stationary and non-stationary cases and takes into account other relevant features that make the model well suited to the analysis of many types of time series frequently addressed...... in macroeconomics and finance. The model makes it possible to examine the time series and cross-sectional dynamics of variables allowing for a rich fractional cointegration analysis. A Monte Carlo simulation is conducted to examine the finite sample features of the suggested procedure. Findings indicate...

  11. Herd-level Risk Factors Associated with Bovine Brucellosis Seropositivity and Abortion in Bangladesh

    OpenAIRE

    Islam, Md. Atiqul

    2011-01-01

    A cross-sectional study was conducted to determine the seroprevalence and to identify the herd level risk factors associated with bovine brucellosis seropositivity and abortion in the Mymensingh and Sherpur districts of Bangladesh.

  12. Individual and community risk factors and sexually transmitted diseases among arrested youths: a two level analysis.

    Science.gov (United States)

    Dembo, Richard; Belenko, Steven; Childs, Kristina; Wareham, Jennifer; Schmeidler, James

    2009-08-01

    High rates of infection for chlamydia and gonorrhea have been noted among youths involved in the juvenile justice system. Although both individual and community-level factors have been found to be associated with sexually transmitted disease (STD) risk, their relative importance has not been tested in this population. A two-level logistic regression analysis was completed to assess the influence of individual-level and community-level predictors on STD test results among arrested youths processed at a centralized intake facility. Results from weighted two level logistic regression analyses (n = 1,368) indicated individual-level factors of gender (being female), age, race (being African American), and criminal history predicted the youths' positive STD status. For the community-level predictors, concentrated disadvantage significantly and positively predicted the youths' STD status. Implications of these findings for future research and public health policy are discussed.

  13. Application of fuzzy synthetic assessment to assess human factors design level on reactor control panel

    International Nuclear Information System (INIS)

    Peng Xuecheng

    1999-01-01

    Reactor control panel design level on human factors must be considered by designer. The author evaluated the human factor design level of arrangement and combinations including the switch buttons, meter dials and indication lamps on Minjiang Reactor and High-Flux Engineer Test Reactor (HFETR) critical device by application of fuzzy synthetic assessment method in mathematics. From the assessment results, the advantages and shortcomings are fount, and some modification suggestions have also been proposed

  14. The relation between serum testosterone levels and cardiovascular risk factors in patients with kidney transplantation

    Directory of Open Access Journals (Sweden)

    Hulya Colak

    2014-01-01

    Full Text Available The objective of the study is to evaluate the relationship between serum testos-terone levels and cardiovascular risk factors (CVRF in patients after kidney transplantation and with chronic kidney disease (CKD. Seventy-five male patients, aged between 18 and 68 years, who had kidney transplantation at least six months earlier, were enrolled into the study. Only renal transplant recipients and CKD patients with a creatinine level of 0.05. Serum testosterone levels were independent risk factors affecting IVC collapse index, systolic BP and LA. m-TORi and CNIs drugs might have no negative effect on serum testosterone levels, and improvement of the serum testosterone levels after transplantation might have a positive contribution on cardiac risk factors.

  15. Influence of perinatal factors on thyroid stimulating hormone level in cord blood

    Directory of Open Access Journals (Sweden)

    Amir-mohammad Armanian

    2013-01-01

    Conclusion: In conclusion we deduce that the only factor that can affect cord blood TSH was method of delivery. Infant with vaginal delivery has higher TSH level in cord blood. Other factors that were evaluated in this study didn′t have any statistically significant relationship.

  16. Factors associated with elevated blood lead levels in inner ·city ...

    African Journals Online (AJOL)

    A cross-sectional analytical study was carried out to determine risk factors for childhood lead exposure. Blood lead levels of inner-city Sub A coloured children living in Woodstock were examined in relation to information obtained by questionnaire on environmental and social factors. The mean blood lead concentration of ...

  17. AFFECTING CUSTOMER LOYALTY: DO DIFFERENT FACTORS HAVE VARIOUS INFLUENCES IN DIFFERENT LOYALTY LEVELS?

    OpenAIRE

    Andres Kuusik

    2007-01-01

    The current paper studies the influence of various factors on customer loyalty. The main hypothesis of the study insists that the list of most important factors affecting loyalty is dependant on the level of loyalty of costumers. LOGIT method was used for testing the hypotheses on the sample of survey data about 1000 private customers of the biggest telecommunication company in Estonia. The results reveal that four analysed factors affecting customer loyalty (satisfaction, trustworthiness, im...

  18. Level-3 Cholesky Factorization Routines Improve Performance of Many Cholesky Algorithms

    DEFF Research Database (Denmark)

    Gustavson, Fred G.; Wasniewski, Jerzy; Dongarra, Jack J.

    2013-01-01

    Four routines called DPOTF3i, i = a,b,c,d, are presented. DPOTF3i are a novel type of level-3 BLAS for use by BPF (Blocked Packed Format) Cholesky factorization and LAPACK routine DPOTRF. Performance of routines DPOTF3i are still increasing when the performance of Level-2 routine DPOTF2 of LAPACK...

  19. A Bayesian Multi-Level Factor Analytic Model of Consumer Price Sensitivities across Categories

    Science.gov (United States)

    Duvvuri, Sri Devi; Gruca, Thomas S.

    2010-01-01

    Identifying price sensitive consumers is an important problem in marketing. We develop a Bayesian multi-level factor analytic model of the covariation among household-level price sensitivities across product categories that are substitutes. Based on a multivariate probit model of category incidence, this framework also allows the researcher to…

  20. Exploring Factors Affecting Girls' Education at Secondary Level: A Case of Karak District, Pakistan

    Science.gov (United States)

    Suleman, Qaiser; Aslam, Hassan Danial; Habib, Muhammad Badar; Yasmeen, Kausar; Jalalian, Mehrdad; Akhtar, Zaitoon; Akhtar, Basreen

    2015-01-01

    The study examined the factors that affect girls' education at secondary school level in Karak District, Khyber Pakhtunkhwa (Pakistan). All the female heads, teachers and students serving and studying at secondary school level in Karak District constituted the population of the study. The study was delimited to only 30 girls' secondary schools in…

  1. Investigation of Primary Education Second Level Students' Motivations toward Science Learning in Terms of Various Factors

    Science.gov (United States)

    Sert Çibik, Ayse

    2014-01-01

    The purpose of this research was to investigate the primary education second level students' motivations towards science learning in terms of various factors. Within the research, the variation of the total motivational scores in science learning according to the gender, class, socio-economic levels, success in science-technology course and…

  2. INTRAOCULAR AND SERUM LEVELS OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN ACUTE RETINAL NECROSIS AND OCULAR TOXOPLASMOSIS

    NARCIS (Netherlands)

    Wiertz, Karin; De Visser, Lenneke; Rijkers, Ger; De Groot-Mijnes, Jolanda; Los, Leonie; Rothova, Aniki

    2010-01-01

    Purpose: To determine the intraocular and serum vascular endothelial growth factor (VEGF) levels in patients with acute retinal necrosis (ARN) and compare those with VEGF levels found in patients with ocular toxoplasmosis (OT). Methods: Paired intraocular fluid and serum samples of 17 patients with

  3. High School 9th Grade Students' Understanding Level and Misconceptions about Temperature and Factors Affecting It

    Science.gov (United States)

    Akbas, Yavuz

    2012-01-01

    The purpose of this study is to explore students' understanding levels and misconceptions about temperature and factors affecting it. The concept of the study was chosen from Geography National Curriculum. In this study, a questionnaire was developed after a pilot study with an aim to ascertain the students' understanding levels of temperature and…

  4. Donor age and gestational age influence on growth factor levels in human amniotic membrane.

    Science.gov (United States)

    López-Valladares, Maria J; Teresa Rodríguez-Ares, M; Touriño, Rosario; Gude, Francisco; Teresa Silva, M; Couceiro, Jose

    2010-09-01

    Amniotic membrane (AM) is used as a biomaterial for reconstruction in ocular surface surgery. This study investigated the influence of interdonor variations and processing and preservation procedures applied to the AM on growth factors and protein levels.  Samples of human AM from thirteen donors were analysed. Collected donor data were age, parity and gestational age. Total protein amount was measured in extracts of intact AM nonpreserved, lyophilized and cryopreserved, at -80°C and in liquid nitrogen. An enzyme-linked immunosorbent assay (ELISA) was used to assay growth factors protein levels for epidermal growth factor, basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), transforming growth factor beta1 (TFG-β(1) ) and nerve growth factor (NGF). Univariate and multivariate statistical analyses were used to study the influence of the preservation method applied and interdonor variations on growth factors levels. We detected important variations in growth factors and protein concentrations between samples from different donors. Total protein amount, bFGF, HGF, KGF and TGF-β(1) showed lower levels in samples from donors with higher gestational ages and donor ages, for all groups. The variability in the biochemical composition of AM from different donors is considerable, and it is related with donor factors as donor age and gestational age. As AM biochemical composition has a role in its therapeutic effects, these variations could affect the clinical results of amniotic membrane transplantation and must be taken into account in donor selection processes. © 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.

  5. Lande gJ factors for even-parity electronic levels in the holmium atom

    Science.gov (United States)

    Stefanska, D.; Werbowy, S.; Krzykowski, A.; Furmann, B.

    2018-05-01

    In this work the hyperfine structure of the Zeeman splitting for 18 even-parity levels in the holmium atom was investigated. The experimental method applied was laser induced fluorescence in a hollow cathode discharge lamp. 20 spectral lines were investigated involving odd-parity levels from the ground multiplet, for which Lande gJ factors are known with high precision, as the lower levels; this greatly facilitated the evaluation of gJ factors for the upper levels. The gJ values for the even-parity levels considered are reported for the first time. They proved to compare fairly well with the values obtained recently in a semi-empirical analysis for the even-parity level system of Ho I.

  6. Investigating Elementary & Intermediate Level Students’ Perspectives towards Demotivating Factors In ESP Classes

    Directory of Open Access Journals (Sweden)

    Masoud Zoghi

    2014-09-01

    Full Text Available In the present study, attempts were made to investigate and contrast the demotivating factors in English classes from the viewpoint of ESP students at different proficiency levels. To this end, 134 ESP students were chosen from Islamic Azad University, Karaj Branch. Based on the scores obtained from Oxford Placement Test, the sample was divided into two groups, i.e. the intermediate level of proficiency students (n=60 and the elementary level of proficiency students (n=74. The data required for the study were collected by means of a demotivating factors questionnaire. The data collected were analyzed using the Minitab statistical package version 16. Results revealed that there were no significant differences among the demotivating factors perceived across the groups. From the viewpoint of both groups, teachers’ attitude and personality, their teaching methods, and the weakness of students in English vocabulary were among the highest frequency mentioned demotivating factors.

  7. The effect of psychosocial factors on the level of cholyglycine before childbirth

    International Nuclear Information System (INIS)

    Zhang Hongmei; Fan Jie; Yu Jie; Wu Aiqin

    2005-01-01

    To observe the effect of psychosocial factors on the level of cholyglycine(CG) before childbirth, 69 gravidas were investigated by using the Gravida General Situation Questionnaire, the A Strait Behavior Questionnaire, and Symptom Checklist-90(SCL-90) in the term of pregnancy till giving birth. The data were subjected to statistical analysis. The result showed that: (1) The level of CG was significantly higher in the group with A-behavior than that in the group with B-or M-Behavior(P<0.05); (2) The incidence of post partum complication in the high CG group (8%) was significantly higher than that in the low CG group (P<0.01); (3)The gestational period, the relation with parents of gravidas husband and SCL-90 panic score were main influencing factors on the level of CG . Besides physiological factors' effecting on CG, psychosocial factors should also be paid attention to. (authors)

  8. Geographic factors related to site suitability of low-level waste disposal

    Science.gov (United States)

    Zittel, H. E.

    Factors related to the site suitability of low level waste disposal sites are discussed including those which might be considered environmental and those dealing with site criteria. Possible population criteria, alternative site selection, transportation criteria, and community involvement are considered. All these factors are based on the premise that the technology exists to carry out low level waste disposal in a manner such that public health and safety can be insured. It is concluded that problems encountered in siting low level waste facilities are largely societal and political in nature.

  9. Human factors programs for high-level radioactive waste handling systems

    International Nuclear Information System (INIS)

    Pond, D.J.

    1992-04-01

    Human Factors is the discipline concerned with the acquisition of knowledge about human capabilities and limitations, and the application of such knowledge to the design of systems. This paper discusses the range of human factors issues relevant to high-level radioactive waste (HLRW) management systems and, based on examples from other organizations, presents mechanisms through which to assure application of such expertise in the safe, efficient, and effective management and disposal of high-level waste. Additionally, specific attention is directed toward consideration of who might be classified as a human factors specialist, why human factors expertise is critical to the success of the HLRW management system, and determining when human factors specialists should become involved in the design and development process

  10. Workplace levels of psychosocial factors as prospective predictors of registered sickness absence

    DEFF Research Database (Denmark)

    Christensen, Karl Bang; Nielsen, Martin L; Rugulies, Reiner

    2005-01-01

    absence in the technical services (rate ratio = 0.66, 95% confidence interval = 0.51-0.86) and high workplace levels of skill discretion predicted low sickness absence in the pharmaceutical company (rate ratio = 0.74, 95% confidence interval = 0.62-0.88) after control for relevant confounders. Workplaces......OBJECTIVE: We sought to investigate whether workplace levels of psychosocial work environment factors predict individual sickness absence. METHODS: Data were collected in a prospective study in 52 Danish workplaces in three organizations: municipal care, technical services, and a pharmaceutical...... company. Psychosocial factors were aggregated as workplace means. We used multilevel Poisson regression models with psychosocial factors as predictors and individual level sickness absence from absence registries as outcome. RESULTS: High workplace levels of decision authority predicted low sickness...

  11. Correlation of transforming growth factor-β1 and tumour necrosis factor levels with left ventricular function in Chagas disease

    Science.gov (United States)

    Curvo, Eduardo OV; Ferreira, Roberto R; Madeira, Fabiana S; Alves, Gabriel F; Chambela, Mayara C; Mendes, Veronica G; Sangenis, Luiz Henrique C; Waghabi, Mariana C; Saraiva, Roberto M

    2018-01-01

    BACKGROUND Transforming growth factor β1 (TGF-β1) and tumour necrosis factor (TNF) have been implicated in Chagas disease pathophysiology and may correlate with left ventricular (LV) function. OBJECTIVES We determined whether TGF-β1 and TNF serum levels correlate with LV systolic and diastolic functions and brain natriuretic peptide (BNP) serum levels in chronic Chagas disease. METHODS This cross-sectional study included 152 patients with Chagas disease (43% men; 57 ± 12 years old), classified as 53 patients with indeterminate form and 99 patients with cardiac form (stage A: 24, stage B: 25, stage C: 44, stage D: 6). TGF-β1, TNF, and BNP were determined by enzyme-linked immunosorbent assay ELISA. Echocardiogram was used to determine left atrial and LV diameters, as well as LV ejection fraction and diastolic function. FINDINGS TGF-b1 serum levels were lower in stages B, C, and D, while TNF serum levels were higher in stages C and D of the cardiac form. TGF-β1 presented a weak correlation with LV diastolic function and LV ejection fraction. TNF presented a weak correlation with left atrial and LV diameters and LV ejection fraction. CONCLUSIONS TNF is increased, while TGF-β1 is decreased in the cardiac form of chronic Chagas disease. TNF and TGF-β1 serum levels present a weak correlation with LV systolic and diastolic function in Chagas disease patients. PMID:29513876

  12. Taxonomy to characterize occupational hazards (risk factors) at the workplace level.

    Science.gov (United States)

    Cabeças, José Martin Miquel

    2015-01-01

    The identification of hazards or risk factors at the workplace level is a crucial procedure to the risk identification, risk analysis and risk evaluation. This article presents a hazard or risk factors taxonomy, to be applied at the workplace level, during the systematic hazards identification. The taxonomy was based on evidences literature, including technical documents, standards, regulations, good-practice documents and toxicology databases. The taxonomy was organized as a matrix (Risk Factors-Disorders Matrix), an extensive list of occupational hazards. Hazards were organized in terms of the potential individual dominant consequences: in terms of accidents (injuries), occupational disease and negative social, mental or physical well-being (like dissatisfaction and discomfort complaints not resulting from injuries or diseases symptomatology). The specific hazards in each work context were characterized by three summary tables: (1) Accidents-Risk Factors Table, (2) Diseases-Risk Factors Table and (3) Negative Well-being-Risk Factors Table. Risk factors are coded according to the Risk Factors-Disorders Matrix and the dominant potential disorders are identified in the Risk Factors Tables. The inclusion of individual, psychosocial, emerging and combined hazards in the Matrix, contributes to focusing the risk identification in non-traditional sources of risk during risk assessment procedures.

  13. [Evaluation of leptin levels in plasma and their reliance on other hormonal factors affecting tissue fat levels in people with various levels of endogenous cotisol].

    Science.gov (United States)

    Robaczyk, Maciej G

    2002-01-01

    The discovery of leptin (LEP) shed new light on mechanisms regulating body fat mass (BFM). In this aspect, interactions between LEP and glucocorticoids at hypothalamic level may be of great importance. Factors that influence plasma LEP levels have not been fully recognized and available data on LEP levels are often inconsistent. The aim of this study was to evaluate absolute and BFM-corrected plasma LEP levels and their diurnal variation, as well as to assess the relationship between LEP levels, body fat distribution, and hormones influencing body fat in subjects with various levels of endogenous cortisol and different nutritional status. Group I was composed of 14 women aged 14-58 yrs, BMI of 23.9-37.1 kg/m2, with hypercortisolism due to ACTH-dependent and ACTH-independent Cushing's syndrome (CUS). 17 women with visceral obesity (OTY) and normal or disturbed carbohydrate metabolism, i.e. impaired glucose tolerance (IGT) and diabetes mellitus (DM), aged 24 do 50 yrs, BMI 30.0-46.1 kg/m2, were included in group II. Group III consisted of 14 women with Addison's disease (AD), aged 18 do 63 yrs, BMI 15.4-31.6 kg/m2. The control group IV (KON) included 17 healthy women with normal BMI. BMI, WHR, body composition, and body fat distribution (DEXA method) were assessed in all subjects. Basal plasma levels of LEP, beta-endorphin (B-EP), cortisol (F), insulin-like growth factor-1 (IGF-1) were measured with RIA test kits. Plasma adrenocorticotrophin (ACTH) levels, serum levels of insulin (IRI) and growth hormone (GH) were measured with IRMA test kits. Blood glucose (G) concentration was determined with an enzymatic method. Adiposity-corrected LEP levels were expressed as LEP/BFM and LEP/%BF indices. Fasting insulin resistance index (FIRI) was also calculated. Higher BFM and %BF values were found in the OTY group as compared with CUS KON and AD groups. BFM distribution did not differ in KON and AD groups whereas CUS subjects exhibited a higher accumulation of fat in the trunk

  14. Kidney fibroblast growth factor 23 does not contribute to elevation of its circulating levels in uremia

    DEFF Research Database (Denmark)

    Mace, Maria L.; Gravesen, Eva; Nordholm, Anders

    2017-01-01

    to normal rats. Removal of the remnant kidney had no effect on plasma FGF23 levels. Well-known regulators of FGF23 expression in bone, such as parathyroid hormone, calcitriol, and inhibition of the FGF receptor by PD173074, had no impact on kidney expression of FGF23. Thus, the only direct contribution......Fibroblast growth factor 23 (FGF23) secreted by osteocytes is a circulating factor essential for phosphate homeostasis. High plasma FGF23 levels are associated with cardiovascular complications and mortality. Increases of plasma FGF23 in uremia antedate high levels of phosphate, suggesting...... of the injured kidney to circulating FGF23 levels in uremia appears to be reduced renal extraction of bone-derived FGF23. Kidney-derived FGF23 does not generate high plasma FGF23 levels in uremia and is regulated differently than the corresponding regulation of FGF23 gene expression in bone....

  15. Academic level and student’s faculty as factors of test anxiety among undergraduates in Nigeria

    Directory of Open Access Journals (Sweden)

    Samuel E. Oladipo

    2013-06-01

    Full Text Available Test anxiety as a prominent problem among students has been a focus of study for decades now, with studies focusing more on such factors as age, gender and study habit in relation to test anxiety. There is a dearth of literature in respect of such factors as academic level and student’s faculty in relation to test anxiety among undergraduates. The focus of the present study therefore, was to investigate academic level and students’ faculty as factors predicting test anxiety among undergraduates in Nigeria. Using simple random sampling technique, a total of 197(126 males and 71 females undergraduates participated in the study. Their ages ranged from 16 to 30years (M=21.6,SD=2.68.Four hypotheses were tested with Pearson Product moment correlation and Multiple regression analysis. The results revealed that academic level and students’ faculty had no correlation with test anxiety. Moreover, the result of the multiple regression analysis showed that academic level and students’ faculty have no independent and joint influence on test anxiety. It was concluded that irrespective of student’s academic level and faculty, test anxiety is unavoidable. Other factors might be responsible for student test anxiety especially among undergraduates Nigeria. It is therefore recommend that more research should be conducted in this area so as to determine the salient factors that predict test anxiety.

  16. [Levels of awareness of occupational and general cardiovascular risk factors among metal industry employees].

    Science.gov (United States)

    Gürdoğan, Muhammet; Paslı Gürdoğan, Eylem; Arı, Hasan; Ertürk, Mehmet; Genç, Ahmet; Uçar, Mehmet Fatih

    2015-06-01

    Long-term exposure to physical, chemical, ergonomic and psychosocial environmental factors may lead to occupational cardiovascular disease in metal industry employees. This study aimed to determine levels of knowledge levels regarding occupational and cardiovascular risk factors among metal industry employees. The study was conducted between 2nd and 6th June 2014 with the participation of 82 employees. All were working in a medium-sized workplace in the metal industry. Data were collected by means of a questionnaire, which included socio-demographic characteristics and occupational cardiovascular risk factors, and a scale developed by Arıkan et al. to measure awareness levels of risk factors for cardiovascular diseases (CARRF-KL). The mean age of employees was 39.97±8.44. Of the participants, 58.5% stated that they had knowledge on cardiac disease risk factors. The mean CARRF-KL score was found to be 18.65±4.04. The percentage of employees stating that they had no knowledge on the occupational risks for such diseases was 79.3%, while 19.5% stated that job stress caused cardiac diseases. One individual (1.2%) stated that one of the chemical solvents used in the working environment was a risk factor. Although awareness among metal industry employees of cardiovascular risk factors was above average, it was determined that they do not have adequate information on occupational risk factors. Prolonged and unprotected levels exposure to environmental factors constitute a risk for cardiovascular disease. This information is important for the development of preventive cardiology.

  17. Work Environment Factors and Their Influence on Urinary Chromium Levels in Informal Electroplating Workers

    Science.gov (United States)

    Setyaningsih, Yuliani; Husodo, Adi Heru; Astuti, Indwiani

    2018-02-01

    One of the informal sector which absorbs labor was electroplating business. This sector uses chromium as coating material because it was strong, corrosion resistant and strong. Nonetheless hexavalent chromium is highly toxic if inhaled, swallowed and contact with skin. Poor hygiene, the lack of work environment factors and sanitation conditions can increase the levels of chromium in the body. This aimed of this study was to analyze the association between work environment factors and levels of urinary chromium in informal electroplating worker. A Purposive study was conducted in Tegal Central Java. The research subjects were 66 male workers. Chi Square analysis was used to establish an association between work environment factors and level of urinary chromium. There is a relationship between heat stress and wind direction to the chromium levels in urine (p relationship between humidity and levels of chromium in the urine (p> 0.05). This explains that work environment factors can increase chromium levels in the urine of informal electroplating workers.

  18. Impairment of Mature B Cell Maintenance upon Combined Deletion of the Alternative NF-κB Transcription Factors RELB and NF-κB2 in B Cells.

    Science.gov (United States)

    De Silva, Nilushi S; Silva, Kathryn; Anderson, Michael M; Bhagat, Govind; Klein, Ulf

    2016-03-15

    BAFF is critical for the survival and maturation of mature B cells. BAFF, via BAFFR, activates multiple signaling pathways in B cells, including the alternative NF-κB pathway. The transcription factors RELB and NF-κB2 (p100/p52) are the downstream mediators of the alternative pathway; however, the B cell-intrinsic functions of these NF-κB subunits have not been studied in vivo using conditional alleles, either individually or in combination. We in this study report that B cell-specific deletion of relb led to only a slight decrease in the fraction of mature splenic B cells, whereas deletion of nfkb2 caused a marked reduction. This phenotype was further exacerbated upon combined deletion of relb and nfkb2 and most dramatically affected the maintenance of marginal zone B cells. BAFF stimulation, in contrast to CD40 activation, was unable to rescue relb/nfkb2-deleted B cells in vitro. RNA-sequencing analysis of BAFF-stimulated nfkb2-deleted versus normal B cells suggests that the alternative NF-κB pathway, in addition to its critical role in BAFF-mediated cell survival, may control the expression of genes involved in the positioning of B cells within the lymphoid microenvironment and in the establishment of T cell-B cell interactions. Thus, by ablating the downstream transcription factors of the alternative NF-κB pathway specifically in B cells, we identify in this study a critical role for the combined activity of the RELB and NF-κB2 subunits in B cell homeostasis that cannot be compensated for by the canonical NF-κB pathway under physiological conditions. Copyright © 2016 by The American Association of Immunologists, Inc.

  19. Associations between national viral hepatitis policies/programmes and country-level socioeconomic factors

    DEFF Research Database (Denmark)

    Lazarus, Jeffrey V; Sperle, Ida; Safreed-Harmon, Kelly

    2017-01-01

    BACKGROUND: As more countries worldwide develop national viral hepatitis strategies, it is important to ask whether context-specific factors affect their decision-making. This study aimed to determine whether country-level socioeconomic factors are associated with viral hepatitis programmes...... regression to examine associations between four survey questions and four socioeconomic factors: country income level, Human Development Index (HDI), health expenditure and physician density. RESULTS: This analysis included 119 MS. MS were more likely to have routine viral hepatitis surveillance and to have...... a national strategy and/or policy/guidelines for preventing infection in healthcare settings if they were in the higher binary categories for income level, HDI, health expenditure and physician density. In multivariable analyses, the only significant finding was a positive association between having routine...

  20. THE FACTORS AFFECTING SATISFACTION LEVELS IN HOSPITALIZED PATIENTS: AN APPLICATION IN PUBLIC HOSPITAL

    Directory of Open Access Journals (Sweden)

    Neşe ACAR

    2017-09-01

    Full Text Available This study was conducted to determine the factors that affect the level of satisfaction of services provided by public hospitals. Patients' satisfaction levels were measured by interviewing 156 patients in a public hospital. Factor analysis of the data obtained from the research resulted in five factors called nurses 'behaviors, physical conditions, doctors' behavior, technical staff behaviors, food and beverage. MANOVA analysis was conducted to determine the differences in the perception of factors with respect to the demographic characteristics of the patients and differences were found in terms of profession. It has been seen that it is important that public hospitals have specialist doctors and modern equipment and that they have qualities such as the quality of the health personnel in preferring patients to public hospitals.

  1. Factors associated with higher levels of depressive symptoms among international university students in the Philippines.

    Science.gov (United States)

    Lee, Romeo B; Maria, Madelene Sta; Estanislao, Susana; Rodriguez, Cristina

    2013-11-01

    Over the years, the number of international university students has been increasing in the Philippines. Depression tends to be common among this demographic sector, because of the varying challenges and expectations associated with studying abroad. Depression can be prevented if its symptoms, particularly those at higher levels, are identified and addressed early and effectively. This survey examined the social and demographic factors that are significantly associated with higher levels of depressive symptoms. One hundred twenty-six international university students were interviewed using the University Students Depression Inventory. Of the 13 factors analyzed, 3 were found with statistically significant associations with more intense levels of depressive symptoms. These factors were: level of satisfaction with one's financial condition, level of closeness with parents, and level of closeness with peers. In identifying international students with greater risk for depression, characteristics related to their financial condition and primary group relationships can be considered. There is a need to carry out more studies to confirm this initial evidence. The findings can help guide further discourse, research and program to benefit international students with higher levels of depressive symptoms.

  2. Air Force Officer Qualifying Test Form T: Initial Item-, Test-, Factor-, and Composite-Level Analyses

    Science.gov (United States)

    2016-12-01

    Air Force Officer Qualifying Test, Form T1 AFOQT T2 Air Force Officer Qualifying Test, Form T2 AGFI Adjusted Goodness of Fit Index AI Air Force...Qualifying Test Electrical Maze subtest g General mental ability factor GFI Goodness of Fit Index GLS Generalized Least Squares GS Air Force...AFRL-RH-WP-TR-2016-0093 AIR FORCE OFFICER QUALIFYING TEST FORM T: INITIAL ITEM-, TEST-, FACTOR-, AND COMPOSITE-LEVEL ANALYSES

  3. Factors driving public tolerance levels and information-seeking behaviour concerning insects in the household environment.

    Science.gov (United States)

    Schoelitsz, Bruce; Poortvliet, P Marijn; Takken, Willem

    2017-12-23

    The public's negative attitudes towards household insects drive tolerance for these insects and their control. Tolerance levels are important in integrated pest management (IPM), as are pest knowledge and information. The risk information seeking and processing (RISP) model describes the relationships between personal factors and information-seeking behaviour. We combined IPM and RISP to determine important relationships between factors driving insect tolerance levels and information-seeking behaviour through an online survey and tested whether this model is valid and generally applicable. Relationships between variables from both IPM and RISP models were tested for seven insect species. Tolerance levels were measured with two factors: willingness to pay for pest control and whether insects are tolerated. Willingness to pay for control was positively affected by age, experience, risk perception, insect characteristics, and negative emotions and affected behavioural intention, by influencing information sufficiency and information-seeking behaviour. Tolerability was influenced by perception of insect characteristics and determines whether control measures are taken. It was possible to combine the RISP and IPM models. Relevant driving factors were a person's age, experience, risk perception, negative affective responses, tolerance levels, relevant channel beliefs about online forums, information sufficiency and information-seeking behaviour. There was, however, variation in important factors between different insects. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

  4. The B-cell-activating factor signalling pathway is associated with Helicobacter pylori independence in gastric mucosa-associated lymphoid tissue lymphoma without t(11;18)(q21;q21).

    Science.gov (United States)

    Kuo, Sung-Hsin; Tsai, Hui-Jen; Lin, Chung-Wu; Yeh, Kun-Huei; Lee, Hsiao-Wei; Wei, Ming-Feng; Shun, Chia-Tung; Wu, Ming-Shiang; Hsu, Ping-Ning; Chen, Li-Tzong; Cheng, Ann-Lii

    2017-02-01

    We previously reported that activation of the B-cell-activating factor (BAFF) pathway upregulates nuclear factor-κB (NF-κB) and induces BCL3 and BCL10 nuclear translocation in Helicobacter pylori (HP)-independent gastric diffuse large B-cell lymphoma (DLBCL) tumours with evidence of mucosa-associated lymphoid tissue (MALT). However, the significance of BAFF expression in HP independence of gastric low-grade MALT lymphomas without t(11;18)(q21;q21) remains unexplored. Sixty-four patients who underwent successful HP eradication for localized HP-positive gastric MALT lymphomas without t(11;18)(q21;q21) were studied. BAFF expression was significantly higher in the HP-independent group than in the HP-dependent group [22/26 (84.6%) versus 8/38 (21.1%); p t(11;18)(q21;q21). The biological significance of BAFF signalling in t(11;18)(q21;q21)-negative lymphoma cells was further studied in two types of lymphoma B cell: OCI-Ly3 [non-germinal centre B-cell origin DLBCL without t(11;18)(q21;q21) cell line] and MA-1 [t(14;18)(q32;q21)/IGH-MALT1-positive DLBCL cell line]. In both cell lines, we found that BAFF activated the canonical NF-κB and AKT pathways, and induced the formation of BCL10-BCL3 complexes, which translocated to the nucleus. BCL10 and BCL3 nuclear translocation and NF-κB (p65) transactivation were inhibited by either LY294002 or by silencing BCL3 or BCL10 with small interfering RNA. BAFF also activated non-canonical NF-κB pathways (p52) through tumour necrosis factor receptor-associated factor 3 degradation, NF-κB-inducing kinase accumulation, inhibitor of κB kinase (IKK) α/β phosphorylation and NF-κB p100 processing in both cell lines. Our data indicate that the autocrine BAFF signal transduction pathway contributes to HP independence in gastric MALT lymphomas without the t(11;18)(q21;q21) translocation. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of

  5. Analysis of factors affecting satisfaction level on problem based learning approach using structural equation modeling

    Science.gov (United States)

    Hussain, Nur Farahin Mee; Zahid, Zalina

    2014-12-01

    Nowadays, in the job market demand, graduates are expected not only to have higher performance in academic but they must also be excellent in soft skill. Problem-Based Learning (PBL) has a number of distinct advantages as a learning method as it can deliver graduates that will be highly prized by industry. This study attempts to determine the satisfaction level of engineering students on the PBL Approach and to evaluate their determinant factors. The Structural Equation Modeling (SEM) was used to investigate how the factors of Good Teaching Scale, Clear Goals, Student Assessment and Levels of Workload affected the student satisfaction towards PBL approach.

  6. Prenatal exposure to lead in Spain: cord blood levels and associated factors.

    Science.gov (United States)

    Llop, Sabrina; Aguinagalde, Xabier; Vioque, Jesus; Ibarluzea, Jesús; Guxens, Mònica; Casas, Maribel; Murcia, Mario; Ruiz, María; Amurrio, Ascensión; Rebagliato, Marisa; Marina, Loreto Santa; Fernandez-Somoano, Ana; Tardon, Adonina; Ballester, Ferran

    2011-05-01

    Lead is a known neurotoxic. Fetuses and infants are very vulnerable to lead exposure, since their blood-brain barrier is not completely formed. Hence, there is an importance for monitoring of blood lead levels prenatally and during early infancy. The aim of this study is to evaluate the prenatal exposure to lead and its association with maternal factors in four population based mother-child cohorts in Spain. The present research was carried out within the framework of the INMA project INfancia y Medio Ambiente (Environment and Childhood). A total of 1462 pregnant women were recruited between 2004 and 2008. Lead was analyzed in a sample of cord blood by thermal decomposition, amalgation, and Atomic Absorption Spectrometry. Maternal sociodemographic, lifestyle and dietary factors were obtained by questionnaires during pregnancy. A multivariate logistic regression model was constructed. The dependent variable was a dichotomous lead level variable (detected vs no detected, i.e. ≥ vs < 2μg/dL). A low percentage of cord blood samples with lead levels ≥ 2μg/dL were found (5.9%). Geometric mean and maximum were 1.06μg/dL and 19μg/dL, respectively. Smoking at the beginning of pregnancy, age, social class, weight gain during pregnancy, gravidity, and place of residence were the maternal factors associated with detectable cord blood lead levels. Mother's diet does not appear to be a determining factor of lead exposure. Nevertheless, daily intake of iron and zinc may act as a protective factor against having cord blood lead levels ≥ 2μg/dL. In the different regions of Spain taking part in this study, lead levels to which newborns are exposed are low. Mobilization of lead from bones may be the main contributor to the cord blood levels. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. The effects of three factor VII polymorphisms on factor VII coagulant levels in healthy Singaporean Chinese, Malay and Indian newborns.

    Science.gov (United States)

    Quek, S C; Low, P S; Saha, N; Heng, C K

    2006-11-01

    Factor VII (FVII) is an independent risk factor for coronary artery disease. Three polymorphisms of the factor VII gene (F7) were studied in a group of healthy newborns comprising 561 Chinese, 398 Malays and 226 Asian Indians from Singapore. The allele frequencies of 3 polymorphisms (R353Q, Promoter 0/10bp Del/Ins and Intron 7) in the FVII gene were ascertained through genotyping by polymerase chain reaction and restriction digestion of amplified fragments. In Chinese the minor allele frequencies are Q: 0.04, Ins: 0.03, R7: 0.44; Malays, Q: 0.06, Ins: 0.10, R7: 0.41; and Indians, Q: 0.25, Ins: 0.23, R7: 0.43. Strong linkage disequilibrium (Delta > 0.7) is observed between the 0/10 bp and the R353Q sites in all ethnic groups. We conclude that: (i) the prevalence of the minor Q and Ins alleles of the R353Q and 0/10 bp polymorphisms are significantly higher in the Indian newborns than the Chinese and Malays; (ii) the Q allele is significantly associated (p = 0.01) with a lower plasma FVII coagulant level in the Indian and Malay neonates; and this polymorphism explains up to 3.8% of the variance in FVII coagulant levels; (iii) there is no significant difference in allele frequencies of the three polymorphisms between neonates with and without family histories of CAD.

  8. Factor Analysis of Residential Energy Consumption at the Provincial Level in China

    Directory of Open Access Journals (Sweden)

    Weibin Lin

    2014-11-01

    Full Text Available This paper analyzes the differences in the amount and the structure of residential energy consumption at the provincial level in China and identifies the hidden factors behind such differences. The econometrical analysis reveals that population, economic development level, energy resource endowment and climatic conditions are the main factors driving residential energy consumption; while the regional differences in energy consumption per capita and the consumption structure can be mainly illustrated by various economic development levels, energy resource endowments and climatic conditions. Economic development level has a significant positive impact on the proportion of gasoline consumption, whereas its impact on the proportion of electricity consumption is not notable; energy resource endowment and climatic condition indirectly affect both the proportion of electricity consumption and that of gasoline consumption, primarily through their impacts on the proportions of coal consumption and heat consumption.

  9. An experimental survey of the factors that affect leaching from low-level radioactive waste forms

    International Nuclear Information System (INIS)

    Dougherty, D.R.; Pietrzak, R.F.; Fuhrmann, M.; Colombo, P.

    1988-09-01

    This report represents the results of an experimental survey of the factors that affect leaching from several types of solidified low-level radioactive waste forms. The goal of these investigations was to determine those factors that accelerate leaching without changing its mechanism(s). Typically, although not in every case,the accelerating factors include: increased temperature, increased waste loading (i.e., increased waste to binder ratio), and decreased size (i.e., decreased waste form volume to surface area ratio). Additional factors that were studied were: increased leachant volume to waste form surface area ratio, pH, leachant composition (groundwaters, natural and synthetic chelating agents), leachant flow rate or replacement frequency and waste form porosity and surface condition. Other potential factors, including the radiation environment and pressure, were omitted based on a survey of the literature. 82 refs., 236 figs., 13 tabs

  10. An experimental survey of the factors that affect leaching from low-level radioactive waste forms

    Energy Technology Data Exchange (ETDEWEB)

    Dougherty, D.R.; Pietrzak, R.F.; Fuhrmann, M.; Colombo, P.

    1988-09-01

    This report represents the results of an experimental survey of the factors that affect leaching from several types of solidified low-level radioactive waste forms. The goal of these investigations was to determine those factors that accelerate leaching without changing its mechanism(s). Typically, although not in every case,the accelerating factors include: increased temperature, increased waste loading (i.e., increased waste to binder ratio), and decreased size (i.e., decreased waste form volume to surface area ratio). Additional factors that were studied were: increased leachant volume to waste form surface area ratio, pH, leachant composition (groundwaters, natural and synthetic chelating agents), leachant flow rate or replacement frequency and waste form porosity and surface condition. Other potential factors, including the radiation environment and pressure, were omitted based on a survey of the literature. 82 refs., 236 figs., 13 tabs.

  11. Acute aerobic exercise increases brain-derived neurotrophic factor levels in elderly with Alzheimer's disease.

    Science.gov (United States)

    Coelho, Flávia Gomes de Melo; Vital, Thays Martins; Stein, Angelica Miki; Arantes, Franciel José; Rueda, André Veloso; Camarini, Rosana; Teodorov, Elizabeth; Santos-Galduróz, Ruth Ferreira

    2014-01-01

    Studies indicate the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of Alzheimer's disease (AD). Decreased BDNF levels may constitute a lack of trophic support and contribute to cognitive impairment in AD. The benefits of acute and chronic physical exercise on BDNF levels are well-documented in humans, however, exercise effects on BDNF levels have not been analyzed in older adults with AD. The aim of this study was to investigate the effects of acute aerobic exercise on BDNF levels in older adults with AD and to verify associations among BDNF levels, aerobic fitness, and level of physical activity. Using a controlled design, twenty-one patients with AD (76.3 ± 6.2 years) and eighteen healthy older adults (74.6 ± 4.7 years) completed an acute aerobic exercise. The outcomes included measures of BDNF plasma levels, aerobic fitness (treadmill grade, time to exhaustion, VO2, and maximal lactate) and level of physical activity (Baecke Questionnaire Modified for the Elderly). The independent t-test shows differences between groups with respect to the BDNF plasma levels at baseline (p = 0.04; t = 4.53; df = 37). In two-way ANOVA, a significant effect of time was found (p = 0.001; F = 13.63; df = 37), the aerobic exercise significantly increased BDNF plasma levels in AD patients and healthy controls. A significant correlation (p = 0.04; r = 0.33) was found between BDNF levels and the level of physical activity. The results of our study suggest that aerobic exercise increases BDNF plasma levels in patients with AD and healthy controls. In addition to that, BDNF levels had association with level of physical activity.

  12. [Benzodiazepine prescription in the elderly in different health care levels: characteristics and related factors].

    Science.gov (United States)

    García-Baztán, Agurne; Roqueta, Cristina; Martínez-Fernández, M Isabel; Colprim, Daniel; Puertas, Pedro; Miralles, Ramón

    2014-01-01

    To determine the prevalence of benzodiazepine (BZD) prescription and the factors related to prescribing them in the elderly in the community, in an acute general hospital (AH) and in a convalescence geriatric unit (CGU). Retrospective study of 334 CGU inpatients discharged from an AH. A comprehensive geriatric assessment included functional and cognitive evaluation before hospitalization, at admission and at discharge from CGU (Barthel index, Lawton index and Folstein Mini-Mental State Examination), as well as comorbidity (Charlson index), polypharmacy and social situation. The percentage of benzodiazepine prescriptions at the different healthcare levels was compared and their related factors were evaluated (Chi-squared test). The prevalence of benzodiazepine prescriptions in the community was 23.6%, and being female and polypharmacy were related factors to prescribing at this level. During AH admission, this proportion increased up to 38.6%, and after CGU admission decreased to 21.,9%. Factors related to prescription in AH were, being female, polypharmacy and osteoarticular-fracture related diagnosis, and in CGU, being female and polypharmacy. The prevalence of benzodiazepine prescribing was high among elderly people at every healthcare level (community, AH and CGU), and polypharmacy was one of the significant factors associated with prescribing. This prescribing was increased during AH admission due to a medical or surgical process. Copyright © 2012 SEGG. Published by Elsevier Espana. All rights reserved.

  13. Factors explaining the level of voluntary human capital disclosure in the Brazilian capital market

    Directory of Open Access Journals (Sweden)

    Fernando Batista Fontana

    2013-04-01

    Full Text Available Purpose: This paper presents a study on factors explaining the level of voluntary human capital information in companies with shares in the Brazilian stock exchange. Assuming the existence of information asymmetry between managers and shareholders, agency theory states that disclosure might lead to a reduction in agency costs. The proprietary costs theory indicates that information disclosure might increase the company’s costs. According to these theories, the likelihood that the managers will voluntarily disclose information depends on certain factors that are characteristic of the company. Understanding the disclosure of information regarding intangible assets, specifically human capital, has strategic relevance for enterprises because these features, although not always recorded in accounting, represent a competitive business edge in the current economy.Design/methodology/approach: The study examined 145 annual reports, representing 29 companies in the period of 2005-2009. The level of voluntary disclosure was determined through content analysis of annual reports using representative indicators of human capital information.Findings: The statistical results indicate that factors such as size, debt, growth and time of registration with the brazilian Securities and Exchange Commission explain the level of voluntary human capital disclosure of the companies studied.Originality/value: An important contribution of this research is the formulation and non-repudiation of the time of registration with the CVM hypothesis as a factor that explains the level of human capital disclosure because none of the revised studies have tested this hypothesis.

  14. Landscape and patch-level factors influence bird communities in an urbanized tropical island

    Science.gov (United States)

    Marcela Suarez-Rubio; John R. Thomlinson

    2009-01-01

    As human population continues to increase and intensification of human land use escalates, it is important to address the role of urban forest patches in supporting bird communities. We related bird species richness and community assemblage to landscape- and patch- level factors in 40 forest patches in the densely populated metropolitan area of San Juan, Puerto Rico....

  15. Factors Associated with Level of Living in Washington County, Mississippi. Technical Bulletin No. 1501.

    Science.gov (United States)

    McCoy, John L.

    Step-wise multiple regression and typological analysis were used to analyze the extent to which selected factors influence vertical mobility and achieved level of living. A sample of 418 male household heads who were 18 to 45 years old in Washington County, Mississippi were interviewed during 1971. A prescreening using census and local housing…

  16. The influence of national level factors on international kaizen transfer: an exploratory study in the Netherlands

    NARCIS (Netherlands)

    Yokozawa, Kodo; Steenhuis, H.J.

    2013-01-01

    Purpose: The purpose of this research study was to examine the international transfer of kaizen or continuous improvement. The central research question was formulated as: what national level factors influence the transfer of kaizen, and how? Design/methodology/approach: In the study, a survey

  17. Effect of allergens and irritants on levels of natural moisturizing factor and corneocyte morphology

    NARCIS (Netherlands)

    Koppes, Sjors A.; Ljubojević Hadžavdić, Suzana; Jakasa, Ivone; Franceschi, Nika; Riethmüller, Christoph; Jurakić Tončic, Ružica; Marinovic, Branka; Raj, Nidhin; Rawlings, Anthony V.; Voegeli, Rainer; Lane, Majella E.; Haftek, Marek; Frings-Dresen, Monique H. W.; Rustemeyer, Thomas; Kezic, Sanja

    2017-01-01

    The irritant sodium lauryl sulfate (SLS) is known to cause a decrease in the stratum corneum level of natural moisturizing factor (NMF), which in itself is associated with changes in corneocyte surface topography. To explore this phenomenon in allergic contact dermatitis. Patch testing was performed

  18. Intraocular and systemic levels of vascular endothelial growth factor in advanced cases of retinopathy of prematurity

    Science.gov (United States)

    Velez-Montoya, Raul; Clapp, Carmen; Rivera, Jose Carlos; Garcia-Aguirre, Gerardo; Morales-Cantón, Virgilio; Fromow-Guerra, Jans; Guerrero-Naranjo, Jose Luis; Quiroz-Mercado, Hugo

    2010-01-01

    Purpose: To measure vitreous, aqueous, subretinal fluid and plasma levels of vascular endothelial growth factor in late stages of retinopathy of prematurity. Methods: Interventional study. We enrolled patients with clinical diagnoses of bilateral stage V retinopathy of prematurity, confirmed by b-scan ultrasound and programmed for vitrectomy. During surgery we took samples from blood, aqueous, vitreous, and subretinal fluids. The vascular endothelial growth factor concentration in each sample was measured by ELISA reaction. A control sample of aqueous, vitreous and blood was taken from patients with congenital cataract programmed for phacoemulsification. For statistical analysis, a Mann–Whitney and a Wilcoxon W test was done with a significant P value of 0.05. Results: We took samples of 16 consecutive patients who met the inclusion criteria. The vascular endothelial growth factor levels in the study group were: aqueous, 76.81 ± 61.89 pg/mL; vitreous, 118.53 ± 65.87 pg/mL; subretinal fluid, 1636.58 ± 356.47 pg/mL; and plasma, 74.64 ± 43.94 pg/mL. There was a statistical difference between the study and the control group (P < 0.001) in the aqueous and vitreous samples. Conclusion: Stage 5 retinopathy of prematurity has elevated intraocular levels of vascular endothelial growth factor, which remains high despite severe retinal lesion. There was no statistical difference in plasma levels of the molecule between the control and study group. PMID:20856587

  19. Prenatal exposure to lead in Spain: Cord blood levels and associated factors

    Energy Technology Data Exchange (ETDEWEB)

    Llop, Sabrina, E-mail: llop_sab@gva.es [Centre of Public Health Research (CSISP), Av Catalunya 21, 46020, Valencia (Spain); Carlos III Health Institute (ISCIII), 20220 Majadahonda, Madrid (Spain); CIBER de Epidemiologia y Salud Publica (CIBERESP), Doctor Aiguader 88, 8003 Barcelona (Spain); Aguinagalde, Xabier [Public Health Laboratory of Alava, Direccion de Salud Publica, Gobierno Vasco, Santiago 11, 01002, Vitoria-Gasteiz, Basque Country (Spain); Vioque, Jesus [CIBER de Epidemiologia y Salud Publica (CIBERESP), Doctor Aiguader 88, 8003 Barcelona (Spain); Universidad Miguel Hernandez, Av de Alicante KM 87, 03550, Sant Joan d' Alacant (Spain); Ibarluzea, Jesus [CIBER de Epidemiologia y Salud Publica (CIBERESP), Doctor Aiguader 88, 8003 Barcelona (Spain); Departamento de Sanidad Gobierno Vasco, Subdireccion de Salud Publica de Gipuzkoa, Avenida de Navarra 4, 20013 San Sebastian (Spain); Biodonostia, Instituto de Investigacion Biomedica, San Sebastian (Spain); Guxens, Monica [CIBER de Epidemiologia y Salud Publica (CIBERESP), Doctor Aiguader 88, 8003 Barcelona (Spain); Centre for Research of Environmental Epidemiology (CREAL), Doctor Aiguader 88, 8003 Barcelona (Spain); Municipal Institute of Medical Research (IMIM-Hospital del Mar), Doctor Aiguader 88, 8003 Barcelona (Spain); Casas, Maribel [Centre for Research of Environmental Epidemiology (CREAL), Doctor Aiguader 88, 8003 Barcelona (Spain); Municipal Institute of Medical Research (IMIM-Hospital del Mar), Doctor Aiguader 88, 8003 Barcelona (Spain); Murcia, Mario [Centre of Public Health Research (CSISP), Av Catalunya 21, 46020, Valencia (Spain); CIBER de Epidemiologia y Salud Publica (CIBERESP), Doctor Aiguader 88, 8003 Barcelona (Spain); Ruiz, Maria [Centre for Research of Environmental Epidemiology (CREAL), Doctor Aiguader 88, 8003 Barcelona (Spain); Municipal Institute of Medical Research (IMIM-Hospital del Mar), Doctor Aiguader 88, 8003 Barcelona (Spain); and others

    2011-05-01

    Introduction and Objective: Lead is a known neurotoxic. Fetuses and infants are very vulnerable to lead exposure, since their blood-brain barrier is not completely formed. Hence, there is an importance for monitoring of blood lead levels prenatally and during early infancy. The aim of this study is to evaluate the prenatal exposure to lead and its association with maternal factors in four population based mother-child cohorts in Spain. The present research was carried out within the framework of the INMA project INfancia y Medio Ambiente (Environment and Childhood). Methods: A total of 1462 pregnant women were recruited between 2004 and 2008. Lead was analyzed in a sample of cord blood by thermal decomposition, amalgation, and Atomic Absorption Spectrometry. Maternal sociodemographic, lifestyle and dietary factors were obtained by questionnaires during pregnancy. A multivariate logistic regression model was constructed. The dependent variable was a dichotomous lead level variable (detected vs no detected, i.e. {>=} vs < 2 {mu}g/dL). Results: A low percentage of cord blood samples with lead levels {>=} 2 {mu}g/dL were found (5.9%). Geometric mean and maximum were 1.06 {mu}g/dL and 19 {mu}g/dL, respectively. Smoking at the beginning of pregnancy, age, social class, weight gain during pregnancy, gravidity, and place of residence were the maternal factors associated with detectable cord blood lead levels. Mother's diet does not appear to be a determining factor of lead exposure. Nevertheless, daily intake of iron and zinc may act as a protective factor against having cord blood lead levels {>=} 2 {mu}g/dL. Conclusion: In the different regions of Spain taking part in this study, lead levels to which newborns are exposed are low. Mobilization of lead from bones may be the main contributor to the cord blood levels. - Research Highlights: {yields} Pb is a ubiquitous environmental pollutant with harmful effects on neurodevelopment. {yields} Cord blood Pb levels in

  20. Prenatal exposure to lead in Spain: Cord blood levels and associated factors

    International Nuclear Information System (INIS)

    Llop, Sabrina; Aguinagalde, Xabier; Vioque, Jesus; Ibarluzea, Jesus; Guxens, Monica; Casas, Maribel; Murcia, Mario; Ruiz, Maria

    2011-01-01

    Introduction and Objective: Lead is a known neurotoxic. Fetuses and infants are very vulnerable to lead exposure, since their blood-brain barrier is not completely formed. Hence, there is an importance for monitoring of blood lead levels prenatally and during early infancy. The aim of this study is to evaluate the prenatal exposure to lead and its association with maternal factors in four population based mother-child cohorts in Spain. The present research was carried out within the framework of the INMA project INfancia y Medio Ambiente (Environment and Childhood). Methods: A total of 1462 pregnant women were recruited between 2004 and 2008. Lead was analyzed in a sample of cord blood by thermal decomposition, amalgation, and Atomic Absorption Spectrometry. Maternal sociodemographic, lifestyle and dietary factors were obtained by questionnaires during pregnancy. A multivariate logistic regression model was constructed. The dependent variable was a dichotomous lead level variable (detected vs no detected, i.e. ≥ vs < 2 μg/dL). Results: A low percentage of cord blood samples with lead levels ≥ 2 μg/dL were found (5.9%). Geometric mean and maximum were 1.06 μg/dL and 19 μg/dL, respectively. Smoking at the beginning of pregnancy, age, social class, weight gain during pregnancy, gravidity, and place of residence were the maternal factors associated with detectable cord blood lead levels. Mother's diet does not appear to be a determining factor of lead exposure. Nevertheless, daily intake of iron and zinc may act as a protective factor against having cord blood lead levels ≥ 2 μg/dL. Conclusion: In the different regions of Spain taking part in this study, lead levels to which newborns are exposed are low. Mobilization of lead from bones may be the main contributor to the cord blood levels. - Research Highlights: → Pb is a ubiquitous environmental pollutant with harmful effects on neurodevelopment. → Cord blood Pb levels in Spanish newborn are low in

  1. Circulating irisin levels are positively associated with metabolic risk factors in sedentary subjects.

    Directory of Open Access Journals (Sweden)

    María Moreno

    Full Text Available A physically active life-style plays an independent role in the protection against type 2 diabetes and cardiovascular diseases. Irisin, a novel exercise-induced myokine, activates thermogenesis in rodents through increasing beige fat cells abundance within white fat. We aimed to investigate circulating irisin levels in association with the degree of physical activity and various metabolic parameters in humans.Circulating irisin levels (ELISA and metabolic parameters were analyzed in 428 subjects (195 men/233 women. Participants were classified according to their self-reported physical activity and to their area of residence.Circulating irisin levels were higher in active than in sedentary subjects (p = 0.006. Rural inhabitants showed higher circulating irisin levels than urban subjects (p < 0.0001. The increase in irisin levels related to an active lifestyle was only observed in rural citizens (p = 0.014. Among sedentary participants, irisin levels were positively associated with metabolic risk factors (BMI, fasting insulin, HOMA and fasting triglycerides. The area of residence (β = - 0.592, p = < 0.0001 contributed independently to circulating irisin levels variance after controlling for age, gender, BMI, HOMAIR, triglycerides and physical activity.In sedentary participants, circulating irisin levels were positively associated with parameters related to an increased cardiometabolic risk. The present study confirmed that an active lifestyle increases circulating irisin levels, but only among subjects living in a rural environment. Area of residence might be a determinant of irisin levels.

  2. Infliximab and adalimumab drug levels in Crohn's disease: contrasting associations with disease activity and influencing factors.

    Science.gov (United States)

    Ward, M G; Warner, B; Unsworth, N; Chuah, S-W; Brownclarke, C; Shieh, S; Parkes, M; Sanderson, J D; Arkir, Z; Reynolds, J; Gibson, P R; Irving, P M

    2017-07-01

    Discriminative drug level thresholds for disease activity endpoints in patients with Crohn's disease. have been consistently demonstrated with infliximab, but not adalimumab. To identify threshold concentrations for infliximab and adalimumab in Crohn's disease according to different disease endpoints, and factors that influence drug levels. We performed a cross-sectional service evaluation of patients receiving maintenance infliximab or adalimumab for Crohn's disease. Serum drug levels were at trough for infliximab and at any time point for adalimumab. Endpoints included Harvey-Bradshaw index, C-reactive protein and faecal calprotectin. 6-tioguanine nucleotide (TGN) concentrations were measured in patients treated with thiopurines. A total of 191 patients (96 infliximab, 95 adalimumab) were included. Differences in infliximab levels were observed for clinical (P=.081) and biochemical remission (P=.003) and faecal calprotectin normalisation (Pinfliximab dose, body mass index and colonic disease independently accounted for 31% of the variation in infliximab levels, and weekly dosing, albumin and weight accounted for 23% of variation in adalimumab levels. TGN levels did not correlate with drug levels. Infliximab drug levels are associated with the depth of response/remission in patients with Crohn's disease, but no such relationship was observed for adalimumab. More data are needed to explain the variation in drug levels. © 2017 John Wiley & Sons Ltd.

  3. [Homocystein serum levels and lipid parameters in children with atherosclerosis risk factors].

    Science.gov (United States)

    Sierakowska-Fijałek, Anna; Kaczmarek, Piotr; Pokoca, Lech; Smorag, Ireneusz; Wosik-Erenbek, Marzenna; Baj, Zbigniew

    2007-02-01

    Atherosclerosis is a disease of adult patients, however, it begins in childhood and progresses from fatty streaks to raised lesions in arteries in adolescence and young adults. Clinical manifestation of atherosclerosis in adulthood depends on the risk factors such as: lipid disorders, obesity, hypertension, smoking habits and family history of CHD. High serum homocysteine concentration is increasingly recognised as a new risk factor for atherosclerosis and other vascular diseases. Atherogenic effect of homocystein is related to cytotoxin action on the endothelial cells and their function. The aim of this study was to estimate relations between the homocysteine serum concentration and the lipid levels in children with atherosclerosis risk factors. The study was carried out on 48 children with atherosclerosis risk factors. The control group consisted of 25 healthy childrens. Total cholesterol (TC), Triglycerides (TG), HDL-C, LDL-C were determined by enzymatic method. Concentration of homocysteine was estimated by immunoenzymatic method (ELISA). Obesity, lipid disorders, and hypertension were the most frequent risk factors in the investigated children. Statistically significant higher concentration of TC, LDL-C, TG and lower HDL-C were observed in children with atherosclerosis risk factors. No significant differences in homocystein concentration were observed in the investigated groups, but homocystein concentration was significantly higher in group of children with atherosclerosis risk factors. We observed that increased number of the risk factors is followed by high homocystein concentration in the serum.

  4. Development of scaling factor prediction method for radionuclide composition in low-level radioactive waste

    International Nuclear Information System (INIS)

    Park, Jin Beak

    1995-02-01

    Low-level radioactive waste management require the knowledge of the natures and quantities of radionuclides in the immobilized or packaged waste. U. S. NRC rules require programs that measure the concentrations of all relevant nuclides either directly or indirectly by relating difficult-to-measure radionuclides to other easy-to-measure radionuclides with application of scaling factors. Scaling factors previously developed through statistical approach can give only generic ones and have many difficult problem about sampling procedures. Generic scaling factors can not take into account for plant operation history. In this study, a method to predict plant-specific and operational history dependent scaling factors is developed. Realistic and detailed approach are taken to find scaling factors at reactor coolant. This approach begin with fission product release mechanisms and fundamental release properties of fuel-source nuclide such as fission product and transuranic nuclide. Scaling factors at various waste streams are derived from the predicted reactor coolant scaling factors with the aid of radionuclide retention and build up model. This model make use of radioactive material balance within the radioactive waste processing systems. Scaling factors at reactor coolant and waste streams which can include the effects of plant operation history have been developed according to input parameters of plant operation history

  5. Identifying and prioritizing industry-level competitiveness factors: evidence from pharmaceutical market.

    Science.gov (United States)

    Shabaninejad, Hosein; Mehralian, Gholamhossein; Rashidian, Arash; Baratimarnani, Ahmad; Rasekh, Hamid Reza

    2014-04-03

    Pharmaceutical industry is knowledge-intensive and highly globalized, in both developed and developing countries. On the other hand, if companies want to survive, they should be able to compete well in both domestic and international markets. The main purpose of this paper is therefore to develop and prioritize key factors affecting companies' competitiveness in pharmaceutical industry. Based on an extensive literature review, a valid and reliable questionnaire was designed, which was later filled up by participants from the industry. To prioritize the key factors, we used the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS). The results revealed that human capital and macro-level policies were two key factors placed at the highest rank in respect of their effects on the competitiveness considering the industry-level in pharmaceutical area. This study provides fundamental evidence for policymakers and managers in pharma context to enable them formulating better polices to be proactively competitive and responsive to the markets' needs.

  6. PBDE levels in human milk: the situation in Germany and potential influencing factors - a controlled study

    Energy Technology Data Exchange (ETDEWEB)

    Vieth, B.; Mielke, H.; Ostermann, B.; Ruediger, T. [Federal Inst. for Risk Assessment, Berlin (Germany); Herrmann, T.; Paepke, O. [ERGO Forschungsgesellschaft mbH, Hamburg (Germany)

    2004-09-15

    An exponential increase of PBDE levels in breast milk from Sweden between 1972 and 1997 has been reported, which is in contrast to the continuous decline of other chlorinated POPs in breast milk. Also in blood samples from Germany, an increasing trend has been observed during the period from 1985 to 1999. The knowledge about human exposure pathways, which contribute to the PBDE body burden, is very limited. Consumption of food of animal origin, inhalation or ingestion of dust and further factors possibly influencing the PBDE levels in human matrices, like age, breast-feeding or smoking are under discussion. Only a few data on PBDE levels in breast milk from Germany have been published. To fill the data gaps, a controlled study was started in 2001 to characterise the PBDE levels in human milk from Germany with special efforts to identify and quantify deca-BDE-209. Furthermore, it was intended to verify potential factors possibly influencing PBDE levels. Two main hypotheses were proposed: (1) Are PBDE levels in breast milk from mothers consuming traditional food (omnivores) higher than those found in breast milk from mothers consuming vegetarian or vegan food? and (2) Are the PBDE levels found in human milk after a three-months period of breast-feeding lower than those detected at the beginning or does breast feeding result in a lower body burden, respectively? This paper summarises preliminary results. Further analytical data and results of data evaluation will be presented at the conference.

  7. Individual and Contextual-Level Factors Associated with Continuity of Care for Adults with Schizophrenia

    Science.gov (United States)

    Guada, Joseph; Phillips, Gary; Ranbom, Lorin; Fortney, John C.

    2013-01-01

    This retrospective cohort study examined rates of conformance to continuity of care treatment guidelines and factors associated with conformance for persons with schizophrenia. Subjects were 8,621 adult Ohio Medicaid recipients, aged 18–64, treated for schizophrenia in 2004. Information on individual-level (demographic and clinical characteristics) and contextual-level variables (county socio-demographic, economic, and health care resources) were abstracted from Medicaid claim files and the Area Resource File. Outcome measures captured four dimensions of continuity of care: (1) regularity of care; (2) transitions; (3) care coordination, and (4) treatment engagement. Multilevel modeling was used to assess the association between individual and contextual-level variables and the four continuity of care measures. The results indicated that conformance rates for continuity of care for adults with schizophrenia are below recommended guidelines and that variations in continuity of care are associated with both individual and contextual-level factors. Efforts to improve continuity of care should target high risk patient groups (racial/ethnic minorities, the dually diagnosed, and younger adults with early onset psychosis), as well as community-level risk factors (provider supply and geographic barriers of rural counties) that impede access to care. PMID:23689992

  8. Increased serum brain-derived neurotrophic factor (BDNF) levels in patients with narcolepsy

    DEFF Research Database (Denmark)

    Klein, Anders B; Jennum, Poul; Knudsen, Stine

    2013-01-01

    Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, sudden loss of muscle tone (cataplexy), fragmentation of nocturnal sleep and sleep paralysis. The symptoms of the disease strongly correlate with a reduction in hypocretin levels in CSF and a reduction in hypoc......Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, sudden loss of muscle tone (cataplexy), fragmentation of nocturnal sleep and sleep paralysis. The symptoms of the disease strongly correlate with a reduction in hypocretin levels in CSF and a reduction...... in hypocretin neurons in hypothalamus in post-mortem tissue. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are important for activity-dependent neuronal function and synaptic modulation and it is considered that these mechanisms are important in sleep regulation. We hypothesised...... that serum levels of these factors are altered in patients with narcolepsy compared to healthy controls without sleep disturbances. Polysomnography data was obtained and serum BDNF and NGF levels measured using ELISA, while hypocretin was measured using RIA. Serum BDNF levels were significantly higher...

  9. The relation between intra- and interpersonal factors and food consumption level among Iranian adolescent girls.

    Science.gov (United States)

    Kazemi, Ashraf; Zahraei, Nafisehsadat Nekuei; Nazarian, Naser

    2016-01-01

    Poor nutrition habits in adolescent girls endanger their health and are followed by serious systemic diseases in adulthood and negative effects on their reproductive health. To design health promotion programs, understanding of the intra- and interpersonal associated factors with treatment is essential, and this was the aim of this study. This cross-sectional study was conducted on 193 adolescent girls of age 11-15 years. Random cluster selection was used for sample selection. Food group consumption pattern was assessed by food frequency questionnaire. Also, perceived susceptibility/severity and nutritional attitude as intrapersonal factors and social support as interpersonal factor were assessed. The relationship between food group consumption level and nutritional attitude and perceived treat (susceptibility/severity) as intrapersonal factors and perceived social support as interpersonal factor were assessed by linear multiple regression and analysis of variance (ANOVA). Results showed that the level of sweetmeat food consumption was related to perceived social support (P = 0.03) and nutritional attitude (P = 0.01) negatively. In addition, an inverse and significant association was found between the level of junk food intake and informational perceived social support (P = 0.004). The association between the level of fast food intake and the perceived parental social support for preparation of healthy food was negatively significant (P = 0.03). Breakfast consumption was related to nutritional attitude (P = 0.03), social support (P = 0.03), and perceived severity (P = 0.045). Results revealed that perceived social support and nutritional attitude are the important and related factors in dietary intake among girls, and promotion of social support and modification of nutritional attitude may lead to healthy nutritional behaviors among them.

  10. The relation between intra- and interpersonal factors and food consumption level among Iranian adolescent girls

    Directory of Open Access Journals (Sweden)

    Ashraf Kazemi

    2016-01-01

    Full Text Available Background: Poor nutrition habits in adolescent girls endanger their health and are followed by serious systemic diseases in adulthood and negative effects on their reproductive health. To design health promotion programs, understanding of the intra- and interpersonal associated factors with treatment is essential, and this was the aim of this study. Materials and Methods: This cross-sectional study was conducted on 193 adolescent girls of age 11-15 years. Random cluster selection was used for sample selection. Food group consumption pattern was assessed by food frequency questionnaire. Also, perceived susceptibility/severity and nutritional attitude as intrapersonal factors and social support as interpersonal factor were assessed. The relationship between food group consumption level and nutritional attitude and perceived treat (susceptibility/severity as intrapersonal factors and perceived social support as interpersonal factor were assessed by linear multiple regression and analysis of variance (ANOVA. Results: Results showed that the level of sweetmeat food consumption was related to perceived social support (P = 0.03 and nutritional attitude (P = 0.01 negatively. In addition, an inverse and significant association was found between the level of junk food intake and informational perceived social support (P = 0.004. The association between the level of fast food intake and the perceived parental social support for preparation of healthy food was negatively significant (P = 0.03. Breakfast consumption was related to nutritional attitude (P = 0.03, social support (P = 0.03, and perceived severity (P = 0.045. Conclusions: Results revealed that perceived social support and nutritional attitude are the important and related factors in dietary intake among girls, and promotion of social support and modification of nutritional attitude may lead to healthy nutritional behaviors among them.

  11. Association between plasma brain-derived neurotrophic factor levels and personality traits in healthy Japanese subjects.

    Science.gov (United States)

    Yasui-Furukori, Norio; Tsuchimine, Shoko; Kaneda, Ayako; Sugawara, Norio; Ishioka, Masamichi; Kaneko, Sunao

    2013-11-30

    Although depression has been associated with decreased brain-derived neurotrophic factor (BDNF) levels for specific personality traits, there is a little information regarding the association between peripheral BDNF levels and such traits. The sample consisted of 178 healthy Japanese subjects (age range, 37.4 ± 11.5 years). All subjects filled out the Temperament and Character Inventory (TCI). Plasma BDNF levels were measured using the enzyme-linked immunosorbent assay. A simple regression analysis revealed that plasma BDNF levels were significantly correlated with harm avoidance (r=-0.177, p=0.018) and self-directedness scores (r=0.165, p=0.028). Our findings suggest that plasma BDNF levels are associated with depression-related personality traits. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. Increased basal plasma brain-derived neurotrophic factor levels in sprint runners.

    Science.gov (United States)

    Correia, Paulo Roberto; Scorza, Fulvio Alexandre; Gomes da Silva, Sérgio; Pansani, Aline; Toscano-Silva, Michelle; de Almeida, Antonio Carlos; Arida, Ricardo Mario

    2011-10-01

    Exercise is known to enhance circulating brain-derived neurotrophic factor (BDNF) levels in healthy humans. BDNF changes have been measured in endurance but not in strength exercise. The present study aimed to investigate whether anaerobic activity such as sprinting differentially alters basal plasma BDNF concentration. Brazilian sprinters (100 m) at either the international (Olympics and Outdoor World Championships) (n = 14) or the domestic level (n = 8), and sedentary subjects (n = 15), were recruited. Plasma BDNF concentrations were analyzed by enzyme-linked immunosorbent assay. The basal plasma BDNF concentrations were significantly higher in the international and the domestic sprinters than in the sedentary subjects. In addition, sprinters at the international level had higher plasma BDNF concentrations than those at the domestic level. Our findings suggest that increased basal plasma BDNF level is related to enhanced exercise performance.

  13. Relationship between increased serum tumor necrosis factor levels and insulin resistance in patients with essential hypertension

    International Nuclear Information System (INIS)

    Wang Weimin; Li Jinliang; Huang Yongqiang

    2010-01-01

    Objective: To investigate the relationship between serum tumor necrosis factor-α (TNF-α) levels and insulin resistance (IR) in patients with essential by pertension. Methods: Serum TNF-α and free insulin (fINS)levels were measured with RIA in 41 patients with essential hypertension and 38 controls. Insulin resistance was calculated with insulin resistance index (HOMA-IR). Results: The serum TNF-α levels were significantly higher in patients with essential hypertension than those in the controls (P<0.001). The HOMA-IR was also significantly higher in hypertension group than that in controls (P<0.001). Serum TNF-α levels was positively correlated with BMI, HOMA-IR and SBP both in hypertension group and control group (P<0.05). Conclusion: Serum TNF-α level was increased in hypertensive patients and positively correlated with obesity and IR. (authors)

  14. Determination of serum insulinlike growth factor II levels in coronary heart disease patient and its significance

    International Nuclear Information System (INIS)

    Fan Bifu; Ji Naijun; Mei Yibin; Wang Chengyao; Zhao Junfei; Guan Lihua; Gao Meiying; Li Jiangao

    2002-01-01

    Objective: To explore the changes and clinical significance of serum insulinlike growth factor II (IGF II) levels in coronary heart disease (CHD) patients. Methods: The serum IGF II levels were determined by radioimmunoassay in 68 patients with coronary heart disease (CHD) and 30 controls with only mild non-cardiac diseases. Results: Compared with the controls, the serum IGF II level in CHD patients were increased significantly (0.66 ± 0.13 μg/L vs 0.51 ± 0.11 μg/L; t = 5.506, p 0.05). Level in patients dies in hospital (n = 9) were much higher than those in patients recovered (n = 59) (t = 2.402, p < 0.05). Conclusion: Serum IGF II levels seems to be related to the seriousness of CHD; the actual mechanism remains to be defined

  15. Main factors determining the KNP units 5 and 6 safety level according to the PSA level 1 result

    International Nuclear Information System (INIS)

    Manchev, B.; Marinova, B.; Nenkova, B.

    2004-01-01

    The Probabilistic Safety Analysis (PSA) is a powerful tool for ascertainment of the safety level reached at nuclear power plants operation. The results of PSA determine very clearly the functions, systems, equipment or operator actions that have to be improved in order to increase the plant safety level as a whole. The present report presents the main results of the last upgraded revision of PSA level 1 of units 5 and 6 of KNPP. The objective of the report is to lay emphasis on the factors determining the result obtained, i.e. to demonstrate the scopes whose improvement leads to an increase of the safety level reached at the units power operation. In the frame of the study presented the following categories of initiating events are included: Internal initiating events; Initiating events result of internal fires; Initiating events result of seismic action; Floods. Only the reactor core is considered as a source of radioactive contamination. Only initiating events related to the reactor work on power are analyzed. Unit 5 of KNPP is accepted as a basic unit for the study. All modifications and design changes implemented up to year 2000 are taken into account. The results of PSA level 1 for units 5 and 6 of KNPP covering the risk of internal initiators are presented. The assessment of the core damage due to internal initiators is based on the analysis of 18 groups of initiating events. 932 consequences and two groups of initial events are identified, leading to core damage. As a result of the quantitative calculation, over 15000 minimal cuts for the core damage are obtained. The first 80 cuts bear over 75% of the frequency obtained, and the first 700 cuts bear over 90%. Distribution of the core damage frequency by different groups of initiators is presented in tables and diagrams. A comparison of the result obtained for the reactor core damage of KNPP units 5 and 6 with assessment obtained for similar power plants is presented. The data for different NPPs are taken

  16. Vascular Endothelial Growth Factor Level as A Predictor of Hepatocellular Carcinoma in Liver Cirrhosis Patients

    Directory of Open Access Journals (Sweden)

    Benyamin Lukito

    2014-12-01

    Full Text Available BACKGROUND: Alpha-fetoprotein (AFP has been used for hepatocellular carcinoma (HCC diagnosis and screening, however, AFP has poor specificity. The extensive hypervascularity associated with HCC could be driven in part by the pro-angiogenic factor known as vascular endothelial growth factor (VEGF. Furthermore, invasiveness of certain HCC lesions has recently been linked to high levels of VEGF. Therefore, circulating VEGF levels of patients with liver cirrhosis (LC and HCC were investigated and analysed. METHODS: An analytical cross sectional study was designed. Diagnosis of HCC and LC was performed using clinical criteria and findings obtained from B-mode ultrasonography (USG, computed tomography (CT angiography, or magnetic resonance imaging (MRI. Blood were collected intravenously from all subjects. Obtained serum and plasma were stored in -80°C for following analyses: hepatitis B surface antigen (HBSAg, hepatitis C virus (HCV, alanine aminotransferase (ALT, total bilirubin, albumin, VEGF and AFP. RESULTS: Levels of VEGF and AFP were significantly higher in HCC group compared with LC group with p=3.05x10-6 and p=8.74x10-5, respectively. There was a significant positive correlation (p=0.029, r=0.309 between VEGF level and tumor size in HCC group. The area under curve (AUC for VEGF level in HCC and LC groups was 0.771. In the level of median 435.6 pg/mL VEGF, the sensitivity was 50% and specificity was 86%. In the level of 199.99 pg/mL VEGF the sensitivity was 74% and specificity was 76%. CONCLUSIONS: The present findings suggested that VEGF level could be a useful marker for the presence of HCC in patients with LC. KEYWORDS: hepatocellular carcinoma, HCC, liver cirrhosis, LC, vascular endothelial growth factor, VEGF, alpha-fetoprotein, AFP.

  17. Comprehensive Transportation Logistics Network Level Layout Based on Principal Component Factor and Cluster Analysis

    Directory of Open Access Journals (Sweden)

    Zhang Jingrong

    2017-01-01

    Full Text Available Comprehensive Transportation Logistics Network (CTLN acts as a crucial prop and fundamental carrier for regional economic and social development. Firstly, an index system for evaluating the development of regional Comprehensive Transportation Logistics (CTL nodes is established; then regional CTLN nodes are ranked according to their importance by the method of Principal Component Analysis(PCA, and main factors affecting the development of regional CTL nodes are analyzed by applying factor analysis, and regional CTL nodes are classified according to their feature similarities by applying cluster analysis; and then level structure of constructing regional CTLN is proposed. Finally, combined with geographic locations of different nodes, level layout model of CTLN of the whole region is obtained. Taking Henan province this region as an instance, level layout model of hub-and-spoke CTLN taking Zhengzhou at its core is proposed after analysis, providing a reference basis for constructing CTLN in whole province scientifically and reasonably.

  18. Elevated levels of plasma brain derived neurotrophic factor in rapid cycling bipolar disorder patients

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Pedersen, Bente Klarlund; Kessing, Lars Vedel

    2014-01-01

    Impaired neuroplasticity may be implicated in the pathophysiology of bipolar disorder, involving peripheral alterations of the neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3). Evidence is limited by methodological issues and is based primarily on case......-control designs. The aim of this study was to investigate whether BDNF and NT-3 levels differ between patients with rapid cycling bipolar disorder and healthy control subjects and whether BDNF and NT-3 levels alter with affective states in rapid cycling bipolar disorder patients. Plasma levels of BDNF and NT-3...... patients during a 6-12 months period and compared with repeated measurements in healthy control subjects. Careful attention was given to standardization of all procedures and adjustment for potential confounders of BDNF and NT-3. In linear mixed models, adjusting for demographical and lifestyle factors...

  19. A STUDY ON PLASMA 25 - HYDROXY VITAMIN D LEVELS AS A RISK FACTOR IN PRIMARY HYPERTENSION

    Directory of Open Access Journals (Sweden)

    Ravinandana Gowda

    2015-07-01

    Full Text Available BACKGROUND: Recent research shows that vitamin D deficiency could be a risk factor in many chronic diseases like hypertension, diabetes mellitus, dyslipidemia, cardiovascular disease, some cancers, auto immune disease and tuberculosis. AIMS AND OBJECTIVES: To determine serum 25 - hydroxy vitamin D levels in patients with primary hypertension. This study also attempts to demonstrate an inverse co - relation between vitamin D levels and primary hypertension. MATERIALS AND METHOD S: 30 patients who are primary hype rtensive were selected, their vitamin D levels measured and the vitamin D levels were compared to age and sex matched non hypertensive controls. STATISTICAL METHODS: Descriptive and inferential statistical analysis has been carried out in the present study . ANOVA test and Chi - square test was applied for quantitative and qualitative data respectively to find significant associations between two variables. RESULTS: It is seen from this study that serum vitamin D levels was lower in hypertensive patients when compared to non - hypertensive controls. Hypertensive patients had lower levels of vitamin D with vitamin D status of deficiency in 50% of the cases and insufficiency in 43.3% of the cases and normal levels in 6.7% of the cases. Non hypertensive controls sho wed vitamin D status of normal in 66.7% of controls and insufficiency in 33.3% of the controls without deficiency. Age of the cases, duration of hypertension, systolic blood pressure and diastolic blood pressure inversely correlated to vitamin D levels. Bo dy mass index, diet of the patient, alcohol consumption, number of anti - hypertensive drugs, drug compliance, family history of hypertension and fundus status did not correlate to vitamin D levels. CONCLUSIONS: Based on the observations of the study, Vitami n D is an independent risk factor that is associated with primary or essential hypertension. The level of vitamin D also correlated inversely to age, duration of

  20. The Evaluation of Psychological Factor and Salivary Cortisol and IgA Levels in

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    Fateme Arbabi-Kalati

    2014-07-01

    Full Text Available Background: Oral lichen planus (OLP is a chronic immunological disorder with unknown etiology. The aim of this study was to determine psychological factors and salivary cortisol, IgA level in patients with oral lichen planus. Materials and Methods: In this experimental study 20 patients with OLP and healthy person were admitted to this study. Saliva samples were collected between - Am. saliva cortisol, IgA level was detected by ELIZA method. In this study, patients with anxiety and depression were measured using the SCL-90 questionnaire. Data analyzed by t-test. Results: The mean salivary cortisol level in patients with OLP was 3.2±1.9 ng/mL and the mean saliva cortisol level in healthy person was 3.5±1.9 ng/mL. Significant difference was observed in the salivary cortisol levels in the 2 study groups (p=0.04. The mean salivary IgA level in patients with OLP was 0.69±0.29 ng/mL and the mean saliva IgA level in healthy person was 0.9±0.43 ng/mL but no significant difference was observed in the salivary cortisol levels in the 2 study groups. Results showed that anxiety levels in patients with oral lichen planus were slightly higher than controls but there was no significant difference between healthy subjects. Conclusion: Finding revealed the mean salivary cortisol level in patient with OLP less than healthy persons. Significant difference was observed in the salivary cortisol levels in the 2 study groups. Based on the t-student test, no significant difference was observed in the salivary IgA levels in the 2 study groups. Anxiety levels in patients with oral lichen planus were slightly higher than controls.

  1. Risk factors for unstable blood glucose level: integrative review of the risk factors related to the nursing diagnosis.

    Science.gov (United States)

    Teixeira, Andressa Magalhães; Tsukamoto, Rosangela; Lopes, Camila Takáo; Silva, Rita de Cassia Gengo E

    2017-06-05

    to identify evidence in the literature on the possible risk factors for the risk of unstable blood glucose diagnosis in individuals with type 2 diabetes mellitus, and to compare them with the risk factors described by NANDA International. an integrative literature review guided by the question: what are the risk factors for unstable blood glucose level in people with type 2 diabetes mellitus? Primary studies were included whose outcomes were variations in glycemic levels, published in English, Portuguese or Spanish, in PubMed or CINAHL between 2010 and 2015. altered levels of glycated hemoglobin, body mass index>31 kg/m2, previous history of hypoglycemia, cognitive deficit/dementia, autonomic cardiovascular neuropathy, comorbidities and weight loss corresponded to risk factors described in NANDA International. Other risk factors identified were: advanced age, black skin color, longer length of diabetes diagnosis, daytime sleepiness, macroalbuminuria, genetic polymorphisms, insulin therapy, use of oral antidiabetics, and use of metoclopramide, inadequate physical activity and low fasting glycemia. risk factors for the diagnosis, risk for unstable blood glucose level, for persons with type 2 diabetes mellitus were identified, and 42% of them corresponded to those of NANDA International. These findings may contribute to the practice of clinical nurses in preventing the deleterious effects of glycemic variation. identificar evidências na literatura acerca de possíveis fatores de risco do diagnóstico risco de glicemia instável para pessoas com diabetes mellitus tipo 2 e compará-los com os fatores de risco descritos pela NANDA International . revisão integrativa norteada pela pergunta: quais são os fatores de risco de glicemia instável em pessoas com diabetes mellitus tipo 2? Incluíram-se estudos primários cujos desfechos eram variações nos níveis glicêmicos, publicados em inglês, português ou espanhol no PubMed ou CINAHL entre 2010 e 2015. observou

  2. Serum brain-derived neurotrophic factor levels and personality traits in patients with major depression.

    Science.gov (United States)

    Nomoto, Hiroshi; Baba, Hajime; Satomura, Emi; Maeshima, Hitoshi; Takebayashi, Naoko; Namekawa, Yuki; Suzuki, Toshihito; Arai, Heii

    2015-03-04

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors. Previous studies have demonstrated lower serum BDNF levels in patients with major depressive disorder (MDD) and reported an association between BDNF levels and depression-related personality traits in healthy subjects. The aim of the present study was to explore for a possible association between peripheral BDNF levels and personality traits in patients with MDD. In this cross-sectional study, a total of 123 inpatients with MDD (Diagnostic and Statistical Manual for Mental Disorders, 4th edition) at the Juntendo University Koshigaya Hospital were recruited. Serum levels of BDNF were measured. Personality traits were assessed using the 125-item short version of the Temperament and Character Inventory (TCI). Multiple regression analysis adjusted for age, sex, body mass index, dose of antidepressant, and depression severity showed that TCI Self-Directedness (SD) scores were negatively associated with serum BDNF levels (β = -0.23, p = 0.026). MDD patients who have low SD did not show the reduction in serum BDNF levels that is normally associated with depressive state. Our findings suggest that depression-related biological changes may not occur in these individuals.

  3. Home radon levels and seasonal correction factors for the Isle of Man

    International Nuclear Information System (INIS)

    Grainger, P.; Preece, A.W.; Goodfellow, S.A.

    2000-01-01

    Ionizing radiation dose levels due to home radon can rise to levels that would be illegal for workers in the nuclear industry. It is well known that radon levels within homes and from home to home, and also from month to month, vary considerably. To define an Isle of Man radon seasonal correction factor, readings were taken in eight homes over a 12 month period. An average island indoor exposure of 48 Bq m -3 (range 4-518 Bq m -3 ) was determined from 285 homes selected from a cohort of 1300 families participating in the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) in the Isle of Man. This compares with a UK home average of 20 Bq m -3 and a European Union average (excluding UK) of 68 Bq m -3 . Ten homes of those measured were found to have radon levels above the National Radiological Protection Board 200 Bq m -3 action level. There are 29 377 homes on the Isle of Man, suggesting that there could be some 900 or more homes above the action level. No statistical difference was found between the NRPB and Isle of Man seasonal correction factors. (author)

  4. Estimation of sources and factors affecting indoor VOC levels using basic numerical methods

    Directory of Open Access Journals (Sweden)

    Sibel Mentese

    2016-11-01

    Full Text Available Volatile Organic Compounds (VOCs are a concern due to their adverse health effects and extensive usage. Levels of indoor VOCs were measured in six homes located in three different towns in Çanakkale, Turkey. Monthly indoor VOC samples were collected by passive sampling throughout a year. The highest levels of total volatile organic compounds (TVOC, benzene, toluene, and xylenes occurred in industrial, rural, and urban sites in a descending order. VOC levels were categorized as average values annually, during the heating period, and non-heating period. Several building/environmental factors together with occupants’ habits were scored to obtain a basic indoor air pollution index (IAPi for the homes. Bivariate regression analysis was applied to find the associations between the pollutant levels and home scores. IAPi scores were found to be correlated with average indoor VOC levels. In particular, very strong associations were found for occupants’ habits. Furthermore, observed indoor VOC levels were categorized by using self-organizing map (SOM and two simple scoring approaches, rounded average and maximum value methods, to classify the indoor environments based on their VOC compositions (IAPvoc. Three classes were used for both IAPi and IAPvoc approaches, namely “good”, “moderate”, and “bad”. There is an urgent need for indexing studies to determine the potential sources and/or factors affecting observed VOCs. This study gives a basic but good start for further studies.

  5. System-level factors affecting clinicians' perceptions and use of interpreter services in California public hospitals.

    Science.gov (United States)

    Baurer, Danielle; Yonek, Julie C; Cohen, Alan B; Restuccia, Joseph D; Hasnain-Wynia, Romana

    2014-04-01

    Professional language interpreters are skilled in the nuances of interpretation and are less likely to make errors of clinical significance but clinicians infrequently use them. We examine system-level factors that may shape clinicians' perceptions and use of professional interpreters. Exploratory qualitative study in 12 California public hospitals. We conducted in-person key informant interviews with hospital leadership, clinical staff, and administrative staff. Five emergent themes highlight system-level factors that may influence clinicians' perceptions and use of professional interpreters in hospitals: (1) organization-wide commitment to improving language access for LEP patients; (2) organizational investment in remote interpreter technologies to increase language access; (3)training clinicians on how to access and work with interpreters; (4) hospital supports the training and certification of bilingual staff to serve as interpreters to expand in-person, on-site, interpreter capacity; and (5)organizational investment in readily accessible telephonic interpretation. Multiple system-level factors underlie clinicians' use of professional interpreters. Interventions that target these factors could improve language services for patients with limited English proficiency.

  6. A meta-analysis of peripheral blood nerve growth factor levels in patients with schizophrenia.

    Science.gov (United States)

    Qin, X-Y; Wu, H-T; Cao, C; Loh, Y P; Cheng, Y

    2017-09-01

    Neurotrophins particularly brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are crucial modulators in the neurodevelopment and maintenance of central and peripheral nervous systems. Neurotrophin hypothesis of schizophrenia (SCZ) postulated that the changes in the brains of SCZ patients are the result of disturbances of developing processes involving neurotrophic factors. This hypothesis was mainly supported by the abnormal regulation of BDNF in SCZ, especially the decreased peripheral blood BDNF levels in SCZ patients validated by several meta-analyses. However, the regulation of NGF in SCZ remains unclear because of the inconsistent findings from the clinical studies. Therefore, we undertook, to the best of our knowledge, the first systematic review with a meta-analysis to quantitatively summarize the peripheral blood NGF data in SCZ patients compared with healthy control (HC) subjects. A systematic search of Pubmed, PsycINFO and Web of Science identified 13 articles encompassing a sample of 1693 individuals for the meta-analysis. Random-effects meta-analysis showed that patients with SCZ had significantly decreased peripheral blood levels of NGF when compared with the HC subjects (Hedges's g=-0.633, 95% confidence interval (CI)=-0.948 to -0.318, Panalysis, whereas disease severity might be a confounding factor for the meta-analysis. These results demonstrated that patients with SCZ are accompanied by the decreased peripheral blood NGF levels, strengthening the clinical evidence of an abnormal neurotrophin profile in the patients with SCZ.

  7. Environmental lead exposure among preschool children in Shanghai, China: blood lead levels and risk factors.

    Directory of Open Access Journals (Sweden)

    Jia Cao

    Full Text Available OBJECTIVE: To determine blood lead levels and to identify related risk factors among children in Shanghai; to explore the lead change trend of children after industrial transformation and to provide data for policy development to control environmental lead pollution in Shanghai. METHODS: A stratified-clustered-random sampling method was used. A tungsten atomizer absorption spectrophotometer was employed to determine blood lead levels. RESULTS: The arithmetic mean, geometric mean and median of blood lead levels of 0- to 6-year-old children from Shanghai were 22.49 µg/L, 19.65 µg/L and 19.5 µg/L, including 0.26% (6/2291 with concentrations ≥100 µg/L and 2.7% (61/2291 with concentrations ≥50 µg/L. Boys' levels (23.57 µg/L were greater than those of girls (21.2 µg/L. The blood lead levels increased with age. This survey showed that the Chongming district was the highest and Yangpu district was the lowest, this result is completely opposite with the earlier survey in Shanghai. Risk factors for lead contamination included housing environment, parents' education levels, social status, hobbies, and children's nutritional status. CONCLUSIONS: The blood lead levels of children in Shanghai were lower than the earlier data of Shanghai and those of published studies in China, but higher than the blood lead levels of developed countries. The blood lead levels of urban districts are higher than the central districts with the industrial transformation. Society and the government should take an active interest in childhood lead poisoning of urban areas.

  8. Serum Osteoprotegerin Levels Related With Cardiovascular Risk Factors in Chronic Kidney Disease.

    Science.gov (United States)

    Demir, Pinar; Erdenen, Fusun; Aral, Hale; Emre, Turker; Kose, Sennur; Altunoglu, Esma; Dolgun, Anil; Inal, Berrin Bercik; Turkmen, Aydin

    2016-11-01

    To evaluate osteoprotegerin (OPG) levels in relation to cardiovascular (CV) risk factors in patients with chronic kidney disease (CKD) on different regimens of renal replacement therapy. A total of 143 patients with CKD and 30 healthy controls were included in this study and divided into five categories, including predialysis patients with chronic renal failure (preD; n = 36), chronic peritoneal dialysis patients (PD; n = 36), hemodialysis patients (HD; n = 35), renal transplant patients (RT; n = 36), and controls (n = 30). Data on demographics, concomitant diseases and CV risk factors, serum OPG levels, and correlates of serum OPG levels were determined. Serum OPG (pmol/l) levels were significantly higher in HD (P <0.001 for each), PD (P <0.001 for each), and preD (P <0.01 vs. control, P <0.05 vs. RT) groups than RT and control groups. Diabetics than nondiabetics in HD (P = 0.008), PD (P = 0.024), and RT (P = 0.004) groups and males than females in PD group (P = 0.021) had higher OPG levels. Serum OPG levels were associated positively with age in HD (P <0.001), PD (P = 0.001), and in overall population (P <0.001). Our findings revealed increased serum levels of OPG in dialysis and preD patients compared to RT and controls. In the patient groups receiving two dialysis treatment, the levels were worse, indicating a more pronounced vascular injury. Age, C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-C), and cystatin C (CysC) in CKD patients, CRP and PTH in the control subjects, and age and BMI in the overall population were the significant correlates of serum OPG levels. © 2016 Wiley Periodicals, Inc.

  9. Primary care team- and clinic level factors affecting HPV vaccine uptake.

    Science.gov (United States)

    Chuang, Emmeline; Cabrera, Claudia; Mak, Selene; Glenn, Beth; Hochman, Michael; Bastani, Roshan

    2017-08-16

    This study examined patient-, care team- and clinic-level factors associated with human papillomavirus (HPV) vaccine initiation and completion. HPV vaccine initiation and completion rates among adolescents aged 9-18years were assessed using administrative data (n=38,277) from a large federally qualified health center serving predominantly Latino patients. Four clinics with particularly high and low adolescent HPV vaccine uptake were selected for in-depth case study analyses. Semi-structured interviews with clinic leaders, providers, and support staff in these clinics (n=36) examined multilevel factors perceived as affecting vaccine initiation and completion. On average, less than half (45%) of patients had initiated the HPV vaccine; of these, 52% of patients completed all recommended doses. Vaccine uptake varied significantly across clinics but was higher among patients seen by providers specializing in pediatrics. Qualitative findings confirmed the importance of provider communication strategies but indicated that other health care team structures and processes also play an important role in vaccine uptake. Care team members in higher performing clinics were more likely to describe vaccination as a team effort rather than solely the provider's responsibility. Support staff in higher performing clinics also spent more time reviewing patient preventive care needs and preparing patients for the provider encounter. Clinic-level factors such as performance management systems and the use of immunization champions were described as important for developing an organizational climate supportive of vaccination. Tracking and reminder systems were described as important but insufficient for ensuring vaccine uptake in the absence of other supports. Efforts to improve HPV initiation and completion could benefit from additional attention to factors at the health care team and clinic levels. Interventions that target factors at multiple levels of influence are most likely to

  10. Contribution of individual and environmental factors to physical activity level among Spanish adults.

    Directory of Open Access Journals (Sweden)

    José Antonio Serrano-Sanchez

    Full Text Available BACKGROUND: Lack of physical activity (PA is a major risk for chronic disease and obesity. The main aims of the present study were to identify individual and environmental factors independently associated with PA and examine the relative contribution of these factors to PA level in Spanish adults. METHODOLOGY/PRINCIPAL FINDINGS: A population-based cross-sectional sample of 3,000 adults (18-75 years old from Gran Canaria (Spain was selected using a multistage stratified random sampling method. The participants were interviewed at home using a validated questionnaire to assess PA as well as individual and environmental factors. The data were analyzed using bivariate and multivariate logistic regression. One demographic variable (education, two cognitive (self-efficacy and perceived barriers, and one social environmental (organized format were independently associated with PA in both genders. Odds ratios ranged between 1.76-2.07 in men and 1.35-2.50 in women (both p<0.05. Individual and environmental factors explained about one-third of the variance in PA level. CONCLUSIONS/SIGNIFICANCE: Self-efficacy and perceived barriers were the most significant factors to meet an adequate level of PA. The risk of insufficient PA was twofold greater in men with primary or lesser studies and who are employed. In women, living in rural environments increased the risk of insufficient PA. The promotion of organized PA may be an efficient way to increase the level of PA in the general population. Improvement in the access to sport facilities and places for PA is a prerequisite that may be insufficient and should be combined with strategies to improve self-efficacy and overcome perceived barriers in adulthood.

  11. Impact of some field factors on inhalation exposure levels to bitumen emissions during road paving operations.

    Science.gov (United States)

    Deygout, François; Auburtin, Guy

    2015-03-01

    Variability in occupational exposure levels to bitumen emissions has been observed during road paving operations. This is due to recurrent field factors impacting the level of exposure experienced by workers during paving. The present study was undertaken in order to quantify the impact of such factors. Pre-identified variables currently encountered in the field were monitored and recorded during paving surveys, and were conducted randomly covering current applications performed by road crews. Multivariate variance analysis and regressions were then used on computerized field data. The statistical investigations were limited due to the relatively small size of the study (36 data). Nevertheless, the particular use of the step-wise regression tool enabled the quantification of the impact of several predictors despite the existing collinearity between variables. The two bitumen organic fractions (particulates and volatiles) are associated with different field factors. The process conditions (machinery used and delivery temperature) have a significant impact on the production of airborne particulates and explain up to 44% of variability. This confirms the outcomes described by previous studies. The influence of the production factors is limited though, and should be complemented by studying factors involving the worker such as work style and the mix of tasks. The residual volatile compounds, being part of the bituminous binder and released during paving operations, control the volatile emissions; 73% of the encountered field variability is explained by the composition of the bitumen batch. © The Author 2014. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

  12. Invited commentary: genetic variants and individual- and societal-level risk factors.

    Science.gov (United States)

    Coughlin, Steven S

    2010-01-01

    Over the past decade, leading epidemiologists have noted the importance of social factors in studying and understanding the distribution and determinants of disease in human populations; but to what extent are epidemiologic studies integrating genetic information and other biologic variables with information about individual-level risk factors and group-level or societal factors related to the broader residential, behavioral, or cultural context? There remains a need to consider ways to integrate genetic information with social and contextual information in epidemiologic studies, partly to combat the overemphasis on the importance of genetic factors as determinants of disease in human populations. Even in genome-wide association studies of coronary heart disease and other common complex diseases, only a small proportion of heritability is explained by the genetic variants identified to date. It is possible that familial clustering due to genetic factors has been overestimated and that important environmental or social influences (acting alone or in combination with genetic variants) have been overlooked. The accompanying article by Bressler et al. (Am J Epidemiol. 2010;171(1):14-23) highlights some of these important issues.

  13. [Elevated levels of homocysteine in plasma as a risk factor for coronary artery disease].

    Science.gov (United States)

    Dzielińska, Z; Kadziela, J; Sitkiewicz, D; Kruk, M; Przyłuski, J; Deptuch, T; Piotrowski, W; Dabrowski, M; Ruzyłło, W

    2000-07-01

    This study was performed to assess the significance of association between coronary artery disease (CAD) and circulating homocysteine concentrations. 100 consecutive CAD patients (78 men and 22 women, aged 31 to 79 years) qualified for PTCA were investigated. At the time of PTCA, the risk factors for CAD and plasma for homocysteine and vitamins were obtained. The controls were without clinical evidence of coronary artery disease and hypertension (90 men and 30 women aged 32 to 81 years). Homocysteine was assayed using ELISA test. Red cell folate and plasma vitamin B12 were assayed by immunofluoroscency (Delphia test). Homocysteine concentrations were higher in patients than in controls (13.61 +/- 4.5 vs 10.99 +/- 4.49 mumol/L, p or = 12.83 mumol/L--was seen in 46% of the patients compared with 20% of the control group (p = 0.001). The odds ratio (OR) for CAD in persons with elevated homocysteine level was 3.1 (95% Cl 1.6-5.8, p < 0.001, adjusted for age). The OR for CAD of 5 mumol/L increment in homocysteine level was 2.1 (95% Cl 1.4-3.1 p < 0.001, adjusted for age). After adjustment for conventional risk factors (age, smoking, hypertension, family history of CAD, hyperlipidemia), elevated homocysteine level remained independent risk factor for CAD (OR 2.88, 95% Cl 1.1-7.8, p < 0.05). We observed inverse correlation between homocysteine and folate level (r = -0.32, p = 0.005) and between homocysteine and vitamin B12 concentrations (r = -0.24, p = 0.03), especially in men. Patients with elevated homocysteine level had lower levels of folate (629.6 +/- 241.2 nmol/L vs 735.1 +/- 252.4 nmol/L, p < 0.05), and vitamin B12 (213.6 +/- 64.4 pmol/L vs 246.6 +/- 62.3 pmol/L, p < 0.05) than patients with normal level of homocysteine. Elevated plasma homocysteine level is a strong risk factor for coronary artery disease. A 5 mumol/L increment in total homocysteine level may be associated with twofold increase of risk for the disease.

  14. Factors associated with low levels of lumbar strength in adolescents in Southern Brazil

    Directory of Open Access Journals (Sweden)

    Diego Augusto Santos Silva

    2014-12-01

    Full Text Available OBJECTIVE: To determine the prevalence and factors associated with low levels of lumbar strength in adolescents.METHOD: This was a cross-sectional study involving 601 adolescents, aged 14 to 17 years, enrolled in public schools in the western region of Santa Catarina State - Southern Brazil. Lumbar strength was analyzed by the lumbar extension test developed by the Canadian Society of Exercise Physiology, which proposes different cutoffs for boys and girls. Independent variables were sex, age, socioeconomic status, dietary habits, alcohol consumption, physical activity, and aerobic fitness. For data analysis, univariate and multivariate logistic regression were used, with significance level of 5%.RESULTS: The prevalence of low levels of lumbar strength was 27.3%. The population subgroups most likely to present low levels of lumbar strength were females (OR: 1.54, 95% CI : 1.06 to 2.23, adolescents with low levels of aerobic fitness (OR: 2.10, 95% CI: 1.41 to 3.11 and the overweight (OR: 2.28, 95% CI: 1.35 to 3.81.CONCLUSION: Almost one-third of the studied students have low levels of lumbar strength. Interventions in the school population should be taken with special attention to female adolescents, those with low levels of aerobic fitness, and those with overweight, as these population subgroups were most likely to demostrate low levels of lumbar strength.

  15. [Factors associated with low levels of lumbar strength in adolescents in Southern Brazil].

    Science.gov (United States)

    Silva, Diego Augusto Santos; Gonçalves, Eliane Cristina de Andrade; Grigollo, Leoberto Ricardo; Petroski, Edio Luiz

    2014-12-01

    To determine the prevalence and factors associated with low levels of lumbar strength in adolescents. This was a cross-sectional study involving 601 adolescents, aged 14 to 17 years, enrolled in public schools in the western region of Santa Catarina State - Southern Brazil. Lumbar strength was analyzed by the lumbar extension test developed by the Canadian Society of Exercise Physiology, which proposes different cutoffs for boys and girls. Independent variables were sex, age, socioeconomic status, dietary habits, alcohol consumption, physical activity, and aerobic fitness. For data analysis, univariate and multivariate logistic regression were used, with significance level of 5%. The prevalence of low levels of lumbar strength was 27.3%. The population subgroups most likely to present low levels of lumbar strength were females (OR: 1.54, 95% CI: 1.06 to 2.23), adolescents with low levels of aerobic fitness (OR: 2.10, 95% CI: 1.41 to 3.11) and the overweight (OR: 2.28, 95% CI: 1.35 to 3.81). Almost one-third of the studied students have low levels of lumbar strength. Interventions in the school population should be taken with special attention to female adolescents, those with low levels of aerobic fitness, and those with overweight, as these population subgroups were most likely to demonstrate low levels of lumbar strength. Copyright © 2014 Associação de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  16. Circulating irisin levels are positively associated with metabolic risk factors in sedentary subjects.

    Science.gov (United States)

    Moreno, María; Moreno-Navarrete, José María; Serrano, Marta; Ortega, Francisco; Delgado, Elías; Sanchez-Ragnarsson, Cecilia; Valdés, Sergio; Botas, Patricia; Ricart, Wifredo; Fernández-Real, José Manuel

    2015-01-01

    A physically active life-style plays an independent role in the protection against type 2 diabetes and cardiovascular diseases. Irisin, a novel exercise-induced myokine, activates thermogenesis in rodents through increasing beige fat cells abundance within white fat. We aimed to investigate circulating irisin levels in association with the degree of physical activity and various metabolic parameters in humans. Circulating irisin levels (ELISA) and metabolic parameters were analyzed in 428 subjects (195 men/233 women). Participants were classified according to their self-reported physical activity and to their area of residence. Circulating irisin levels were higher in active than in sedentary subjects (p = 0.006). Rural inhabitants showed higher circulating irisin levels than urban subjects (p sedentary participants, irisin levels were positively associated with metabolic risk factors (BMI, fasting insulin, HOMA and fasting triglycerides). The area of residence (β = - 0.592, p = sedentary participants, circulating irisin levels were positively associated with parameters related to an increased cardiometabolic risk. The present study confirmed that an active lifestyle increases circulating irisin levels, but only among subjects living in a rural environment. Area of residence might be a determinant of irisin levels.

  17. Problem solving, loneliness, depression levels and associated factors in high school adolescents.

    Science.gov (United States)

    Sahin, Ummugulsum; Adana, Filiz

    2016-01-01

    To determine problem solving, loneliness, depression levels and associated factors in high school adolescents. This cross-sectional study was conducted in a city west of Turkey (Bursa) in a public high school and the population was 774 and the sampling was 394 students. Students to be included in the study were selected using the multiple sampling method. A personal Information Form with 23 questions, Problem Solving Inventory (PSI), Loneliness Scale (UCLA), Beck Depression Inventory (BDI) were used as data collection tools in the study. Basic statistical analyses, t-test, Kruskall Wallis-H, One Way Anova and Pearson Correlation test were used to evaluate the data. Necessary permissions were obtained from the relevant institution, students, parents and the ethical committee. The study found significant differences between "problem solving level" and family type, health assessment, life quality and mothers', fathers' siblings' closeness level; between "loneliness level" and gender, family income, health assessment, life quality and mothers', fathers', siblings' closeness level; between "depression level" and life quality, family income, fathers' closeness level. Unfavorable socio-economic and cultural conditions can have an effect on the problem solving, loneliness and depression levels of adolescents. Providing structured education to adolescents at risk under school mental health nursing practices is recommended.

  18. The macroeconomic factors impact on the Level of Food Expenditure of St. Petersburg Residents

    OpenAIRE

    Bulatova Anastasiia

    2016-01-01

    The topic of this research is the impact of the macroeconomic factors on food spending residents of St. Petersburg. The problem of the study is the ambiguity of the food sanctions impact on the consumer spending on food. The aim of the work are the trend analyze in the level of food spending in St. Petersburg since the first quarter of 2007 to the third quarter 2015, and the identifying of factors influencing these food waste. St. Petersburg was chosen because it is a city with a large popula...

  19. Association between age at onset of multiple sclerosis and vitamin D level-related factors

    DEFF Research Database (Denmark)

    Laursen, Julie Hejgaard; Søndergaard, Helle Bach; Sørensen, Per Soelberg

    2016-01-01

    OBJECTIVE: To compare vitamin D level-associated single-nucleotide polymorphisms (SNPs) in GC and CYP2R1, multiple sclerosis (MS) risk SNPs in CYP27B1, CYP24A1, and HLA-DRB1*1501, and adolescent exposure to environmental risk factors for hypovitaminosis D, with MS age at onset. METHODS: This cross....... No association was found between age at onset and any of the other SNPs or vitamin D-associated environmental factors. CONCLUSION: We demonstrate an independent effect by HLA-DRB1*1501, adolescent summer sun habits, and body mass index at the age of 20 on age at onset of MS....

  20. Decreased plasma levels of factor II + VII + X correlate with increased levels of soluble cytokine receptors in patients with malaria and meningococcal infections

    DEFF Research Database (Denmark)

    Bygbjerg, I C; Hansen, M B; Rønn, A M

    1997-01-01

    necrosis factor-I (sTNF-RI) in patients with malaria and meningococcal infections. Elevated sIL-2R and sTNF-RI levels and decreased coagulation factors reverted to normal within 3-5 days after initiation of therapy in P. falciparum patients followed consecutively. Estimation of coagulation factors may...

  1. Association of dental enamel lead levels with risk factors for environmental exposure

    Directory of Open Access Journals (Sweden)

    Kelly Polido Kaneshiro Olympio

    2010-10-01

    Full Text Available OBJECTIVE: To analyze household risk factors associated with high lead levels in surface dental enamel. METHODS: A cross-sectional study was conducted with 160 Brazilian adolescents aged 14-18 years living in poor neighborhoods in the city of Bauru, southeastern Brazil, from August to December 2008. Body lead concentrations were assessed in surface dental enamel acid-etch microbiopsies. Dental enamel lead levels were measured by graphite furnace atomic absorption spectrometry and phosphorus levels were measured by inductively coupled plasma optical emission spectrometry. The parents answered a questionnaire about their children's potential early (05 years old exposure to well-known lead sources. Logistic regression was used to identify associations between dental enamel lead levels and each environmental risk factor studied. Social and familial covariables were included in the models. RESULTS: The results suggest that the adolescents studied were exposed to lead sources during their first years of life. Risk factors associated with high dental enamel lead levels were living in or close to a contaminated area (OR = 4.49; 95% CI: 1.69;11.97; and member of the household worked in the manufacturing of paints, paint pigments, ceramics or batteries (OR = 3.43; 95% CI: 1.31;9.00. Home-based use of lead-glazed ceramics, low-quality pirated toys, anticorrosive paint on gates and/or sale of used car batteries (OR = 1.31; 95% CI: 0.56;3.03 and smoking (OR = 1.66; 95% CI: 0.52;5.28 were not found to be associated with high dental enamel lead levels. CONCLUSIONS: Surface dental enamel can be used as a marker of past environmental exposure to lead and lead concentrations detected are associated to well-known sources of lead contamination.

  2. Intraocular VEGF level as a risk factor for postoperative complications after vitrectomy for proliferative diabetic retinopathy.

    Science.gov (United States)

    Wakabayashi, Yoshihiro; Usui, Yoshihiko; Okunuki, Yoko; Ueda, Shunichiro; Kimura, Keisuke; Muramatsu, Daisuke; Kezuka, Takeshi; Goto, Hiroshi

    2012-09-21

    To investigate whether vitreous and aqueous humor concentrations of vascular endothelial growth factor (VEGF) predict postoperative complications after vitrectomy for proliferative diabetic retinopathy (PDR). Sixty eyes of 52 patients with PDR who underwent vitrectomy were enrolled. Vitreous and aqueous humor were obtained from eyes with PDR during primary vitrectomy and the levels of VEGF were measured using a commercial flow cytometer. Patients were followed for more than 6 months after surgery. Demographic data and both intraoperative and postoperative findings were recorded. The relationship between VEGF levels in ocular fluids and the main postoperative complications of early vitreous hemorrhage (VH) and neovascular glaucoma (NVG) occurring during follow-up was analyzed. Logistic regression analyses were performed to examine risk factors related to postoperative complications. Early VH occurred in 25%, and NVG occurred in 8% of 60 eyes. The vitreous levels of VEGF were significantly higher (P = 0.015) in eyes with early VH than in those without. The aqueous humor and vitreous levels of VEGF were significantly higher (P = 0.005 and P = 0.001, respectively) in eyes with NVG than in those without. Axial length was significantly shorter in eyes with early VH than in those without (P = 0.028). Multivariate logistic regression analysis showed that the higher vitreous VEGF level was associated with a risk of early VH after vitrectomy for PDR (odds ratio, 5.1; P = 0.020). High intraocular VEGF level at the time of primary vitrectomy in patients with PDR was identified as a significant risk factor for postoperative early VH.

  3. Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

    International Nuclear Information System (INIS)

    Tormoen, Garth W; Khader, Ayesha; Gruber, András; McCarty, Owen J T

    2013-01-01

    Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis. (paper)

  4. Individual- and contextual-level factors associated with client-initiated HIV testing

    Directory of Open Access Journals (Sweden)

    Claudia Renata dos Santos Barros

    Full Text Available ABSTRACT: Background: Knowing the reasons for seeking HIV testing is central for HIV prevention. Despite the availability of free HIV counseling and testing in Brazil, coverage remains lacking. Methods: Survey of 4,760 respondents from urban areas was analyzed. Individual-level variables included sociodemographic characteristics; sexual and reproductive health; HIV/AIDS treatment knowledge and beliefs; being personally acquainted with a person with HIV/AIDS; and holding discriminatory ideas about people living with HIV. Contextual-level variables included the Human Development Index (HDI of the municipality; prevalence of HIV/AIDS; and availability of local HIV counseling and testing (CT services. The dependent variable was client-initiated testing. Multilevel Poisson regression models with random intercepts were used to assess associated factors. Results: Common individual-level variables among men and women included being personally acquainted with a person with HIV/AIDS and age; whereas discordant variables included those related to sexual and reproductive health and experiencing sexual violence. Among contextual-level factors, availability of CT services was variable associated with client-initiated testing among women only. The contextual-level variable “HDI of the municipality” was associated with client-initiated testing among women. Conclusion: Thus, marked gender differences in HIV testing were found, with a lack of HIV testing among married women and heterosexual men, groups that do not spontaneously seek testing.

  5. Interleukin-10 and tumour necrosis factor-alpha serum levels in chronic Chagas disease patients.

    Science.gov (United States)

    Vasconcelos, R H T; Azevedo, E de A N; Diniz, G T N; Cavalcanti, M da G A de M; de Oliveira, W; de Morais, C N L; Gomes, Y de M

    2015-07-01

    In Chagas disease, chronically infected individuals may be asymptomatic or may present cardiac or digestive complications, and it is well known that the human immune response is related to different clinical manifestations. Different patterns of cytokine levels have been previously described in different clinical forms of this disease, but contradictory results are reported. Our aim was to evaluate the serum levels of interleukin-10 and tumour necrosis factor-alpha in patients with asymptomatic and cardiac Chagas disease. The serum interleukin-10 levels in patients with cardiomyopathy were higher than those in asymptomatic patients, mainly in those without heart enlargement. Although no significant difference was observed in serum tumour necrosis factor-alpha levels among the patients, we found that cardiac patients also present high levels of this cytokine, largely those with heart dilatation. Therefore, these cytokines play an important role in chronic Chagas disease cardiomyopathy. Follow-up investigations of these and other cytokines in patients with chronic Chagas disease need to be conducted to improve the understanding of the immunopathology of this disease. © 2015 John Wiley & Sons Ltd.

  6. High Serum Interleukin-10 and Tumor Necrosis Factor Alpha Levels in Chronic Paracoccidioidomycosis

    Science.gov (United States)

    Fornari, M. C.; Bava, A. J.; Guereño, M. T.; Berardi, V. E.; Silaf, M. R.; Negroni, R.; Diez, R. A.

    2001-01-01

    In patients with chronic paracoccidioidomycosis (n = 10), levels of tumor necrosis factor alpha, interleukin-10, and interleukin-2 in serum, measured by enzyme-linked immunosorbent assay (in picograms per milliliter, as mean ± standard error of the mean), were higher than in normal controls (n = 8): 186 ± 40 versus 40 ± 7 (P < 0.05), 203 ± 95 versus 20 ± 8 (P = 0.001), and 96.3 ± 78.57 versus 1.19 ± 1.19 (P = 0.045), respectively. Gamma interferon and interleukin-4 levels were similar in patients and controls. PMID:11527826

  7. Exercise training normalizes skeletal muscle vascular endothelial growth factor levels in patients with essential hypertension

    DEFF Research Database (Denmark)

    Hansen, Ane Håkansson; Nielsen, Jens Jung; Saltin, Bengt

    2010-01-01

    METHODS: Vascular endothelial growth factor (VEGF) protein and capillarization were determined in muscle vastus lateralis biopsy samples in individuals with essential hypertension (n = 10) and normotensive controls (n = 10). The hypertensive individuals performed exercise training for 16 weeks....... Muscle samples as well as muscle microdialysis fluid samples were obtained at rest, during and after an acute exercise bout, performed prior to and after the training period, for the determination of muscle VEGF levels, VEGF release, endothelial cell proliferative effect and capillarization. RESULTS......: Prior to training, the hypertensive individuals had 36% lower levels of VEGF protein and 22% lower capillary density in the muscle compared to controls. Training in the hypertensive group reduced (P

  8. Analysis of Traffic Safety Factors at Level Rail-Road Crossings

    Directory of Open Access Journals (Sweden)

    Tomislav Mlinarić

    2012-10-01

    Full Text Available The paper analyses the main factors of traffic safety andreliabilityat level crossings. The number and causes of accidentsare stated, that result from ignorance, insufficient training ofthe traffic participants, their ilnsponsibility and insufficient orincomplete legislation, as well as from insufficiently professionaland scientifically not serious enough approach to solvingthis cardinal problem in road and railway traffic. Based on theanalysis the causes are determined and solutions proposed, aswell as more efficient methods to improve safety and reduce thenumber of traffic accidents at level crossings.

  9. Antioxidant factors, nitric oxide levels, and cellular damage in leprosy patients

    Directory of Open Access Journals (Sweden)

    Taysa Ribeiro Schalcher

    2013-09-01

    Full Text Available Introduction The immune response caused by Mycobacterium leprae is a risk factor for the development of oxidative stress (OS in leprosy patients. This study aimed to assess OS in leprosy patients before the use of a multidrug therapy. Methods We evaluated the nitric oxide (NO concentration; antioxidant capacity; levels of malondialdehyde, methemoglobin and reduced glutathione; and the activity of catalase and superoxide dismutase (SOD in leprosy patients. Results We observed lower SOD activity in these leprosy patients; however, the NO levels and antioxidant capacity were increased. Conclusions The infectious process in response to M. leprae could primarily be responsible for the OS observed in these patients.

  10. Herd-Level Risk Factors for Bovine Tuberculosis: A Literature Review

    Directory of Open Access Journals (Sweden)

    Robin A. Skuce

    2012-01-01

    Full Text Available Bovine tuberculosis (TB, caused by Mycobacterium bovis, is one of the most challenging endemic diseases currently facing government, the veterinary profession, and the farming industry in the United Kingdom and Ireland and in several other countries. The disease has a notoriously complex epidemiology; the scientific evidence supports both cattle-cattle and wildlife-cattle transmission routes. To produce more effective ways of reducing such transmission, it is important to understand those risk factors which influence the presence or absence of bovine TB in cattle herds. Here we review the literature on herd-level risk factor studies. Whilst risk factors operate at different scales and may vary across regions, epidemiological studies have identified a number of risk factors associated with bovine TB herd breakdowns, including the purchase of cattle, the occurrence of bovine TB in contiguous herds, and/or the surrounding area as well as herd size. Other factors identified in some studies include farm and herd management practices, such as, the spreading of slurry, the use of certain housing types, farms having multiple premises, and the use of silage clamps. In general, the most consistently identified risk factors are biologically plausible and consistent with known transmission routes involving cattle-cattle and wildlife-cattle pathways.

  11. Prenatal care utilization in Zimbabwe: Examining the role of community-level factors.

    Science.gov (United States)

    Makate, Marshall; Makate, Clifton

    2017-12-01

    This paper assesses the importance of community-level factors on prenatal care utilization in Zimbabwe. The analysis is performed using data from the two most recent rounds of the nationally representative Demographic and Health Survey for Zimbabwe conducted in 2005/06 and 2010/11 linked with other community-level data. We use logistic, generalized linear regressions as well as multilevel mixed models to examine the factors associated with the frequency, timing and quality of prenatal care. Our results suggest that contraceptive prevalence, religious composition, density of nurses, health expenditures per capita and availability of government hospitals in communities are important predictors of prenatal care use in Zimbabwe. These findings have important implications for public health policy in Zimbabwe - a country with unfavorable maternal and child health outcomes. Copyright © 2017 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

  12. Hepcidin is an endogenous protective factor for osteoporosis by reducing iron levels.

    Science.gov (United States)

    Zhang, Peng; Wang, Liang; Wang, Sheng; Shan, Binchen; Zhou, Zhiqiang; Zhang, Hui; Yang, Fan; Wang, Xiao; Yuan, Ye; Xu, Youjia

    2018-03-21

    Postmenopausal osteoporosis is a global health issue. Although a lack of estrogen is considered the major reason for postmenopausal osteoporosis, other factors might also contribute the etiology of the disease. In previous reports, we and others proposed that iron accumulation after menopause accelerates osteoporosis, and here we genetically modified the expression of an endogenous hormone, hepcidin, to modulate iron status in a mouse model. Our results show that hepcidin levels negatively correlate with bone loss in both knockout and overexpression (with ovariectomy) murine models. In addition, iron overload enhances reactive oxygen species (ROS) activity and attenuates the functions of primary osteoblasts, while iron depletion could reverse this phenomenon through inhibiting the functions of primary osteoclasts. Therefore, our results provide more evidence of the "iron accumulation" hypothesis, which suggests that high iron levels are risk factors for osteoporosis, and the "Huang's hypothesis" that hepcidin is a potential drug target for the prevention of postmenopausal osteoporosis.

  13. Partner Violence During Adolescence and Young Adulthood: Individual and Relationship Level Risk Factors.

    Science.gov (United States)

    Novak, Jamie; Furman, Wyndol

    2016-09-01

    Violence within romantic relationships is a significant public health concern. Previous research largely explores partner violence at one or two time points, and often examines a limited set of risk factors. The present study explored both individual and relationship-level risk factors and their associations with physical victimization and perpetration across more than 10 years using a community sample of 200 participants (50 % female; M age Wave 1 = 15.8). Additionally, we explored the effects of previous partner violence on the likelihood of future partner violence. Survival analysis indicated that externalizing symptoms and negative interactions (e.g., relationship conflict) were associated with both perpetration and victimization. Reporting an experience of partner violence did not significantly alter an individual's risk of future partner violence. Overall, men were significantly more likely to report victimization; perpetration rates did not vary by gender. The results highlight the importance of examining multiple levels of risk.

  14. Serum nerve growth factor (NGF) levels in children with attention deficit/hyperactivity disorder (ADHD).

    Science.gov (United States)

    Guney, Esra; Ceylan, Mehmet Fatih; Kara, Mehmet; Tekin, Neslihan; Goker, Zeynep; Senses Dinc, Gulser; Ozturk, Onder; Eker, Sevda; Kizilgun, Murat

    2014-02-07

    Attention deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed neurobehavioral disorder of childhood. The etiopathogeny of ADHD has not been totally defined. Recent reports have suggested a pathophysiological role of neurotrophins in ADHD. In this study, we evaluated serum levels of nerve growth factor (NGF) in patients with ADHD. The sample population consisted of 44 child or adolescent patients diagnosed with ADHD according to DSM-IV criteria; 36 healthy subjects were included in the study as controls. Venous blood samples were collected, and NGF levels were measured. The mean serum NGF levels of the ADHD patients were significantly higher than those of the controls. Age and gender of the patients were not correlated with serum NGF levels. There were no significant differences in NGF levels among the combined and predominantly inattentive subtypes of ADHD. Our study suggests that there are higher levels of serum NGF in drug naive ADHD patients, and that increased levels of NGF might have an important role in the pathophysiology of ADHD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Community pharmacists' burnout levels and related factors: an example from Turkey.

    Science.gov (United States)

    Calgan, Zeynep; Aslan, Dilek; Yegenoglu, Selen

    2011-02-01

    To determine community pharmacists' burnout levels and prevalences as well as factors associated with burnout. Study was conducted in Ankara, the capital of Turkey. In this cross-sectional study, 251 pharmacists were randomly selected from 1,504 community pharmacists registered in Ankara Chamber of Pharmacists. A questionnaire including questions related to pharmacists' individual and professional characteristics and Maslach Burnout Inventory was administered. The data was collected between February 27 and May 25, 2007. Three Maslach Burnout Inventory subscales (emotional exhaustion-EE, depersonalization-D, and personal accomplishment-PA) scores. Pharmacists' mean emotional exhaustion score was found to be 16.84 (SD: 6.25), depersonalization score was 4 (Range: 0-14), and personal accomplishment score was 22 (Range: 9-32). Of the pharmacists, 1.2% had high level of EE, .8% had high level of D, and 71.3% had high level of inefficacy. Age, marital status, work experience, work contentment, workload, time pressure, stress, and satisfaction with customers were found to be related with pharmacists' burnout levels. It can be useful to monitor pharmacists' burnout levels and prevalences periodically. Interventions on individual and organizational basis were needed to cope with burnout, respond to job demands, minimize the level of chronic stress, and increase work contentment and satisfaction.

  16. Individual-level factors related to better mental health outcomes following child maltreatment among adolescents.

    Science.gov (United States)

    Cheung, Kristene; Taillieu, Tamara; Turner, Sarah; Fortier, Janique; Sareen, Jitender; MacMillan, Harriet L; Boyle, Michael H; Afifi, Tracie O

    2018-02-22

    Research on factors associated with good mental health following child maltreatment is often based on unrepresentative adult samples. To address these limitations, the current study investigated the relationship between individual-level factors and overall mental health status among adolescents with and without a history of maltreatment in a representative sample. The objectives of the present study were to: 1) compute the prevalence of mental health indicators by child maltreatment types, 2) estimate the prevalence of overall good, moderate, and poor mental health by child maltreatment types; and 3) examine the relationship between individual-level factors and overall mental health status of adolescents with and without a history of maltreatment. Data were from the National Comorbidity Survey of Adolescents (NCS-A; n = 10,123; data collection 2001-2004); a large, cross-sectional, nationally representative sample of adolescents aged 13-17 years from the United States. All types of child maltreatment were significantly associated with increased odds of having poor mental health (adjusted odds ratios ranged from 3.2 to 9.5). The individual-level factors significantly associated with increased odds of good mental health status included: being physically active in the winter; utilizing positive coping strategies; having positive self-esteem; and internal locus of control (adjusted odds ratios ranged from 1.7 to 38.2). Interventions targeted to adolescents with a history of child maltreatment may want to test for the efficacy of the factors identified above. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  17. Analysis of the effects of individual and community level factors on childhood immunization in Malawi.

    Science.gov (United States)

    Ntenda, Peter Austin Morton; Chuang, Kun-Yang; Tiruneh, Fentanesh Nibret; Chuang, Ying-Chih

    2017-04-04

    Empirical evidence regarding the relationship between childhood immunization and individual- and community-level factors in low-income countries has received little attention. We compared the trends and the effects of a wide range of individual- and community-level socioeconomic factors on the likelihood of a child being immunized between 2004 and 2010 in Malawi. We used data from the 2004 and 2010 Malawi Demographic and Health Survey and applied generalized estimating logistic regression equation to analyze data respectively on 2042 and 3496 children aged 12-23months. We compared the relationship between individual- and community-level socioeconomic factors and a child's vaccination status for four basic vaccines recommended by the World Health Organization: bacillus Calmette-Guérin (BCG) vaccine, diphtheria-tetanus-pertussis (DPT3) vaccine, oral polio vaccine (OPV3), and measles-containing vaccine 1 (MCV1). The trends of vaccination had a similar pattern in 2004 and 2010. The coverage of the four vaccinations was highest for BCG and lowest for OPV3 and complete immunization was higher in 2010. The multivariate analyses show that mother's low education, having one or none antenatal visits, having no immunization card, having immunization card but not seen, residing in poor households, and living in central region were the most significant factors associated with decreased odds of achieving vaccination coverage and complete vaccination in both 2004 and 2010. However, maternal education was more likely to be associated with children's immunization in 2010, while the geographical region was more likely to be associated with children's immunization in 2004. There were marked improvements in the national immunization coverage from 2004 to 2010. In order to achieve complete immunization, to further enhance the national immunization coverage as well as to lessen the gaps and disparities in childhood vaccination in Malawi, policy makers should design interventions based

  18. DEGREE OF BURNOUT AMONG EMERGENCY HEALTHCARE WORKERS AND FACTORS INFLUENCING LEVEL OF BURNOUT: A STUDY PROTOCOL

    OpenAIRE

    Shyamanta; Sashibha; Navoneela; Marami; Bornali; Sakhee; Anjana; Dipesh

    2015-01-01

    BACKGROUND Burnout is a feeling of failure and exhaustion. It is felt both at the physical and emotional level. Depletion of the person’s resources is a consequence and also has an impact on the organisation. Nature of the work itself makes emergency healthcare workers vulnerable to burnout. METHOD This study is designed to measure the degree of burnout among emergency healthcare workers in a hospital and to identify the factors that influence burnout. The study h...

  19. Factors Associated with Elevated HIV RNA Levels in HIV-Infected Individuals

    OpenAIRE

    Degener, Tyler; Allen, Sara; Wilson, Alicia; Baranoski, Amy

    2017-01-01

    Abstract Background Virologic suppression is necessary to reduce the risk of complications from HIV infection and to prevent transmission to other individuals. Understanding factors associated with elevated HIV RNA levels in HIV-infected individuals could lead to interventions to improve engagement in care. Methods This retrospective, observational study assessed HIV-infected individuals engaged in care in an urban HIV clinic between April 1, 2015 and March 31, 2016. The electronic medical re...

  20. Factors Influencing the Measurement of Plasma/Serum Surfactant Protein D Levels by ELISA

    OpenAIRE

    Bratcher, Preston E.; Gaggar, Amit

    2014-01-01

    BACKGROUND: Extensive variations in human surfactant protein D (SP-D) levels in circulation as measured by ELISA exist in the published literature. In order to determine the source of these variations, factors influencing the measurement by ELISA were explored. MATERIALS AND METHODS: Peripheral blood from healthy individuals was collected into various vacutainers during the same blood draw. Recombinant SP-D was diluted into different matrices and used for a standard curve. Samples were analyz...

  1. Factors affecting mortality after penetrating cardiac injuries: 10-year experience at urban level I trauma center.

    Science.gov (United States)

    Mina, Michael J; Jhunjhunwala, Rashi; Gelbard, Rondi B; Dougherty, Stacy D; Carr, Jacquelyn S; Dente, Christopher J; Nicholas, Jeffrey M; Wyrzykowski, Amy D; Salomone, Jeffrey P; Vercruysse, Gary A; Feliciano, David V; Morse, Bryan C

    2017-06-01

    Despite the lethality of injuries to the heart, optimizing factors that impact mortality for victims that do survive to reach the hospital is critical. From 2003 to 2012, prehospital data, injury characteristics, and clinical patient factors were analyzed for victims with penetrating cardiac injuries (PCIs) at an urban, level I trauma center. Over the 10-year study, 80 PCI patients survived to reach the hospital. Of the 21 factors analyzed, prehospital cardiopulmonary resuscitation (odds ratio [OR] = 30), scene time greater than 10 minutes (OR = 58), resuscitative thoracotomy (OR = 19), and massive left hemothorax (OR = 15) had the greatest impact on mortality. Cardiac tamponade physiology demonstrated a "protective" effect for survivors to the hospital (OR = .08). Trauma surgeons can improve mortality after PCI by minimizing time to the operating room for early control of hemorrhage. In PCI patients, tamponade may provide a physiologic advantage (lower mortality) compared to exsanguination. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. A cross-country analysis of total factor productivity using micro-level data

    Directory of Open Access Journals (Sweden)

    Murat Şeker

    2018-03-01

    Full Text Available Total factor productivity (TFP is a crucial measure of efficiency and thus an important tool for policymakers. However, research on comparison of TFP performances using micro-level data across developing countries has been limited due to the unavailability of homogenous data sources. This study aims to fill this crucial gap by using a data set which has been collected through a large body of surveys conducted across 69 developing countries following the same methodology. The homogenous nature of the data and the diverse set of questions included in the surveys provide unique opportunity to compare average productivity performances of firms across a large set of characteristics and business environment factors. The analysis performed here provides the groundwork for testing various stylized facts about TFP and its related factors such as exporting, innovation, access to finance, foreign ownership, and regulations across developing countries.

  3. Zinc Serum Level Can Be a Risk Factor In Babol Stroke Patients?

    Directory of Open Access Journals (Sweden)

    Alijan AhmadiAhangar

    2017-02-01

    Full Text Available Background and Purpose: Stroke is the second leading cause of death worldwide. The role of zinc as a contributing factor in the pathogenesis of stroke was considered. Results: This cross-sectional study on 100 stroke patients in Ayatollah Rouhani Hospital and 100 control group from cohort master plan "Ageing and health projects Amirkola was conducted. Zinc levels Serum simultaneously with other blood tests in the early hours of hospitalization. Zinc serum level was defined 70 to 120 micrograms per deciliter. Findings: The difference in mean of zinc level in patients and control group was not significant (102.6±47.7 in control group vs 100.9±35.8 in patient, p=0.7. Difference in zinc Serum level had statically significant with IHD (under70 0 cases (0, 70 to120 8 cases (24, 120 and upper24 cases (75, p=0.003 and with type of stroke (under70 (3(3.3 hemorrhagic vs 0(0 ischemic, 70 to 120(19(21 vs6 (60, 120 and upper68 (75.6 vs4 (40, p=0.025 and also with patient and control group (under70 (3(3 in patient's vs 20(20 control group, 70 to 120(25(25 vs54 (54, 120 and upper72 (72 vs26 (26, p<0001. In patients group 72(73.5 of cases had zinc serum level above 120. HLP difference was significant in patient and control group (50(50 in control group vs 35(35 in patients, p=0.04. Regression logistic show that IHD (p<0001, OR=30, CI=6-152, HLP (p<0001, OR=4, CI=9.09-1.85, zinc serum level (p<0001, OR=15.5, CI=4-59.8 had significant role. Conclusions: Zinc serum levels, Ischemic Heart Disease, Hyperlipidemia were most risk factor that play role in Babol stroke patients.

  4. [Risk factors and burnout levels in Primary Care nurses: A systematic review].

    Science.gov (United States)

    Gómez-Urquiza, Jose L; Monsalve-Reyes, Carolina S; San Luis-Costas, Concepción; Fernández-Castillo, Rafael; Aguayo-Estremera, Raimundo; Cañadas-de la Fuente, Guillermo A

    2017-02-01

    To determine the risk factors and levels of burnout in Primary Care nurses. A systematic review was performed. CINAHL, CUIDEN, LILACS, PubMed, ProQuest, ScienceDirect and Scopus databases were consulted. Search equations were 'burnout AND community health nursing' and 'burnout AND primary care nursing'. The search was performed in October 2015. The final sample was n=12 studies. Quantitative primary studies that used Maslach Burnout Inventory for burnout assessment in Primary Care nurses were included without restriction by publication date. The main variables were the mean and standard deviation of the three burnout dimensions, high, medium and low prevalence rates of each dimension, and socio-demographic, occupational and psychological variables that potentially influence burnout level. Studies show high prevalence rates, generally between 23% and 31%, of emotional exhaustion. The prevalence rates of high depersonalisation and low personal accomplishment show heterogeneity, varying between 8%-32% and 4%-92% of the sample, respectively. Studies show that older nurses with more seniority, anxiety and depression, among other variables, have higher burnout levels, while nurses with higher salary, high job satisfaction, organisational support, and good self-concept have less burnout. High emotional exhaustion is the main affected dimension of burnout in Primary Care nursing. There is heterogeneity in depersonalisation and personal accomplishment. Burnout must be prevented in these professionals, by increasing protective factors and monitoring its appearance in those with risk factors. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  5. Multiple Levels of Family Factors and Oppositional Defiant Disorder Symptoms Among Chinese Children.

    Science.gov (United States)

    Lin, Xiuyun; Li, Longfeng; Heath, Melissa A; Chi, Peilian; Xu, Shousen; Fang, Xiaoyi

    2018-03-01

    Family factors are closely associated with child developmental outcomes. This study examined the relationship of oppositional defiant disorder (ODD) symptoms and factors at whole family, dyadic, and individual levels in Chinese children. Participants, who were recruited from 14 primary schools in north, east, and south-west China, included 80 father-child dyads and 169 mother-child dyads. Children in the participating dyads were previously diagnosed with ODD. Results revealed that family cohesion/adaptability was indirectly associated with ODD symptoms via parent-child relationship and child emotion regulation. Parent-child relationship affected ODD symptoms directly and indirectly through child emotion regulation. In addition, the effects of family cohesion/adaptability on parent emotion regulation and child emotion regulation were mediated by the parent-child relationship. The tested model provides a comprehensive framework of how family factors at multiple levels are related to child ODD symptoms and highlights the importance of understanding child emotional and behavioral problems within the family context, more specifically within the multiple levels of family relationships. © 2016 Family Process Institute.

  6. Thyroid hormone regulation of epidermal growth factor receptor levels in mouse mammary glands

    International Nuclear Information System (INIS)

    Vonderhaar, B.K.; Tang, E.; Lyster, R.R.; Nascimento, M.C.

    1986-01-01

    The specific binding of iodinated epidermal growth factor ([ 125 I]iodo-EGF) to membranes prepared from the mammary glands and spontaneous breast tumors of euthyroid and hypothyroid mice was measured in order to determine whether thyroid hormones regulate the EGF receptor levels in vivo. Membranes from hypothyroid mammary glands of mice at various developmental ages bound 50-65% less EGF than those of age-matched euthyroid controls. Treatment of hypothyroid mice with L-T4 before killing restored binding to the euthyroid control level. Spontaneous breast tumors arising in hypothyroid mice also bound 30-40% less EGF than tumors from euthyroid animals even after in vitro desaturation of the membranes of endogenous growth factors with 3 M MgCl2 treatment. The decrease in binding in hypothyroid membranes was due to a decrease in the number of binding sites, not to a change in affinity of the growth factor for its receptor, as determined by Scatchard analysis of the binding data. Both euthyroid and hypothyroid membranes bound EGF primarily to a single class of high affinity sites [dissociation constant (Kd) = 0.7-1.8 nM]. Euthyroid membranes bound 28.4 +/- (SE) 0.6 fmol/mg protein, whereas hypothyroid membranes bound 15.5 +/- 1.0 fmol/mg protein. These data indicate that EGF receptor levels in normal mammary glands and spontaneous breast tumors in mice are subject to regulation by thyroid status

  7. Plasma Tissue Factor Pathway Inhibitor Levels in Angiographically Defined Coronary Artery Disease Among Saudis

    Directory of Open Access Journals (Sweden)

    Syed Shahid Habib

    2013-05-01

    Full Text Available Objectives: This study was aimed to determine plasma levels of total (TFPI-T and free (TFPI-F tissue factor pathway inhibitor, plasminogen activator inhibitor-1 (PAI-1, and tissue plasminogen activator (t-PA in a cohort of Saudi patients with chronic stable angiographically defined coronary artery disease (CAD and to determine its correlation with its severity.Methods: This cross sectional study was conducted in the department of physiology and department of cardiology, College of Medicine, and King Khalid University Hospital and King Saud University, Riyadh. Sixty known cases of CAD who had undergone angiography (35 males and 25 females were selected. A control group included 39 (20 males and 19 females healthy subjects. Fasting venous blood samples were analyzed for total (TFPI-T and free (TFPI-F tissue factor pathway inhibitor, plasminogen activator inhibitor-1 (PAI-1, and tissue plasminogen activator (t-PA. Gensini scores and vessel scores were determined for assessing CAD severity.Results: There were non-significant differences between age, body mass index (BMI and Blood pressure between the controls and CAD subjects. A comparison of hemostatic markers between control and CAD patients showed significantly higher levels of Fibrinogen, PAI-1, TFPI-T and TFPI-F in CAD patients compared to control subjects. But there was no difference in plasma t-PA levels. TFPI-T had a significant positive correlation with severity of disease determined by Gensini Scores (r=0.344; p=0.006 and vessel scores (r=0.338; p=0.015.Conclusion: Plasma levels of total tissue factor pathway inhibitor are significantly related with the presence and severity of CAD. Elevated levels of TFPI-T may be considered as useful diagnostic and prognostic markers in patients with CAD.

  8. Regional factors interact with educational and income tax levels to influence food intake in France.

    Science.gov (United States)

    Wyndels, K; Dallongeville, J; Simon, C; Bongard, V; Wagner, A; Ruidavets, J-B; Arveiler, D; Ferrières, J; Amouyel, P; Dauchet, L

    2011-09-01

    The goal of the present study was to assess whether geographic factors affect the relationship between socioeconomic indicators and adherence to the French National Nutritional Health Programme (Programme National Nutrition Santé (PNNS)) guidelines. The MONA LISA-NUT study (2005-2007) is a cross-sectional survey of a representative sample from northern, northeastern and southwestern France. Educational level and household income tax were recorded by trained interviewers. Food intake was assessed with a 3-day food diary in 3188 subjects aged from 35-64 years. Adherence to the PNNS guidelines was assessed with a validated score (the French score of indicators of the PNNS objective (FSIPO)). Multivariate analyses were adjusted for gender, age, marital status, body mass index, energy intake and medically prescribed diets. The FSIPO score was higher in southwestern France than in the two other regions (Ptax level and the FSIPO score were positively correlated (Ptax interaction: P=0.09). The relationship between educational level and adherence to the national nutritional health guidelines differs from one region of France to another, suggesting that nutrition education programmes should perhaps be adapted on a regional basis. In contrast, guideline adherence is correlated with income tax level independently of geographical factors, suggesting that financial constraints on food choices are uniform across France.

  9. Socio-demographic factors affecting knowledge level of Tuberculosis patients in Rajshahi City, Bangladesh.

    Science.gov (United States)

    Mondal, M N I; Nazrul, Hoque M; Chowdhury, M R K; Howard, J

    2014-12-01

    The Tuberculosis (TB) control program in Bangladesh is still unsatisfactory due to insufficient knowledge and stigma about TB. Patients with low knowledge may be at higher risk of experiencing delays in diagnosis and appropriate treatment. The aims of this study were to identify the knowledge levels of TB and investigate the factors associated with knowledge level among the TB patients in Bangladesh. A cross-sectional study was conducted at Rajshahi City, Bangladesh. A total of 384 TB patients were interviewed through a pretested, structured questionnaire using purposive sampling techniques. Logistic regression analysis was used to evaluate the effects of selected socio-demographic factors on TB knowledge level. The results revealed that pulmonary TB patients had greater knowledge than that of extra-pulmonary patients, and that sex, age, educational status and TB type were significantly associated with knowledge level. In general, males and young adults, ages 21-35, had greater awareness about transmission and prevention of TB than females and adults over 35. Individuals with higher education and urban area patients were comparatively better informed about TB infection. Patients with greater knowledge about TB were also less likely to experience delays in seeking treatment.

  10. Serum Growth Hormone and Insulin-Like Growth Factor-1 Levels in Women with Postadolescent Acne

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    Mualla Polat

    2010-06-01

    Full Text Available Background and Design: Acne vulgaris is an inflammatory disease of pilosebaceous unit. It usually starts after puberty but may continue into adulthood. We studied Growth hormone (GH and insulin-like growth factor (IGF-1 levels in women patients with acne vulgaris in whom all other hormon levels were normal. We aimed to show any relation of the acne vulgaris lesion type and GH and IGF-1 levels. Material and Method: The study conducted on the postadolesance period woman patients applying to out patient dermatology department with complaint of acne symptoms between Semtember 2005 and July 2006. All other hormonal parameters were normal in patients. 25 healthy similar age women were accepted as control. IGF-I and GH were quantified by solid-phase competitive chemiluminescence assays. Results: There was no difference according to age between the groups (p=0.726. The mean IGF-1 level was 336.5±112.88 ng/ml in patients and 194±31.32 ng/ml in control; the difference was significantly important (p=0.000. The mean GH level was 3.16±4.35 µIU/ml in patients and 1.15±1.21 µIU/ml in control; and the diffrence was not found as important (p=0.03. IGF-1 level was significantly important in patients with noduler involvement (p=0.015, and GH level was also significantly important in patients with cystic involvement (p=0.05. Conclusion: We supported the hypothesis that GH and IGF-1 levels were important in postadolasence period women patients with acne vulgaris. We recommend new studies comparing GH and IGF-1 levels in adolesence and postadolesence period women patients in order to support the role of these hormones in pathogenesis of acne vulgaris.

  11. Factors influencing the level of self-stigmatisation in people with mental illness.

    Science.gov (United States)

    Kalisova, Lucie; Michalec, Jiri; Hadjipapanicolaou, Demetra; Raboch, Jiri

    2018-03-01

    The aim of this study was to assess sociodemographic factors and factors connected with treatment of mental illness and to decide whether they can influence the level of self-stigma. Sociodemographic characteristics (age, gender, family status, level of employment, level of education) and characteristics related to illness and treatment (diagnosis, length of treatment, adherence to treatment) were gathered in a group of patients in stable mental condition, without acute symptoms of mental illness. Self-stigma was measured using the Self-stigma of Mental Illness Scale - short form (SSMIS-SF). The sample included 197 patients: 99 patients in group 1 (G1) with psychosis and 98 in group 2 (G2) with anxious and affective disorders. The average age was 44.15 ± 12.91 years, the length of illness was 11.67 ± 9.21 years and 48% of patients were men. The total average SSMIS-SF score was 61.54 ± 23.34. We found no statistically significant difference in the total level of self-stigmatisation between these groups ( t(197) = 0.77; p = .441). The level of self-stigmatisation (total score of SSMIS-SF) in patients in G1 (psychosis) increased with the length of illness r(99) = .253; p = .011. Employment status seems to correlate with the level of self-stigmatisation ( F(3, 184) = 5.27; p = .002). Patients unemployed and on disability pension had higher levels of self-stigmatisation than patients working full-time. Patients who took medication regularly (full medical adherence) had lower scores of SSMIS-SF total scores in comparison with patients with lower compliance ( t(195) = 3.476; p = .001; Cohen's d = .25). According to our results, with regard to the factors that were followed, self-stigmatisation correlates with the presence of employment (social inclusion), duration of illness in patients with psychosis and treatment adherence. We did not find a statistically significant influence of age, gender, marital status or clinical diagnosis on the level of self-stigma.

  12. Measurement Levels of the Spatial Integration – Suggestions for a Central-European Factor Group

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    Andrea Uszkai

    2015-10-01

    Full Text Available The objective of the study is to point out, what kind of measurement methodologies and factor groups are used to determinate the depth of the spatial integration in the national and international scientific literature. Integration means in this sense the interconnection of several (spatial units (Kulcsár-Rostás, 1989; Kovács, 2001; Kiss, 2005. One of the most widely interpreted types of the integration is the economic integration, which can be applied to enterprises and spatial units as well. This study focuses on the last one and examines it at three territorial levels, distinguishing global, supranational (among national states and subnational levels. The possible measurement methods are significantly determined by the spatial levels. The paper makes some suggestions for the possible measurement method in Cenrtral-European context.

  13. Pressure ulcer prevention in nursing homes: nurse descriptions of individual and organization level factors.

    Science.gov (United States)

    Dellefield, Mary Ellen; Magnabosco, Jennifer L

    2014-01-01

    Sustaining pressure ulcer prevention (PUP) in nursing homes has been difficult to achieve. Implementation science researchers suggest that identification of individual staff and organizational factors influencing current practices is essential to the development of an effective and customized plan to implement practice changes in a specific setting. A mixed methods approach was used to describe nurses' perceptions of individual and organization-level factors influencing performance of PUP in two Veterans Health Administration (VHA) nursing homes prior to implementation of a national VHA initiative on Hospital Acquired Pressure Ulcers (HAPUs). Individual interviews of 16 nursing staff were conducted. Individual factors influencing practice were a personal sense of responsibility to Veterans and belief in the effectiveness and importance of preventive measures. Organizational factors were existence of cooperative practices between nursing assistants and licensed nurses in assessing risk; teamwork, communication, and a commitment to Veterans' well-being. Integration and reinforcement of such factors in the development and maintenance of customized plans of PUP initiatives is recommended. Published by Mosby, Inc.

  14. Studies on levels and interactions of contact activation factors in plasma

    International Nuclear Information System (INIS)

    Hoem, N.O.

    1992-01-01

    Summary of findings and conclusions of relevance: A part of the thesis concerns the effects of intravenous contrast media on the blood pressure and on factors of the contact activation system in the rat. The intravenous injection of dextran induced a profound and lasting fall in blood pressure, preceded by significant lowering in prekallikrein and activation factor 12. The non-ionic radiographic contrast media iohexol caused no significant alterations, neither in blood pressure, nor in levels of contact factors, whereas the ionic radiographic contrast media iodipamide had effects. It induced a rapid, but short-lived, fall in blood pressure and a small, but statistically significant reduction in the measurable amount of activation factor 12a. An observation of significance was that pretreatment of the rats with iodipamide almost blocked the dextran-induced blood pressure fall, and abolished the reduction in prekallikrein and activation factor 12a. It is concluded that the ionic radiographic contrast media used was capable of blocking dextran shock in the rat by preventing an activation of contact activation system. 130 refs., 5 figs

  15. Decreased brain-derived neurotrophic factor plasma levels in psoriasis patients

    Directory of Open Access Journals (Sweden)

    A.R. Brunoni

    2015-08-01

    Full Text Available Brain-derived neurotrophic factor (BDNF is associated with neuroplasticity and synaptic strength, and is decreased in conditions associated with chronic stress. Nevertheless, BDNF has not yet been investigated in psoriasis, a chronic inflammatory systemic disease that is exacerbated by stress. Therefore, our aim was to determine BDNF plasma levels in psoriasis patients and healthy controls. Adult patients (n=94 presenting with psoriasis for at least 1 year were enrolled, and age- and gender-matched with healthy controls (n=307 from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil. Participants had neither a previous history of coronary artery disease nor current episode of major depression. BDNF plasma levels were determined using the Promega ELISA kit. A general linear model was used to compare BDNF levels in psoriasis patients and controls, with age, gender, systolic blood pressure, serum fasting glucose, blood lipid levels, triglycerides, smoking status, and body mass index examined. After adjusting for clinical and demographic variables, significantly decreased BNDF plasma levels were observed in psoriasis patients (P=0.01 (estimated marginal means of 3922 pg/mL; 95%CI=2660-5135 compared with controls (5788 pg/mL; 95%CI=5185-6442. Similar BDNF levels were found in both mild and severe cases of psoriasis. Our finding, that BDNF is decreased in psoriasis, supports the concept of a brain-skin connection in psoriasis. Further studies should determine if BDNF is increased after specific psoriasis treatments, and associated with different disease stages.

  16. Serum TSH levels are associated with cardiovascular risk factors in overweight and obese adolescents.

    Science.gov (United States)

    Souza, Luciana Lopes de; Guedes, Erika Paniago; Teixeira, Patrícia Fátima Dos Santos; Moreira, Rodrigo Oliveira; Godoy-Matos, Amelio Fernando; Vaisman, Mario

    2016-01-01

    To investigate the relationship between serum thyrotropin (TSH), insulin resistance (IR), and cardiovascular risk factors (CRF) in a sample of overweight and obese Brazilian adolescents. A retrospective, longitudinal analysis of 199 overweight and obese pubescent adolescents was performed. The TSH and free T4 (fT4) levels, anthropometric measurements, and laboratory test results of these patients were analyzed. 27 individuals (13.56%) presented with TSH levels above the normal level (subclinical hypothyroidism [SCH]). Their waist circumference (WC) was significantly higher than those of euthyroid individuals. Serum TSH was positively correlated with the homeostasis model assessment of insulin resistance (HOMA-IR) index, triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). Using TSH and BMI as independent variables, TSH levels were shown to be independently related to HOMA-IR (p=0.001) and TG (p=0.007). Among euthyroid subjects, individuals with TSH values <2.5mIU/mL exhibited statistically significant decreases in waist-to-hip ratio, HDL-C levels, and HOMA-IR scores and a tendency toward lower WC values. SCH in overweight and obese adolescents appears to be associated with excess weight, especially visceral weight. In euthyroid adolescents, there appears to be a direct relationship between TSH and some CRF. In conclusion, in the present sample of overweight and obese adolescents, TSH levels appear to be associated with IR and CRF. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  17. Parathyroid hormone 1-84 alters circulating vascular endothelial growth factor levels in hypoparathyroidism.

    Science.gov (United States)

    Cusano, Natalie E; Rubin, Mishaela R; Zhang, Chiyuan; Anderson, Laura; Levy, Elizabeth; Costa, Aline G; Irani, Dinaz; Bilezikian, John P

    2014-10-01

    We previously reported on four patients treated with PTH(1-84) who recovered from postoperative hypoparathyroidism many years after onset. Because vascular endothelial growth factor (VEGF) has been shown to be necessary for the induction of PTH-mediated angiogenesis, we postulated a possible role for VEGF in the recovery of parathyroid function in these subjects. Our objective was to measure VEGF levels in subjects with hypoparathyroidism who regained parathyroid gland function and matched controls. Subjects with hypoparathyroidism who regained parathyroid gland function were each matched to two hypoparathyroid controls by postoperative etiology, age (within 5 y), menopausal status, and duration of hypoparathyroidism. We measured serum VEGF levels at baseline and through 48 months of PTH(1-84) therapy. VEGF levels increased after the initiation of PTH(1-84) therapy for the entire cohort, from 309.7 ± 162 pg/ml at baseline to 380.2 ± 178 pg/ml at 12 months (P = .03). Levels trended downward thereafter. There were no significant differences in VEGF levels between the subjects with recovery of parathyroid function and the matched controls. PTH(1-84) alters serum VEGF levels in subjects with hypoparathyroidism. Additional investigation is necessary to understand the mechanisms by which some subjects with postoperative hypoparathyroidism recover parathyroid gland function.

  18. Factors associated with elevated serum chromogranin A levels in patients with autoimmune gastritis.

    Science.gov (United States)

    Kalkan, Çağdaş; Karakaya, Fatih; Soykan, İrfan

    2016-11-01

    Chromogranin A is an important tool in the diagnosis of neuroendocrine tumors. Autoimmune gastritis is an autoimmune disorder marked by hypergastrinemia, which stimulates enterochromaffin-like cell proliferation. Chromogranin A is also elevated in autoimmune gastritis patients with a different level of increase in each patient. The goal of this study is to explore constituents that influence serum chromogranin A levels in autoimmune gastritis patients. One hundred and eighty-eight autoimmune gastritis patients and 20 patients with type I gastric carcinoid tumors were analyzed retrospectively and compared to 110 functional dyspepsia patients in terms of factors that might affect serum chromogranin A levels. The mean serum chromogranin A level was 171.17±67.3 ng/mL in autoimmune gastritis patients (n=62) without enterochromaffin-like cell hyperplasia, and 303.3±102.82 ng/mL in patients (n=126) with enterochromaffin-like cell hyperplasia (pgastritis were the presence of ECL cell hyperplasia and serum gastrin levels. Serum chromogranin A levels maybe helpful in distinguishing autoimmune gastritis patients and gastric carcinoid type I from the control group, but not useful in the differentiation of individuals with autoimmune gastritis from patients with gastric carcinoids.

  19. Ecological and physiological factors affecting brood patch area and prolactin levels in arctic-nesting geese

    Science.gov (United States)

    Jonsson, J.E.; Afton, A.D.; Alisauskas, R.T.; Bluhm, C.K.; El Halawani, M.E.

    2006-01-01

    We investigated effects of ecological and physiological factors on brood patch area and prolactin levels in free-ranging Lesser Snow Geese (Chen caerulescens caerulescens; hereafter “Snow Geese”) and Ross's Geese (C. rossii). On the basis of the body-size hypothesis, we predicted that the relationships between prolactin levels, brood patch area, and body condition would be stronger in Ross's Geese than in the larger Snow Geese. We found that brood patch area was positively related to clutch volume and inversely related to prolactin levels in Ross's Geese, but not in Snow Geese. Nest size, nest habitat, and first egg date did not affect brood patch area in either species. Prolactin levels increased as incubation progressed in female Snow Geese, but this relationship was not significant in Ross's Geese. Prolactin levels and body condition (as indexed by size-adjusted body mass) were inversely related in Ross's Geese, but not in Snow Geese. Our findings are consistent with the prediction that relationships between prolactin levels, brood patch area, and body condition are relatively stronger in Ross's Geese, because they mobilize endogenous reserves at faster rates than Snow Geese.

  20. Decreased brain-derived neurotrophic factor plasma levels in psoriasis patients.

    Science.gov (United States)

    Brunoni, A R; Lotufo, P A; Sabbag, C; Goulart, A C; Santos, I S; Benseñor, I M

    2015-08-01

    Brain-derived neurotrophic factor (BDNF) is associated with neuroplasticity and synaptic strength, and is decreased in conditions associated with chronic stress. Nevertheless, BDNF has not yet been investigated in psoriasis, a chronic inflammatory systemic disease that is exacerbated by stress. Therefore, our aim was to determine BDNF plasma levels in psoriasis patients and healthy controls. Adult patients (n=94) presenting with psoriasis for at least 1 year were enrolled, and age- and gender-matched with healthy controls (n=307) from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Participants had neither a previous history of coronary artery disease nor current episode of major depression. BDNF plasma levels were determined using the Promega ELISA kit. A general linear model was used to compare BDNF levels in psoriasis patients and controls, with age, gender, systolic blood pressure, serum fasting glucose, blood lipid levels, triglycerides, smoking status, and body mass index examined. After adjusting for clinical and demographic variables, significantly decreased BNDF plasma levels were observed in psoriasis patients (P=0.01) (estimated marginal means of 3922 pg/mL; 95%CI=2660-5135) compared with controls (5788 pg/mL; 95%CI=5185-6442). Similar BDNF levels were found in both mild and severe cases of psoriasis. Our finding, that BDNF is decreased in psoriasis, supports the concept of a brain-skin connection in psoriasis. Further studies should determine if BDNF is increased after specific psoriasis treatments, and associated with different disease stages.

  1. Factors influencing upstairs and downstairs radon levels in two-storey dwellings

    Energy Technology Data Exchange (ETDEWEB)

    Denman, A.R.; Groves-Kirkby, C.J.; Groves-Kirkby, N.P. [Northampton General Hospital, Medical Physics Dept. (United Kingdom); Crockett, R.G.M.; Phillips, P.S.; Woolridge, A.C. [Northampton Univ., School of Applied Sciences (United Kingdom); Woolridge, A.C. [Northampton Univ., School of Health (United Kingdom)

    2006-07-01

    seasonal factors. Ratios in single-storey homes clustered around 1.0, indicating that house design, rather than lifestyle, is the dominant factor in determining bedroom radon levels. Homes with higher mean annual radon levels showed lower bedroom/living-room ratios, supporting our proposal that radon emanation from building materials comprises a significant component of the overall level. (authors)

  2. Factors influencing upstairs and downstairs radon levels in two-storey dwellings

    International Nuclear Information System (INIS)

    Denman, A.R.; Groves-Kirkby, C.J.; Groves-Kirkby, N.P.; Crockett, R.G.M.; Phillips, P.S.; Woolridge, A.C.; Woolridge, A.C.

    2006-01-01

    on seasonal factors. Ratios in single-storey homes clustered around 1.0, indicating that house design, rather than lifestyle, is the dominant factor in determining bedroom radon levels. Homes with higher mean annual radon levels showed lower bedroom/living-room ratios, supporting our proposal that radon emanation from building materials comprises a significant component of the overall level. (authors)

  3. Increased serum levels of macrophage migration inhibitory factor (MIF in patients with microscopic polyangiitis

    Directory of Open Access Journals (Sweden)

    Hirohito Kanemitsu

    2009-03-01

    Full Text Available Hirohito Kanemitsu, Mizuho Matsunawa, Kuninobu Wakabayashi, Michihito Sato, Ryo Takahashi, Tsuyoshi Odai, Takeo Isozaki, Nobuyuki Yajima, Yusuke Miwa, Tsuyoshi KasamaDivision of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo, JapanObjective: To test the hypothesis that macrophage migration inhibitory factor (MIF is involved in the disease activity of systemic vasculitis.Methods: Patients with systemic vasculitis were divided into three groups based on the size of the affected vessels. Microscopic polyangiitis (MPA was considered as small vessel vasculitis (SVV, polyarteritis nodosa as medium-sized vessel vasculitis (MVV, and giant cell arteritis and Takayasu arteritis as large vessel vasculitis (LVV. Sera from patients with systemic vasculitis and healthy individuals were collected, and MIF levels were measured using an enzyme-linked immunosorbent assay. Disease activity of vasculitis was assessed using the Birmingham Vasculitis Activity Score (BVAS.Results: Serum MIF levels were significantly higher in the vasculitis patients than in healthy individuals. Among the vasculitis patients, MIF levels were significantly higher in patients in the SVV group (median; 4161.7 pg/ml than in the other groups (MVV; 1443.2 pg/ml and LVV; 1576.7 pg/ml. In patients with MPA, a positive correlation was observed between serum MIF levels and CRP levels and disease activity (BVAS. Notably, serum MIF levels were significantly diminished after clinical improvement.Conclusions: Our findings suggest that MIF may have an important role in small vessel vasculopathy and serve as a useful serologic marker of MPA disease activity.Keywords: macrophage migration inhibitory factor, systemic vasculitis, microscopic polyangiitis, cytokine

  4. College Students’ Drinking Motives and Social-Contextual Factors: Comparing Associations across Levels of Analysis

    Science.gov (United States)

    O'Hara, Ross E.; Armeli, Stephen; Tennen, Howard

    2014-01-01

    Prior investigations have established between-person associations between drinking motives and both levels of alcohol use and social-contextual factors surrounding that use, but these relations have yet to be examined at the within-person level of analysis. Moreover, exploring previously posited subtypes of coping motives (i.e., coping with depression, anxiety, and anger) may shed light on the within-person processes underlying drinking to cope. In this daily diary study of college student drinking (N = 722; 54% female), students reported each day how many drinks they consumed the previous evening in both social and nonsocial settings along with their motives for each drinking episode. Additionally, they reported whether they attended a party the evening before, the number of people they were with, the gender makeup of that group, and their perceptions of their companions’ drinking prevalence and quantity. External reasons for drinking—social and conformity motives—showed patterns largely consistent across levels of analysis and in agreement with motivational models. However, internal reasons for drinking—enhancement and coping motives—demonstrated divergent associations that suggest different processes across levels of analysis. Finally, coping subtypes showed differing associations with drinking levels and social-contextual factors dependent on the predisposing emotion and the level of analysis. These results suggest that internal drinking motives have unique state and trait components, which could have important implications for the application of motivational models to prevention and treatment efforts. We recommend including drinking motives (including coping subtypes) as within-person measures in future micro-longitudinal studies. PMID:25546143

  5. Achievement motivation level in students of Shiraz University of Medical Sciences and its influential factors.

    Science.gov (United States)

    Kavousipour, Somayeh; Noorafshan, Ali; Pourahmad, Saeedeh; Dehghani-Nazhvani, Ali

    2015-01-01

    Many studies have investigated the relationship between motivation and educational outcomes. The present study was conducted to determine whether the students' motivation in Shiraz University of Medical Sciences (SUMS) decreases during educational years. 770 students in SUMS were selected by multi-stage stratified random sampling from each field and entrance year. The first questionnaire contained 57 questions on the effect of economic, social, educational, geographical and personality factors on the students' motivation. The second one was based on 50 incomplete sentences. The validity and reliability of these questionnaires were approved by the experts and Cronbach's Alpha coefficients (85% and 90%, respectively). In this cross-sectional study, ANOVA, t-test and Chi-square tests were applied for data analysis at the 0.05 significance level. Six factors with the most effect on academic motivation were "family attitudes", "getting good jobs in future", "respect for themselves", " the ability to learn", "believing their role in victory and defeat" and "the tendency toward optimism about themselves". In addition, comparing professional doctorate and basic sciences' results revealed no significant relationship between academic motivation and educational years (F=0.819, p=0.397). But comparing field by field showed that Dentistry and Hospital Management and Medical Information (HMMI) had a significant decrease in motivation score by increase in educational years (F=3.991, p=0.015). Achievement motivation level in SUMS students was higher than average and did not decrease during educational years. Also, the results showed that personal, social and educational related factors affected motivation level more than economic and environmental factors.

  6. Achievement motivation level in students of Shiraz University of Medical Sciences and its influential factors

    Directory of Open Access Journals (Sweden)

    SOMAYEH KAVOUSIPOUR

    2015-01-01

    Full Text Available Introduction: Many studies have investigated the relationship between motivation and educational outcomes. The present study was conducted to determine whether the students’ motivation in Shiraz University of Medical Sciences (SUMS decreases during educational years. Methods: 770 students in SUMS were selected by multi-stage stratified random sampling from each field and entrance year. The first questionnaire contained 57 questions on the effect of economic, social, educational, geographical and personality factors on the students’ motivation. The second one was based on 50 incomplete sentences. The validity and reliability of these questionnaires were approved by the experts and Cronbach’s Alpha coefficients (85% and 90%, respectively. In this cross-sectional study, ANOVA, t-test and Chisquare tests were applied for data analysis at the 0.05 significance level. Results: Six factors with the most effect on academic motivation were “family attitudes”, “getting good jobs in future”, “respect for themselves”, “ the ability to learn”, “believing their role in victory and defeat” and “the tendency toward optimism about themselves”. In addition, comparing professional doctorate and basic sciences’ results revealed no significant relationship between academic motivation and educational years (F=0.819, p=0.397. But comparing field by field showed that Dentistry and Hospital Management and Medical Information (HMMI had a significant decrease in motivation score by increase in educational years (F=3.991, p=0.015. Conclusion: Achievement motivation level in SUMS students was higher than average and did not decrease during educational years. Also, the results showed that personal, social and educational related factors affected motivation level more than economic and environmental factors.

  7. Emotions and personality traits as high-level factors in visual attention: a review

    Directory of Open Access Journals (Sweden)

    Kai eKaspar

    2012-11-01

    Full Text Available The visual sense has outstanding significance for human perception and behavior, and visual attention plays a central role in the processing of the sensory input. Thereby, multiple low- and high-level factors contribute to the guidance of attention. The present review focuses on two neglected high-level factors: emotion and personality. The review starts with an overview of different models of attention, providing a conceptual framework and illustrating the nature of low- and high-level factors in visual attention. Then, the ambiguous concept of emotion is described, and recommendations are made for the experimental practice. In the following, we present several studies showing the influence of emotion on overt attention, whereby the distinction between internally and externally located emotional impacts is emphasized. We also provide evidence showing that emotional stimuli influence perceptual processing outside of the focus of attention, whereby results in this field are mixed. Then, we present some detached studies showing the reversed causal effect: attention can also affect emotional responses. The final section on emotion–attention interactions addresses the interplay on the neuronal level, which has been neglected for a long time in neuroscience. In this context, several conceptual recommendations for future research are made. Finally, based on findings showing inter-individual differences in human sensitivity to emotional items, we introduce the wide range of time-independent personality traits that also influence attention, and in this context we try to raise awareness of the consideration of inter-individual differences in the field of neuroscience.

  8. Aqueous transforming growth factor-beta-I levels in rabbit eyes after excimer laser photoablation.

    Science.gov (United States)

    Bilgihan, K; Gürelik, G; Okur, H; Bilgihan, A; Hasanreisoglu, B; Imir, T

    1997-01-01

    Transforming growth factor beta (TGF-beta) plays an important role in anterior segment wound healing, by controlling the cell proliferation and differentiation, angiogenesis, extracellular matrix composition and mediating the immunosuppressive properties of the aqueous humor. The present study was undertaken to clarify the possible changes of aqueous humor TGF-betaI levels after excimer laser photoablation. Twenty-eight New Zealand rabbits were divided into four groups of 7 rabbits each. Group 1 served as control, the central 7 mm of corneal epithelium was removed in groups 2, 3 and 4. We performed 50-microm corneal photoablation in group 3, and 100-microm ablation in group 4. After 48 h we measured the TGF-betaI levels of the aqueous humor by ELISA method. The mean TGF-betaI value of the aqueous humor was found to be 162.94+/-13.73 pg/ml in the control group. Mechanical deepithelialization did not change the TGF-betaI levels of the aqueous humor (p > 0.05). There was no significant difference between the 50-microm photoablated group and the controls (p > 0.05), but the TGF-betaI levels of the 100-microm photoablated group were found to be significantly higher than those of both the control group and 50-microm photoablated group (p < 0.05). Many factors and cytokines may induce corneal haze and myopic regression after excimer laser photoablation; our study demonstrated that TGF-betaI is one of these factors and there is a positive correlation between the depth of corneal photoablation and aqueous TGF-betaI concentrations.

  9. FACTOR-ANALYSIS OF THE LEVEL OF EXPRESSED EMOTION SCALE, A QUESTIONNAIRE INTENDED TO MEASURE PERCEIVED EXPRESSED EMOTION

    NARCIS (Netherlands)

    GERLSMA, C; VANDERLUBBE, PM; VANNIEUWENHUIZEN, C

    When the factor structure and psychometric qualities of the Level of Expressed Emotion scale, an instrument intended to assess patient's perceptions of expressed emotion, were evaluated, three moderately intercorrelated factors emerged, with good internal consistency; these were lack of emotional

  10. Changes in Insulin-like Growth Factor-1 Level in Patients with Sepsis and Septic Shock

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    Sang Hoon Lee

    2016-11-01

    Full Text Available Background Despite many ongoing, prospective studies on the topic, sepsis still remains one of the main causes of death in hospital. The hormone insulin-like growth factor 1 (IGF-1 has a similar molecular structure to that of insulin. IGF-1 exerts anabolic effects and plays important roles in both normal physiology and pathologic processes. Previous studies have observed low serum IGF-1 level in patients with critical illnesses. Here, we evaluated changes in IGF-1 level based on survival of septic patients. Methods We evaluated 140 patients with sepsis and septic shock (21 with sepsis and 119 with septic shock admitted to the intensive care unit of a university-affiliated hospital in Korea. Serum IGF-1 level was measured on days 0, 1, 3, and 7. Patients with liver disease were excluded from this study. All data were analyzed using SPSS version 20 (SPSS Inc., Chicago, IL, USA. Results Patients with septic shock had significantly lower serum IGF-1 level on days 1 and 3 than patients without septic shock (p = 0.002 and p = 0.007, respectively. Generally, there was a negative relationship between IGF-1 and serum cortisol levels; however, this relationship was only significant on day 3 (p = 0.029. Furthermore, renin showed significantly negative correlation with IGF-1 on day 3 (p = 0.038. IGF-1 level did not show significant difference between survivors and non-survivors. Conclusions Our results showed that IGF-1 was associated with septic shock, and that the IGF-1 axis is severely disrupted in septic patients. Additionally, serum cortisol and renin levels were associated with IGF-1 level.

  11. Plasma intact fibroblast growth factor 23 levels in women with anorexia nervosa

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    Otani Makoto

    2008-04-01

    Full Text Available Abstract Background Fibroblast growth factor (FGF23 is a novel phosphaturic factor associated with inorganic phosphate homeostasis. Previous human studies have shown that serum FGF23 levels increase in response to a high phosphate diet. For anorexia nervosa (AN patients, inorganic phosphate homeostasis is important in the clinical course, such as in refeeding syndrome. The purpose of this study was to determine plasma levels of intact FGF23 (iFGF23 in restricting-type AN (AN-R patients, binge-eating/purging-type AN (AN-BP patients, and healthy controls. Methods The subjects consisted of 6 female AN-R patients, 6 female AN-BP patients, and 11 healthy female controls; both inpatients and outpatients were included. Plasma iFGF23, 1,25-dihydroxyvitamin D (1,25-(OH2D, and 25-hydroxyvitamin D (25-OHD levels were measured. Data are presented as the median and the range. A two-tailed Mann-Whitney U-test with Bonferroni correction was used to assess differences among the three groups, and a value of p Results There were no differences between AN-R patients and controls in the iFGF23 and 1,25-(OH2D levels. In AN-BP patients, the iFGF23 level (41.3 pg/ml; range, 6.1–155.5 pg/ml was significantly higher than in controls (3.8 pg/ml; range, not detected-21.3 pg/ml; p = 0.001, and the 1,25-(OH2D was significantly lower in AN-BP patients (7.0 pg/ml; range, 4.2–33.7 pg/ml than in controls (39.7 pg/ml; range, 6.3–58.5 pg/ml; p = 0.015. No differences in plasma 25-OHD levels were observed among the groups. Conclusion This preliminary study is the first to show that plasma iFGF23 levels are increased in AN-BP patients, and that these elevated plasma FGF23 levels might be related to the decrease in plasma 1,25-(OH2D levels.

  12. Identification of risk factors for Campylobacter contamination levels on broiler carcasses during the slaughter process.

    Science.gov (United States)

    Seliwiorstow, Tomasz; Baré, Julie; Berkvens, Dirk; Van Damme, Inge; Uyttendaele, Mieke; De Zutter, Lieven

    2016-06-02

    Campylobacter carcass contamination was quantified across the slaughter line during processing of Campylobacter positive batches. These quantitative data were combined together with information describing slaughterhouse and batch related characteristics in order to identify risk factors for Campylobacter contamination levels on broiler carcasses. The results revealed that Campylobacter counts are influenced by the contamination of incoming birds (both the initial external carcass contamination and the colonization level of caeca) and the duration of transport and holding time that can be linked with feed withdrawal period. In addition, technical aspects of the slaughter process such as a dump based unloading system, electrical stunning, lower scalding temperature, incorrect setting of plucking, vent cutter and evisceration machines were identified as risk factors associated with increased Campylobacter counts on processed carcasses. As such the study indicates possible improvements of the slaughter process that can result in better control of Campylobacter numbers under routine processing of Campylobacter positive batches without use of chemical or physical decontamination. Moreover, all investigated factors were existing variations of the routine processing practises and therefore proposed interventions are practically and economically achievable. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Influence of perinatal factors on thyroid stimulating hormone level in cord blood.

    Science.gov (United States)

    Armanian, Amir-Mohammad; Hashemipour, Mahin; Esnaashari, Azadeh; Kelishadi, Roya; Farajzadegan, Ziba

    2013-01-01

    The aim of the present study was to determine the effect of various perinatal factors on cord blood TSH among newborns in Isfahan, Iran. This was a descriptive-analytic cross sectional study which performed in Isfahan Iran. During a period of four months, since February to May 2012 a total number of 440 newborns delivered in Alzahra and Shahid beheshti hospitals were enrolled in the study. For all newborns one mL blood sample from umbilical vein was obtained by one of the project investigators and sent to laboratory for further examinations. Cord blood TSH and birth body weight (BBW), gestational age, history of gestational diabetes mellitus (GDM), apgar at one minute, apgar at five minute, newborn gender and the mother's age were documented. Differences considered statistically significant if P BBW, gestational age, GDM, apgar at one minute, apgar at five minute, newborn gender and the mother's age didn't have statistically significant relationship with cord TSH level. In conclusion we deduce that the only factor that can affect cord blood TSH was method of delivery. Infant with vaginal delivery has higher TSH level in cord blood. Other factors that were evaluated in this study didn't have any statistically significant relationship.

  14. Socio-Psychological Factors Affecting Participatory Planning Processes At Interactional Level

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    Neslihan KULÖZÜ

    2014-02-01

    Full Text Available Today, it is widely accepted that communities need to collaborate when making decisions on behalf of the individual, society and the environment. Hence, planners engaged in participatory initiatives need to understand how best to design and carry out a participatory planning process. In order to answer this question, all factors affecting participatory processes need to be determined, since only then can steps be taken to design and execute the best participatory process for each stakeholder in every unique context. By focusing particularly on the factors affecting participatory processes at interactional level, this study aims to determine the socio-psychological dimensions of participatory planning processes, the aim being to bring to light some hitherto unexplained factors involved and thus help to improve these processes. Based on previous discussions in participation literature, the ultimate aim of this study is to provide subsequent researchers and those involved in participatory planning practices with a framework on the socio-psychological dimensions, namely communication, power, attribution, relationships and persuasion, of participatory processes at interactional level.

  15. Endotoxin levels and contribution factors of endotoxins in resident, school, and office environments - A review

    Science.gov (United States)

    Salonen, Heidi; Duchaine, Caroline; Létourneau, Valérie; Mazaheri, Mandana; Laitinen, Sirpa; Clifford, Sam; Mikkola, Raimo; Lappalainen, Sanna; Reijula, Kari; Morawska, Lidia

    2016-10-01

    As endotoxin exposure has known effects on human health, it is important to know the generally existing levels of endotoxins as well as their contributing factors. This work reviews current knowledge on the endotoxin loads in settled floor dust, concentrations of endotoxins in indoor air, and different environmental factors potentially affecting endotoxin levels. The literature review consists of peer-reviewed manuscripts located using Google and PubMed, with search terms based on individual words and combinations. References from relevant articles have also been searched. Analysis of the data showed that in residential, school, and office environments, the mean endotoxin loads in settled floor dust varied between 660 and 107,000 EU/m2, 2180 and 48,000 EU/m2, and 2700 and 12,890 EU/m2, respectively. Correspondingly, the mean endotoxin concentrations in indoor air varied between 0.04 and 1610 EU/m3 in residences, and 0.07 and 9.30 EU/m3 in schools and offices. There is strong scientific evidence indicating that age of houses (or housing unit year category), cleaning, farm or rural living, flooring materials (the presence of carpets), number of occupants, the presence of dogs or cats indoors, and relative humidity affect endotoxin loads in settled floor dust. The presence of pets (especially dogs) was extremely strongly associated with endotoxin concentrations in indoor air. However, as reviewed articles show inconsistency, additional studies on these and other possible predicting factors are needed.

  16. Urinary Nerve Growth Factor Levels in Overactive Bladder Syndrome and Lower Urinary Tract Disorders

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    Hsin-Tzu Liu

    2010-12-01

    Full Text Available Overactive bladder (OAB is a syndrome based on self-reported symptoms of urgency and frequency with or without urge incontinence. Although urgency is the core symptom of OAB, patients might have difficulty to distinguish urgency from the urge to void. Urodynamic study is a useful diagnostic tool to discover detrusor overactivity (DO in patients with OAB; however, not all OAB patients have DO. Therefore, a more objective and non-invasive way to diagnose and assess OAB including DO is needed. Recent research has focused on urinary biomarkers in assessment of OAB. Urinary nerve growth factor (NGF level increases in patients with OAB-wet, bladder outlet obstruction, mixed urinary incontinence and urodynamic DO. Urinary NGF levels are correlated with severity of OAB symptoms. In patients with OAB and DO who have been well treated with antimuscarinics or botulinum toxin injection, urinary NGF levels have been shown to decrease significantly in association with reduction of urgency severity. However, not all patients with OAB have an elevated urinary NGF level. It might also be increased in patients with interstitial cystitis/painful bladder syndrome, cerebrovascular accident and lower urinary tract diseases such as urinary tract stone, bacterial infection and urothelial tumor. It is possible to use urinary NGF levels as a bio-marker for diagnosis of OAB as well as for the assessment of therapeutic outcome in patients with OAB or DO. Here, we review the latest medical advances in this field.

  17. Socio-economic factors, food habits and phosphorus levels in patients on hemodialysis

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    Domenico Santoro

    2012-06-01

    To explore the association between socio-economic factors and serum phosphorus levels, we enrolled 100 patients on periodic hemodialysis treatment from 3 different units. Information, on social, cultural, economic, diet habits, therapy for hyperphosphoremia and haematological and clinical parameters had been collected through specific questionnaires administered by a physician. Statistical analysis was performed using correlation between variables with the linear regression analysis, and the stepwise logistic regression analysis, either analysis preceded by log-10 transformation if the distribution of the variables was non-gaussian. The level of statistical significance was always set at P < 0.05 Results showed serum phosphorus level was reduced in patients who live alone compared to patients in family (P=0,04, in self-sufficient (P=0,05 and in patients belonging to medium-higher versus lower socio-economic groups (P=0,003. Fast foods intakes correlates with increase in phosphorus serum levels (P=0,002, whilst the same correlation was not found for cheese intake. Our data show that socio-economic status and food habits are useful predictors of phosphorus serum levels . In conclusion, dietary counselling of patients on hemodialysis is mandatory. Interventions that consider the socio-economic situation allow to deliver important messages on foods with the least amount of phosphates, and adequate protein content, and they may be a successful strategy in targeting patients at a higher risk of hyperphosphoremia.

  18. The correlation between perceived social support, cortisol and brain derived neurotrophic factor levels in healthy women.

    Science.gov (United States)

    Ma, Doy Yung; Chang, Wei Hung; Chi, Mei Hung; Tsai, Hsin Chun; Yang, Yen Kuang; Chen, Po See

    2016-05-30

    In this study, the role of brain derived neurotrophic factor (BDNF) in stress resilience was investigated. With a focus on healthy subjects, we explored whether plasma BDNF levels are correlated with the dexamethasone suppression test (DST) and subjectively perceived social support status. Moreover, we examined the possible interacting effect of DST status and perceived social support on BDNF levels. Seventy-two healthy volunteers, 44 females and 28 males, were recruited from the community and completed the perceived routine support subscale of Measurement of Support Function (PRS_MSF) questionnaire. Plasma BDNF levels and DST suppression rate with the low dose DST were measured. There was a significant positive correlation between BDNF and DST suppression rate in the female subjects. This was also true for the plasma BDNF levels and PRS_MSF in the female subjects. The positive correlation between BDNF and PRS_MSF was significant only in female subjects with low DST suppression rates. Plasma BDNF levels were associated with stress resilience in a sex-specific manner. Subjects' belief in social support might buffer the biological stress reactions. Differences in social perception and the biological stress response between men and women merits further investigation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Serum and Peritoneal Fluid Levels of Vascular Endothelial Growth Factor in Women with Endometriosis

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    Fatemeh Eshraghi-Jazi

    2013-01-01

    Full Text Available Background: Endometriosis is known as one of the most common disease in women ofreproductive age. Due to important role of vascular endothelial growth factor (VEGF inneo-vascularization for the implantation of endometrial cell, and also presence of differentstudies reported VEGF level in the serum and peritoneal fluid (PF in endometriosispatients, this study was designed to determine the serum and PF levels of VEGF in endometriosispatients, and to compare with normal subjects.Materials and Methods: In this descriptive study, 179 women subjected to laparoscopyfor the evaluation of infertility or pelvic pain were allocated into the following two groups:group I: different types of endometriosis patients (n=90 and group II: non-endometriosispatients (n=89. The PF from pelvis and venous blood samples were obtained. The VEGFconcentration of the serum and PF were measured using enzyme immunoassay kit and werecompared using t test.Results: The level of VEGF in serum was significantly less than that in PF in both groups(p=0.00. However, endometriosis patients had significantly higher level of VEGF inperitoneal fluid than non-endometriosis patients (p=0.043.Conclusion: According to our findings, endometriosis is not associated with change inthe level of circulating VEGF.

  20. Plasma Levels of Tumor Necrosis Factor-Alpha and Interleukin-6 in Obsessive Compulsive Disorder

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    N. Konuk

    2007-01-01

    Full Text Available Aim. Recent research implicated place of an immune mechanism in the pathophysiology of obsessive-compulsive disorder (OCD. Despite increasing evidence involvement of cytokine release in OCD, results of the studies are inconsistent. The aim of this study was to evaluate the plasma levels of the cytokines; tumor necrosis factor-alpha (TNF-α and interleukin-6 (IL-6 in OCD patients. Methods. Plasma concentrations of TNF-α and IL-6 were measured in 31 drug-free outpatients with OCD, and 31-year age and sex-matched healthy controls. TNF-α and IL-6 concentrations in blood were determined by enzyme-linked immunosorbent assay (ELISA. Results. Both TNF-α and IL-6 levels showed statistically significant increases in OCD patients compared to controls (P<.000, P<.001, resp.. In addition, the age of onset was negatively correlated with TNF-α level (r=−.402, P=.025 and duration of illness was weakly correlated with IL-6 levels (r:.357; P:.048 in patients group. Conclusion. OCD patients showed increases in TNF-α and IL-6 levels compared to the healthy controls. This study provides evidence for alterations in the proinflamatory cytokines which suggest the involvement of the immune system in the pathophysiology of OCD.

  1. Circulating Tissue Factor Levels and Risk of Stroke: Findings From the EPICOR Study.

    Science.gov (United States)

    Iacoviello, Licia; Di Castelnuovo, Augusto; de Curtis, Amalia; Agnoli, Claudia; Frasca, Graziella; Mattiello, Amalia; Matullo, Giuseppe; Ricceri, Fulvio; Sacerdote, Carlotta; Grioni, Sara; Tumino, Rosario; Napoleone, Emanuela; Lorenzet, Roberto; de Gaetano, Giovanni; Panico, Salvatore; Donati, Maria Benedetta

    2015-06-01

    Tissue factor (TF) expression is increased in inflammatory atherosclerotic plaques and has been related to their thrombogenicity. Blood-borne TF has been also demonstrated to contribute to thrombogenesis. However, few studies have evaluated the association of circulating levels of TF with stroke. We investigated the association of baseline circulating levels of TF with stroke events occurred in the European Prospective Investigation into Cancer and Nutrition-Italy cohort. Using a nested case-cohort design, a center-stratified random sample of 839 subjects (66% women; age range, 35-71 years) was selected as subcohort and compared with 292 strokes in a mean follow-up of 9 years. Blood samples were collected at baseline in citrate, plasma was stored in liquid nitrogen and TF was measured by ELISA (IMUBIND, TF ELISA, Instrumentation Laboratory, Milan, Italy). The odd ratios and 95% confidence intervals, adjusted by relevant confounders (covariates of TF) and stratified by center, were estimated by a Cox regression model using Prentice method. Individuals in the highest compared with the lowest quartile of TF plasma levels had significantly increased risk of stroke (odds ratioIVvsI quartile, 2.01; 95% confidence interval, 1.25-3.23). The association was independent from several potential confounders (odds ratioIVvsI quartile, 1.91; 95% confidence interval, 1.15-3.19). No differences were observed between men and women. The increase in risk was restricted to ischemic strokes (odds ratioIVvsI quartile, 2.13; 95% confidence interval, 1.10-4.12; fully adjusted model), whereas high levels of TF were not associated with the risk of hemorrhagic stroke (odds ratioIVvsI quartile, 1.12; 95% confidence interval, 0.49-2.55; fully adjusted model). Our data provide evidence that elevated levels of circulating TF are potential risk factors for ischemic strokes. © 2015 American Heart Association, Inc.

  2. Population-Level Prediction of Type 2 Diabetes From Claims Data and Analysis of Risk Factors.

    Science.gov (United States)

    Razavian, Narges; Blecker, Saul; Schmidt, Ann Marie; Smith-McLallen, Aaron; Nigam, Somesh; Sontag, David

    2015-12-01

    We present a new approach to population health, in which data-driven predictive models are learned for outcomes such as type 2 diabetes. Our approach enables risk assessment from readily available electronic claims data on large populations, without additional screening cost. Proposed model uncovers early and late-stage risk factors. Using administrative claims, pharmacy records, healthcare utilization, and laboratory results of 4.1 million individuals between 2005 and 2009, an initial set of 42,000 variables were derived that together describe the full health status and history of every individual. Machine learning was then used to methodically enhance predictive variable set and fit models predicting onset of type 2 diabetes in 2009-2011, 2010-2012, and 2011-2013. We compared the enhanced model with a parsimonious model consisting of known diabetes risk factors in a real-world environment, where missing values are common and prevalent. Furthermore, we analyzed novel and known risk factors emerging from the model at different age groups at different stages before the onset. Parsimonious model using 21 classic diabetes risk factors resulted in area under ROC curve (AUC) of 0.75 for diabetes prediction within a 2-year window following the baseline. The enhanced model increased the AUC to 0.80, with about 900 variables selected as predictive (p process of diabetes development compared with obesity-related factors such as hypertension and high hemoglobin A1c. In conclusion, population-level risk prediction for type 2 diabetes using readily available administrative data is feasible and has better prediction performance than classical diabetes risk prediction algorithms on very large populations with missing data. The new model enables intervention allocation at national scale quickly and accurately and recovers potentially novel risk factors at different stages before the disease onset.

  3. Plasma levels of hypoxia-regulated factors in patients with age-related macular degeneration.

    Science.gov (United States)

    Ioanna, Zygoula; Christian, Schori; Christian, Grimm; Daniel, Barthelmes

    2018-02-01

    Various hypoxia-related proteins are differentially expressed in the retina and secreted to the vitreous and/or aqueous humor of patients affected by dry or neovascular age-related macular degeneration (nAMD). To determine whether these conditions alter concentrations of cytokines also in the systemic circulation, we measured plasma levels of six hypoxia-related proteins. Plasma was prepared from EDTA blood that was collected from patients affected by dry AMD (n = 5), nAMD (n = 11), proliferative diabetic retinopathy (PDR; n = 9), and patients with an epiretinal membrane (ERM; n = 11). ERM samples served as negative controls, PDR samples as positive controls. Protein concentrations of vascular endothelial growth factor (VEGF), erythropoietin (EPO), angiopoietin-like 4 (ANGPTL4), placental growth factor (PlGF), tumor necrosis factor alpha (TNF-α), and pigment epithelium-derived factor (PEDF) were determined by enzyme-linked immunosorbent assay (ELISA). The concentration of PlGF was significantly increased in plasma of patients affected by nAMD. Although no statistically significant differences were found for EPO, ANGPTL4, PlGF, TNF-α, and PEDF, the mean concentration of VEGF was lowest in the nAMD group. Plasma concentrations of the six factors did not correlate with gender or age of patients. nAMD may increase plasma concentrations of PlGF, making it a candidate as a biomarker for the neovascular form of AMD. Other factors, however, were not differentially regulated, suggesting that their systemic concentrations are not generally increased in hypoxia-related retinal diseases.

  4. Factors that affect the ecological footprint depending on the different income levels

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    Sheng-Tung Chen

    2016-05-01

    Full Text Available The ecological footprint provides a method for measuring how much lands can support the consumption of the natural resources. Development and biocapacity debates revolve mainly around the factors that affect the ecological footprint and the approaches to improve the environmental quality. Therefore, we conducted the panel analysis of data for 99 countries from 1981 to 2006 to determine what factors affect the ecological footprint. The empirical results show that the effect of GDP per capita on the ecological footprint varies for different income levels. The effect of urbanization is significantly positive across income levels, which means that the higher the rate of urbanization in high or low income country, the higher the ecological footprint. As developing countries pursue economic development, there will be an impact on the environment. The developed countries may seek to develop their economies through activities that are more detrimental to the environment. Additionally, the export of goods and services divided by GDP is significant, which means that the higher the volume of exports, the greater the burden on the environment. However, this effect is not significant across different income level models. The income effect may explain the diverse effects of export on the environment. Therefore, panel data analysis and income classification are necessary to discuss the effect of export on the environment.

  5. Disclosure Level of CPC 29 Biological Assets: Analysis of Determining Factors in Brazilian companies

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    Daniel Ramos Nogueira

    2017-04-01

    Full Text Available The research question guiding this research is "What are the Determining Factors of CPC 29 Disclosure in Brazilian Companies?". In this aspect, the research objective was to evaluate the main factors that affect the disclosure of information related to biological assets. For this, 5 variables highlighted in the literature were selected as evidence influencers. The sample was composed of Brazilian companies with biological assets in the Balance Sheet. From this list, financial statements, explanatory notes, corporate management level and independent auditing company for the 6 years (2010 to 2015 were collected. With the collected information, the dependent variable (Disclosure level of CPC 29 and the independent variables of each year were verified. At the end (after exclusions, 100 observations were analyzed. The results indicated that the variables Size, Representativeness of Biological Assets and Effectiveness of OCPC 07 positively impacted the level of Disclosure. The first two confirmed the predicted hypothesis and OCPC 07 presented a relation that was different from what was expected, showing an increase and not a reduction in the number of disclosures in the years 2014 and 2015.

  6. Matematical modeling of galophytic plants productivity taking into account the temperature factor and soil salinity level

    Science.gov (United States)

    Natalia, Slyusar; Pisman, Tamara; Pechurkin, Nikolai S.

    Among the most challenging tasks faced by contemporary ecology is modeling of biological production process in different plant communities. The difficulty of the task is determined by the complexity of the study material. Models showing the influence of climate and climate change on plant growth, which would also involve soil site parameters, could be of both practical and theoretical interest. In this work a mathematical model has been constructed to describe the growth dynamics of different plant communities of halophytic meadows as dependent upon the temperature factor and soil salinity level, which could be further used to predict yields of these plant communities. The study was performed on plants of halophytic meadows in the coastal area of Lake of the Republic of Khakasia in 2004 - 2006. Every plant community grew on the soil of a different level of salinity - the amount of the solid residue of the saline soil aqueous extract. The mathematical model was analyzed using field data of 2004 and 2006, the years of contrasting air temperatures. Results of model investigations show that there is a correlation between plant growth and the temperature of the air for plant communities growing on soils containing the lowest (0.1Thus, results of our study, in which we used a mathematical model describing the development of plant communities of halophytic meadows and field measurements, suggest that both climate conditions (temperature) and ecological factors of the plants' habitat (soil salinity level) should be taken into account when constructing models for predicting crop yields.

  7. Level of evidence of clinical spinal research and its correlation with journal impact factor.

    Science.gov (United States)

    Amiri, Amir Reza; Kanesalingam, Kavitha; Cro, Suzie; Casey, Adrian T H

    2013-09-01

    Over the past two decades, there has been a growing recognition and emphasis on the practice of evidence-based medicine (EBM). The level of evidence (LOE) is used to classify clinical studies based on their quality and design. To compare the quality of scientific journals, the impact factor (IF) is the most widely used ranking measure. However, the calculation of IF is not directly dependent on the quality or LOE of clinical articles published in a journal. The primary aim of this study was to evaluate the current LOE for clinical research in leading spinal journals and assess the relationship between LOE and IF. We hypothesized that most clinical research would provide level IV evidence, and that a positive correlation would exist between the proportion of high LOE articles and the journal IF. A systematic review of all the articles in five general spinal journals was undertaken during 2010. All online articles in The Spine Journal, Spine, European Spine Journal, Journal of Neurosurgery: Spine, and Journal of Spinal Disorders and Techniques during 2010, as well as supplements were included. The LOE for each clinical study was assessed using guidelines produced by the Oxford Centre for Evidence-Based Medicine. Two reviewers independently assessed all articles. Overall 703 articles were suitable for LOE grading. Of these, 4.7% provided level I evidence, 23.2% level II, 12.5% level III, and 59.6% level IV. There was a significant association between LOE and type of study (pevidence. There was a strong positive correlation between the proportion of level I and II evidence and the journal impact factor (ρ=0.9; 95% confidence interval 0.1 to 0.99; p=.037). Spinal surgery journals with a higher IF contain a larger proportion of studies with high LOE, however most clinical articles provide level IV evidence of which the highest proportion are therapeutic studies. Clinicians, researchers, and journal editors should work hand in hand to enhance evidence-based practice in

  8. Serum CCL-18 level is a risk factor for COPD exacerbations requiring hospitalization

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    Dilektasli AG

    2017-01-01

    Full Text Available Asli Gorek Dilektasli,1 Ezgi Demirdogen Cetinoglu,1 Esra Uzaslan,1 Ferah Budak,2 Funda Coskun,1 Ahmet Ursavas,1 Ilker Ercan,3 Ercument Ege1 1Department of Pulmonary Disesaes, 2Department of Immunology, 3Department of Biostatistics, Uludag University Faculty of Medicine, Bursa, Turkey Introduction: Chemokine (C-C motif ligand 18 (CCL-18 has been shown to be elevated in chronic obstructive pulmonary disease (COPD patients. This study primarily aimed to evaluate whether the serum CCL-18 level differentiates the frequent exacerbator COPD phenotype from infrequent exacerbators. The secondary aim was to investigate whether serum CCL-18 level is a risk factor for exacerbations requiring hospitalization. Materials and methods: Clinically stable COPD patients and participants with smoking history but normal spirometry (NSp were recruited for the study. Modified Medical Research Council Dyspnea Scale, COPD Assessment Test, spirometry, and 6-min walking test were performed. Serum CCL-18 levels were measured with a commercial ELISA Kit. Results: Sixty COPD patients and 20 NSp patients were recruited. Serum CCL-18 levels were higher in COPD patients than those in NSp patients (169 vs 94 ng/mL, P<0.0001. CCL-18 level was significantly correlated with the number of exacerbations (r=0.30, P=0.026, although a difference in CCL-18 values between infrequent and frequent exacerbator COPD (168 vs 196 ng/mL subgroups did not achieve statistical significance (P=0.09. Serum CCL-18 levels were significantly higher in COPD patients who had experienced at least one exacerbation during the previous 12 months. Overall, ROC analysis revealed that a serum CCL-18 level of 181.71 ng/mL could differentiate COPD patients with hospitalized exacerbations from those who were not hospitalized with a 88% sensitivity and 88.2% specificity (area under curve: 0.92. Serum CCL-18 level had a strong correlation with the frequency of exacerbations requiring hospitalization (r=0.68, P<0

  9. Exploratory Two-Level Analysis of Individual- and School-Level Factors on Truant Youth Emotional/Psychological Functioning

    Science.gov (United States)

    Dembo, Richard; Wareham, Jennifer; Schmeidler, James; Winters, Ken C.

    2016-01-01

    Research on samples of truant adolescents is limited, with little known about mental health problems among truant youths. This study provided an exploratory, multilevel examination of mental health problems for a sample of 300 truant adolescents. Confirmatory factor analysis indicated a single factor of multiple mental health problems at the…

  10. Socio-Economic Factors, Food Habits and Phosphorus Levels in Patients on Hemodialysis.

    Science.gov (United States)

    Santoro, Domenico; Ingegnieri, Maria Teresa; Vita, Giuseppe; Lucisano, Silvia; Zuppardo, Carmelo; Canale, Valeria; Savica, Vincenzo; Buemi, Michele

    2015-07-01

    Hyperphosphoremia is one of the most important risk factors for morbidity and mortality for chronic kidney disease (CKD) patients, and also, for the general population. Excessive dietary intake of phosphate (P) is one of the key factors. In particular, P in its inorganic form, which is contained in food additives, is more readily absorbed. Unfortunately, these food additives are mostly present in convenience so called "fast foods" (pre-cooked), soft drinks, which represent the typical food consumed by our hemodialysis (HD) population, composed by elderly people, mostly low-socio economic class, who often live alone. We performed an observational retrospective multicenter study to find any association between social, cultural and economic situation, as well as food habits, and P levels in a cohort of patients on HD. Secondarily; we also examined the association between the fast food consumption and increased P levels, as well as patient compliance for P binding products. To explore the association between socio-economic factors and serum P levels, we enrolled 100 patients on periodic HD treatment from three different units. Information on social, cultural, economic, diet habits, therapy for hyperphosphoremia and hematological and clinical parameters had been collected through specific questionnaires, administered by a physician. Results showed serum P level was reduced in patients who live alone compared to patients in family (P = 0.04), in self-sufficient (P = 0.05) and in patients belonging to middle-upper class, versus low-class (P = 0.003). Fast foods intake correlates with increase in P serum levels (P = 0.002), whilst the same correlation was not found for cheese intake. Our data show that socio-economic status and food habits are useful predictors of P serum levels. In conclusion, dietary counseling of patients on HD is mandatory. Interventions that consider the socio-economic situation allow delivering important messages on foods with the least amount of P

  11. Tumor necrosis factor-α serum levels in healthy smokers and nonsmokers

    Directory of Open Access Journals (Sweden)

    Florin Petrescu

    2010-07-01

    Full Text Available Florin Petrescu1, Sebastian Cosmin Voican1, Isabela Silosi21Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, Craiova, Romania; 2Department of Immunology, University of Medicine and Pharmacy of Craiova, Craiova, RomaniaBackground: Tobacco smoking is the most important risk factor for chronic obstructive pulmonary disease (COPD development. Inhaled cigarette smoke can induce tumor necrosis factor-a (TNF-a production by alveolar macrophages, which in turn may enhance the production of metalloproteinases (MMPs. MMPs have been involved in mediating airway inflammation and lung destruction.Objectives: We aimed to measure the TNF-a serum levels in healthy heavy smokers and healthy nonsmokers to determine the dose-response relationship based on the cigarette smoke exposure.Subjects and methods: We included in our study 43 healthy heavy smokers and 19 healthy nonsmokers (the control group. The smokers group was classified as less than one pack, one pack, and more than one pack per day. A clinical and paraclinical evaluation was performed in both groups, without any evidence of infection or COPD. The serum levels of TNF-a were assessed by ELISA.Results: The TNF-a serum levels were significantly higher for the group of smokers compared to the group of nonsmokers (P < 0.004. We also noticed an increased TNF-a concentration in the serum of smokers with more than one pack per day compared with those with less than one pack per day (P < 0.03. There was a positive correlation between the serum level of TNF-a and tobacco smoke exposure.Conclusions: The high levels of TNF-a in the serum of smokers suggest an imbalance between the proinflammatory and anti-inflammatory factors as a result of tobacco smoke exposure. The concentration of TNF-a is elevated in the serum of healthy heavy smokers in a cigarette dose-dependent manner. We speculate that the serum level of TNF-a might be a useful biomarker for the selection of heavy smokers

  12. Venom Concentrations and Clotting Factor Levels in a Prospective Cohort of Russell's Viper Bites with Coagulopathy.

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    Geoffrey K Isbister

    Full Text Available Russell's viper envenoming is a major problem in South Asia and causes venom induced consumption coagulopathy. This study aimed to investigate the kinetics and dynamics of venom and clotting function in Russell's viper envenoming.In a prospective cohort of 146 patients with Russell's viper envenoming, we measured venom concentrations, international normalised ratio [INR], prothrombin time (PT, activated partial thromboplastin time (aPTT, coagulation factors I, II, V, VII, VIII, IX and X, and von Willebrand factor antigen. The median age was 39 y (16-82 y and 111 were male. The median peak INR was 6.8 (interquartile range [IQR]: 3.7 to >13, associated with low fibrinogen [median,3 at 6 h post-antivenom but had reduced to <2, by 24 h. The aPTT had also returned to close to normal (<50 sec at 24 h. Factor VII, VIII and IX levels were unusually high pre-antivenom, median peak concentrations of 393%, 307% and 468% respectively. Pre-antivenom venom concentrations and the INR (r = 0.20, p = 0.02 and aPTT (r = 0.19, p = 0.03 were correlated (non-parametric Spearman analysis.Russell's viper coagulopathy results in prolonged aPTT, INR, low fibrinogen, factors V, VIII and X which recover over 48 h. Severity of clotting abnormalities was associated with venom concentrations.

  13. THE LEVEL OF GRAMMAR SCHOOL STUDENTS' KNOWLEDGE ON CARDIOVASCULAR DISEASE RISK FACTORS.

    Science.gov (United States)

    Jaraković, Milana; Mihajlović, Bojan; Ćemerlić, Snežana; Ađić, Filip; Sladojević, Miroslava; Mihajlović, Boaoliub

    2015-01-01

    Cardiovascular diseases are one of the leading causes of mortality and morbidity worldwide. The atherosclerotic process in the aorta starts in childhood, while atheroclerotic changes of coronary heart vessels start in adolescence. The aim of the study was to evaluate the knowledge of the students attending all four grades of grammar school about the risk factors for cardiovascular disease, with special attention to the risk factors that can be influenced by modification of life-style. Data from the entrance and exit tests were collected from 197 students attending a grammar school in Novi Sad. Chi-square test and Student T-test or Mann-Whitney U test were used to examine the statistical difference between categorized variables and the continuous variables, respectively. The difference between the number of correct answers for all the students on the entrance test and exit test was statistically significant (pgrammar school and after the lectures, the student's knowledge level was increased by 82.3% (p<0.0005). Children and adolescents from Vojvodina and Serbia should be well informed about the cardiovascular disease risk factors and their prevention with special attention paid to the risk factors that can be influenced by changing lifestyle habits.

  14. Animal level risk factors associated with Babesia and Theileria infections in cattle in Egypt.

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    Rizk, Mohamed Abdo; Salama, Akram; El-Sayed, Shimaa Abd-El-Salam; Elsify, Ahmed; El-Ashkar, Maged; Ibrahim, Hussam; Youssef, Mohamed; El-Khodery, Sabry

    2017-12-20

    In present study, blood samples were collected randomly from 439 cows at three main regions of Egypt (northern, central and southern). Molecular diagnosis of Babesia and Theileria infections by PCR amplification of DNA (gene) fragments, then cloning and sequencing of the positive samples were conducted. A questionnaire was created to imply the assumed risk factors and logistic regression statistical analysis was carried out to appraise the potential factors on the animal level. The results revealed that 49 (11.16%) and 45 (10.25%) cattle were infected with Babesia and Theileria parasites, respectively. B. bigemina (7.97%) and T. annulata (9.56%) were the most prevalent parasites. For Babesia sp., final multivariate logistic regression analysis showed a significant association between the infection and irregular use of antiprotozoal drugs (P = 0.003; OR: 0.28; 95% CI: 0.12-0.65), management practice (P = 0.029; OR: 6.66; 95% CI: 1.21-36.59) and ecology area (P = 0.006; OR: 5.62; 95% CI: 1.63-19.31). However, for Theileria sp. infection, animal breed (P = 0.003; OR: 0.44; 95% CI: .45-1.00) and irregular use of antiprotozoal drugs (PBabesia and Theileria sp. in Egypt based on molecular description. An impression on the potential risk factors associated with infections was obtained. Recognition of the potential risk factors associated with tick borne disease may be helpful to construct the best preventive measures.

  15. Levothyroxine treatment restored the decreased circulating fibroblast growth factor 21 levels in patients with hypothyroidism.

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    Wang, Guang; Liu, Jia; Yang, Ning; Hu, Yanjin; Zhang, Heng; Miao, Li; Yao, Zhi; Xu, Yuan

    2016-06-01

    Fibroblast growth factor 21 (FGF21) is an important endogenous regulator of energy metabolism. Thyroid hormone has been shown to regulate hepatic FGF21 expression in rodents. The goal of this study was to evaluate the plasma FGF21 levels in participants with normal thyroid function, subclinical hypothyroidism, or overt hypothyroidism and to investigate the change of plasma FGF21 levels in patients with overt hypothyroidism after levothyroxine treatment. A total of 473 drug-naive participants were recruited, including 250 healthy control subjects, 116 patients with subclinical hypothyroidism, and 107 patients with overt hypothyroidism. Thirty-eight patients with overt hypothyroidism were assigned to receive levothyroxine treatment. The overt hypothyroidism group had decreased FGF21 levels compared with the control and subclinical hypothyroidism groups (PLevothyroxine treatment markedly attenuated the increased circulating levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), high-sensitivity C-reactive protein (hsCRP), and homeostasis model assessment index of insulin resistance (HOMA-IR) in patients with overt hypothyroidism. A significant increase in plasma FGF21 levels was observed after levothyroxine treatment (Plevothyroxine treatment (FT3: r=0.44; FT4: r=0.53; all PLevothyroxine treatment ameliorated metabolic disorders and restored the decreased circulating FGF21 levels in patients with overt hypothyroidism. The increase in FGF21 levels after levothyroxine treatment might be partly associated with the amelioration of metabolic disorders in patients with hypothyroidism. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  16. Serum insulin-like growth factor-1 levels in patients with pseudoexfoliation syndrome and glaucoma.

    Science.gov (United States)

    Dogan, Aysun Sanal; Kabatas, Naciye; Erden, Gonul; Celikay, Osman; Arzuhal, Abdullah Ercan; Gurdal, Canan

    2017-04-01

    Insulin-like growth factor-1 (IGF-1) is altered in several neurodegenerative diseases, the association between serum IGF-1 levels and glaucoma has not been evaluated. This study was designed to evaluate whether serum IGF-1 levels are different in patients with Pseudoexfoliation (PEX) with or without glaucoma. The study was conducted with 110 participants aged 65 years or older who were divided into three groups: group 1, patients with PEX syndrome; group 2, patients with PEX glaucoma; and group 3, participants without PEX or glaucoma. All participants underwent full ophthalmological examination and a detailed medical history was recorded. Patients with known neurodegenerative diseases other than PEX glaucoma were excluded. Serum IGF-1 levels were measured by automated chemiluminescent assay. Groups 1, 2, and 3 included 35, 34, and 41 patients, respectively; there were no differences regarding age, gender, or systemic disease status. There were also no statistically significant differences between the groups in terms of IGF-1 levels, which were 91.7 ± 39.1, 101.1 ± 40.