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Sample records for activation marker cd69

  1. The early activation marker CD69 regulates the expression of chemokines and CD4 T cell accumulation in intestine.

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    Katarina Radulovic

    Full Text Available Migration of naïve and activated lymphocytes is regulated by the expression of various molecules such as chemokine receptors and ligands. CD69, the early activation marker of C-type lectin domain family, is also shown to regulate the lymphocyte migration by affecting their egress from the thymus and secondary lymphoid organs. Here, we aimed to investigate the role of CD69 in accumulation of CD4 T cells in intestine using murine models of inflammatory bowel disease. We found that genetic deletion of CD69 in mice increases the expression of the chemokines CCL-1, CXCL-10 and CCL-19 in CD4(+ T cells and/or CD4(- cells. Efficient in vitro migration of CD69-deficient CD4 T cells toward the chemokine stimuli was the result of increased expression and/or affinity of chemokine receptors. In vivo CD69(-/- CD4 T cells accumulate in the intestine in higher numbers than B6 CD4 T cells as observed in competitive homing assay, dextran sodium sulphate (DSS-induced colitis and antigen-specific transfer colitis. In DSS colitis CD69(-/- CD4 T cell accumulation in colonic lamina propria (cLP was associated with increased expression of CCL-1, CXCL-10 and CCL-19 genes. Furthermore, treatment of DSS-administrated CD69(-/- mice with the mixture of CCL-1, CXCL-10 and CCL-19 neutralizing Abs significantly decreased the histopathological signs of colitis. Transfer of OT-II×CD69(-/- CD45RB(high CD4 T cells into RAG(-/- hosts induced CD4 T cell accumulation in cLP. This study showed CD69 as negative regulator of inflammatory responses in intestine as it decreases the expression of chemotactic receptors and ligands and reduces the accumulation of CD4 T cells in cLP during colitis.

  2. Activated umbilical cord blood cells from pre-term and term neonates express CD69 and synthesize IL-2 but are unable to produce IFN-gamma.

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    Cérbulo-Vázquez, Arturo; Valdés-Ramos, Roxana; Santos-Argumedo, Leopoldo

    2003-01-01

    The immune response exhibits quantitative and qualitative differences throughout human development. Both phenotypical and functional immaturity of newborn immune cellular components have been reported. We aimed to analyze possible differences in cellular activation assessed by expression of surface CD69 and cytokine production in mononuclear peripheral blood cells from premature (term (>37 weeks of gestation) neonates compared to adult donors. Ten persons from each group were selected; none was infected, immunodepressed, under medical treatment, or had any congenital abnormalities. Blood was obtained from umbilical cord of term and pre-term donors and vein punction of adults. All samples were collected in heparin and subsequently activated with PHA-L or PMA plus ionomycin at 37 degrees C for 4 h. After incubation, cells were labeled to determine CD69 expression on CD3+CD4+, CD3+CD8+, CD19+, and CD16+56+ subpopulations. Intracellular staining was performed to analyze IFN-gamma, IL-2, and CD69 in CD3+ cells. After staining, cells were analyzed by flow cytometry. We first found a substantially higher number of CD3+CD4+CD69+ cells in premature and term neonates than in adults. Secondly, percentage of CD3+CD8+, CD56+, and CD19+ cells expressing CD69 was similar among the three groups. Thirdly, expression of CD69 was higher in CD19+ cells than in CD16+56+ cells of all three groups. Regarding cytokine production, IFN-gamma was detected only in cells from adults and was consistent in all individuals analyzed. In sharp contrast, IL-2 and intracellular CD69 (iCD69) were detected in all three groups, with no significant differences among them. Induction of IL-2 and iCD69 showed that lack of response with IFN-gamma was restricted to pre-term and newborn populations. In summary, our results showed that a) CD69 is an early activation marker of both mononuclear umbilical cord and peripheral blood cells activated by a mitogenic stimulus, and b) newborn CD3+ cells probably lack

  3. Role of P-glycoprotein on CD69+CD4+ cells in the pathogenesis of proliferative lupus nephritis and non-responsiveness to immunosuppressive therapy.

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    Tsujimura, Shizuyo; Adachi, Tomoko; Saito, Kazuyoshi; Tanaka, Yoshiya

    2017-01-01

    P-glycoprotein (P-gp) expression on activated lymphocytes in systemic lupus erythematosus (SLE) plays a role in active efflux of intracellular drugs, resulting in drug resistance. The role of P-gp-expressing lymphocytes in the pathogenesis of SLE remains unclear. The aim of this study was to determine the importance of P-gp + CD4 + cells in organ manifestations in refractory SLE. The proportion of P-gp + CD4 + cells was determined by flow cytometry in peripheral blood of patients with SLE (n=116) and healthy adults (n=10). Renal biopsy specimens were examined by immunohistochemistry for P-gp expression. CD69 is a marker of CD4 cell activation. The proportion of both P-gp-expressing CD4 + cells and CD69-expressing CD4 + cells in peripheral blood was higher in SLE than control. The proportion of P-gp + CD69 + CD4 + cells correlated with Systemic Lupus Erythematosus Disease Activity Index and was higher in poor responders to corticosteroids. Furthermore, the proportion of P-gp + CD69 + CD4 + cells was significantly higher in proliferative lupus nephritis (LN) with poor response to corticosteroids. The efficacy of immunosuppressive therapy depended on the regulation of the proportion of P-gp + CD69 + CD4 + cells. Marked accumulation of P-gp + CD4 + cells in renal interstitial tissue and high proportion of peripheral P-gp + CD69 + CD4 + cells were noted in patients with proliferative LN. The results showed high proportion of P-gp + CD69 + CD4 + cells in peripheral blood and their accumulation in renal tissue in patients with proliferative LN refractory to CS therapy, suggesting that P-gp expression on activated CD4 + T cells is a potentially useful marker for refractoriness to treatment and a novel target for treatment.

  4. Induction of CD69 expression by cagPAI-positive Helicobacter pylori infection

    Institute of Scientific and Technical Information of China (English)

    Naoki Mori; Chie Ishikawa; Masachika Senba

    2011-01-01

    AIM: To investigate and elucidate the molecular mech-anism that regulates inducible expression of CD69 by Helicobacter pylori (H. pylori ) infection.METHODS: The expression levels of CD69 in a T-cell line, Jurkat, primary human peripheral blood mononu-clear cells (PBMCs), and CD4+T cells, were assessed by immunohistochemistry, reverse transcription polymerase chain reaction, and flow cytometry. Activation of CD69 promoter was detected by reporter gene. Nuclear factor (NF)-κB activation in Jurkat cells infected with H. pylori was evaluated by electrophoretic mobility shift assay. The role of NF-κB signaling in H. pylori -induced CD69 expression was analyzed using inhibitors of NF-κB and dominant-negative mutants. The isogenic mutants with disrupted cag pathogenicity island ( cagPAI) and virD4 were used to elucidate the role of cagPAI-encoding type Ⅳ secretion system and CagA in CD69 expression.RESULTS: CD69 staining was detected in mucosal lymphocytes and macrophages in specimens of pa-tients with H. pylori -positive gastritis. Although cagPAI-positive H. pylori and an isogenic mutant of virD4 induced CD69 expression, an isogenic mutant of cag-PAI failed to induce this in Jurkat cells. H. pylori also induced CD69 expression in PBMCs and CD4+T cells. The activation of the CD69 promoter by H. pylori was mediated through NF-κB. Transfection of dominant-negative mutants of IκBs, IκB kinases, and NF-κB-inducing kinase inhibited H. pylori -induced CD69 activation. Inhibitors of NF-κB suppressed H. pylori -induced CD69 mRNA expression.CONCLUSION: The results suggest that H. pylori in-duces CD69 expression through the activation of NF-κB. cagPAI might be relevant in the induction of CD69 expression in T cells. CD69 in T cells may play a role in H. pylori -induced gastritis.

  5. Quantitative and functional analysis of CD69+ T regulatory lymphocytes in patients with periodontal disease.

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    Vitales-Noyola, Marlen; Martínez-Martínez, Rita; Loyola-Rodríguez, Juan P; Baranda, Lourdes; Niño-Moreno, Perla; González-Amaro, Roberto

    2017-08-01

    Periodontal disease is chronic inflammatory process that affects the attachment structures of the teeth and constitutes a significant cause of tooth loss in adults. Although different bacteria play an important role in the triggering of this condition, the progression and severity of the disease are strongly affected by the host immune response, which is under the control of different immune regulatory mechanisms, including T regulatory (Treg) cells. The aim of this study was to assess the frequency and function of CD69 + Treg lymphocytes in patients with chronic periodontal disease. Peripheral blood samples (n = 33) and gingival tissue (n = 9) were obtained from patients with chronic periodontal disease. Blood samples from 25 healthy individuals were also studied. Levels of CD69 + Treg lymphocytes in peripheral blood and gingival tissue were determined by six-color multiparametric flow cytometry, immunofluorescence, and immunohistochemistry. The immune regulatory function of CD69 + Treg cells was tested by an in vitro assay of inhibition of lymphocyte activation. Percentages of CD69 + Treg cells were significantly higher in the peripheral blood from patients with active periodontal disease compared to healthy controls, and these percentages inversely correlated with the periodontal attachment loss. Increased numbers of these Treg cells were detected in the gingival tissue from active PD patients compared to their peripheral blood. However, the suppressive function of CD69 + Treg cells was significantly diminished in patients with periodontal disease compared to healthy controls. Our data suggest that CD69 + Treg cells seem to be another important piece in the complex immunopathogenesis of periodontal disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Reactive glia promote development of CD103+ CD69+ CD8+ T-cells through programmed cell death-ligand 1 (PD-L1).

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    Prasad, Sujata; Hu, Shuxian; Sheng, Wen S; Chauhan, Priyanka; Lokensgard, James R

    2018-06-01

    Previous work from our laboratory has demonstrated in vivo persistence of CD103 + CD69 + brain resident memory CD8 + T-cells (bT RM ) following viral infection, and that the PD-1: PD-L1 pathway promotes development of these T RM cells within the brain. Although glial cells express low basal levels of PD-L1, its expression is upregulated upon IFN-γ-treatment, and they have been shown to modulate antiviral T-cell effector responses through the PD-1: PD-L1 pathway. We performed flow cytometric analysis of cells from co-cultures of mixed glia and CD8 + T-cells obtained from wild type mice to investigate the role of glial cells in the development of bT RM . In this study, we show that interactions between reactive glia and anti-CD3 Ab-stimulated CD8 + T-cells promote development of CD103 + CD69 + CD8 + T-cells through engagement of the PD-1: PD-L1 pathway. These studies used co-cultures of primary murine glial cells obtained from WT animals along with CD8 + T-cells obtained from either WT or PD-1 KO mice. We found that αCD3 Ab-stimulated CD8 + T-cells from WT animals increased expression of CD103 and CD69 when co-cultured with primary murine glial cells. In contrast, significantly reduced expression of CD103 and CD69 was observed using CD8 + T-cells from PD-1 KO mice. We also observed that reactive glia promoted high levels of CD127, a marker of memory precursor effector cells (MPEC), on CD69 + CD8 + T-cells, which promotes development of T RM cells. Interestingly, results obtained using T-cells from PD-1 KO animals showed significantly reduced expression of CD127 on CD69 + CD8 + cells. Additionally, blocking of glial PD-L1 resulted in decreased expression of CD103, along with reduced CD127 on CD69 + CD8 + T-cells. Taken together, these results demonstrate a role for activated glia in promoting development of bT RM through the PD-1: PD-L1 pathway. © 2018 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

  7. Study of CD69 antigen expression and integrity of leukocyte cellular membrane in stored platelet concentrates following irradiation and treatment with Mirasol® PRT System.

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    Lachert, Elżbieta; Woźniak, Jolanta; Antoniewicz-Papis, Jolanta; Krzywdzińska, Agnieszka; Kubis, Jolanta; Mikołowska, Agata; Letowska, Magdalena

    2017-01-01

    Leukocytes in transfused blood components, particularly residual lymphocytes, have been shown to contribute to the occurrence of various adverse reactions. One of the most severe is transfusionassociated graft versus host disease (TA-GvHD) following transfusion of blood components contaminated with immunocompetent T lymphocytes. Irradiation is a routine method for protection against TA-GvHD. According to the literature, some pathogen reduction methods have also been proven effective for the inactivation of T lymphocytes, and so they may be considered as an alternative to irradiation. Comparison of CD69 antigen expression and the integrity of the leukocyte cellular membrane in stored platelet concentrates (PCs) following irradiation with the Gammacell 3000 Elan (Nordion Inc., Ottawa, Canada) and treatment with the Mirasol® Pathogen Reduction Technology (PRT) System (Terumo BCT, Lakewood, USA). The study included seven experiments. For each experiment we used 3 PCs, for Mirasol® PRT System treatment (M), for Gammacell 3000 Elan irradiation (R), and for the control (C). 7-amino-actinomycin D (7-AAD, Becton Dickinson, Franklin Lakes, USA) permeability was used to determine lymphocyte viability while CD69 antigen expression was the marker of lymphocyte activation. Analyses of 7-AAD and CD69 antigen expression were performed in a FACS Canto I flow cytometer (Becton Dickinson, USA). During 6 storage days, viable lymphocyte count decreased to 28% (p = 0.001) in the Mirasol® PRT System treated PCs and to 65% (p = 0.004) in the irradiated PCs. A statistically significant increase in CD69 expression in the irradiated PCs was observed; 1.3-fold on day 3 and 1.5-fold on day 6. In the Mirasol ® PRT System treated PCs, no statistically significant increase was observed. The in vitro results suggest that the Mirasol® PRT System is as effective as irradiation due to donor leukocyte inactivation capacity.

  8. Increased CD69 Expression on Peripheral Eosinophils from Patients with Food Protein-Induced Enterocolitis Syndrome.

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    Wada, Taizo; Matsuda, Yusuke; Toma, Tomoko; Koizumi, Eiko; Okamoto, Hiroyuki; Yachie, Akihiro

    2016-01-01

    Food protein-induced enterocolitis syndrome (FPIES) is an uncommon, non-IgE-mediated food allergy. We recently described a significant increase in fecal eosinophil-derived neurotoxin (EDN) after ingestion of the causative food. However, little is known about the activation status of circulating eosinophils in patients with an acute FPIES reaction. Surface CD69 expression was assessed by flow cytometry on peripheral eosinophils from 5 patients with FPIES before and after ingestion of the causative food. Fecal EDN was measured by enzyme-linked immunosorbent assay. No eosinophil activation was observed before ingestion; however, a significant increase in CD69 expression on eosinophils after an acute FIPES reaction was demonstrated in all of the patients. There was no significant change in absolute eosinophil counts in the peripheral blood. The levels of fecal EDN increased on the day after ingestion of the causative food in all patients. These results suggest that circulating eosinophils as well as eosinophils in the intestinal mucosal tissue are activated in acute FPIES reactions and might be associated with systemic immune events in FPIES. © 2016 S. Karger AG, Basel.

  9. Non-traditional CD4+CD25-CD69+ regulatory T cells are correlated to leukemia relapse after allogeneic hematopoietic stem cell transplantation.

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    Zhao, Xiao-su; Wang, Xu-hua; Zhao, Xiang-yu; Chang, Ying-jun; Xu, Lan-ping; Zhang, Xiao-hui; Huang, Xiao-jun

    2014-07-01

    Non-traditional CD4+CD25-CD69+ T cells were found to be involved in disease progression in tumor-bearing mouse models and cancer patients recently. We attempted to define whether this subset of T cells were related to leukemia relapse after allogeneic hematopoietic cell transplantation (allo-HSCT). The frequency of CD4+CD25-CD69+ T cells among the CD4+ T cell population from the bone marrow of relapsed patients, patients with positive minimal residual disease (MRD+) and healthy donors was examined by flow cytometry. The CD4+CD25-CD69+ T cells were also stained with the intracellular markers to determine the cytokine (TGF-β, IL-2 and IL-10) secretion. The results showed that the frequency of CD4+CD25-CD69 + T cells was markedly increased in patients in the relapsed group and the MRD + group compared to the healthy donor group. The percentage of this subset of T cells was significantly decreased after effective intervention treatment. We also analyzed the reconstitution of CD4+CD25-CD69+ T cells at various time points after allo-HSCT, and the results showed that this subset of T cells reconstituted rapidly and reached a relatively higher level at +60 d in patients compared to controls. The incidence of either MRD+ or relapse in patients with a high frequency of CD4+CD25-CD69+ T cells (>7%) was significantly higher than that of patients with a low frequency of CD4+CD25-CD69+ T cells at +60 d, +90 d and +270 d after transplant. However, our preliminary data indicated that CD4+CD25-CD69+ T cells may not exert immunoregulatory function via cytokine secretion. This study provides the first clinical evidence of a correlation between non-traditional CD4+CD25-CD69+ Tregs and leukemia relapse after allo-HSCT and suggests that exploration of new methods of adoptive immunotherapy may be beneficial. Further research related to regulatory mechanism behind this phenomenon would be necessary.

  10. Type II membrane protein CD69 regulates the formation of resting T-helper memory.

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    Shinoda, Kenta; Tokoyoda, Koji; Hanazawa, Asami; Hayashizaki, Koji; Zehentmeier, Sandra; Hosokawa, Hiroyuki; Iwamura, Chiaki; Koseki, Haruhiko; Tumes, Damon J; Radbruch, Andreas; Nakayama, Toshinori

    2012-05-08

    Memory T-helper (Th) lymphocytes are crucial for the maintenance of acquired immunity to eliminate infectious pathogens. We have previously demonstrated that most memory Th lymphocytes reside and rest on stromal niches of the bone marrow (BM). Little is known, however, regarding the molecular basis for the generation and maintenance of BM memory Th lymphocytes. Here we show that CD69-deficient effector CD4 T lymphocytes fail to relocate into and persist in the BM and therefore to differentiate into memory cells. Consequently, CD69-deficient CD4 T cells fail to facilitate the production of high-affinity antibodies and the generation of BM long-lived plasma cells in the late phase of immune responses. Thus, CD69 is critical for the generation and maintenance of professional memory Th lymphocytes, which can efficiently help humoral immunity in the late phase. The deficit of immunological memory in CD69-deficient mice also highlights the essential role of BM for the establishment of Th memory.

  11. Type II membrane protein CD69 regulates the formation of resting T-helper memory.

    OpenAIRE

    Shinoda, K.; Tokoyoda, K.; Hanazawa, A.; Hayashizaki, K.; Zehentmeier, S.; Hosokawa, H.; Iwamura, C.; Koseki, H.; Tumes, D. J.; Radbruch, A.; Nakayama, T.

    2012-01-01

    Memory T-helper (Th) lymphocytes are crucial for the maintenance of acquired immunity to eliminate infectious pathogens. We have previously demonstrated that most memory Th lymphocytes reside and rest on stromal niches of the bone marrow (BM). Little is known, however, regarding the molecular basis for the generation and maintenance of BM memory Th lymphocytes. Here we show that CD69-deficient effector CD4 T lymphocytes fail to relocate into and persist in the BM and therefore to differentiat...

  12. CD25 and CD69 induction by α4β1 outside-in signalling requires TCR early signalling complex proteins

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    Cimo, Ann-Marie; Ahmed, Zamal; McIntyre, Bradley W.; Lewis, Dorothy E.; Ladbury, John E.

    2013-01-01

    Distinct signalling pathways producing diverse cellular outcomes can utilize similar subsets of proteins. For example, proteins from the TCR (T-cell receptor) ESC (early signalling complex) are also involved in interferon-α receptor signalling. Defining the mechanism for how these proteins function within a given pathway is important in understanding the integration and communication of signalling networks with one another. We investigated the contributions of the TCR ESC proteins Lck (lymphocyte-specific kinase), ZAP-70 (ζ-chain-associated protein of 70 kDa), Vav1, SLP-76 [SH2 (Src homology 2)-domain-containing leukocyte protein of 76 kDa] and LAT (linker for activation of T-cells) to integrin outside-in signalling in human T-cells. Lck, ZAP-70, SLP-76, Vav1 and LAT were activated by α4β1 outside-in signalling, but in a manner different from TCR signalling. TCR stimulation recruits ESC proteins to activate the mitogen-activated protein kinase ERK (extracellular-signal-regulated kinase). α4β1 outside-in-mediated ERK activation did not require TCR ESC proteins. However, α4β1 outside-in signalling induced CD25 and co-stimulated CD69 and this was dependent on TCR ESC proteins. TCR and α4β1 outside-in signalling are integrated through the common use of TCR ESC proteins; however, these proteins display functionally distinct roles in these pathways. These novel insights into the cross-talk between integrin outside-in and TCR signalling pathways are highly relevant to the development of therapeutic strategies to overcome disease associated with T-cell deregulation. PMID:23758320

  13. Patterns of Expression of Vaginal T-Cell Activation Markers during Estrogen-Maintained Vaginal Candidiasis

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    Al-Sadeq Ameera

    2008-12-01

    Full Text Available The immunosuppressive activity of estrogen was further investigated by assessing the pattern of expression of CD25, CD28, CD69, and CD152 on vaginal T cells during estrogen-maintained vaginal candidiasis. A precipitous and significant decrease in vaginal fungal burden toward the end of week 3 postinfection was concurrent with a significant increase in vaginal lymphocyte numbers. During this period, the percentage of CD3+, CD3+CD4+, CD152+, and CD28+ vaginal T cells gradually and significantly increased. The percentage of CD3+ and CD3+CD4+ cells increased from 43% and 15% at day 0 to 77% and 40% at day 28 postinfection. Compared with 29% CD152+ vaginal T cells in naive mice, > 70% of vaginal T cells were CD152+ at day 28 postinfection. In conclusion, estrogen-maintained vaginal candidiasis results in postinfection time-dependent changes in the pattern of expression of CD152, CD28, and other T-cell markers, suggesting that T cells are subject to mixed suppression and activation signals.

  14. Re-Evaluation of Binding Properties of Recombinant Lymphocyte Receptors NKR-P1A and CD69 to Chemically Synthesized Glycans and Peptides

    Czech Academy of Sciences Publication Activity Database

    Rozbeský, Daniel; Krejzová, Jana; Křenek, Karel; Prchal, J.; Hrabal, R.; Kožíšek, Milan; Weignerová, Lenka; Fiore, M.; Dumy, P.; Renaudet, O.; Křen, Vladimír

    2014-01-01

    Roč. 15, č. 1 (2014), s. 1271-1283 E-ISSN 1422-0067 R&D Projects: GA MŠk(CZ) LD13042 Institutional support: RVO:61388971 ; RVO:61388963 Keywords : CD69 * NKR-P1A * NMR titration Subject RIV: CE - Biochemistry Impact factor: 2.862, year: 2014

  15. Deoxynojirimycin and its hexosaminyl derivatives bind to natural killer cell receptors rNKR-P1A and hCD69

    Czech Academy of Sciences Publication Activity Database

    Catelani, G.; D’Andrea, F.; Griselli, A.; Guazelli, L.; Němcová, P.; Bezouška, K.; Křenek, Karel; Křen, Vladimír

    2010-01-01

    Roč. 20, č. 15 (2010), s. 4645-4648 ISSN 0960-894X R&D Projects: GA MŠk OC 136; GA MŠk(CZ) LC06010 Institutional research plan: CEZ:AV0Z50200510 Keywords : Deoxynojirimycin * NK cells * hCD69 receptors Subject RIV: CC - Organic Chemistry Impact factor: 2.661, year: 2010

  16. Early bichemical markers of effects: Enzyme induction, oncogene activation and markers of oxidative damage

    DEFF Research Database (Denmark)

    Poulsen, Henrik E.; Loft, Steffen

    1995-01-01

    Early bichemical marker, enzyme induction, oncogene activation, oxidative damage, low-density lipoprotein......Early bichemical marker, enzyme induction, oncogene activation, oxidative damage, low-density lipoprotein...

  17. T cells in chronic lymphocytic leukemia display dysregulated expression of immune checkpoints and activation markers.

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    Palma, Marzia; Gentilcore, Giusy; Heimersson, Kia; Mozaffari, Fariba; Näsman-Glaser, Barbro; Young, Emma; Rosenquist, Richard; Hansson, Lotta; Österborg, Anders; Mellstedt, Håkan

    2017-03-01

    Chronic lymphocytic leukemia is characterized by impaired immune functions largely due to profound T-cell defects. T-cell functions also depend on co-signaling receptors, inhibitory or stimulatory, known as immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1). Here we analyzed the T-cell phenotype focusing on immune checkpoints and activation markers in chronic lymphocytic leukemia patients (n=80) with different clinical characteristics and compared them to healthy controls. In general, patients had higher absolute numbers of CD3 + cells and the CD8 + subset was particularly expanded in previously treated patients. Progressive patients had higher numbers of CD4 + and CD8 + cells expressing PD-1 compared to healthy controls, which was more pronounced in previously treated patients ( P =0.0003 and P =0.001, respectively). A significant increase in antigen-experienced T cells was observed in patients within both the CD4 + and CD8 + subsets, with a significantly higher PD-1 expression. Higher numbers of CD4 + and CD8 + cells with intracellular CTLA-4 were observed in patients, as well as high numbers of proliferating (Ki67 + ) and activated (CD69 + ) CD4 + and CD8 + cells, more pronounced in patients with active disease. The numbers of Th1, Th2, Th17 and regulatory T cells were substantially increased in patients compared to controls ( P leukemia T cells display increased expression of immune checkpoints, abnormal subset distribution, and a higher proportion of proliferating cells compared to healthy T cells. Disease activity and previous treatment shape the T-cell profile of chronic lymphocytic leukemia patients in different ways. Copyright© Ferrata Storti Foundation.

  18. Inactivated probiotic Bacillus coagulans GBI-30 induces complex immune activating, anti-inflammatory, and regenerative markers in vitro

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    Jensen, Gitte S; Cash, Howard A; Farmer, Sean; Keller, David

    2017-01-01

    Objective The aim of this study was to document the immune activating and anti-inflammatory effects of inactivated probiotic Bacillus coagulans GBI-30, 6086 (Staimune™) cells on human immune cells in vitro. Methods In vitro cultures of human peripheral blood mononuclear cells (PBMC) from healthy blood donors were treated with inactivated B. coagulans GBI-30, 6086 cells for 24 hours. After incubation, the PBMC were stained with fluorochrome-labeled monoclonal antibodies for CD3, CD56, and CD69 to monitor cellular activation by flow cytometry. The culture supernatants were tested for cytokine profile using a 27-plex Luminex array, including pro- and anti-inflammatory cytokines, chemokines, and growth factors. Results Inactivated B. coagulans GBI-30, 6086 cells induced the CD69 early activation marker on CD3+ CD56− T lymphocytes, CD3+ CD56+ NKT cells, CD3−CD56+ NK cells, and also some cells within the CD3−CD56− non-T non-NK cell subset. Culture supernatants showed robust increases in the immune-activating cytokines IL-1β, IL-6, IL-17A, and TNF-α. IFN-γ levels were increased, along with three chemokines, MCP-1, MIP-1α, and MIP-1β. The two anti-inflammatory cytokines IL-1ra and IL-10 showed increases, as well as the G-CSF growth factor involved in repair and stem cell biology. In contrast, GM-CSF levels showed a mild decrease, showing a highly selective growth factor response. Conclusion The inactivated B. coagulans GBI-30, 6086 cells activated human immune cells and altered the production of both immune activating and anti-inflammatory cytokines and chemokines. Of special importance is the novel demonstration of a selective upregulation of the G-CSF growth factor involved in postinjury and postinflammation repair and regeneration. This suggests that important immunogenic cell wall components, such as lipoteichoic acid, are undamaged after the inactivation and retain the complex beneficial biological activities previously demonstrated for the cell walls

  19. Inactivated probiotic Bacillus coagulans GBI-30 induces complex immune activating, anti-inflammatory, and regenerative markers in vitro

    Directory of Open Access Journals (Sweden)

    Jensen GS

    2017-08-01

    Full Text Available Gitte S Jensen,1 Howard A Cash,2 Sean Farmer,2 David Keller2 1NIS Labs, Esplanade, Klamath Falls, OR, USA, 2Ganeden Biotech Inc., Landerbrook Drive Suite, Mayfield Heights, OH, USA Objective: The aim of this study was to document the immune activating and anti-inflammatory effects of inactivated probiotic Bacillus coagulans GBI-30, 6086 (Staimune™ cells on human immune cells in vitro.Methods: In vitro cultures of human peripheral blood mononuclear cells (PBMC from healthy blood donors were treated with inactivated B. coagulans GBI-30, 6086 cells for 24 hours. After incubation, the PBMC were stained with fluorochrome-labeled monoclonal antibodies for CD3, CD56, and CD69 to monitor cellular activation by flow cytometry. The culture supernatants were tested for cytokine profile using a 27-plex Luminex array, including pro- and anti-inflammatory cytokines, chemokines, and growth factors.Results: Inactivated B. coagulans GBI-30, 6086 cells induced the CD69 early activation marker on CD3+ CD56− T lymphocytes, CD3+ CD56+ NKT cells, CD3−CD56+ NK cells, and also some cells within the CD3−CD56− non-T non-NK cell subset. Culture supernatants showed robust increases in the immune-activating cytokines IL-1β, IL-6, IL-17A, and TNF-α. IFN-γ levels were increased, along with three chemokines, MCP-1, MIP-1α, and MIP-1β. The two anti-inflammatory cytokines IL-1ra and IL-10 showed increases, as well as the G-CSF growth factor involved in repair and stem cell biology. In contrast, GM-CSF levels showed a mild decrease, showing a highly selective growth factor response.Conclusion: The inactivated B. coagulans GBI-30, 6086 cells activated human immune cells and altered the production of both immune activating and anti-inflammatory cytokines and chemokines. Of special importance is the novel demonstration of a selective upregulation of the G-CSF growth factor involved in postinjury and postinflammation repair and regeneration. This suggests that

  20. Inactivated probiotic Bacillus coagulans GBI-30 induces complex immune activating, anti-inflammatory, and regenerative markers in vitro.

    Science.gov (United States)

    Jensen, Gitte S; Cash, Howard A; Farmer, Sean; Keller, David

    2017-01-01

    The aim of this study was to document the immune activating and anti-inflammatory effects of inactivated probiotic Bacillus coagulans GBI-30, 6086 (Staimune™) cells on human immune cells in vitro. In vitro cultures of human peripheral blood mononuclear cells (PBMC) from healthy blood donors were treated with inactivated B. coagulans GBI-30, 6086 cells for 24 hours. After incubation, the PBMC were stained with fluorochrome-labeled monoclonal antibodies for CD3, CD56, and CD69 to monitor cellular activation by flow cytometry. The culture supernatants were tested for cytokine profile using a 27-plex Luminex array, including pro- and anti-inflammatory cytokines, chemokines, and growth factors. Inactivated B. coagulans GBI-30, 6086 cells induced the CD69 early activation marker on CD3 + CD56 - T lymphocytes, CD3 + CD56 + NKT cells, CD3 - CD56 + NK cells, and also some cells within the CD3 - CD56 - non-T non-NK cell subset. Culture supernatants showed robust increases in the immune-activating cytokines IL-1β, IL-6, IL-17A, and TNF-α. IFN-γ levels were increased, along with three chemokines, MCP-1, MIP-1α, and MIP-1β. The two anti-inflammatory cytokines IL-1ra and IL-10 showed increases, as well as the G-CSF growth factor involved in repair and stem cell biology. In contrast, GM-CSF levels showed a mild decrease, showing a highly selective growth factor response. The inactivated B. coagulans GBI-30, 6086 cells activated human immune cells and altered the production of both immune activating and anti-inflammatory cytokines and chemokines. Of special importance is the novel demonstration of a selective upregulation of the G-CSF growth factor involved in postinjury and postinflammation repair and regeneration. This suggests that important immunogenic cell wall components, such as lipoteichoic acid, are undamaged after the inactivation and retain the complex beneficial biological activities previously demonstrated for the cell walls from live B. coagulans GBI-30, 6086

  1. Cooperation between subunits is essential for high-affinity binding of N-acetyl-D-hexosamines to dimeric soluble and dimeric cellular forms of human CD69

    Czech Academy of Sciences Publication Activity Database

    Kavan, Daniel; Kubíčková, M.; Bílý, J.; Vaněk, O.; Hofbauerová, Kateřina; Mrázek, H.; Rozbeský, Daniel; Bojarová, Pavla; Křen, Vladimír; Žídek, L.; Sklenář, V.; Bezouška, K.

    2010-01-01

    Roč. 49, č. 19 (2010), s. 4060-4067 ISSN 0006-2960 R&D Projects: GA MŠk 1M0505; GA ČR GA303/09/0477; GA ČR GD305/09/H008; GA ČR GP203/09/P024 Institutional research plan: CEZ:AV0Z50200510 Keywords : cd 69 * N-acetyl-D-hexosamines * lymphocyte Subject RIV: CE - Biochemistry Impact factor: 3.226, year: 2010

  2. Peroxidase activity as a marker for estrogenicity

    International Nuclear Information System (INIS)

    Levy, J.; Liel, Y.; Glick, S.M.

    1981-01-01

    We examined the possibility that peroxidase activity might be a marker for estrogen activity in established estrogen-dependent tissues: dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumours and human breast cancer. In DMBA-induced tumours undergoing regression after ovariectomy or tamoxifen treatment, tumour size decreased by 50%, estradiol receptors (ER) and progesterone receptors (PgR) decreased by 25 and 20%, respectively, but peroxidase activity paradoxically increased six- to sevenfold. In DMBA tumours stimulated by estradiol treatment or by the cessation of tamoxifen administration in intact rats, tumour size increased threefold. ER and PgR increased two- and threefold, respectively, while peroxidase activity decreased 50%. These data indicate an inverse relation between tumour growth, ER and PgR on the one hand, and peroxidase activity on the other. In the human breast cancers there was a singificant negative relation between the presence of ER and peroxidase activity. By using a calibrated Sephadex G-100 column it was shown that uterine peroxidase differs in molecular weight from the peroxidase of rat mammary tumours and that of human breast cancer. (author)

  3. Established and emerging biological activity markers of inflammatory bowel disease

    DEFF Research Database (Denmark)

    Nielsen, O H; Vainer, B; Madsen, S M

    2000-01-01

    Assessment of disease activity in inflammatory bowel disease (IBD), i.e., ulcerative colitis (UC) and Crohn's disease (CD), is done using clinical parameters and various biological disease markers. Ideally, a disease marker must: be able to identify individuals at risk of a given disorder......, be disease specific, mirror the disease activity and, finally, be easily applicable for routine clinical purposes. However, no such disease markers have yet been identified for IBD. In this article, classical disease markers including erythrocyte sedimentation rate, acute phase proteins (especially...... orosomucoid and CRP), leukocyte and platelet counts, albumin, neopterin, and beta2-microglobulin will be reviewed together with emerging disease markers such as antibodies of the ANCA/ASCA type, cytokines (e.g., IL-1, IL-2Ralpha, IL-6, IL-8, TNF-alpha, and TNF-alpha receptors) and with various adhesion...

  4. Established and emerging biological activity markers of inflammatory bowel disease

    DEFF Research Database (Denmark)

    Nielsen, O H; Vainer, B; Madsen, S M

    2000-01-01

    orosomucoid and CRP), leukocyte and platelet counts, albumin, neopterin, and beta2-microglobulin will be reviewed together with emerging disease markers such as antibodies of the ANCA/ASCA type, cytokines (e.g., IL-1, IL-2Ralpha, IL-6, IL-8, TNF-alpha, and TNF-alpha receptors) and with various adhesion......Assessment of disease activity in inflammatory bowel disease (IBD), i.e., ulcerative colitis (UC) and Crohn's disease (CD), is done using clinical parameters and various biological disease markers. Ideally, a disease marker must: be able to identify individuals at risk of a given disorder......, be disease specific, mirror the disease activity and, finally, be easily applicable for routine clinical purposes. However, no such disease markers have yet been identified for IBD. In this article, classical disease markers including erythrocyte sedimentation rate, acute phase proteins (especially...

  5. Markers

    Science.gov (United States)

    Healthy Schools Network, Inc., 2011

    2011-01-01

    Dry erase whiteboards come with toxic dry erase markers and toxic cleaning products. Dry erase markers labeled "nontoxic" are not free of toxic chemicals and can cause health problems. Children are especially vulnerable to environmental health hazards; moreover, schools commonly have problems with indoor air pollution, as they are more densely…

  6. Expression of the activation antigen CD69 predicts functionality of in vitro expanded peripheral blood mononuclear cells (PBMC) from healthy donors and HIV-infected patients

    DEFF Research Database (Denmark)

    Nielsen, S D; Afzelius, P; Ersbøll, A K

    1998-01-01

    Gene therapy for AIDS necessitates harvest and expansion of PBMC from HIV-infected patients. We expanded PBMC from healthy blood donors and HIV-infected patients for up to 14 days using four expansion protocols: 3 days of phytohaemagglutinin (PHA) stimulation, continuous PHA stimulation, 3 days...... examined for apoptosis. Only a minor fraction was primed for apoptosis, and this fraction could be significantly reduced by addition of IL-2 to the culture medium (P

  7. Increased expression of T-helper cell activation markers in ...

    African Journals Online (AJOL)

    Ehab

    expression of these activation markers would be of value in monitoring asthma severity and the response to ... Key words: Children, atopic asthma, T-helper cell subsets, glucocorticoid inhalation, lower respiratory infections, CD45RO ...... budesonide, and placebo on mucosal inflammation and clinical indices in mild asthma.

  8. Platelet activation and inflammation markers as emerging risk ...

    African Journals Online (AJOL)

    Platelet activation and inflammation markers were assessed by measuring plasma levels of sP-selectin, platelet factor 4 (PF4), IL-6 and tumor necrosis factor alpha (TNF-α). Results: HIV infected patients had higher levels of sP- selectin, PF4 and IL-6 than uninfected controls (p<0.001). ART naïve subjects had higher levels ...

  9. Association of neopterin as a marker of immune system activation and juvenile rheumatoid arthritis activity

    Directory of Open Access Journals (Sweden)

    Mones M. Abu Shady

    2015-07-01

    Conclusion: The elevation of plasma neopterin concentrations in early JIA patients may indicate stimulation of immune response. Serum neopterin can be used as a sensitive marker for assaying background inflammation and disease activity score in JIA patients.

  10. Bidirectional Prospective Associations Between Cardiac Autonomic Activity and Inflammatory Markers.

    Science.gov (United States)

    Hu, Mandy Xian; Lamers, Femke; Neijts, Melanie; Willemsen, Gonneke; de Geus, Eco J C; Penninx, Brenda W J H

    2018-06-01

    Autonomic nervous system (ANS) imbalance has been cross-sectionally associated with inflammatory processes. Longitudinal studies are needed to shed light on the nature of this relationship. We examined cross-sectional and bidirectional prospective associations between cardiac autonomic measures and inflammatory markers. Analyses were conducted with baseline (n = 2823), 2-year (n = 2099), and 6-year (n = 1774) data from the Netherlands Study of Depression and Anxiety. To compare the pattern of results, prospective analyses with ANS (during sleep, leisure time, and work) and inflammation were conducted in two data sets from the Netherlands Twin Register measured for 4.9 years (n = 356) and 5.4 years (n = 472). Autonomic nervous system measures were heart rate (HR) and respiratory sinus arrhythmia (RSA). Inflammatory markers were C-reactive protein (CRP) and interleukin (IL)-6. The Netherlands Study of Depression and Anxiety results showed that higher HR and lower RSA were cross-sectionally significantly associated with higher inflammatory levels. Higher HR predicted higher levels of CRP (B = .065, p < .001) and IL-6 (B = .036, p = .014) at follow-up. Higher CRP levels predicted lower RSA (B = -.024, p = .048) at follow-up. The Netherlands Twin Register results confirmed that higher HR was associated with higher CRP and IL-6 levels 4.9 years later. Higher IL-6 levels predicted higher HR and lower RSA at follow-up. Autonomic imbalance is associated with higher levels of inflammation. Independent data from two studies converge in evidence that higher HR predicts subsequent higher levels of CRP and IL-6. Inflammatory markers may also predict future ANS activity, but evidence for this was less consistent.

  11. Fingolimod modulates microglial activation to augment markers of remyelination

    Directory of Open Access Journals (Sweden)

    Baker David

    2011-07-01

    Full Text Available Abstract Introduction Microglial activation in multiple sclerosis has been postulated to contribute to long-term neurodegeneration during disease. Fingolimod has been shown to impact on the relapsing remitting phase of disease by modulating autoreactive T-cell egress from lymph organs. In addition, it is brain penetrant and has been shown to exert multiple effects on nervous system cells. Methods In this study, the impact of fingolimod and other sphingosine-1-phosphate receptor active molecules following lysophosphotidyl choline-induced demyelination was examined in the rat telencephalon reaggregate, spheroid cell culture system. The lack of immune system components allowed elucidation of the direct effects of fingolimod on CNS cell types in an organotypic situation. Results Following demyelination, fingolimod significantly augmented expression of myelin basic protein in the remyelination phase. This increase was not associated with changes in neurofilament levels, indicating de novo myelin protein expression not associated with axonal branching. Myelin wrapping was confirmed morphologically using confocal and electron microscopy. Increased remyelination was associated with down-regulation of microglial ferritin, tumor necrosis factor alpha and interleukin 1 during demyelination when fingolimod was present. In addition, nitric oxide metabolites and apoptotic effectors caspase 3 and caspase 7 were reduced during demyelination in the presence of fingolimod. The sphingosine-1-phosphate receptor 1 and 5 agonist BAF312 also increased myelin basic protein levels, whereas the sphingosine-1-phosphate receptor 1 agonist AUY954 failed to replicate this effect on remyelination. Conclusions The results presented indicate that modulation of S1P receptors can ameliorate pathological effectors associated with microglial activation leading to a subsequent increase in protein and morphological markers of remyelination. In addition, sphingosine-1-phosphate

  12. Active MMPs captured by alpha2Macroglobulin as a marker of disease activity in rheumatoid arthritis

    NARCIS (Netherlands)

    Tchetverikov, I.; Verzijl, N.; Huizinga, T.W.J.; TeKoppele, J.M.; Hanemaaijer, R.; Groot, J. de

    2003-01-01

    Objective. The aim of the present study was to analyze α2Macroglobulin/MMP (α2M/MMP) complex formation and to investigate whether MMP activity in α2M/MMP complexes in serum can be used as a disease marker in rheumatoid arthritis (RA). Methods. High and low molecular weight (H/LMW) substrates and

  13. Serum Inflammatory Mediators as Markers of Human Lyme Disease Activity

    Science.gov (United States)

    Soloski, Mark J.; Crowder, Lauren A.; Lahey, Lauren J.; Wagner, Catriona A.

    2014-01-01

    Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low) of acute Lyme patients with distinct cytokine signatures that also differed significantly (pLyme disease (p = 0.01) and the decrease correlates with chemokine levels (p = 0.0375). The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations. PMID:24740099

  14. Serum inflammatory mediators as markers of human Lyme disease activity.

    Directory of Open Access Journals (Sweden)

    Mark J Soloski

    Full Text Available Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low of acute Lyme patients with distinct cytokine signatures that also differed significantly (p<0.0005 in symptom presentation. In particular, the T cell chemokines CXCL9 (MIG, CXCL10 (IP-10 and CCL19 (MIP3B were coordinately increased in the mediator-high group and levels of these chemokines could be associated with seroconversion status and elevated liver function tests (p = 0.027 and p = 0.021 respectively. There was also upregulation of acute phase proteins including CRP and serum amyloid A. Consistent with the role of CXCL9/CXCL10 in attracting immune cells to the site of infection, CXCR3+ CD4 T cells are reduced in the blood of early acute Lyme disease (p = 0.01 and the decrease correlates with chemokine levels (p = 0.0375. The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations.

  15. Identification of laboratory markers of disease activity in rheumatoid arthritis abstract objective

    International Nuclear Information System (INIS)

    Naqi, N.; Ahmed, T.A.; Malik, J.M.

    2012-01-01

    To identify the laboratory markers of disease activity, by finding relationship of biochemical markers with clinical disease activity measurement in patients suffering from rheumatoid arthritis (RA). Study Design: Cross sectional analytical study. Place and duration of study: Department of Immunology, Armed Forces Institute of Pathology (AFIP), Rawalpindi from January 2009 to January 2010 in collaboration with Fauji Foundation Hospital and Military Hospital Rawalpindi. Patients and Methods: One hundred patients diagnosed as having rheumatoid arthritis (RA) as per American college of Rheumatology (ACR) revised criteria 1987 and fulfilling the study's inclusion criteria were studied. These patients were assessed clinically according to Simplified Disease Activity Index (SDAI) and divided into three groups which were mild, moderate and severe based on disease activity. These three groups were then assessed for disease activity by Rheumatoid factor (RA factor), Anti Cyclic Citrullinated Peptide antibodies (anti CCP antibodies), Erythrocyte Sedimentation Rate (ESR) and C- Reactive Proteins (CRP). The association of these laboratory markers with three groups of disease activity was analyzed to detect most sensitive disease activity markers for RA. Results: All the assessed laboratory markers that are RA factor, anti CCP antibodies, ESR and CRP are directly related with RA disease activity and any of them can be used to assess disease activity in RA. However a combination of the tests, analyzed in this study markers maybe used for better prediction of disease activity Conclusion: The identification of the laboratory markers of disease activity may help physician to diagnose aggressive disease early and evaluate prognosis in RA patients. (author)

  16. 78 FR 21008 - Proposed Information Collection (NCA Customer Satisfaction Surveys (Headstone/Marker) Activity...

    Science.gov (United States)

    2013-04-08

    ... Customer Satisfaction Surveys (Headstone/Marker) Activity: Comment Request AGENCY: National Cemetery... estimates relating to customer satisfaction surveys involving the National Cemetery Administration (NCA.... Title: Generic Clearance for NCA, and IG Customer Satisfaction Surveys. OMB Control Number: 2900-0571...

  17. Epithelial cell proliferative activity of Barrett's esophagus : methodology and correlation with traditional cancer risk markers

    NARCIS (Netherlands)

    Peters, FTM; Ganesh, S; Kuipers, EJ; De Jager-Krikken, A; Karrenbeld, A; Harms, Geert; Sluiter, WJ; Koudstaal, J; Klinkenberg-Knol, EC; Lamers, CBHW; Kleibeuker, JH

    Barrett's esophagus (BE) is a premalignant condition, due to chronic gastroesophageal reflux. Effective antireflux therapy may diminish cancer risk. To evaluate this option an intermediate marker is needed. We developed a methodology for measurement of epithelial cell proliferative activity of

  18. Does physical activity during pregnancy adversely influence markers of the metabolic syndrome in adult offspring?

    DEFF Research Database (Denmark)

    Danielsen, Inge; Granström, Charlotta; Rytter, Dorte

    2013-01-01

    It is unknown whether physical activity during pregnancy (PA) has long-term impact on the metabolic profile of the offspring. We investigated associations of PA with markers of the metabolic syndrome (MS) in 20y old offspring.......It is unknown whether physical activity during pregnancy (PA) has long-term impact on the metabolic profile of the offspring. We investigated associations of PA with markers of the metabolic syndrome (MS) in 20y old offspring....

  19. Association of neopterin as a marker of immune system activation and juvenile rheumatoid arthritis activity

    Directory of Open Access Journals (Sweden)

    Mones M. Abu Shady

    2015-08-01

    Full Text Available OBJECTIVE: To evaluate neopterin plasma concentrations in patients with active juvenile idiopathic arthritis (JIA and correlate them with disease activity.METHODS: Sixty patients diagnosed as active JIA, as well as another 60 apparently healthy age- and gender-matched children as controls, were recruited from the Pediatrics Allergy and Immunology Clinic, Ain Shams University. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score 27 (JADAS-27. Laboratory investigations were performed for all patients, including determination of hemoglobin concentration (Hgb, erythrocyte sedimentation rate (ESR, and C-reactive protein. Serum concentrations of tumor necrosis factor-alpha (TNF-a, interleukin-6 (IL-6, monocyte chemoattractant protein-1 (MCP-1, and neopterin were measured.RESULTS: Significant differences were found between JIA patients and controls with regard to the mean levels of Hgb, ESR, TNF-a, IL-6, and MCP-1 (p 0.05. Multiple linear regression analysis showed that JADAS- 27 and ESR were the main variables associated with serum neopterin in JIA patients (p < 0.05.CONCLUSION: The elevation of plasma neopterin concentrations in early JIA patients may indicate stimulation of immune response. Serum neopterin can be used as a sensitive marker for assaying background inflammation and disease activity score in JIA patients.

  20. Phytochelatin synthase activity as a marker of metal pollution

    Energy Technology Data Exchange (ETDEWEB)

    Zitka, Ondrej; Krystofova, Olga; Sobrova, Pavlina [Department of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno (Czech Republic); Adam, Vojtech [Department of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno (Czech Republic); Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-616 00 Brno (Czech Republic); Zehnalek, Josef; Beklova, Miroslava [Department of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno (Czech Republic); Kizek, Rene, E-mail: kizek@sci.muni.cz [Department of Chemistry and Biochemistry, Faculty of Agronomy, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno (Czech Republic); Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-616 00 Brno (Czech Republic)

    2011-08-30

    Highlights: {yields} New tool for determination of phytochelatin synthase activity. {yields} The optimization of experimental condition for determination of the enzyme activity. {yields} First evaluation of K{sub m} for the enzyme. {yields} The effects of cadmium (II) not only on the activity of the enzyme but also on K{sub m}. -- Abstract: The synthesis of phytochelatins is catalyzed by {gamma}-Glu-Cys dipeptidyl transpeptidase called phytochelatin synthase (PCS). Aim of this study was to suggest a new tool for determination of phytochelatin synthase activity in the tobacco BY-2 cells treated with different concentrations of the Cd(II). After the optimization steps, an experiment on BY-2 cells exposed to different concentrations of Cd(NO{sub 3}){sub 2} for 3 days was performed. At the end of the experiment, cells were harvested and homogenized. Reduced glutathione and cadmium (II) ions were added to the cell suspension supernatant. These mixtures were incubated at 35 {sup o}C for 30 min and analysed using high performance liquid chromatography coupled with electrochemical detector (HPLC-ED). The results revealed that PCS activity rises markedly with increasing concentration of cadmium (II) ions. The lowest concentration of the toxic metal ions caused almost three fold increase in PCS activity as compared to control samples. The activity of PCS (270 fkat) in treated cells was more than seven times higher in comparison to control ones. K{sub m} for PCS was estimated as 2.3 mM.

  1. Phytochelatin synthase activity as a marker of metal pollution

    International Nuclear Information System (INIS)

    Zitka, Ondrej; Krystofova, Olga; Sobrova, Pavlina; Adam, Vojtech; Zehnalek, Josef; Beklova, Miroslava; Kizek, Rene

    2011-01-01

    Highlights: → New tool for determination of phytochelatin synthase activity. → The optimization of experimental condition for determination of the enzyme activity. → First evaluation of K m for the enzyme. → The effects of cadmium (II) not only on the activity of the enzyme but also on K m . -- Abstract: The synthesis of phytochelatins is catalyzed by γ-Glu-Cys dipeptidyl transpeptidase called phytochelatin synthase (PCS). Aim of this study was to suggest a new tool for determination of phytochelatin synthase activity in the tobacco BY-2 cells treated with different concentrations of the Cd(II). After the optimization steps, an experiment on BY-2 cells exposed to different concentrations of Cd(NO 3 ) 2 for 3 days was performed. At the end of the experiment, cells were harvested and homogenized. Reduced glutathione and cadmium (II) ions were added to the cell suspension supernatant. These mixtures were incubated at 35 o C for 30 min and analysed using high performance liquid chromatography coupled with electrochemical detector (HPLC-ED). The results revealed that PCS activity rises markedly with increasing concentration of cadmium (II) ions. The lowest concentration of the toxic metal ions caused almost three fold increase in PCS activity as compared to control samples. The activity of PCS (270 fkat) in treated cells was more than seven times higher in comparison to control ones. K m for PCS was estimated as 2.3 mM.

  2. Telomerase activity as a marker for malignancy in feline tissues.

    Science.gov (United States)

    Cadile, C D; Kitchell, B E; Biller, B J; Hetler, E R; Balkin, R G

    2001-10-01

    To establish the diagnostic significance of the telomeric repeat amplification protocol (TRAP) assay in detecting feline malignancies. Solid tissue specimens collected from 33 client-owned cats undergoing diagnostic or therapeutic procedures at the University of Illinois Veterinary Medical Teaching Hospital between July 1997 and September 1999 and an additional 20 tissue samples were collected from 3 clinically normal control cats euthanatized at the conclusion of an unrelated study. The TRAP assay was used for detection of telomerase activity. Each result was compared to its respective histopathologic diagnosis. Twenty-nine of 31 malignant and 1 of 22 benign or normal tissue samples had telomerase activity, indicating 94% sensitivity and 95% specificity of the TRAP assay in our laboratory. The diagnostic significance of telomerase activity has been demonstrated in humans and recently in dogs by our laboratory. We tested feline samples to determine whether similar patterns of telomerase activity exist. On the basis of our results, the TRAP assay may be clinically useful in providing a rapid diagnosis of malignancy in cats. The telomerase enzyme may also serve as a therapeutic target in feline tumors.

  3. Monocyte-Derived Signals Activate Human Natural Killer Cells in Response to Leishmania Parasites

    Science.gov (United States)

    Messlinger, Helena; Sebald, Heidi; Heger, Lukas; Dudziak, Diana; Bogdan, Christian; Schleicher, Ulrike

    2018-01-01

    Activated natural killer (NK) cells release interferon (IFN)-γ, which is crucial for the control of intracellular pathogens such as Leishmania. In contrast to experimental murine leishmaniasis, the human NK cell response to Leishmania is still poorly characterized. Here, we investigated the interaction of human blood NK cells with promastigotes of different Leishmania species (Leishmania major, Leishmania mexicana, Leishmania infantum, and Leishmania donovani). When peripheral blood mononuclear cells or purified NK cells and monocytes (all derived from healthy blood donors from Germany without a history of leishmaniasis) were exposed to promastigotes, NK cells showed increased surface expression of the activation marker CD69. The extent of this effect varied depending on the Leishmania species; differences between dermotropic and viscerotropic L. infantum strains were not observed. Upregulation of CD69 required direct contact between monocytes and Leishmania and was partly inhibitable by anti-interleukin (IL)-18. Unexpectedly, IL-18 was undetectable in most of the supernatants (SNs) of monocyte/parasite cocultures. Confocal fluorescence microscopy of non-permeabilized cells revealed that Leishmania-infected monocytes trans-presented IL-18 to NK cells. Native, but not heat-treated SNs of monocyte/Leishmania cocultures also induced CD69 on NK cells, indicating the involvement of a soluble heat-labile factor other than IL-18. A role for the NK cell-activating cytokines IL-1β, IL-2, IL-12, IL-15, IL-21, and IFN-α/β was excluded. The increase of CD69 was not paralleled by NK cell IFN-γ production or enhanced cytotoxicity. However, prior exposure of NK cells to Leishmania parasites synergistically increased their IFN-γ release in response to IL-12, which was dependent on endogenous IL-18. CD1c+ dendritic cells were identified as possible source of Leishmania-induced IL-12. Finally, we observed that direct contact between Leishmania and NK cells reduced the

  4. Monocyte-Derived Signals Activate Human Natural Killer Cells in Response to Leishmania Parasites

    Directory of Open Access Journals (Sweden)

    Helena Messlinger

    2018-01-01

    Full Text Available Activated natural killer (NK cells release interferon (IFN-γ, which is crucial for the control of intracellular pathogens such as Leishmania. In contrast to experimental murine leishmaniasis, the human NK cell response to Leishmania is still poorly characterized. Here, we investigated the interaction of human blood NK cells with promastigotes of different Leishmania species (Leishmania major, Leishmania mexicana, Leishmania infantum, and Leishmania donovani. When peripheral blood mononuclear cells or purified NK cells and monocytes (all derived from healthy blood donors from Germany without a history of leishmaniasis were exposed to promastigotes, NK cells showed increased surface expression of the activation marker CD69. The extent of this effect varied depending on the Leishmania species; differences between dermotropic and viscerotropic L. infantum strains were not observed. Upregulation of CD69 required direct contact between monocytes and Leishmania and was partly inhibitable by anti-interleukin (IL-18. Unexpectedly, IL-18 was undetectable in most of the supernatants (SNs of monocyte/parasite cocultures. Confocal fluorescence microscopy of non-permeabilized cells revealed that Leishmania-infected monocytes trans-presented IL-18 to NK cells. Native, but not heat-treated SNs of monocyte/Leishmania cocultures also induced CD69 on NK cells, indicating the involvement of a soluble heat-labile factor other than IL-18. A role for the NK cell-activating cytokines IL-1β, IL-2, IL-12, IL-15, IL-21, and IFN-α/β was excluded. The increase of CD69 was not paralleled by NK cell IFN-γ production or enhanced cytotoxicity. However, prior exposure of NK cells to Leishmania parasites synergistically increased their IFN-γ release in response to IL-12, which was dependent on endogenous IL-18. CD1c+ dendritic cells were identified as possible source of Leishmania-induced IL-12. Finally, we observed that direct contact between Leishmania and NK cells

  5. Physical Activity, Physical Performance, and Biological Markers of Health among Sedentary Older Latinos

    Directory of Open Access Journals (Sweden)

    Gerardo Moreno

    2014-01-01

    Full Text Available Background. Physical activity is associated with better physical health, possibly by changing biological markers of health such as waist circumference and inflammation, but these relationships are unclear and even less understood among older Latinos—a group with high rates of sedentary lifestyle. Methods. Participants were 120 sedentary older Latino adults from senior centers. Community-partnered research methods were used to recruit participants. Inflammatory (C-reactive protein and metabolic markers of health (waist circumference, HDL-cholesterol, triglycerides, insulin, and glucose, physical activity (Yale physical activity survey, and physical performance (short physical performance NIA battery were measured at baseline and 6-month followup. Results. Eighty percent of the sample was female. In final adjusted cross-sectional models, better physical activity indices were associated with faster gait speed (P<0.05. In adjusted longitudinal analyses, change in self-reported physical activity level correlated inversely with change in CRP (β=-0.05; P=0.03 and change in waist circumference (β=-0.16; P=0.02. Biological markers of health did not mediate the relationship between physical activity and physical performance. Conclusion. In this community-partnered study, higher physical activity was associated with better physical performance in cross-sectional analyses. In longitudinal analysis, increased physical activity was associated with improvements in some metabolic and inflammatory markers of health.

  6. Physical Activity and Adiposity Markers at Older Ages: Accelerometer Vs Questionnaire Data

    Science.gov (United States)

    Sabia, Séverine; Cogranne, Pol; van Hees, Vincent T.; Bell, Joshua A.; Elbaz, Alexis; Kivimaki, Mika; Singh-Manoux, Archana

    2015-01-01

    Objective Physical activity is critically important for successful aging, but its effect on adiposity markers at older ages is unclear as much of the evidence comes from self-reported data on physical activity. We assessed the associations of questionnaire-assessed and accelerometer-assessed physical activity with adiposity markers in older adults. Design/Setting/Participants This was a cross-sectional study on 3940 participants (age range 60-83 years) of the Whitehall II study who completed a 20-item physical activity questionnaire and wore a wrist-mounted accelerometer for 9 days in 2012 and 2013. Measurements Total physical activity was estimated using metabolic equivalent hours/week for the questionnaire and mean acceleration for the accelerometer. Time spent in moderate-and-vigorous physical activity (MVPA) was also assessed by questionnaire and accelerometer. Adiposity assessment included body mass index, waist circumference, and fat mass index. Fat mass index was calculated as fat mass/height² (kg/m²), with fat mass estimated using bioimpedance. Results Greater total physical activity was associated with lower adiposity for all adiposity markers in a dose-response manner. In men, the strength of this association was 2.4 to 2.8 times stronger with the accelerometer than with questionnaire data. In women, it was 1.9 to 2.3 times stronger. For MVPA, questionnaire data in men suggested no further benefit for adiposity markers past 1 hour/week of activity. This was not the case for accelerometer-assessed MVPA where, for example, compared with men undertaking physical activity with adiposity markers in older adults was stronger when physical activity was assessed by accelerometer compared with questionnaire, suggesting that physical activity might be more important for adiposity than previously estimated. PMID:25752539

  7. Trichloroethylene and Its Oxidative Metabolites Enhance the Activated State and Th1 Cytokine Gene Expression in Jurkat Cells.

    Science.gov (United States)

    Pan, Yao; Wei, Xuetao; Hao, Weidong

    2015-08-28

    Trichloroethylene (TCE) is an occupational and ubiquitous environmental contaminant, and TCE exposure will increase the risk of autoimmune diseases and allergic diseases. T cells play an important role in the pathogenesis of TCE-related immune disorders, but the effect of TCE and its oxidative metabolites, trichloroacetic acid (TCA) and dichloroacetic acid (DCA), on the activation of human T cells is still unknown. In this study, Jurkat cells were pre-treated with TCE, TCA and DCA overnight and then stimulated with phorbol 12-myristate 13-acetate and ionomycin for another 4, 8 and 24 hours. IL-2 secretion was detected by ELISA; the expressions of CD25 and CD69 were tested by flow cytometry; and IFN-γ and IL-2 mRNA expression levels were investigated by real-time PCR. The results showed that TCE and its oxidative metabolites, TCA and DCA, significantly enhanced IL-2 releasing and the expression of T cell activation markers, CD25 and CD69. Consistent with this result, these compounds markedly up-regulated the expression levels of IFN-γ and IL-2 mRNA. Collectively, these findings suggest that TCE and its metabolites, TCA and DCA, might enhance the activation of T cells and disrupt various activities of peripheral T cells.

  8. Trichloroethylene and Its Oxidative Metabolites Enhance the Activated State and Th1 Cytokine Gene Expression in Jurkat Cells

    Directory of Open Access Journals (Sweden)

    Yao Pan

    2015-08-01

    Full Text Available Trichloroethylene (TCE is an occupational and ubiquitous environmental contaminant, and TCE exposure will increase the risk of autoimmune diseases and allergic diseases. T cells play an important role in the pathogenesis of TCE-related immune disorders, but the effect of TCE and its oxidative metabolites, trichloroacetic acid (TCA and dichloroacetic acid (DCA, on the activation of human T cells is still unknown. In this study, Jurkat cells were pre-treated with TCE, TCA and DCA overnight and then stimulated with phorbol 12-myristate 13-acetate and ionomycin for another 4, 8 and 24 hours. IL-2 secretion was detected by ELISA; the expressions of CD25 and CD69 were tested by flow cytometry; and IFN-γ and IL-2 mRNA expression levels were investigated by real-time PCR. The results showed that TCE and its oxidative metabolites, TCA and DCA, significantly enhanced IL-2 releasing and the expression of T cell activation markers, CD25 and CD69. Consistent with this result, these compounds markedly up-regulated the expression levels of IFN-γ and IL-2 mRNA. Collectively, these findings suggest that TCE and its metabolites, TCA and DCA, might enhance the activation of T cells and disrupt various activities of peripheral T cells.

  9. Understanding the Mysterious M2 Macrophage through Activation Markers and Effector Mechanisms

    Science.gov (United States)

    Rőszer, Tamás

    2015-01-01

    The alternatively activated or M2 macrophages are immune cells with high phenotypic heterogeneity and are governing functions at the interface of immunity, tissue homeostasis, metabolism, and endocrine signaling. Today the M2 macrophages are identified based on the expression pattern of a set of M2 markers. These markers are transmembrane glycoproteins, scavenger receptors, enzymes, growth factors, hormones, cytokines, and cytokine receptors with diverse and often yet unexplored functions. This review discusses whether these M2 markers can be reliably used to identify M2 macrophages and define their functional subdivisions. Also, it provides an update on the novel signals of the tissue environment and the neuroendocrine system which shape the M2 activation. The possible evolutionary roots of the M2 macrophage functions are also discussed. PMID:26089604

  10. Markers of oxidative stress and erythrocyte antioxidant enzyme activity in older men and women with differing physical activity.

    Science.gov (United States)

    Rowiński, Rafał; Kozakiewicz, Mariusz; Kędziora-Kornatowska, Kornelia; Hübner-Woźniak, Elżbieta; Kędziora, Józef

    2013-11-01

    The aim of the present study was to examine the relationship between markers of oxidative stress and erythrocyte antioxidant enzyme activity and physical activity in older men and women. The present study included 481 participants (233 men and 248 women) in the age group 65-69 years (127 men and 125 women) and in the age group 90 years and over (106 men and 123 women). The classification of respondents by physical activity was based on answers to the question if, in the past 12 months, they engaged in any pastimes which require physical activity. The systemic oxidative stress status was assessed by measuring plasma iso-PGF2α and protein carbonyl concentration as well as erythrocyte antioxidant enzymes activity, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). The concentration of plasma iso-PGF2α and protein carbonyls (CP) was lower in groups of younger men and women compared to the respective older groups. In all examined groups, physical activity resulted in decrease of these oxidative stress markers and simultaneously caused adaptive increase in the erythrocyte SOD activity. Additionally, in active younger men CAT, GPx, and GR activities were higher than in sedentary ones. In conclusion, oxidative stress increase is age-related, but physical activity can reduce oxidative stress markers and induce adaptive increase in the erythrocyte antioxidant enzyme activity, especially SOD, even in old and very old men and women. © 2013.

  11. Macrophage activation marker soluble CD163 may predict disease progression in hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Kazankov, Konstantin; Rode, Anthony; Simonsen, Kira Schreiner

    2016-01-01

    BACKGROUND: Tumor associated macrophages are present in hepatocellular carcinoma (HCC) and associated with a poor prognosis. The aim of the present study was to investigate the levels and dynamics of soluble (s)CD163, a specific macrophage activation marker, in patients with HCC. METHODS: In a co...

  12. 78 FR 38809 - Agency Information Collection (NCA Customer Satisfaction Surveys (Headstone/Marker)) Activity...

    Science.gov (United States)

    2013-06-27

    ... Customer Satisfaction Surveys (Headstone/Marker)) Activity Under OMB Review AGENCY: National Cemetery... Customer Satisfaction Surveys. OMB Control Number: 2900-0571. Type of Review: Revision of a currently approved collection. Abstract: Executive Order 12862, Setting Customer Service Standards, requires Federal...

  13. 75 FR 3539 - Agency Information Collection (NCA Customer Satisfaction Surveys (Headstone/Marker)) Activity...

    Science.gov (United States)

    2010-01-21

    ... Customer Satisfaction Surveys (Headstone/Marker)) Activity Under OMB Review AGENCY: National Cemetery... Clearance for NCA, and IG Customer Satisfaction Surveys. OMB Control Number: 2900-0571. Type of Review... National Customer Satisfaction Survey (Mail to 4,000 respondents/30 minutes per survey) = 2,000 hours. c...

  14. Integrating marker passing and problem solving a spreading activation approach to improved choice in planning

    CERN Document Server

    Hendler, James A

    2014-01-01

    A recent area of interest in the Artificial Intelligence community has been the application of massively parallel algorithms to enhance the choice mechanism in traditional AI problems. This volume provides a detailed description of how marker-passing -- a parallel, non-deductive, spreading activation algorithm -- is a powerful approach to refining the choice mechanisms in an AI problem-solving system. The author scrutinizes the design of both the algorithm and the system, and then reviews the current literature and research in planning and marker passing. Also included: a comparison of this

  15. Signaling pathways activation profiles make better markers of cancer than expression of individual genes

    OpenAIRE

    Borisov, Nikolay M.; Terekhanova, Nadezhda V.; Aliper, Alexander M.; Venkova, Larisa S.; Smirnov, Philip Yu; Roumiantsev, Sergey; Korzinkin, Mikhail B.; Zhavoronkov, Alex A.; Buzdin, Anton A.

    2014-01-01

    Identification of reliable and accurate molecular markers remains one of the major challenges of contemporary biomedicine. We developed a new bioinformatic technique termed OncoFinder that for the first time enables to quantatively measure activation of intracellular signaling pathways basing on transcriptomic data. Signaling pathways regulate all major cellular events in health and disease. Here, we showed that the Pathway Activation Strength (PAS) value itself may serve as the biomarker for...

  16. Overexpression of Fc receptor-like 1 associated with B-cell activation during hepatitis B virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ke [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province (China); Pei, Hao [Wuxi Hospital of Infectious Disease, Wuxi, Jiangsu Province (China); Huang, Biao; Yang, Run-Lin [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province (China); Wu, Hang-Yuan [Wuxi Hospital of Infectious Disease, Wuxi, Jiangsu Province (China); Zhu, Xue; Zhu, Lan [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province (China)

    2012-08-17

    The role of B cells in the pathogenesis of hepatitis B virus (HBV) infection has not been explored in depth. In the present study, the activation status of B cells from peripheral blood of healthy controls (N = 20) and patients with acute hepatitis B (AHB, N = 15) or chronic hepatitis B (CHB, N = 30) was evaluated by measuring the expression levels of B-cell activation markers CD69 and CD86, using quantitative real-time PCR and flow cytometry. Moreover, the potential mechanism underlying B-cell activation during HBV infection was further investigated by analyzing the expression profile of FCRL1, an intrinsic activation molecule of B cells. An elevation in the levels of B-cell activation markers including CD69 and CD86 was observed in the AHB patients (44.31 ± 9.27, 27.64 ± 9.26%) compared to CHB patients (30.35 ± 11.27, 18.41 ± 6.56%, P < 0.05), which was still higher than healthy controls (12.23 ± 7.84, 8.22 ± 3.43%, P < 0.05). Furthermore, the expression of FCRL1 was found to be similar to B-cell activation markers, which was highest in AHB patients (70.15 ± 17.11%), lowest in healthy donors (36.32 ± 9.98%, P < 0.05) and half-way between these levels in patients with CHB (55.17 ± 12.03%, P < 0.05). The results were positively associated with aberrant B-cell activation. These data suggest that B cells can play a role in HBV infection, and therefore more effort should be devoted to exploring their functions.

  17. Tenascin-C is not a useful marker for disease activity in psoriasis.

    Science.gov (United States)

    Latijnhouwers, M A; Bergers, M; Kuijpers, A L; van der Vleuten, C J; Dijkman, H; van de Kerkhof, P C; Schalkwijk, J

    1998-09-01

    Tenascin-C is an extracellular matrix glycoprotein that is markedly upregulated in the dermis of psoriatic skin. In this study, we have addressed the question whether the presence of tenascin-C in the lesion or in serum is a marker for disease activity. Immunohistochemical staining of tenascin-C before and after treatment with different topical and systemic medication showed that tenascin-C remained abundant after clinical remission of lesions, indicating that downregulation of tenascin-C to normal values is a slow process. By using a sensitive enzyme-linked immunosorbent assay to measure levels of serum tenascin-C in psoriatic patients and unaffected individuals, we found that tenascin-C levels in most patients were within the normal range. Moreover, tenascin-C values did not correlate with disease activity. We conclude that tenascin-C is not useful as a marker for disease activity in psoriasis.

  18. EFFECT OF PHYSICAL ACTIVITY ON CARDIOMETABOLIC MARKERS IN ADOLESCENTS: SYSTEMATIC REVIEW

    Directory of Open Access Journals (Sweden)

    Valter Paulo Neves Miranda

    Full Text Available ABSTRACT The accumulation of body fat is a major risk factor for cardiometabolic diseases. Obesity can be considered a chronic systemic inflammatory disease in adults and younger people. The control of subclinical inflammation process through the practice of physical activity (PA can mitigate the effects of risk factors that trigger atherosclerosis that worsens with advancing age. The objective of this study was to conduct a systematic review of the influence of physical activity and/or exercise on cardiometabolic markers and othrer risk factors of cardiovascular disease in adolescents. A systematic review was conducted in electronic databases Scopus, Pubmed, Conchrane Collection and SciELO. The terms used in the search were "cardiovascular diseases AND inflammation AND adolescents AND physical activity OR exercise". A total of 24 original articles were evaluated, being 14 longitudinal and 10 cross-sectional studies. Overall, 16 articles (66.66% showed that PA, exercise and/or sedentary behavior may have influenced or have been related to the concentration of cardiometabolic markers. All studies that examined lifestyle changes showed reduction of cardiometabolic markers. Some limitations were observed: reduced samples, lack of dietary prescription, evaluation and control of volume and intensity of exercise. Most of the studies analyzed showed that the physical activity could influence and decrease the concentrations of cardiometabolic markers in adolescents. However, studies with representative sample size and precise control in assessing the level of physical activity and/or exercise are required to determine accurately the changes that the more active lifestyle can bring on inflammatory process, as well as other risk factors for cardiometabolic diseases in adolescents.

  19. Magnetic Resonance Imaging Features as Surrogate Markers of X-Linked Hypophosphatemic Rickets Activity.

    Science.gov (United States)

    Lempicki, Marta; Rothenbuhler, Anya; Merzoug, Valérie; Franchi-Abella, Stéphanie; Chaussain, Catherine; Adamsbaum, Catherine; Linglart, Agnès

    2017-01-01

    X-linked hypophosphatemic rickets (XLH) is the most common form of inheritable rickets. Rickets treatment is monitored by assessing alkaline phosphatase (ALP) levels, clinical features, and radiographs. Our objectives were to describe the magnetic resonance imaging (MRI) features of XLH and to assess correlations with disease activity. Twenty-seven XLH patients (median age 9.2 years) were included in this prospective single-center observational study. XLH activity was assessed using height, leg bowing, dental abscess history, and serum ALP levels. We looked for correlations between MRI features and markers of disease activity. On MRI, the median maximum width of the physis was 5.6 mm (range 4.8-7.8; normal 1.5 mm in all of the patients. The appearance of the zone of provisional calcification was abnormal on 21 MRI images (78%), Harris lines were present on 24 (89%), and bone marrow signal abnormalities were present on 16 (59%). ALP levels correlated with the maximum physeal widening and with the transverse extent of the widening. MRI of the knee provides precise rickets patterns that are correlated with ALP, an established biochemical marker of the disease, avoiding X-ray exposure and providing surrogate quantitative markers of disease activity. © 2017 S. Karger AG, Basel.

  20. Association of molecular markers with polyphenol oxidase activity in selected wheat genotypes

    International Nuclear Information System (INIS)

    Abbas, Z.; Javad, B.; Majeed, N.; Naqvi, S.

    2016-01-01

    Wheat (Triticum aestivum L.), a major staple food for the people of Pakistan and other Asian countries, is used as bread, chapatti, porridge, noodles and many other. It is established that color quality of wheat products depend on chemical and enzymatic factors especially the polyphenol oxidases (PPOs). These are copper containing enzymes which induce browning in wheat-based products. Various procedures for determining PPO activity available and differences in PPO activity among wheat genotypes have been documented. In present study, an attempt was made to establish the association of molecular markers with polyphenol oxidase activity in wheat genotypes having very high or very low PPO activities. Twelve pairs of markers were used out of which only three primer pairs viz. PPO43, PPO30 and WP2-2 yielded specific pattern discriminating high and low PPO genotypes. Cluster analysis for all 12 markers revealed that all the low PPO lline share the same sub cluster, but high PPO lines were dispersed in different clusters. (author)

  1. Impact of physical activity on ovarian reserve markers in normal, overweight and obese reproductive age women.

    Science.gov (United States)

    Surekha, T; Himabindu, Y; Sriharibabu, M; Pandey, Anil Kumar

    2014-01-01

    Physical inactivity is a leading risk factor for overweight and obesity in the society. Prevalence of overweight and obesity in the reproductive age group women not only affects maternal health but also the health of the off spring. Infertility is a common problem in India affecting 13-19 million people at any given time. Even though it is not life threatening, infertility causes intense mental agony and trauma that can only be best described by infertile couples themselves. Infertility is more common in overweight and obese individuals compared to normal weight individuals. Decreasing ovarian reserve is an important factor for infertility in women. This study examined the impact of physical activity on ovarian reserve markers in normal, overweight and obese reproductive age women. The observations made in this study reveal that physical activity improves ovarian reserve markers in all reproductive age women but this improvement is more distinct and statistically significant in overweight and obese women compared to normal weight women.

  2. Beyond Neuronal Activity Markers: Select Immediate Early Genes in Striatal Neuron Subtypes Functionally Mediate Psychostimulant Addiction

    Directory of Open Access Journals (Sweden)

    Ramesh Chandra

    2017-06-01

    Full Text Available Immediate early genes (IEGs were traditionally used as markers of neuronal activity in striatum in response to stimuli including drugs of abuse such as psychostimulants. Early studies using these neuronal activity markers led to important insights in striatal neuron subtype responsiveness to psychostimulants. Such studies have helped identify striatum as a critical brain center for motivational, reinforcement and habitual behaviors in psychostimulant addiction. While the use of IEGs as neuronal activity markers in response to psychostimulants and other stimuli persists today, the functional role and implications of these IEGs has often been neglected. Nonetheless, there is a subset of research that investigates the functional role of IEGs in molecular, cellular and behavioral alterations by psychostimulants through striatal medium spiny neuron (MSN subtypes, the two projection neuron subtypes in striatum. This review article will address and highlight the studies that provide a functional mechanism by which IEGs mediate psychostimulant molecular, cellular and behavioral plasticity through MSN subtypes. Insight into the functional role of IEGs in striatal MSN subtypes could provide improved understanding into addiction and neuropsychiatric diseases affecting striatum, such as affective disorders and compulsive disorders characterized by dysfunctional motivation and habitual behavior.

  3. Elevated circulating soluble thrombomodulin activity, tissue factor activity and circulating procoagulant phospholipids: new and useful markers for pre-eclampsia?

    Science.gov (United States)

    Rousseau, Aurélie; Favier, Rémi; Van Dreden, Patrick

    2009-09-01

    One of the most frequently proposed mechanisms for pre-eclampsia refers to uteroplacental thrombosis. However, the contribution of classical thrombotic risk factors remains questionable. The aims of this study were to investigate the activities of thrombomodulin, tissue factor and procoagulant phospholipids to assess endothelial cell injury in pregnant women with pre-eclampsia and to compare them with other classical markers of vascular injury and thrombotic risk. Using three new functional assays we studied the plasma levels of these new markers in 35 healthy women, 30 healthy pregnant women, and 35 women with pre-eclampsia. We found that plasma levels of thrombomodulin activity, tissue factor activity and procoagulant phospholipids were significantly elevated in women with pre-eclampsia versus normal pregnant and non-pregnant women. It is thus suggested that elevated levels of these parameters in pre-eclampsia may reflect vascular endothelium damage, and may be a more valuable biomarker than antigen for the assessment of endothelial damage in pre-eclampsia. The high increased levels of procoagulant phospholipids and tissue factor activities in pre-eclampsia could suggest that the procoagulant potential may be implicated in this complication and makes these markers very promising for the understanding, follow-up and therapeutic handling of complicated pregnancy.

  4. Serum Calprotectin in Rheumatoid Arthritis: A Promising Diagnostic Marker, How Far Is It Related to Activity and Sonographic Findings?

    Directory of Open Access Journals (Sweden)

    H.E. Mansour

    2017-03-01

    Conclusion: Calprotectin was found to have high association with laboratory and ultrasonography markers of inflammation in RA patients, so it is recommended for use as a marker of inflammatory activity in RA patients especially for the follow-up of patients on biological therapy to assess its efficacy.

  5. Discourse marker acquisition and out-of-school activities: evidence from EFL writing

    Directory of Open Access Journals (Sweden)

    Gloria Vickov

    2015-05-01

    Full Text Available The present paper attempts to investigate what out-of-school activities might positively affect the acquisition of discourse markers (DMs which seems to be one of the most demanding areas for EFL learners. Two equal size groups of Croatian primary and secondary school learners (N = 200 completed a writing test in English and a questionnaire aimed at establishing the degree to which the respondents were exposed to out-of-school activities. The results reveal that the out-of-school activity which EFL learners might best benefit from is reading authentic English literature. It is followed by watching English TV programs and surfing English websites. The findings of the study reflect a need for enhancing EFL learners´ awareness of the benefits and possibilities for out-of-school activities by incorporating tasks and teaching materials that bring the out-of-school activities into EFL classrooms.

  6. The immune privilege of the eye: human retinal pigment epithelial cells selectively modulate T-cell activation in vitro

    DEFF Research Database (Denmark)

    Kaestel, Charlotte G; Lovato, Paola; Ødum, Niels

    2005-01-01

    PURPOSE: To examine the effect of human retinal pigment epithelial (RPE) cells on phytohemagglutinin (PHA) activation of T cells. METHODS: Resting peripheral blood lymphocytes (PBLs) were stimulated with PHA with or without the presence of gamma-irradiated RPE cells. Proliferation and the cell...... in cell culture supernatant was measured by ELISA. RESULTS: Human RPE cells were found to suppress PHA-induced proliferation, cyclin A, IL-2R-alpha and -gamma, and CD71 expression and decrease the production of IL-2; but RPE cells do not inhibit the PHA-induced expression of early activation markers CD69......, MHC class I and II, and of cyclin D of the PBLs. CONCLUSIONS: These results are the first to indicate that RPE cells impede generation of activated T cells by interfering with the induction of high-affinity IL-2R-alphabetagamma, IL-2 production, and the expression of CD71 and cyclin A....

  7. Plasma markers of inflammation and hemostatic and endothelial activity in naturally overweight and obese dogs.

    Science.gov (United States)

    Barić Rafaj, R; Kuleš, J; Marinculić, A; Tvarijonaviciute, A; Ceron, J; Mihaljević, Ž; Tumpa, A; Mrljak, V

    2017-01-06

    Obesity is one of the most prevalent health problems in the canine population. While haemostatic parameters and markers of endothelial function have been evaluated in various disease conditions in dogs, there are no studies of these markers in canine obesity. This study was designed to evaluate the effect of naturally gained weight excess and obesity on inflammatory, hemostatic and endothelial biomarkers in dogs. A total of 37 overweight and obese dogs were compared with 28 normal weight dogs. Overweight and obese dogs had significantly elevated concentrations of serum interleukin-6 (IL-6) and C-reactive protein (hsCRP). Number of platelets, activity of factor X and factor VII were significantly higher, while activated partial thromboplastine time (aPTT) and soluble plasminogen activator receptor (suPAR) were significantly decreased. Statistical analysis of high mobility group box - 1 protein (HMGB-1), soluble intercellular adhesive molecule -1 (sICAM-1) and plasminogen activator inhibitor type 1 (PAI-1) concentrations did not show significant differences between the total overweight and obese group and the normal weight group of dogs. Analytical changes in the dogs in our study reflects that weight excess in dogs can be associated with a chronic low degree of inflammation and a hypercoagulable state, where primary and secondary hemostasis are both affected. However obesity is not associated with impairment of endothelial function in dogs.

  8. Physical activity, exercise, and inflammatory markers in older adults : findings from the Health, Aging and Body Composition Study

    NARCIS (Netherlands)

    Colbert, Lisa H; Visser, Marjolein; Simonsick, Eleanor M; Tracy, Russell P; Newman, Anne B; Kritchevsky, Stephen B; Pahor, Marco; Taaffe, Dennis R; Brach, Jennifer S; Rubin, Susan; Harris, Tamara B

    OBJECTIVES: To examine the association between physical activity and inflammatory markers, with consideration for body fatness and antioxidant use. DESIGN: Cross-sectional study, using baseline data from the Health, Aging and Body Composition Study. SETTING: Metropolitan areas surrounding

  9. Quality control in the neutron activation analysis of biological markers for selenium in epidemiological investigations

    International Nuclear Information System (INIS)

    Morris, J.S.; Ngwenyama, R.A.; Guthrie, J.M.; Brockman, J.D.; Spate, V.L.; Robertson, J.D.

    2008-01-01

    Instrumental neutron activation analysis is routinely used at the MURR to quantify selenium in prospectively-collected biologic markers including blood serum and toenails. These specimens are typically collected from well-defined cohort populations participating in investigations assessing selenium intake and incidence of chronic disease endpoints. These epidemiological investigations, whether observational (case-control) or clinical (intervention), typically generate thousands of samples. The purpose of this paper is to assess, through evaluation of quality control results, if the achievable accuracy and precision in the measurement of selenium using NAA is adequate to determine a relative risk of 1.2 at high confidence in epidemiological studies. (author)

  10. [Serum anticholinergic activity: relationship with clinical symptoms in Alzheimer's disease and proposal of new biological marker].

    Science.gov (United States)

    Hori, Koji; Konishi, Kimiko; Hachisu, Mitsugu

    2011-06-01

    We reviewed the importance of measuring serum anticholinergic activity (SAA) in patients with Alzheimer's disease (AD). Since Tune and Coyle reported a simple method for assessing SAA using radioreceptor-binding assay, SAA is assumed to be the cumulative activity of parent medications and their metabolites and its relationship with delirium and cognitive functions has been debated. However, we evaluated the SAA in AD patients and SAA was correlated with prescription of antipsychotic medications, cognitive dysfunctions, severity of AD and psychotic symptoms, especially, with delusion and diurnal rhythm disturbance. From these results, we should not only pay attention to avoiding the prescription of medications with anticholinergic activity but also we speculated that AA appeared endogenously in AD and accelerated AD pathology. Moreover, there might be the possibility that SAA has predictive value for assessing the progressiveness of AD and as a biological marker for AD.

  11. Gamma-glutamyltransferase activity in exosomes as a potential marker for prostate cancer.

    Science.gov (United States)

    Kawakami, Kyojiro; Fujita, Yasunori; Matsuda, Yoko; Arai, Tomio; Horie, Kengo; Kameyama, Koji; Kato, Taku; Masunaga, Koichi; Kasuya, Yutaka; Tanaka, Masashi; Mizutani, Kosuke; Deguchi, Takashi; Ito, Masafumi

    2017-05-05

    Exosomes or extracellular vesicles have the potential as a diagnostic marker for various diseases including cancer. In order to identify novel exosomal markers for prostate cancer (PC), we performed proteomic analysis of exosomes isolated from PC cell lines and examined the usefulness of the marker in patients. Exosomes isolated by differential centrifugation from the culture medium of androgen-dependent LNCaP prostate cancer cell line and its sublines of partially androgen-independent C4, androgen-independent C4-2 and bone metastatic C4-2B were subjected to iTRAQ-based proteomic analysis. Exosomes were also isolated by immunocapture and separated by size exclusion chromatography and density gradient centrifugation. Protein expression was determined by Western blot analysis. GGT activity was measured using a fluorescent probe, γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG). Immunohistochemical analysis of tissues was performed using anti-GGT1 antibody. Among proteins upregulated in C4-2 and C4-2B cells than in LNCaP cells, we focused on gamma-glutamyltransferase 1 (GGT1), a cell-surface enzyme that regulates the catabolism of extracellular glutathione. The levels of both GGT1 large and small subunits were elevated in exosomes isolated from C4-2 and C4-2B cells by differential centrifugation and by immunocapture with anti-CD9 or -prostate-specific membrane antigen (PSMA) antibody. In cell lysates and exosomes, GGT1 expression correlated with GGT activity. Size exclusion chromatography of human serum demonstrated the presence of GGT activity and GGT1 subunits in fractions positive for CD9. Density gradient centrifugation revealed the co-presence of GGT1 subunits with CD9 in exosomes isolated by differential centrifugation from human serum. Since GGT activity correlated with GGT1 expression in serum exosomes isolated by differential centrifugation, we measured serum exosomal GGT activity in patients. Unexpectedly, we found that serum exosomal GGT activity was

  12. Host markers in Quantiferon supernatants differentiate active TB from latent TB infection: preliminary report

    Directory of Open Access Journals (Sweden)

    Walzl Gerhard

    2009-05-01

    Full Text Available Abstract Background Interferon gamma release assays, including the QuantiFERON® TB Gold In Tube (QFT have been shown to be accurate in diagnosing Mycobacterium tuberculosis infection. These assays however, do not discriminate between latent TB infection (LTBI and active TB disease. Methods We recruited twenty-three pulmonary TB patients and 34 household contacts from Cape Town, South Africa and performed the QFT test. To investigate the ability of new host markers to differentiate between LTBI and active TB, levels of 29 biomarkers in QFT supernatants were evaluated using a Luminex multiplex cytokine assay. Results Eight out of 29 biomarkers distinguished active TB from LTBI in a pilot study. Baseline levels of epidermal growth factor (EGF soluble CD40 ligand (sCD40L, antigen stimulated levels of EGF, and the background corrected antigen stimulated levels of EGF and macrophage inflammatory protein (MIP-1β were the most informative single markers for differentiation between TB disease and LTBI, with AUCs of 0.88, 0.84, 0.87, 0.90 and 0.79 respectively. The combination of EGF and MIP-1β predicted 96% of active TB cases and 92% of LTBIs. Combinations between EGF, sCD40L, VEGF, TGF-α and IL-1α also showed potential to differentiate between TB infection states. EGF, VEGF, TGF-α and sCD40L levels were higher in TB patients. Conclusion These preliminary data suggest that active TB may be accurately differentiated from LTBI utilizing adaptations of the commercial QFT test that includes measurement of EGF, sCD40L, MIP-1β, VEGF, TGF-α or IL-1α in supernatants from QFT assays. This approach holds promise for development as a rapid diagnostic test for active TB.

  13. Muscle sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy individuals.

    Directory of Open Access Journals (Sweden)

    Yrsa Bergmann Sverrisdóttir

    Full Text Available BACKGROUND: Evidence from animal studies indicates the importance of an interaction between the sympathetic nervous system and the endothelium for cardiovascular regulation. However the interaction between these two systems remains largely unexplored in humans. The aim of this study was to investigate whether directly recorded sympathetic vasoconstrictor outflow is related to a surrogate marker of endothelial function in healthy individuals. METHODS AND RESULTS: In 10 healthy normotensive subjects (3 f/7 m, (age 37+/-11 yrs, (BMI 24+/-3 kg/m(2 direct recordings of sympathetic action potentials to the muscle vascular bed (MSNA were performed and endothelial function estimated with the Reactive Hyperaemia- Peripheral Arterial Tonometry (RH-PAT technique. Blood samples were taken and time spent on leisure-time physical activities was estimated. In all subjects the rate between resting flow and the maximum flow, the Reactive Hyperemic index (RH-PAT index, was within the normal range (1.9-3.3 and MSNA was as expected for age and gender (13-44 burst/minute. RH-PAT index was inversely related to MSNA (r = -0.8, p = 0.005. RH-PAT index and MSNA were reciprocally related to time (h/week spent on physical activity (p = 0.005 and p = 0.006 respectively and platelet concentration (PLT (p = 0.02 and p = 0.004 respectively. CONCLUSIONS: Our results show that sympathetic nerve activity is related to a surrogate marker of endothelial function in healthy normotensive individuals, indicating that sympathetic outflow may be modulated by changes in endothelial function. In this study time spent on physical activity is identified as a predictor of sympathetic nerve activity and endothelial function in a group of healthy individuals. The results are of importance in understanding mechanisms underlying sympathetic activation in conditions associated with endothelial dysfunction and emphasise the importance of a daily exercise routine for maintenance of cardiovascular

  14. Elevated amygdala activity to sad facial expressions: a state marker of bipolar but not unipolar depression.

    Science.gov (United States)

    Almeida, Jorge R C; Versace, Amelia; Hassel, Stefanie; Kupfer, David J; Phillips, Mary L

    2010-03-01

    Difficulties in emotion processing and poor social function are common to bipolar disorder (BD) and major depressive disorder (MDD) depression, resulting in many BD depressed individuals being misdiagnosed with MDD. The amygdala is a key region implicated in processing emotionally salient stimuli, including emotional facial expressions. It is unclear, however, whether abnormal amygdala activity during positive and negative emotion processing represents a persistent marker of BD regardless of illness phase or a state marker of depression common or specific to BD and MDD depression. Sixty adults were recruited: 15 depressed with BD type 1 (BDd), 15 depressed with recurrent MDD, 15 with BD in remission (BDr), diagnosed with DSM-IV and Structured Clinical Interview for DSM-IV Research Version criteria; and 15 healthy control subjects (HC). Groups were age- and gender ratio-matched; patient groups were matched for age of illness onset and illness duration; depressed groups were matched for depression severity. The BDd were taking more psychotropic medication than other patient groups. All individuals participated in three separate 3T neuroimaging event-related experiments, where they viewed mild and intense emotional and neutral faces of fear, happiness, or sadness from a standardized series. The BDd-relative to HC, BDr, and MDD-showed elevated left amygdala activity to mild and neutral facial expressions in the sad (p sad and neutral faces might be a depression-specific marker in BD but not MDD, suggesting different pathophysiologic processes for BD versus MDD depression. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. Relationship between physical activity and markers of oxidative stress in independent community-living elderly individuals.

    Science.gov (United States)

    Fraile-Bermúdez, A B; Kortajarena, M; Zarrazquin, I; Maquibar, A; Yanguas, J J; Sánchez-Fernández, C E; Gil, J; Irazusta, A; Ruiz-Litago, F

    2015-10-01

    The aim of the present study was to examine the relationship between objective data of physical activity and markers of oxidative stress in older men and women. Participants were old adults, aged≥60years (61 women and 34 men) who were all capable of performing basic daily activities by themselves and lived on their own. To describe physical activity we used objective data measured by accelerometers which record active and sedentary periods during everyday life for five days. Determination of oxidative stress was conducted from three perspectives: determination plasma total antioxidant status (TAS), plasma antioxidant enzyme activities, i.e., glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD), and membrane lipid peroxidation (TBARS). In the group of women, those who met physical activity recommendations (WR) had lower level of TAS. In addition, the moderate to vigorous physical activity (MVPA) was negatively correlated with TAS. Simultaneously, MVPA was correlated with increase in the GPx antioxidant enzyme activity, and the counts per minute were positively correlated with CAT activity. In the group of men, the cpm and the MVPA were negatively correlated with lipid peroxidation while lifestyle physical activity was positively correlated with CAT activity. These findings suggest that MVPA in the elderly although it is related to a decrease in the TAS in women, induces adaptive increase in antioxidant enzyme activity and decreases lipid peroxidation in both women and men. These results suggest that at this time of life, it is not only the amount of physical activity performed that is important but also its intensity. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Clinical significance of nailfold capillaroscopy in systemic lupus erythematosus: correlation with endothelial cell activation markers and disease activity.

    Science.gov (United States)

    Kuryliszyn-Moskal, A; Ciolkiewicz, M; Klimiuk, P A; Sierakowski, S

    2009-01-01

    To evaluate whether nailfold capillaroscopy (NC) changes are associated with the main serum endothelial cell activation markers and the disease activity of systemic lupus erythematosus (SLE). Serum levels of vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble E-selectin (sE-selectin), and soluble thrombomodulin (sTM) were determined by an enzyme-linked immunosorbent assay (ELISA) in 80 SLE patients and 33 healthy controls. Nailfold capillary abnormalities were seen in 74 out of 80 (92.5%) SLE patients. A normal capillaroscopic pattern or mild changes were found in 33 (41.25%) and moderate/severe abnormalities in 47 (58.75%) of all SLE patients. In SLE patients a capillaroscopic score >1 was more frequently associated with the presence of internal organ involvement (p 1 and controls. SLE patients with severe/moderate capillaroscopic abnormalities showed significantly higher VEGF serum levels than patients with mild changes (p < 0.001). Moreover, there was a significant positive correlation between the severity of capillaroscopic changes and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (p < 0.005) as well as between capillaroscopic score and VEGF serum levels (p < 0.001). Our findings confirm the usefulness of NC as a non-invasive technique for the evaluation of microvascular involvement in SLE patients. A relationship between changes in NC, endothelial cell activation markers and clinical features of SLE suggest an important role for microvascular abnormalities in clinical manifestation of the disease.

  17. Changes in urinary amino acids excretion in relationship with muscle activity markers over a professional cycling stage race: in search of fatigue markers.

    Science.gov (United States)

    Corsetti, Roberto; Barassi, Alessandra; Perego, Silvia; Sansoni, Veronica; Rossi, Alessandra; Damele, Clara Anna Linda; Melzi D'Eril, Gianlodovico; Banfi, Giuseppe; Lombardi, Giovanni

    2016-01-01

    The aim of this study was to identify the relationship between metabolic effort, muscular damage/activity indices, and urinary amino acids profile over the course of a strenuous prolonged endurance activity, as a cycling stage race is, in order to identify possible fatigue markers. Nine professional cyclists belonging to a single team, competing in the Giro d'Italia cycling stage race, were anthropometrically characterized and sampled for blood and urine the day before the race started, and on days 12 and 23 of the race. Diet was kept the same over the race, and power output and energy expenditure were recorded. Sera were assayed for muscle markers (lactate dehydrogenase, aspartate aminotransferase, and creatine kinase activities, and blood urea nitrogen), and creatinine, all corrected for plasma volume changes. Urines were profiled for amino acid concentrations, normalized on creatinine excretion. Renal function, in terms of glomerular filtration rate, was monitored by MDRD equation corrected on body surface area. Creatine kinase activity and blood urea were increased during the race as did serum creatinine while kidney function remained stable. Among the amino acids, taurine, glycine, cysteine, leucine, carnosine, 1-methyl histidine, and 3-methyl histidine showed a net decreased, while homocysteine was increased. Taurine and the dipeptide carnosine (β-alanyl-L-histidine) were significantly correlated with the muscle activity markers and the indices of effort. In conclusion, the metabolic profile is modified strikingly due to the effort. Urinary taurine and carnosine seem useful tools to evaluate the muscle damage and possibly the fatigue status on a long-term basis.

  18. Quantitative rest activity in ambulatory monitoring as a physiological marker of restless legs syndrome: a controlled study.

    Science.gov (United States)

    Tuisku, Katinka; Holi, Matti Mikael; Wahlbeck, Kristian; Ahlgren, Aulikki Johanna; Lauerma, Hannu

    2003-04-01

    An objective marker of restless legs syndrome (RLS) is needed for developing diagnostic tools and monitoring symptoms. Actometric ambulatory monitoring of 15 RLS patients and 15 healthy controls was undertaken in order to differentiate between RLS-related motor symptoms and normal motor activity. Nocturnal lower-limb activity per minute differentiated and discriminated between groups with no overlap, whereas the periodic limb movement index and the controlled rest activity during sitting showed less discriminative power. The naturalistic recording of nocturnal activity by actometry may prove useful for assessing the severity of RLS and for finding an objective marker to support the diagnosis of RLS. Copyright 2002 Movement Disorder Society

  19. CEA in activated macrophages. New diagnostic possibilities for tumor markers in early colorectal cancer.

    Science.gov (United States)

    Japink, Dennis; Leers, Mathie P G; Sosef, Meindert N; Nap, Marius

    2009-08-01

    Serum tumor markers show low sensitivity, making them unsuitable for early detection of cancer. Activated macrophages (AM) from peripheral blood can accumulate tumor marker substances and facilitate early detection in prostate cancer. Here it was investigated whether carcinoembryonic antigen (CEA)-containing macrophages (CEACM) can be used to detect colorectal cancer (CRC) at earlier stages than can serum CEA. Peripheral blood was collected from patients with CRC (n=48), inflammatory colorectal disease (n=5) and from healthy controls (n=18). After separating and labeling AM with CD14-APC/CD16-FITC, AM were intracellularly labeled with anti-CEA antibody and flow cytometrically analyzed. Serum CEA and C-reactive protein (CRP) were measured. The fraction-size of CEACM discriminated between controls and CRC patients, irrespective of AJCC stage (AJCC stage I-IV, pCEA values were significantly elevated in AJCC stage II, III and IV (p=0.02, 0.006 and <0.0001, respectively). Combining CEACM with CRP levels separated CRC from inflammatory colorectal disease. CEACM combined with CRP appears to have diagnostic potential in early CRC.

  20. Selection of discrimination marker from various propolis for mapping and identify anti Candida albicans activity

    Science.gov (United States)

    Mahadewi, Alfiani Guntari; Christina, Daisy; Hermansyah, Heri; Wijanarko, Anondho; Farida, Siti; Adawiyah, Robiatul; Rohmatin, Etin; Sahlan, Muhamad

    2018-02-01

    The increase in fungal resistance against antifungal drugs available in the market will reduce the effectiveness of treatment for Candidiasis. Propolis contains various compounds with antifungal properties Candida albicans, but the content of each type is very diverse. The sample used was Sulawesi propolis type smooth (taken from inside the nest), rough (taken from outside the hive) and mix (a combination of both). Anti-C. albicans molecule marker is a marker compound for selecting propolis with the ability to overcome Candidiasis. The initial step was to test the levels of flavonoids and phenolic by using UV-Vis spectrometry method. It was founded that each sample was not always superior to any substance, so propolis cannot be directly selected. In Phenolic content, mix propolis has the highest value than other 5.109%. In Flavonoid content, propolis smooth has the highest value than other, 16.38%. Furthermore, propolis selected by antifungal activity test with good diffusion method at the concentration propolis 5% either 7%, the inhibitory diameter zone propolis smooth and rough has same value 10 mm. Propolis mix has an advantage while propolis smooth and rough have the same capability range 12 mm and 13 mm. In this study, the phenolic content plays a major role in antifungal cases.

  1. Characterizing proton-activated materials to develop PET-mediated proton range verification markers

    Science.gov (United States)

    Cho, Jongmin; Ibbott, Geoffrey S.; Kerr, Matthew D.; Amos, Richard A.; Stingo, Francesco C.; Marom, Edith M.; Truong, Mylene T.; Palacio, Diana M.; Betancourt, Sonia L.; Erasmus, Jeremy J.; DeGroot, Patricia M.; Carter, Brett W.; Gladish, Gregory W.; Sabloff, Bradley S.; Benveniste, Marcelo F.; Godoy, Myrna C.; Patil, Shekhar; Sorensen, James; Mawlawi, Osama R.

    2016-06-01

    Conventional proton beam range verification using positron emission tomography (PET) relies on tissue activation alone and therefore requires particle therapy PET whose installation can represent a large financial burden for many centers. Previously, we showed the feasibility of developing patient implantable markers using high proton cross-section materials (18O, Cu, and 68Zn) for in vivo proton range verification using conventional PET scanners. In this technical note, we characterize those materials to test their usability in more clinically relevant conditions. Two phantoms made of low-density balsa wood (~0.1 g cm-3) and beef (~1.0 g cm-3) were embedded with Cu or 68Zn foils of several volumes (10-50 mm3). The metal foils were positioned at several depths in the dose fall-off region, which had been determined from our previous study. The phantoms were then irradiated with different proton doses (1-5 Gy). After irradiation, the phantoms with the embedded foils were moved to a diagnostic PET scanner and imaged. The acquired data were reconstructed with 20-40 min of scan time using various delay times (30-150 min) to determine the maximum contrast-to-noise ratio. The resultant PET/computed tomography (CT) fusion images of the activated foils were then examined and the foils’ PET signal strength/visibility was scored on a 5 point scale by 13 radiologists experienced in nuclear medicine. For both phantoms, the visibility of activated foils increased in proportion to the foil volume, dose, and PET scan time. A linear model was constructed with visibility scores as the response variable and all other factors (marker material, phantom material, dose, and PET scan time) as covariates. Using the linear model, volumes of foils that provided adequate visibility (score 3) were determined for each dose and PET scan time. The foil volumes that were determined will be used as a guideline in developing practical implantable markers.

  2. Delta-aminolevulinate dehydratase activity and oxidative stress markers in preeclampsia.

    Science.gov (United States)

    de Lucca, Leidiane; Rodrigues, Fabiane; Jantsch, Letícia B; Kober, Helena; Neme, Walter S; Gallarreta, Francisco M P; Gonçalves, Thissiane L

    2016-12-01

    Preeclampsia is an important pregnancy-specific multisystem disorder characterized by the onset of hypertension and proteinuria. It is of unknown etiology and involves serious risks for the pregnant women and fetus. One of the main factors involved in the pathophysiology of preeclampsia is oxidative stress, where excess free radicals produce harmful effects, including damage to macromolecules such as lipids, proteins and DNA. In addition, the sulfhydryl delta-aminolevulinate dehydratase enzyme (δ-ALA-D) that is part of the heme biosynthetic pathway in pro-oxidant conditions can be inhibited, which may result in the accumulation of 5-aminolevulinic acid (ALA), associated with the overproduction of free radicals, suggesting it to be an indirect marker of oxidative stress. As hypertensive pregnancy complications are a major cause of morbidity and mortality maternal and fetal where oxidative stress appears to be an important factor involved in preeclampsia, the aim of this study was to evaluate the activity of δ-ALA-D and classic oxidative stress markers in the blood of pregnant women with mild and severe preeclampsia. The analysis and quantification of the following oxidative stress markers were performed: thiobarbituric acid-reactive species (TBARS); presence of protein and non-protein thiol group; quantification of vitamin C; Catalase and δ-ALA--D activities in samples of blood of pregnant women with mild preeclampsia (n=25), with severe preeclampsia (n=30) and in a control group of healthy pregnant women (n=30). TBARS was significantly higher in women with preeclampsia, while the presence of thiol groups, levels of vitamin C, catalase and δ-ALA-D activity were significantly lower in groups of pregnant women with preeclampsia compared with healthy women. In addition, the results showed no significant difference between groups of pregnant women with mild and severe preeclampsia. The data suggest a state of increased oxidative stress in pregnant women with

  3. CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells.

    Science.gov (United States)

    Abdel-Mohsen, Mohamed; Kuri-Cervantes, Leticia; Grau-Exposito, Judith; Spivak, Adam M; Nell, Racheal A; Tomescu, Costin; Vadrevu, Surya Kumari; Giron, Leila B; Serra-Peinado, Carla; Genescà, Meritxell; Castellví, Josep; Wu, Guoxin; Del Rio Estrada, Perla M; González-Navarro, Mauricio; Lynn, Kenneth; King, Colin T; Vemula, Sai; Cox, Kara; Wan, Yanmin; Li, Qingsheng; Mounzer, Karam; Kostman, Jay; Frank, Ian; Paiardini, Mirko; Hazuda, Daria; Reyes-Terán, Gustavo; Richman, Douglas; Howell, Bonnie; Tebas, Pablo; Martinez-Picado, Javier; Planelles, Vicente; Buzon, Maria J; Betts, Michael R; Montaner, Luis J

    2018-04-18

    The persistence of HIV reservoirs, including latently infected, resting CD4 + T cells, is the major obstacle to cure HIV infection. CD32a expression was recently reported to mark CD4 + T cells harboring a replication-competent HIV reservoir during antiretroviral therapy (ART) suppression. We aimed to determine whether CD32 expression marks HIV latently or transcriptionally active infected CD4 + T cells. Using peripheral blood and lymphoid tissue of ART-treated HIV + or SIV + subjects, we found that most of the circulating memory CD32 + CD4 + T cells expressed markers of activation, including CD69, HLA-DR, CD25, CD38, and Ki67, and bore a T H 2 phenotype as defined by CXCR3, CCR4, and CCR6. CD32 expression did not selectively enrich for HIV- or SIV-infected CD4 + T cells in peripheral blood or lymphoid tissue; isolated CD32 + resting CD4 + T cells accounted for less than 3% of the total HIV DNA in CD4 + T cells. Cell-associated HIV DNA and RNA loads in CD4 + T cells positively correlated with the frequency of CD32 + CD69 + CD4 + T cells but not with CD32 expression on resting CD4 + T cells. Using RNA fluorescence in situ hybridization, CD32 coexpression with HIV RNA or p24 was detected after in vitro HIV infection (peripheral blood mononuclear cell and tissue) and in vivo within lymph node tissue from HIV-infected individuals. Together, these results indicate that CD32 is not a marker of resting CD4 + T cells or of enriched HIV DNA-positive cells after ART; rather, CD32 is predominately expressed on a subset of activated CD4 + T cells enriched for transcriptionally active HIV after long-term ART. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  4. Right Inferior Frontal Gyrus Activation as a Neural Marker of Successful Lying

    Directory of Open Access Journals (Sweden)

    Oshin eVartanian

    2013-10-01

    Full Text Available There is evidence to suggest that successful lying necessitates cognitive effort. We tested this hypothesis by instructing participants to lie or tell the truth under conditions of high and low working memory (WM load. The task required participants to register a response on 80 trials of identical structure within a 2 (WM Load: high, low × 2 (Instruction: truth or lie repeated-measures design. Participants were less accurate and responded more slowly when WM load was high, and also when they lied. High WM load activated the fronto-parietal WM network including dorsolateral prefrontal cortex (PFC, middle frontal gyrus, precuneus, and intraparietal cortex. Lying activated areas previously shown to underlie deception, including middle and superior frontal gyrus and precuneus. Critically, successful lying in the high vs. low WM load condition was associated with longer response latency, and it activated the right inferior frontal gyrus—a key brain region regulating inhibition. The same pattern of activation in the inferior frontal gyrus was absent when participants told the truth. These findings demonstrate that lying under high cognitive load places a burden on inhibition, and that the right inferior frontal gyrus may provide a neural marker for successful lying.

  5. Right inferior frontal gyrus activation as a neural marker of successful lying.

    Science.gov (United States)

    Vartanian, Oshin; Kwantes, Peter J; Mandel, David R; Bouak, Fethi; Nakashima, Ann; Smith, Ingrid; Lam, Quan

    2013-01-01

    There is evidence to suggest that successful lying necessitates cognitive effort. We tested this hypothesis by instructing participants to lie or tell the truth under conditions of high and low working memory (WM) load. The task required participants to register a response on 80 trials of identical structure within a 2 (WM Load: high, low) × 2 (Instruction: truth or lie) repeated-measures design. Participants were less accurate and responded more slowly when WM load was high, and also when they lied. High WM load activated the fronto-parietal WM network including dorsolateral prefrontal cortex (PFC), middle frontal gyrus, precuneus, and intraparietal cortex. Lying activated areas previously shown to underlie deception, including middle and superior frontal gyrus and precuneus. Critically, successful lying in the high vs. low WM load condition was associated with longer response latency, and it activated the right inferior frontal gyrus-a key brain region regulating inhibition. The same pattern of activation in the inferior frontal gyrus was absent when participants told the truth. These findings demonstrate that lying under high cognitive load places a burden on inhibition, and that the right inferior frontal gyrus may provide a neural marker for successful lying.

  6. Association of neopterin as a marker of immune system activation and juvenile rheumatoid arthritis activity

    Directory of Open Access Journals (Sweden)

    Mones M. Abu Shady

    2015-07-01

    Full Text Available Objective: To evaluate neopterin plasma concentrations in patients with active juvenile idiopathic arthritis (JIA and correlate them with disease activity. Methods: Sixty patients diagnosed as active JIA, as well as another 60 apparently healthy age- and gender-matched children as controls, were recruited from the Pediatrics Allergy and Immunology Clinic, Ain Shams University. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score 27 (JADAS-27. Laboratory investigations were performed for all patients, including determination of hemoglobin concentration (Hgb, erythrocyte sedimentation rate (ESR, and C-reactive protein. Serum concentrations of tumor necrosis factor-alpha (TNF-α, interleukin-6 (IL-6, monocyte chemoattractant protein-1 (MCP-1, and neopterin were measured. Results: Significant differences were found between JIA patients and controls with regard to the mean levels of Hgb, ESR, TNF-α, IL-6, and MCP-1 (p  0.05. Multiple linear regression analysis showed that JADAS- 27 and ESR were the main variables associated with serum neopterin in JIA patients (p  0,05. A análise de regressão linear múltipla mostrou que o JADAS-27 e a TSE foram as principais variáveis associadas à neopterina sérica em pacientes com AIJ (p < 0,05. Conclusão: A elevação das concentrações plasmáticas de neopterina em pacientes com AIJ precoce pode indicar um estímulo de resposta imune. A neopterina sérica pode ser usada como um indicador sensível para analisar o histórico de inflamações e o escore de atividade da doença em pacientes com AIJ. Keywords: MCP-1, TNF-α, Rheumatoid arthritis, Palavras-chave: MCP-1, FNT-α, Artrite reumatoide

  7. Increased serum ß2-microglobulin is associated with clinical and immunological markers of disease activity in systemic lupus erythematosus patients

    DEFF Research Database (Denmark)

    Hermansen, M-L F; Hummelshøj, L; Lundsgaard, Dorte

    2012-01-01

    The objective of this study was to explore the relationship between serum levels of ß2-microglobulin (ß2MG), which some studies suggest reflect disease activity in systemic lupus erythematosus (SLE), and various clinical and immunological markers of disease activity in SLE. Twenty-six SLE patients...

  8. 2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated disruption of the CD40 ligand-induced activation of primary human B cells

    International Nuclear Information System (INIS)

    Lu Haitian; Crawford, Robert B.; Kaplan, Barbara L.F.; Kaminski, Norbert E.

    2011-01-01

    Suppression of the primary antibody response is particularly sensitive to suppression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice; however, surprisingly little is known concerning the effects of TCDD on humoral immunity or B cell function in humans. Results from a limited number of previous studies, primarily employing in vitro activation models, suggested that human B cell effector function is suppressed by TCDD. The present study sought to extend these findings by investigating, in primary human B cells, the effects of TCDD on several critical stages leading to antibody secretion including activation and plasmacytic differentiation using an in vitro CD40 ligand activation model. These studies revealed important differences in the response of human and mouse B cells to TCDD, the most striking being altered expression of plasmacytic differentiation regulators, B lymphocyte-induced maturation protein 1 and paired box protein 5, in mouse but not human B cells. The activation of human B cells was profoundly impaired by TCDD, as evidenced by decreased expression of activation markers CD80, CD86, and CD69. The impaired activation correlated with decreased cell viability, which prevented the progression of human B cells toward plasmacytic differentiation. TCDD treatment also attenuated the early activation of mitogen-activated protein kinases (MAPK) and Akt signaling in human B cells. Collectively, the present study provided experimental evidence for novel mechanisms by which TCDD impairs the effector function of primary human B cells. - Highlights: → In this study primary human and mouse B cell toxicity to TCDD was compared. → TCDD altered the expression of Blimp-1 and Pax5 in mouse but not human B cells. → TCDD markedly suppressed human B cell activation as characterized by CD80, CD86 and CD69 expression. → TCDD inhibited ERK, p38, and Akt phosphorylation in human B cells.

  9. Specific marker of feigned memory impairment: The activation of left superior frontal gyrus.

    Science.gov (United States)

    Chen, Zi-Xiang; Xue, Li; Liang, Chun-Yu; Wang, Li-Li; Mei, Wei; Zhang, Qiang; Zhao, Hu

    2015-11-01

    Faking memory impairment means normal people complain lots of memory problems without organic damage in forensic assessments. Using alternative forced-choice paradigm, containing digital or autobiographical information, previous neuroimaging studies have indicated that faking memory impairment could cause the activation in the prefrontal and parietal regions, and might involve a fronto-parietal-subcortical circuit. However, it is still unclear whether different memory types have influence on faking or not. Since different memory types, such as long-term memory (LTM) and short-term memory (STM), were found supported by different brain areas, we hypothesized that feigned STM or LTM impairment had distinct neural activation mapping. Besides that, some common neural correlates may act as the general characteristic of feigned memory impairment. To verify this hypothesis, the functional magnetic resonance imaging (fMRI) combined with an alternative word forced-choice paradigm were used in this study. A total of 10 right-handed participants, in this study, had to perform both STW and LTM tasks respectively under answering correctly, answering randomly and feigned memory impairment conditions. Our results indicated that the activation of the left superior frontal gyrus and the left medial frontal gyrus was associated with feigned LTM impairment, whereas the left superior frontal gyrus, the left precuneus and the right anterior cingulate cortex (ACC) were highly activated while feigning STM impairment. Furthermore, an overlapping was found in the left superior frontal gyrus, and it suggested that the activity of the left superior frontal gyrus might be acting as a specific marker of feigned memory impairment. Copyright © 2015. Published by Elsevier Ltd.

  10. Relationship between Inflammation markers, Coagulation Activation and Impaired Insulin Sensitivity in Obese Healthy Women

    International Nuclear Information System (INIS)

    Soliman, S.Et; Shousha, M.A.

    2011-01-01

    Obesity, insulin resistance syndrome, and atherosclerosis are closely linked phenomena, often connected with a chronic low grade inflammatory state and pro thrombotic hypo fibrinolytic condition. This study investigated the relationship between impaired insulin sensitivity and selected markers of inflammation and thrombin generation in obese healthy women. The study included 36 healthy obese women (body mass index ≥ 30), with normal insulin sensitivity (NIS, n = 18) or impaired insulin sensitivity (IIS, n 18), and 10 non obese women (body mass index < 25).Impaired insulin sensitivity patients had significantly higher levels of high sensitivity C-reactive protein (hs-CRP), transforming growth factor -β1(TGF-β1), plasminogen activator inhibitor-1 (PAI-1), activated factor VII (VIIa), and prothrombin fragments 1 + 2 (F1 + 2) compared with either control subjects or normal insulin sensitivity patients. On the other hand, NIS patients had higher hs-CRP, TGF-β1, PAI-1, and factor VIIa, but not F1 + 2, levels than controls. Significant inverse correlations were observed between the insulin sensitivity index and TGF-β1, hs-CRP, PAI-1; factor VIIa, and F1 + 2 levels. Moreover, significant direct correlations were noted between TGF-β1 and CRP, PAI-1, factor VIIa, and F1 + 2 concentrations. Finally, multiple regressions revealed that TGF-β1 and the insulin sensitivity index were independently related to F1 + 2. These results document an in vivo relationship between insulin sensitivity and coagulation activation in obesity. Here we report that obesity is associated with higher TGF-β, PAI-1, prothrombin fragments 1 and 2 (F1 + 2), and activated factor VII (VIIa) plasma levels, and that insulin resistance exacerbates these alterations. The elevated TGF-β1 levels detected in the obese population may provide a biochemical link between insulin resistance and an increased risk for cardiovascular disease

  11. The use of trypsin-like blood activity as a marker of pulmonary fibrosis severity.

    Directory of Open Access Journals (Sweden)

    V. V. Rodionova

    2018-05-01

    Full Text Available Purpose – to determine changes in the trypsin-like blood activity and its relationship with acute phase indices of inflammation in patients with pulmonary fibrosis (PF as a marker of course severity and prognosis of the disease. Materials and Methods: The study included 18 patients: 15 (83% women and 3 (17% men, mean age 53±2.5 years. The control group included 15 practically healthy persons. All the examined patients (n=18 were divided into two groups: with mild or moderately severe PF – 8 (44.4% patients (group I, severe PF – 10 (55.6% of patients (group II. Duration of the disease - from 1 month. up to 4 years. Patients underwent clinic-laboratory and anthropometric studies, a mMRC questionnaire was used, blood saturation was measured, lung radiography in 2 projections, echocardiography, and if necessary a high-resolution computer tomography etc were performed. Results and discussion: More than half of the patients were overweight (44,4% or had obesity of І-ІІІ st. (27.8%. The severity of dyspnea according to mMRC scale was 3.0 (3.0-4.0 points in patients of group II and 2.5 (2.0-3.0 points in patients of group I. There was a decrease in C-reactive protein (CRP in group I and a tendency to increase in patients of group II. When analyzing the indicator of trypsin-like blood activity (TLA, it was found that the median TLA at the beginning of the observation was twice as high as in healthy individuals, direct correlation was established between the level of TLA and the severity of the disease course. After treatment the level of TLA decreased in group I patients. In the severe course of PF, the average TLA level remained high. The progredient course of LF is characterized by severe clinical symptoms, a significant increase in TLA, CRP, reduced O2 saturation, a lack of response to treatment and an unfavorable prognosis. The TLA index can be used as a biochemical marker of the severity of PF along with the CRPindex, O2 saturation and

  12. Feasibility of proton-activated implantable markers for proton range verification using PET

    Science.gov (United States)

    Cho, Jongmin; Ibbott, Geoffrey; Gillin, Michael; Gonzalez-Lepera, Carlos; Titt, Uwe; Paganetti, Harald; Kerr, Matthew; Mawlawi, Osama

    2013-11-01

    Proton beam range verification using positron emission tomography (PET) currently relies on proton activation of tissue, the products of which decay with a short half-life and necessitate an on-site PET scanner. Tissue activation is, however, negligible near the distal dose fall-off region of the proton beam range due to their high interaction energy thresholds. Therefore Monte Carlo simulation is often supplemented for comparison with measurement; however, this also may be associated with systematic and statistical uncertainties. Therefore, we sought to test the feasibility of using long-lived proton-activated external materials that are inserted or infused into the target volume for more accurate proton beam range verification that could be performed at an off-site PET scanner. We irradiated samples of ≥98% 18O-enriched water, natural Cu foils, and >97% 68Zn-enriched foils as candidate materials, along with samples of tissue-equivalent materials including 16O water, heptane (C7H16), and polycarbonate (C16H14O3)n, at four depths (ranging from 100% to 3% of center of modulation (COM) dose) along the distal fall-off of a modulated 160 MeV proton beam. Samples were irradiated either directly or after being embedded in Plastic Water® or balsa wood. We then measured the activity of the samples using PET imaging for 20 or 30 min after various delay times. Measured activities of candidate materials were up to 100 times greater than those of the tissue-equivalent materials at the four distal dose fall-off depths. The differences between candidate materials and tissue-equivalent materials became more apparent after longer delays between irradiation and PET imaging, due to the longer half-lives of the candidate materials. Furthermore, the activation of the candidate materials closely mimicked the distal dose fall-off with offsets of 1 to 2 mm. Also, signals from the foils were clearly visible compared to the background from the activated Plastic Water® and balsa wood

  13. Cell Adhesion Molecule and Lymphocyte Activation Marker Expression during Experimental Vaginal Candidiasis

    Science.gov (United States)

    Wormley, Floyd L.; Chaiban, Joseph; Fidel, Paul L.

    2001-01-01

    Cell-mediated immunity by Th1-type CD4+ T cells is the predominant host defense mechanism against mucosal candidiasis. However, studies using an estrogen-dependent murine model of vaginal candidiasis have demonstrated little to no change in resident vaginal T cells during infection and no systemic T-cell infiltration despite the presence of Candida-specific systemic Th1-type responses in infected mice. The present study was designed to further investigate these observations by characterizing T-cell activation and cell adhesion molecule expression during primary and secondary C. albicans vaginal infections. While flow cytometry analysis of activation markers showed some evidence for activation of CD3+ draining lymph node and/or vaginal lymphocytes during both primary and secondary vaginal Candida infection, CD3+ cells expressing the homing receptors and integrins α4β7, αM290β7, and α4β1 in draining lymph nodes of mice with primary and secondary infections were reduced compared to results for uninfected mice. At the local level, few vaginal lymphocytes expressed integrins, with only minor changes observed during both primary and secondary infections. On the other hand, immunohistochemical analysis of vaginal cell adhesion molecule expression showed increases in mucosal addressin cell adhesion molecule 1 and vascular cell adhesion molecule 1 expression during both primary and secondary infections. Altogether, these data suggest that although the vaginal tissue is permissive to cellular infiltration during a vaginal Candida infection, the reduced numbers of systemic cells expressing the reciprocal cellular adhesion molecules may preempt cellular infiltration, thereby limiting Candida-specific T-cell responses against infection. PMID:11447188

  14. Mucosal CCR1 gene expression as a marker of molecular activity in Crohn's disease: preliminary data.

    Science.gov (United States)

    Dobre, Maria; Mănuc, Teodora Ecaterina; Milanesi, Elena; Pleşea, Iancu Emil; Ţieranu, Eugen Nicolae; Popa, Caterina; Mănuc, Mircea; Preda, Carmen Monica; Ţieranu, Ioana; Diculescu, Mihai Mircea; Ionescu, Elena Mirela; Becheanu, Gabriel

    2017-01-01

    A series of mechanisms of immune response, inflammation and apoptosis have been demonstrated to contribute to the appearance and evolution of Crohn's disease (CD) through the overexpression of several cytokines and chemokines in a susceptible host. The aim of this study was to identify the differences in gene expression profiles analyzing a panel of candidate genes in the mucosa from patients with active CD (CD-A), patients in remission (CD-R), and normal controls. Nine individuals were enrolled in the study: six CD patients (three with active lesions, three with mucosal healing) and three controls without inflammatory bowel disease (IBD) seen on endoscopy. All the individuals underwent mucosal biopsy during colonoscopy. Gene expression levels of 84 genes previously associated with CD were evaluated by polymerase chain reaction (PCR) array. Ten genes out of 84 were found significantly differentially expressed in CD-A (CCL11, CCL25, DEFA5, GCG, IL17A, LCN2, REG1A, STAT3, MUC1, CCR1) and eight genes in CD-R (CASP1, IL23A, STAT1, STAT3, TNF, CCR1, CCL5, and HSP90B1) when compared to controls. A quantitative gene expression analysis revealed that CCR1 gene was more expressed in CD-A than in CD-R. Our data suggest that CCR1 gene may be a putative marker of molecular activity of Crohn's disease. Following these preliminary data, a confirmation in larger cohort studies could represent a useful method in order to identify new therapeutic targets.

  15. Physical activity intensity and surrogate markers for cardiovascular health in adolescents.

    Science.gov (United States)

    Radtke, Thomas; Kriemler, Susi; Eser, Prisca; Saner, Hugo; Wilhelm, Matthias

    2013-05-01

    We examined the impact of physical activity (PA) on surrogate markers of cardiovascular health in adolescents. 52 healthy students (28 females, mean age 14.5 ± 0.7 years) were investigated. Microvascular endothelial function was assessed by peripheral arterial tonometry to determine reactive hyperemic index (RHI). Vagal activity was measured using 24 h analysis of heart rate variability [root mean square of successive normal-to-normal intervals (rMSSD)]. Exercise testing was performed to determine peak oxygen uptake ([Formula: see text]) and maximum power output. PA was assessed by accelerometry. Linear regression models were performed and adjusted for age, sex, skinfolds, and pubertal status. The cohort was dichotomized into two equally sized activity groups (low vs. high) based on the daily time spent in moderate-to-vigorous PA (MVPA, 3,000-5,200 counts(.)min(-1), model 1) and vigorous PA (VPA, >5,200 counts(.)min(-1), model 2). MVPA was an independent predictor for rMSSD (β = 0.448, P = 0.010), and VPA was associated with maximum power output (β = 0.248, P = 0.016). In model 1, the high MVPA group exhibited a higher vagal tone (rMSSD 49.2 ± 13.6 vs. 38.1 ± 11.7 ms, P = 0.006) and a lower systolic blood pressure (107.3 ± 9.9 vs. 112.9 ± 8.1 mmHg, P = 0.046). In model 2, the high VPA group had higher maximum power output values (3.9 ± 0.5 vs. 3.4 ± 0.5 W kg(-1), P = 0.012). In both models, no significant differences were observed for RHI and [Formula: see text]. In conclusion, in healthy adolescents, PA was associated with beneficial intensity-dependent effects on vagal tone, systolic blood pressure, and exercise capacity, but not on microvascular endothelial function.

  16. Antismooth muscle and antiactin antibodies are indirect markers of histological and biochemical activity of autoimmune hepatitis.

    Science.gov (United States)

    Couto, Claudia A; Bittencourt, Paulo L; Porta, Gilda; Abrantes-Lemos, Clarice P; Carrilho, Flair J; Guardia, Bianca D; Cançado, Eduardo L R

    2014-02-01

    Reactivity and titers of autoantibodies vary during the course of autoimmune hepatitis (AIH), and some autoantibodies have been associated with disease activity and adverse outcomes after treatment. The aim of this study was to assess the autoantibody behavior in AIH and its significance as predictors of biochemical and histological remission. A total of 117 patients with AIH (mean age 18.6 [4-69] years) were evaluated and tested for autoantibodies at disease onset and successively (mean 3.2 [2-6] times) after a mean follow-up evaluation of 70 [20-185] months. Antismooth muscle (ASMA), antiliver kidney microsome type 1 (anti-LKM1), antiliver cytosol type 1 (anti-LC1), antimitochondrial, antinuclear (ANA), and antiactin antibodies (AAA) were determined at disease onset and 379 other times during the follow-up evaluation through indirect immunofluorescence in rodent tissues, HEp-2 cells, and human fibroblasts. Anti-SLA/LP were assessed 45 times in the follow-up evaluation of 19 patients using enzyme-linked immunosorbent assay (ELISA). Upon admission, AIH types 1 and 2 were observed in 95 and 17 patients, respectively. Five subjects had AIH with anti-SLA/LP as the sole markers. Patients initially negative for AAA did not develop these antibodies thereafter. ANA were detected de novo in six and three subjects with AIH types 1 and 2, respectively. After treatment, only ASMA (>1:80) and AAA (>1:40) were significantly associated with biochemical (76.9% and 79.8%) and histological features (100% and 100%) of disease activity (P < 0.001). With the exception of ANA, the autoantibody profile does not markedly vary in the course of AIH. The persistence of high titers of ASMA and/or AAA in patients with AIH is associated with disease activity. © 2013 by the American Association for the Study of Liver Diseases.

  17. Effects of Ingestion of Different Amounts of Carbohydrate after Endurance Exercise on Circulating Cytokines and Markers of Neutrophil Activation

    Directory of Open Access Journals (Sweden)

    Kumpei Tanisawa

    2018-04-01

    Full Text Available We aimed to examine the effects of ingestion of different amounts of carbohydrate (CHO after endurance exercise on neutrophil count, circulating cytokine levels, and the markers of neutrophil activation and muscle damage. Nine participants completed three separate experimental trials consisting of 1 h of cycling exercise at 70% V · O2 max, followed by ingestion of 1.2 g CHO·kg body mass−1·h−1 (HCHO trial, 0.2 g CHO·kg body mass−1·h−1 (LCHO trial, or placebo (PLA trial during the 2 h recovery phase in random order. Circulating glucose, insulin, and cytokine levels, blood cell counts, and the markers of neutrophil activation and muscle damage were measured. The concentrations of plasma glucose and serum insulin at 1 h after exercise were higher in the HCHO trial than in the LCHO and PLA trials. Although there were significant main effects of time on several variables, including neutrophil count, cytokine levels, and the markers of neutrophil activation and muscle damage, significant time × trial interactions were not observed for any variables. These results suggest that CHO ingestion after endurance exercise does not enhance exercise-induced increase in circulating neutrophil and cytokine levels and markers of neutrophil activation and muscle damage, regardless of the amount of CHO ingested.

  18. Sulforhodamine 101, a widely used astrocyte marker, can induce cortical seizure-like activity at concentrations commonly used

    DEFF Research Database (Denmark)

    Rasmussen, Rune; Nedergaard, Maiken; Petersen, Nicolas Caesar

    2016-01-01

    Sulforhodamine 101 (SR101) is a preferential astrocyte marker widely used in 2-photon microscopy experiments. Here we show, that topical loading of two commonly used SR101 concentrations, 100 μM and 250 μM when incubated for 10 min, can induce seizure-like local field potential (LFP) activity in ...

  19. ADENOSINE DEAMINASE ACTIVITY AND SERUM C-REACTIVE PROTEIN AS PROGNOSTIC MARKERS OF CHAGAS DISEASE SEVERITY

    Directory of Open Access Journals (Sweden)

    Iván Darío BRAVO-TOBAR

    2015-10-01

    Full Text Available SUMMARY Chagas disease is a public health problem worldwide. The availability of diagnostic tools to predict the development of chronic Chagas cardiomyopathy is crucial to reduce morbidity and mortality. Here we analyze the prognostic value of adenosine deaminase serum activity (ADA and C-reactive protein serum levels (CRP in chagasic individuals. One hundred and ten individuals, 28 healthy and 82 chagasic patients were divided according to disease severity in phase I (n = 35, II (n = 29, and III (n = 18. A complete medical history, 12-lead electrocardiogram, chest X-ray, and M-mode echocardiogram were performed on each individual. Diagnosis of Chagas disease was confirmed by ELISA and MABA using recombinant antigens; ADA was determined spectrophotometrically and CRP by ELISA. The results have shown that CRP and ADA increased linearly in relation to disease phase, CRP being significantly higher in phase III and ADA at all phases. Also, CRP and ADA were positively correlated with echocardiographic parameters of cardiac remodeling and with electrocardiographic abnormalities, and negatively with ejection fraction. CRP and ADA were higher in patients with cardiothoracic index ≥ 50%, while ADA was higher in patients with ventricular repolarization disturbances. Finally, CRP was positively correlated with ADA. In conclusion, ADA and CRP are prognostic markers of cardiac dysfunction and remodeling in Chagas disease.

  20. Longitudinal relationship between inflammatory markers in adolescents and childhood fatness, fitness and physical activity

    DEFF Research Database (Denmark)

    Bugge, Anna; Hermansen, Bianca El-Naaman; Froberg, Karsten

    Low-grade inflammation may provide a mechanism linking obesity with cardiometabolic diseases and is also related to aerobic fitness (VO2max) and physical activity (PA). However, the longitudinal associations between these factors over the course of childhood and young adolescence are yet....... PA was measured for four consecutive days (Actigraph). VO2max was directly measured. Fasting blood samples were analyzed for inflammatory markers. RESULTS: Significant correlations were found between S4SF at age 6 and C-reactive protein (CRP) level at age 13 for both boys and girls (r=0.330 and 0.......293 respectively, p=0.0001). S4SF at age 6 was related to interleukin-6 (IL6) level at age 13 only for boys (r=0.165, p=0.019). Children in the highest tertile of S4SF at age 6 had an odds ratio of 3.68 (p=0.0001) being in the highest tertile of CRP at age 13, compared to the lowest tertile. VO2max at age 6...

  1. Markers of endogenous desaturase activity and risk of coronary heart disease in the CAREMA cohort study.

    Directory of Open Access Journals (Sweden)

    Yingchang Lu

    Full Text Available BACKGROUND: Intakes of n-3 polyunsaturated fatty acids (PUFAs, especially EPA (C20:5n-3 and DHA (C22:6n-3, are known to prevent fatal coronary heart disease (CHD. The effects of n-6 PUFAs including arachidonic acid (C20:4n-6, however, remain unclear. δ-5 and δ-6 desaturases are rate-limiting enzymes for synthesizing long-chain n-3 and n-6 PUFAs. C20:4n-6 to C20:3n-6 and C18:3n-6 to C18:2n-6 ratios are markers of endogenous δ-5 and δ-6 desaturase activities, but have never been studied in relation to incident CHD. Therefore, the aim of this study was to investigate the relation between these ratios as well as genotypes of FADS1 rs174547 and CHD incidence. METHODS: We applied a case-cohort design within the CAREMA cohort, a large prospective study among the general Dutch population followed up for a median of 12.1 years. Fatty acid profile in plasma cholesteryl esters and FADS1 genotype at baseline were measured in a random subcohort (n = 1323 and incident CHD cases (n = 537. Main outcome measures were hazard ratios (HRs of incident CHD adjusted for major CHD risk factors. RESULTS: The AA genotype of rs174547 was associated with increased plasma levels of C204n-6, C20:5n-3 and C22:6n-3 and increased δ-5 and δ-6 desaturase activities, but not with CHD risk. In multivariable adjusted models, high baseline δ-5 desaturase activity was associated with reduced CHD risk (P for trend = 0.02, especially among those carrying the high desaturase activity genotype (AA: HR (95% CI = 0.35 (0.15-0.81 for comparing the extreme quintiles. High plasma DHA levels were also associated with reduced CHD risk. CONCLUSION: In this prospective cohort study, we observed a reduced CHD risk with an increased C20:4n-6 to C20:3n-6 ratio, suggesting that δ-5 desaturase activity plays a role in CHD etiology. This should be investigated further in other independent studies.

  2. Evaluation of Fibroblast Activation Protein-Alpha (FAP) as a Diagnostic Marker and Therapeutic Target in Prostate Cancer

    Science.gov (United States)

    2009-12-01

    low molecular weight recombinant human gelatin: development of a substitute for animal- derived gelatin with superior features, Protein Expr. Purif...by the honey - bee , could be modified to a form that was no longer hydro- lyzed by the native activator protease DPP4 but, instead, was hydrolyzed by...TITLE: Evaluation of Fibroblast Activation Protein -Alpha (FAP) as a Diagnostic Marker and Therapeutic Target in Prostate Cancer PRINCIPAL

  3. Association of inflammatory markers with physical activity, family history and other diabetic complications in patients of diabetic retinopathy

    International Nuclear Information System (INIS)

    Zaidi, A.; Rashif, A.; Waheed, P.; Ishaq, M.

    2017-01-01

    Objective: To study the association of inflammatory markers with physical activity, family history and other complications among patients of diabetic retinopathy. Study Design: Cross sectional comparative study. Place and Duration of Study: Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi in collaboration with Armed Forces Institute of Ophthalmology (AFIO) and Military Hospital Laboratories, Rawalpindi from Jan 2016 to Jun 2016. Material and Methods: A total of 90 diagnosed patients of diabetic retinopathy of ages 40-70 years were enrolled from Armed Forces Institute of Ophthalmology, Rawalpindi. Their inflammatory markers (ESR and CRP) were assessed and their levels were compared with their physical activity, family history and other complications of diabetes already developed in them. These were then compared with those of 90 normal healthy controls enrolled from general population using independent student's t test and one way Anova test for scale variables and Chi square test for nominal variables. Results: Both patients and controls were age and gender matched with mean age of 60 +- 8.9 years in patients and 59 +- 13.02 years in controls. Among 90 patients enrolled 51(56.7 percent) were males and 39 (43.3) were females. And among 90 controls 49 (54.4 percent) were males and 41(45.6 percent) were females. An inverse association was observed between inflammatory markers and physical activity with ap-value of 0.001. On the contrary a strong positive association was observed between inflammatory markers and family history and complications of diabetes with a p-value 0.001. Conclusion: There is an inverse association of inflammatory markers with physical activity and a direct association of these with family history and complications of diabetes among patients of diabetic retinopathy. (author)

  4. Minocycline attenuates HIV-1 infection and suppresses chronic immune activation in humanized NOD/LtsZ-scidIL-2Rγnull mice

    Science.gov (United States)

    Singh, Maneesh; Singh, Pratibha; Vaira, Dolores; Amand, Mathieu; Rahmouni, Souad; Moutschen, Michel

    2014-01-01

    More than a quarter of a century of research has established chronic immune activation and dysfunctional T cells as central features of chronic HIV infection and subsequent immunodeficiency. Consequently, the search for a new immunomodulatory therapy that could reduce immune activation and improve T-cell function has been increased. However, the lack of small animal models for in vivo HIV study has hampered progress. In the current study, we have investigated a model of cord blood haematopoietic progenitor cells (CB-HPCs) -transplanted humanized NOD/LtsZ-scidIL-2Rγnull mice in which progression of HIV infection is associated with widespread chronic immune activation and inflammation. Indeed, HIV infection in humanized NSG mice caused up-regulation of several T-cell immune activation markers such as CD38, HLA-DR, CD69 and co-receptor CCR5. T-cell exhaustion markers PD-1 and CTLA-4 were found to be significantly up-regulated on T cells. Moreover, increased plasmatic levels of lipopolysaccharide, sCD14 and interleukin-10 were also observed in infected mice. Treatment with minocycline resulted in a significant decrease of expression of cellular and plasma immune activation markers, inhibition of HIV replication and improved T-cell counts in HIV-infected humanized NSG mice. The study demonstrates that minocycline could be an effective, low-cost adjunctive treatment to regulate chronic immune activation and replication of HIV. PMID:24409837

  5. Circulating macrophage activation markers, CD163 and CD206, are associated with disease severity and treatment response in patients with autoimmune hepatitis

    DEFF Research Database (Denmark)

    Grønbæk, Henning; Kazankov, Konstantin; Jessen, Niels

    Circulating macrophage activation markers, CD163 and CD206, are associated with disease severity and treatment response in patients with autoimmune hepatitis......Circulating macrophage activation markers, CD163 and CD206, are associated with disease severity and treatment response in patients with autoimmune hepatitis...

  6. Analysis of correlations between selected endothelial cell activation markers, disease activity, and nailfold capillaroscopy microvascular changes in systemic lupus erythematosus patients.

    Science.gov (United States)

    Ciołkiewicz, Mariusz; Kuryliszyn-Moskal, Anna; Klimiuk, Piotr Adrian

    2010-02-01

    The aim of the study was to evaluate the correlation between selected serum endothelial cell activation markers such as vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble thrombomodulin (sTM), soluble E-selectin (sE-selectin), disease activity, and microvascular changes determined by nailfold capillaroscopy in patients with systemic lupus erythematosus (SLE). Serum levels of VEGF, ET-1, sTM, and sE-selectin were determined by an enzyme-linked immunosorbent assay in 80 SLE patients. The disease activity was measured with Systemic Lupus Erythematosus Disease Activity Index score. Nailfold capillaroscopy was performed in all patients. Positive correlation was found between VEGF and both ET-1 (r = 0.294, p nailfold capillaroscopy (r = 0.458, p nailfold capillaroscopy. The relationship between changes in nailfold capillaroscopy, endothelial cell activation markers, and the clinical activity of SLE points to an important role of microvascular abnormalities in the clinical manifestation of the disease.

  7. The Relevance of Osteoclastic and Osteoblastic Activity Markers Follow-Up in Patients on Antiresorptive Osteoporosis Treatment.

    Science.gov (United States)

    Smilic, Tanja N; Novakovic, Tatjana R; Markovic-Jovanovic, Snezana R; Smilic, Ljiljana L J; Mitic, Javorka S; Radunovic, Miodrag L

    2017-11-02

    In general, markers of bone formation and markers of bone resorption are changing synergistically, so the monitoring of any osteoclastic and any osteoblastic marker should reflect the rate of bone transformation. The aim of the study is to monitor the bone metabolism markers in postmenopausal women with osteoporosis and osteopenia along with the variations caused by the effects of bisphosphonate therapy. The study involved 55 women of average age of 57.95 years, with osteopenia or osteoporosis. The patients with osteoporosis were treated with bisphosphonates (75 mg once a week); the laboratory tests were performed before the treatment and 6 months later. Patients with osteopenia were evaluated at the first assessment and 6 months later. The tests included bone densitometry, dual-energy X-ray absorptiometry, osteocalcin, alkaline phosphatase, collagen 1 N-terminal pro-peptide (P1NP), and beta C telopeptide of type I collagen (CTX). The mean T-score was -2.80 ± 0.63 before therapy and -2.64 ± 0.45 6 months later (p < 0.001). Women with osteoporosis had elevated levels of osteocalcin and P1NP at the first assessment, whereas the alkaline phosphatase level did not change with the treatment. After the introduction of antiresorptive therapy, the levels of osteocalcin and P1NP significantly decreased (p < 0.001). In the group with osteopenia, the biochemical markers activity were increased in both assessments. In patients with osteoporosis, Beta-CTX was increased in the first evaluation, and decreased after treatment (p = 0.001). The results indicate that the assessment of biochemical markers of bone metabolism show excellent results in the assessment of prognosis, monitoring the course and the response to various treatment regimens of osteoporosis and evince strong correlation with standard densitometry and dual-energy X-ray absorptiometry procedures. P1NP and CTX show better diagnostic applicability compared with osteocalcin and alkaline phosphatase

  8. Modification of T-cells activation markers expression of peripheral T lymphocytes of people, who dwell in radiation polluted zone

    International Nuclear Information System (INIS)

    Baeva, E.V.; Sokolenko, V.L.; Bazyka, D.A.

    1998-01-01

    Effect of ionizing radiation low doses on the expression of activation surface markers of T-cells in residents of contaminated areas resulted from the Chernobyl accident is studied. Increase in the number of T-lymphocytes with CD4 + CD25 + and CD4 + HLA-DR + membrane phenotypes in peripheral blood is observed. Appearance of non mature CD4 + CD8 + phenotype T-cells inclined to the apoptosis development in population circulation is accentuated [ru

  9. Hair cortisol levels as a retrospective marker of hypothalamic-pituitary axis activity throughout pregnancy: Comparison to salivary cortisol

    OpenAIRE

    D’Anna-Hernandez, Kimberly L.; Ross, Randal G.; Natvig, Crystal L.; Laudenslager, Mark L.

    2011-01-01

    Maternal stress during pregnancy is associated with negative maternal/child outcomes. One potential biomarker of the maternal stress response is cortisol, a product of activity of the hypothalamic-pituitary-adrenal axis. This study evaluated cortisol levels in hair throughout pregnancy as a marker of total cortisol release. Cortisol levels in hair have been shown to be easily quantifiable and may be representative of total cortisol release more than single saliva or serum measures. Hair corti...

  10. Immune activation markers in peripartum women in Botswana: association with feeding strategy and maternal morbidity.

    Directory of Open Access Journals (Sweden)

    Elizabeth S Russell

    Full Text Available Hormone levels shift the immune state in HIV-uninfected pregnant and breastfeeding women away from Th1 responses and toward regulation to permit fetal tolerance. Limited data exist on inflammation during pregnancy or postpartum in HIV-infected women, though certain inflammatory markers are associated with adverse health outcomes among HIV-infected persons. We measured hsCRP, D-dimer, IFN-γ, IL-6, IL-10 and TNF-α at 34 weeks gestation and six months postpartum in HIV-infected women from the Botswana Mashi PMTCT trial who were randomized to breastfeeding or formula-feeding. Differences in inflammatory markers between gestation and postpartum periods, and by randomized feeding method, were estimated using generalized estimating equations, adjusting for baseline plasma HIV-1 viral load, CD4 count, calendar time, and antiretroviral treatment status. Additionally, we studied the association between marker concentrations at six months postpartum and major adverse clinical events over the following 4.5 years, using case-cohort sampling and adjusted Cox proportional hazards models. In 86 breastfeeding and 75 formula-feeding women, hsCRP and D-dimer decreased significantly between 34 weeks gestation and six months postpartum, while IFN-γ increased. There was no significant association between inflammatory marker change and randomized feeding method after adjusting for multiple comparisons and removing outliers. In univariate analysis, TNF-α, D-dimer, and IFN-γ concentrations at six months postpartum were significant predictors of subsequent clinical events, and TNF-α remained significant in multivariate analysis (HR = 4.16, p = 0.001. In young HIV-infected women in Botswana inflammatory marker concentrations did not differ significantly between women who breast- vs. formula-fed. However, postpartum TNF-α level was predictive of subsequent adverse clinical event.

  11. Palmitic Acid Reduces Circulating Bone Formation Markers in Obese Animals and Impairs Osteoblast Activity via C16-Ceramide Accumulation.

    Science.gov (United States)

    Alsahli, Ahmad; Kiefhaber, Kathryn; Gold, Tziporah; Muluke, Munira; Jiang, Hongfeng; Cremers, Serge; Schulze-Späte, Ulrike

    2016-05-01

    Obesity and impaired lipid metabolism increase circulating and local fatty acid (FA) levels. Our previous studies showed that a high high-saturated -fat diet induced greater bone loss in mice than a high high-unsaturated-fat diet due to increased osteoclast numbers and activity. The impact of elevated FA levels on osteoblasts is not yet clear. We induced obesity in 4 week old male mice using a palmitic acid (PA)- or oleic acid (OA)-enriched high fat high-fat diet (HFD) (20 % of calories from FA), and compared them to mice on a normal (R) caloric diet (10 % of calories from FA). We collected serum to determine FA and bone metabolism marker levels. Primary osteoblasts were isolated; cultured in PA, OA, or control (C) medium; and assessed for mineralization activity, gene expression, and ceramide levels. Obese animals in the PA and OA groups had significantly lower serum levels of bone formation markers P1NP and OC compared to normal weight animals (*p < 0.001), with the lowest marker levels in animals on an PA-enriched HFD (*p < 0.001). Accordingly, elevated levels of PA significantly reduced osteoblast mineralization activity in vitro (*p < 0.05). Elevated PA intake significantly increased C16 ceramide accumulation. This accumulation was preventable through inhibition of SPT2 (serine palmitoyl transferase 2) using myriocin. Elevated levels of PA reduce osteoblast function in vitro and bone formation markers in vivo. Our findings suggest that saturated PA can compromise bone health by affecting osteoblasts, and identify a potential mechanism through which obesity promotes bone loss.

  12. Dietary Fructo-Oligosaccharides Attenuate Early Activation of CD4+ T Cells Which Produce both Th1 and Th2 Cytokines in the Intestinal Lymphoid Tissues of a Murine Food Allergy Model.

    Science.gov (United States)

    Tsuda, Masato; Arakawa, Haruka; Ishii, Narumi; Ubukata, Chihiro; Michimori, Mana; Noda, Masanari; Takahashi, Kyoko; Kaminogawa, Shuichi; Hosono, Akira

    2017-01-01

    Fructo-oligosaccharides (FOS) are prebiotic agents with immunomodulatory effects involving improvement of the intestinal microbiota and metabolome. In this study, we investigated the cellular mechanisms through which FOS modulate intestinal antigen-specific CD4+ T cell responses in food allergy, using OVA23-3 mice. OVA23-3 mice were fed an experimental diet containing either ovalbumin (OVA) or OVA and FOS for 1 week. Body weight and mucosal mast cell protease 1 in the serum were measured as the indicator of intestinal inflammation. Single-cell suspensions were prepared from intestinal and systemic lymphoid tissues for cellular analysis. Cytokine production was measured by ELISA. Activation markers and intracellular cytokines in CD4+ T cells were analyzed by flow cytometry. Activated CD4+ T cells were purified to examine cytokine production. Dietary intake of FOS provided moderate protection from the intestinal inflammation induced by the OVA-containing diet. FOS significantly reduced food allergy-induced Th2 cytokine responses in intestinal tissues but not in systemic tissues. FOS decreased OVA diet-induced IFN-γ+IL-4+ double-positive CD4+ T cells and early-activated CD45RBhighCD69+CD4+ T cells in the mesenteric lymph nodes. Furthermore, we confirmed that these CD45RBhighCD69+CD4+ T cells are able to produce high levels of IFN-γ and moderate level of IL-4, IL-10, and IL-13. Dietary intake of FOS during the development of food allergy attenuates the induction of intestinal Th2 cytokine responses by regulating early activation of naïve CD4+ T cells, which produce both Th1 and Th2 cytokines. Our results suggest FOS might be a potential food agent for the prevention of food allergy by modulating oral sensitization to food antigens. © 2017 S. Karger AG, Basel.

  13. Natalizumab stabilizes physical, cognitive, MRI, and OCT markers of disease activity: A prospective, non-randomized pilot study.

    Directory of Open Access Journals (Sweden)

    Garrick D Talmage

    Full Text Available Natalizumab is an effective therapy for multiple sclerosis (MS. Its effectiveness has been demonstrated in several clinical and imaging studies. The objective of this study was to further demonstrate the efficacy of natalizumab using a comprehensive battery of clinical and imaging markers in the same cohort of patients followed longitudinally, hence capturing the multi-faceted nature of the MS disease process. A prospective, open-label, pilot study of 20 MS patients treated with natalizumab was conducted. High resolution MRI, Symbol-Digit Modalities Test (SDMT, and Optical Coherence Tomography (OCT scans were obtained at baseline, 48, and 96 weeks. 15 patients completed the study. Natalizumab treatment decreased Expanded Disability Status Scale score (EDSS and no change in SDMT, Brain Parenchymal Fraction (BPF, or any of the OCT markers of retinal degeneration was observed. Thalamic and whole brain volume as assessed by Percentage Brain Volume Change (PBVC showed continuous deterioration. Higher baseline T2 lesion load correlated with increased rate of PBVC at 96-weeks (r = 0.566, R2 = 0.320, p = 0.035 and thalamic volume loss (r = -0.586, R2 = 0.344, p = 0.027. Most patients, 93%, achieved no evidence of disease activity (NEDA at 2 years, likely due to early disease duration and lower initial baseline lesion load. This study further demonstrates stabilization of clinical and imaging markers of disease activity during natalizumab treatment.

  14. Generation of Trichoderma atroviride mutants with constitutively activated G protein signaling by using geneticin resistance as selection marker

    Directory of Open Access Journals (Sweden)

    Gruber Sabine

    2012-11-01

    Full Text Available Abstract Background Species of the fungal genus Trichoderma are important industrial producers of cellulases and hemicellulases, but also widely used as biocontrol agents (BCAs in agriculture. In the latter function Trichoderma species stimulate plant growth, induce plant defense and directly antagonize plant pathogenic fungi through their mycoparasitic capabilities. The recent release of the genome sequences of four mycoparasitic Trichoderma species now forms the basis for large-scale genetic manipulations of these important BCAs. Thus far, only a limited number of dominant selection markers, including Hygromycin B resistance (hph and the acetamidase-encoding amdS gene, have been available for transformation of Trichoderma spp. For more extensive functional genomics studies the utilization of additional dominant markers will be essential. Results We established the Escherichia coli neomycin phosphotransferase II-encoding nptII gene as a novel selectable marker for the transformation of Trichoderma atroviride conferring geneticin resistance. The nptII marker cassette was stably integrated into the fungal genome and transformants exhibited unaltered phenotypes compared to the wild-type. Co-transformation of T. atroviride with nptII and a constitutively activated version of the Gα subunit-encoding tga3 gene (tga3Q207L resulted in a high number of mitotically stable, geneticin-resistant transformants. Further analyses revealed a co-transformation frequency of 68% with 15 transformants having additionally integrated tga3Q207L into their genome. Constitutive activation of the Tga3-mediated signaling pathway resulted in increased vegetative growth and an enhanced ability to antagonize plant pathogenic host fungi. Conclusion The neomycin phosphotransferase II-encoding nptII gene from Escherichia coli proved to be a valuable tool for conferring geneticin resistance to the filamentous fungus T. atroviride thereby contributing to an enhanced genetic

  15. Time-course of changes in neuronal activity markers following iTBS-TMS of the rat neocortex.

    Science.gov (United States)

    Hoppenrath, Kathrin; Funke, Klaus

    2013-03-01

    In a rat model of transcranial magnetic stimulation we could recently show that intermittent theta-burst stimulation (iTBS) affects the neocortical expression of the immediate early gene products c-Fos and zif268 as well as that of the two glutamic acid decarboxylase isoforms GAD65 and GAD67 and that of the calcium-binding proteins calbindin (CB) and parvalbumin (PV), known as markers of excitatory and inhibitory activity. We now analyzed in more detail the time course of changes in the expression of these proteins at 10, 20, 40, 80 and 160min following a single block of iTBS consisting of 600 stimuli. Initial increase in c-Fos, zif268 and GAD65 (20min) signals transient activation of excitatory and inhibitory neurons, thereafter first followed by a decrease in markers of activity of inhibitory neurons (GAD67, PV, CB: 20-80min) and then by a late decrease in c-Fos and GAD65 expression (160min). The results demonstrate that one iTBS block may have an after-effect of at least two different phases, an early phase with increased neuronal activity (c-Fos, zif268) but also the likelihood of increased GABA-release (GAD65), followed by a late phase (>40min) of reduced neuronal activity in excitatory and inhibitory systems which may indicate a state of reduced excitability. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. Serum neopterin and soluble CD163 as markers of macrophage activation in paracetamol (acetaminophen)-induced human acute liver injury.

    Science.gov (United States)

    Craig, D G; Lee, P; Pryde, E A; Hayes, P C; Simpson, K J

    2013-12-01

    Macrophage activation is implicated in the pathogenesis of the systemic inflammatory response syndrome (SIRS) following paracetamol (acetaminophen) overdose (POD). Neopterin is synthesised from macrophages and reflects the intensity of monocyte/macrophage activation. Soluble CD163 (sCD163) is a marker of alternatively activated M2 macrophages. To examine neopterin and sCD163 levels in a cohort of acute liver injury patients. Consecutive patients (n = 41, (18 (43.9%) male) with acute liver injury were enrolled. Neopterin and sCD163 levels were measured by ELISA. A total of 24/33 (72.7%) POD patients developed hepatic encephalopathy (HE), and therefore acute liver failure. Both neopterin and sCD163 levels were significantly higher in PODs compared with chronic liver disease (neopterin P paracetamol overdose, and reflect the degree of macrophage activation in this condition. Serum neopterin in particular may have value as an early proxy marker of macrophage activation following paracetamol overdose. © 2013 John Wiley & Sons Ltd.

  17. Activation states of blood eosinophils in asthma

    Science.gov (United States)

    Johansson, Mats W.

    2014-01-01

    Asthma is characterized by airway inflammation rich in eosinophils. Airway eosinophilia is associated with exacerbations and has been suggested to play a role in airway remodeling. Recruitment of eosinophils from the circulation requires that blood eosinophils become activated, leading to their arrest on the endothelium and extravasation. Circulating eosinophils can be envisioned as potentially being in different activation states, including non-activated, pre-activated or “primed”, or fully activated. In addition, the circulation can potentially be deficient of pre-activated or activated eosinophils, because such cells have marginated on activated endothelium or extravasated into the tissue. A number of eosinophil-surface proteins, including CD69, L-selectin, intercellular adhesion molecule-1 (ICAM-1, CD54), CD44, P-selectin glycoprotein ligand-1 (PSGL-1, CD162), cytokine receptors, Fc receptors, integrins including αM integrin (CD11b), and activated conformations of Fc receptors and integrins have been proposed to report cell activation. Variation in eosinophil activation states may be associated with asthma activity. Eosinophil-surface proteins proposed to be activation markers, with a particular focus on integrins, and evidence for associations between activation states of blood eosinophils and features of asthma are reviewed here. Partial activation of β1 and β2 integrins on blood eosinophils, reported by monoclonal antibodies (mAb) N29 and KIM-127, is associated with impaired pulmonary function and airway eosinophilia, respectively, in non-severe asthma. The association with lung function does not occur in severe asthma, presumably due to greater eosinophil extravasation, specifically of activated or pre-activated cells, in severe disease. PMID:24552191

  18. Mucosal-associated invariant T cell is a potential marker to distinguish fibromyalgia syndrome from arthritis.

    Directory of Open Access Journals (Sweden)

    Chie Sugimoto

    Full Text Available Fibromyalgia (FM is defined as a widely distributed pain. While many rheumatologists and pain physicians have considered it to be a pain disorder, psychiatry, psychology, and general medicine have deemed it to be a syndrome (FMS or psychosomatic disorder. The lack of concrete structural and/or pathological evidence has made patients suffer prejudice that FMS is a medically unexplained symptom, implying inauthenticity. Furthermore, FMS often exhibits comorbidity with rheumatoid arthritis (RA or spondyloarthritis (SpA, both of which show similar indications. In this study, disease specific biomarkers were sought in blood samples from patients to facilitate objective diagnoses of FMS, and distinguish it from RA and SpA.Peripheral blood mononuclear cells (PBMCs from patients and healthy donors (HD were subjected to multicolor flow cytometric analysis. The percentage of mucosal-associated invariant T (MAIT cells in PBMCs and the mean fluorescent intensity (MFI of cell surface antigen expression in MAIT cells were analyzed.There was a decrease in the MAIT cell population in FMS, RA, and SpA compared with HD. Among the cell surface antigens in MAIT cells, three chemokine receptors, CCR4, CCR7, and CXCR1, a natural killer (NK receptor, NKp80, a signaling lymphocyte associated molecule (SLAM family, CD150, a degrunulation marker, CD107a, and a coreceptor, CD8β emerged as potential biomarkers for FMS to distinguish from HD. Additionally, a memory marker, CD44 and an inflammatory chemokine receptor, CXCR1 appeared possible markers for RA, while a homeostatic chemokine receptor, CXCR4 deserved for SpA to differentiate from FMS. Furthermore, the drug treatment interruption resulted in alternation of the expression of CCR4, CCR5, CXCR4, CD27, CD28, inducible costimulatory molecule (ICOS, CD127 (IL-7 receptor α, CD94, NKp80, an activation marker, CD69, an integrin family member, CD49d, and a dipeptidase, CD26, in FMS.Combined with the currently available

  19. Mucosal-associated invariant T cell is a potential marker to distinguish fibromyalgia syndrome from arthritis.

    Science.gov (United States)

    Sugimoto, Chie; Konno, Takahiko; Wakao, Rika; Fujita, Hiroko; Fujita, Hiroyoshi; Wakao, Hiroshi

    2015-01-01

    Fibromyalgia (FM) is defined as a widely distributed pain. While many rheumatologists and pain physicians have considered it to be a pain disorder, psychiatry, psychology, and general medicine have deemed it to be a syndrome (FMS) or psychosomatic disorder. The lack of concrete structural and/or pathological evidence has made patients suffer prejudice that FMS is a medically unexplained symptom, implying inauthenticity. Furthermore, FMS often exhibits comorbidity with rheumatoid arthritis (RA) or spondyloarthritis (SpA), both of which show similar indications. In this study, disease specific biomarkers were sought in blood samples from patients to facilitate objective diagnoses of FMS, and distinguish it from RA and SpA. Peripheral blood mononuclear cells (PBMCs) from patients and healthy donors (HD) were subjected to multicolor flow cytometric analysis. The percentage of mucosal-associated invariant T (MAIT) cells in PBMCs and the mean fluorescent intensity (MFI) of cell surface antigen expression in MAIT cells were analyzed. There was a decrease in the MAIT cell population in FMS, RA, and SpA compared with HD. Among the cell surface antigens in MAIT cells, three chemokine receptors, CCR4, CCR7, and CXCR1, a natural killer (NK) receptor, NKp80, a signaling lymphocyte associated molecule (SLAM) family, CD150, a degrunulation marker, CD107a, and a coreceptor, CD8β emerged as potential biomarkers for FMS to distinguish from HD. Additionally, a memory marker, CD44 and an inflammatory chemokine receptor, CXCR1 appeared possible markers for RA, while a homeostatic chemokine receptor, CXCR4 deserved for SpA to differentiate from FMS. Furthermore, the drug treatment interruption resulted in alternation of the expression of CCR4, CCR5, CXCR4, CD27, CD28, inducible costimulatory molecule (ICOS), CD127 (IL-7 receptor α), CD94, NKp80, an activation marker, CD69, an integrin family member, CD49d, and a dipeptidase, CD26, in FMS. Combined with the currently available

  20. Role of PARP activity in lung cancer-induced cachexia: Effects on muscle oxidative stress, proteolysis, anabolic markers, and phenotype.

    Science.gov (United States)

    Chacon-Cabrera, Alba; Mateu-Jimenez, Mercè; Langohr, Klaus; Fermoselle, Clara; García-Arumí, Elena; Andreu, Antoni L; Yelamos, Jose; Barreiro, Esther

    2017-12-01

    Strategies to treat cachexia are still at its infancy. Enhanced muscle protein breakdown and ubiquitin-proteasome system are common features of cachexia associated with chronic conditions including lung cancer (LC). Poly(ADP-ribose) polymerases (PARP), which play a major role in chromatin structure regulation, also underlie maintenance of muscle metabolism and body composition. We hypothesized that protein catabolism, proteolytic markers, muscle fiber phenotype, and muscle anabolism may improve in respiratory and limb muscles of LC-cachectic Parp-1-deficient (Parp-1 -/- ) and Parp-2 -/- mice. In diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing mice (wild type, Parp-1 -/- , and Parp-2 -/- ), PARP activity (ADP-ribose polymers, pADPr), redox balance, muscle fiber phenotype, apoptotic nuclei, tyrosine release, protein ubiquitination, muscle-specific E3 ligases, NF-κB signaling pathway, markers of muscle anabolism (Akt, mTOR, p70S6K, and mitochondrial DNA) were evaluated along with body and muscle weights, and limb muscle force. Compared to wild type cachectic animals, in both respiratory and limb muscles of Parp-1 -/- and Parp-2 -/- cachectic mice: cancer induced-muscle wasting characterized by increased PARP activity, protein oxidation, tyrosine release, and ubiquitin-proteasome system (total protein ubiquitination, atrogin-1, and 20S proteasome C8 subunit) were blunted, the reduction in contractile myosin and atrophy of the fibers was attenuated, while no effects were seen in other structural features (inflammatory cells, internal or apoptotic nuclei), and markers of muscle anabolism partly improved. Activation of either PARP-1 or -2 is likely to play a role in muscle protein catabolism via oxidative stress, NF-κB signaling, and enhanced proteasomal degradation in cancer-induced cachexia. Therapeutic potential of PARP activity inhibition deserves attention. © 2017 Wiley Periodicals, Inc.

  1. Chitotriosidase enzyme activity: is this a possible chronic inflammation marker in children with common variable immunodeficiency and early atherosclerosis?

    Science.gov (United States)

    Azarsız, Elif; Karaca, Neslihan; Levent, Erturk; Kutukculer, Necil; Sozmen, Eser

    2017-11-01

    Background Common variable immunodeficiency is a rare clinically symptomatic primary immunodeficiency disorder which manifests a wide variability of symptoms, complications. Atherosclerosis in common variable immunodeficiency patients has not been investigated yet contrary to other severe clinical complications. We aimed to investigate the chitotriosidase enzyme's role as an inflammation and atherosclerosis marker in paediatric common variable immunodeficiency patients. Methods Common variable immunodeficiency patients (n = 24) and healthy controls (n = 23) evaluated for chitotriosidase activity with other inflammation markers (hsCRP, myeloperoxidase, serum amyloid A, ferritin), lipid profile and echocardiographic findings (carotid artery intima media thickness - cIMT, brachial artery flow-mediated vazodilatation - FMD%). Results In patients, the mean chitotriosidase activity (8.98 ± 6.28) was significantly higher than the controls (5.17 ± 3.42) ( P = 0.014). Chitotriosidase showed positive relation with hs-CRP ( P = 0.011) and SAA ( P = 0.011) but had no relation with ferritin ( P = 0.155), HDL ( P = 0.152) or LDL-cholesterol ( P = 0.380). Mean cIMT increased in patients compared with the controls ( P variable immunodeficiency patients demonstrated in vivo the presence of activated macrophages indicating ongoing inflammation. Echocardiographic diastolic functional deficiency, increased cIMT and decreased FMD% may be accepted as early atherosclerotic findings, but none of them showed relationship with chitotriosidase activities.

  2. Clinical laboratory markers of inflammation as determinants of chronic graft-versus-host disease activity and NIH global severity.

    Science.gov (United States)

    Grkovic, L; Baird, K; Steinberg, S M; Williams, K M; Pulanic, D; Cowen, E W; Mitchell, S A; Hakim, F T; Martires, K J; Avila, D N; Taylor, T N; Salit, R B; Rowley, S D; Zhang, D; Fowler, D H; Bishop, M R; Gress, R E; Pavletic, S Z

    2012-04-01

    Chronic graft-versus-host disease (cGVHD) remains a major cause of non-relapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Currently there are no accepted measures of cGVHD activity to aid in clinical management and disease staging. We analyzed clinical markers of inflammation in the sera of patients with established cGVHD and correlated those with definitions of disease activity. In all, 189 adults with cGVHD (33% moderate and 66% severe according to National Institutes of Health (NIH) global scoring) were consecutively enrolled onto a cross-sectional prospective cGVHD natural history study. At the time of evaluation, 80% were receiving systemic immunosuppression and failed a median of four prior systemic therapies (PST) for their cGVHD. Lower albumin (P<0.0001), higher C-reactive protein (P = 0.043), higher platelets (P = 0.030) and higher number of PST (P<0.0001) were associated with active disease defined as clinician's intention to intensify or alter systemic therapy due to the lack of response. Higher platelet count (P = 0.021) and higher number of PST (P<0.0001) were associated with more severe diseased defined by NIH global score. This study identified common laboratory indicators of inflammation that can serve as markers of cGVHD activity and severity.

  3. The Evaluation of Protein C Activity and Some Inflammatory Markers in Synovia of Patients Undergoing Total Knee Arthroplasty

    Directory of Open Access Journals (Sweden)

    Ahmet Ata Alturfan

    2011-06-01

    Full Text Available Objective: Total knee arthroplasty (TKA is a major risk factor for thrombosis in patients over 40 years of age and this risk persists for several weeks after the surgery. Since inflammatory mechanisms affect coagulation and the natural anticoagulant system, we aimed to investigate protein C activities and inflammatory markers in patients undergoing TKA surgery.Material and Methods: We included 20 osteoarthritis patients and 20 healthy controls. Protein C activity and tumor necrosis factor-α (TNF-α levels in plasma and synovia were evaluated by ELISA technique. Results: In the patient group, protein C activities decreased and TNF-α levels increased significantly both in synovia and plasma when compared with the controls. Erythrocyte sedimentation rate of the patient group was found to be significantly elevated in comparison to the controls. On the other hand, serum C reactive protein values increased insignificantly when compared to controls.Conclusion: The decreased activity of protein C and increased levels of inflammatory markers in preoperative plasma and synovia of the patient group may enhance the risk for developing thrombosis.

  4. Soluble CD163, a marker of Kupffer cell activation, is related to portal hypertension in patients with liver cirrhosis

    DEFF Research Database (Denmark)

    Grønbaek, H; Sandahl, T D; Mortensen, C

    2012-01-01

    BACKGROUND: Activation of Kupffer cells may be involved in the pathogenesis of portal hypertension by release of vasoconstrictive substances and fibrosis due to co-activation of hepatic stellate cells. AIM: To study soluble plasma (s) CD163, a specific marker of activated macrophages......, as a biomarker for portal hypertension in patients with liver cirrhosis. METHODS: We measured sCD163 concentration and the hepatic venous pressure gradient (HVPG) by liver vein catheterisation in 81 cirrhosis patients (Child-Pugh CP-A: n = 26, CP-B: n = 29, CP-C: n = 26) and 22 healthy subjects. We also measured...... for HVPG. These findings support a primary role of macrophage activation in portal hypertension, and may indicate a target for biological intervention....

  5. Effect of Comprehensive School Physical Activity Programming on Cardiometabolic Health Markers in Children From Low-Income Schools.

    Science.gov (United States)

    Burns, Ryan D; Brusseau, Timothy A; Hannon, James C

    2017-09-01

    The purpose of this study was to examine the effect of a 36-week Comprehensive School Physical Activity Program (CSPAP) on cardiometabolic health markers in children from low-income schools. Participants were 217 school-aged children (mean age = 10.1 ± 1.1 years; 114 girls, 103 boys) recruited from 5 low-income elementary schools. Cardiometabolic health markers were collected in a fasted state at 2 time-points, before commencement of the CSPAP for classroom and school level clustering and the modifying effects of grade level and sex, there were statistically significant improvements in HDL cholesterol (Δ = 3.6 mg/dL, 95% CI: 1.4 mg/dL to 5.8 mg/dL, P = .039), triglycerides (Δ = -14.1 mg/dL, 95% CI: -21.4 mg/dL to -6.8 mg/dL, P = .022), and mean arterial pressure (Δ = -4.3 mmHg, 95% CI: -8.5 mmHg to -0.1 mmHg, P = .041) following the 36-week CSPAP intervention. Sixth-grade children showed decreases in LDL cholesterol (Δ = -15.3 mg/dL, 95% CI: -30.5 mg/dL to -0.1 mg/dL, P = .033). Improvements in specific cardiometabolic health markers were found following a 36-week CSPAP in children from low-income schools.

  6. Effect of re-irradiation for painful bone metastases on urinary markers of osteoclast activity (NCIC CTG SC.20U)

    International Nuclear Information System (INIS)

    Chow, Edward; DeAngelis, Carlo; Chen, Bingshu E.; Azad, Azar; Meyer, Ralph M.; Wilson, Carolyn; Kerba, Marc; Bezjak, Andrea; Wilson, Paula; Nabid, Abdenour; Greenland, Jonathan; Rees, Gareth; Vieth, Reinhold; Wong, Rebecca K.S.; Hoskin, Peter

    2015-01-01

    Purpose: The NCIC CTG Symptom Control.20 randomized trial (SC.20) confirmed the effectiveness of re-irradiation to painful bone metastases. This companion study correlates urinary markers of osteoclast activity with response to re-irradiation, survival and skeletal related events (SREs). Methods: Pain response was assessed using the International Consensus Endpoints. Urinary markers of bone turnover-pyridinoline (PYD), deoxypyridinoline (DPD), N-telopeptide (NTX), Alpha and Beta cross-laps of C-telopeptide (CTX)-before and 1 month after re-irradiation were correlated to response to re-irradiation and then to both, either or none of the initial and re-irradiation: frequent responders (response to both); eventual responders (response to re-irradiation only); eventual non-responders (response to initial radiation only), and absolute non-responders (no response to both). Results: Significant differences between 40 responders and 69 non-responders to re-irradiation existed for PYD (p = 0.03) and DPD (p = 0.04) at baseline. When patients were categorized as frequent responders (N = 34), eventual responders (6), eventual non-responders (59) and absolute non-responders (10), the mean values of all markers in the absolute non-responders at baseline and the follow-up were about double those for the other three groups with statistically significant difference for DPD (p = 0.03) at baseline. Absolute non-responders had the worst survival. The few occurrences of the SREs did not allow meaningful comparisons among the groups. Conclusion: There were significant differences between responders and non-responders to re-irradiation for PYD and DPD at baseline. The urinary markers in the absolute non-responders were markedly elevated at both baseline and follow-up with a statistically significant difference for DPD at baseline

  7. Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP.

    Science.gov (United States)

    Elkord, Eyad; Abd Al Samid, May; Chaudhary, Belal

    2015-08-21

    Regulatory T cells (Tregs) are key players of immune regulation/dysregulation both in physiological and pathophysiological settings. Despite significant advances in understanding Treg function, there is still a pressing need to define reliable and specific markers that can distinguish different Treg subpopulations. Herein we show for the first time that markers of activated Tregs [latency associated peptide (LAP) and glycoprotein A repetitions predominant (GARP, or LRRC32)] are expressed on CD4+FoxP3- T cells expressing Helios (FoxP3-Helios+) in the steady state. Following TCR activation, GARP/LAP are up-regulated on CD4+Helios+ T cells regardless of FoxP3 expression (FoxP3+/-Helios+). We show that CD4+GARP+/-LAP+ Tregs make IL-10 immunosuppressive cytokine but not IFN-γ effector cytokine. Further characterization of FoxP3/Helios subpopulations showed that FoxP3+Helios+ Tregs proliferate in vitro significantly less than FoxP3+Helios- Tregs upon TCR stimulation. Unlike FoxP3+Helios- Tregs, FoxP3+Helios+ Tregs secrete IL-10 but not IFN-γ or IL-2, confirming they are bona fide Tregs with immunosuppressive characteristics. Taken together, Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP, and FoxP3+Helios+ Tregs have more suppressive characteristics, compared with FoxP3+Helios- Tregs. Our work implies that therapeutic modalities for treating autoimmune and inflammatory diseases, allergies and graft rejection should be designed to induce and/or expand FoxP3+Helios+ Tregs, while therapies against cancers or infectious diseases should avoid such expansion/induction.

  8. Age-associated changes in monocyte and innate immune activation markers occur more rapidly in HIV infected women.

    Directory of Open Access Journals (Sweden)

    Genevieve E Martin

    Full Text Available Aging is associated with immune dysfunction and the related development of conditions with an inflammatory pathogenesis. Some of these immune changes are also observed in HIV infection, but the interaction between immune changes with aging and HIV infection are unknown. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women.This cross-sectional study of HIV positive and negative women used whole blood flow cytometric analysis to characterize monocyte and CD8(+ T cell subsets. Plasma markers of innate immune activation were measured using standard ELISA-based assays.HIV positive women exhibited elevated plasma levels of the innate immune activation markers CXCL10 (p<0.001, soluble CD163 (sCD163, p = 0.001, sCD14 (p = 0.022, neopterin (p = 0.029 and an increased proportion of CD16(+ monocytes (p = 0.009 compared to uninfected controls. Levels of the innate immune aging biomarkers sCD163 and the proportion of CD16(+ monocytes were equivalent to those observed in HIV negative women aged 14.5 and 10.6 years older, respectively. CXCL10 increased with age at an accelerated rate in HIV positive women (p = 0.002 suggesting a synergistic effect between HIV and aging on innate immune activation. Multivariable modeling indicated that age-related increases in innate immune biomarkers CXCL10 and sCD163 are independent of senescent changes in CD8(+ T lymphocytes.Quantifying the impact of HIV on immune aging reveals that HIV infection in women confers the equivalent of a 10-14 year increase in the levels of innate immune aging markers. These changes may contribute to the increased risk of inflammatory age-related diseases in HIV positive women.

  9. Age-associated changes in monocyte and innate immune activation markers occur more rapidly in HIV infected women.

    Science.gov (United States)

    Martin, Genevieve E; Gouillou, Maelenn; Hearps, Anna C; Angelovich, Thomas A; Cheng, Allen C; Lynch, Fiona; Cheng, Wan-Jung; Paukovics, Geza; Palmer, Clovis S; Novak, Richard M; Jaworowski, Anthony; Landay, Alan L; Crowe, Suzanne M

    2013-01-01

    Aging is associated with immune dysfunction and the related development of conditions with an inflammatory pathogenesis. Some of these immune changes are also observed in HIV infection, but the interaction between immune changes with aging and HIV infection are unknown. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women. This cross-sectional study of HIV positive and negative women used whole blood flow cytometric analysis to characterize monocyte and CD8(+) T cell subsets. Plasma markers of innate immune activation were measured using standard ELISA-based assays. HIV positive women exhibited elevated plasma levels of the innate immune activation markers CXCL10 (p<0.001), soluble CD163 (sCD163, p = 0.001), sCD14 (p = 0.022), neopterin (p = 0.029) and an increased proportion of CD16(+) monocytes (p = 0.009) compared to uninfected controls. Levels of the innate immune aging biomarkers sCD163 and the proportion of CD16(+) monocytes were equivalent to those observed in HIV negative women aged 14.5 and 10.6 years older, respectively. CXCL10 increased with age at an accelerated rate in HIV positive women (p = 0.002) suggesting a synergistic effect between HIV and aging on innate immune activation. Multivariable modeling indicated that age-related increases in innate immune biomarkers CXCL10 and sCD163 are independent of senescent changes in CD8(+) T lymphocytes. Quantifying the impact of HIV on immune aging reveals that HIV infection in women confers the equivalent of a 10-14 year increase in the levels of innate immune aging markers. These changes may contribute to the increased risk of inflammatory age-related diseases in HIV positive women.

  10. Macrophage activation markers predict mortality in patients with liver cirrhosis without or with acute-on-chronic liver failure (ACLF)

    DEFF Research Database (Denmark)

    Grønbæk, Henning; Rødgaard-Hansen, Sidsel; Aagaard, Niels Kristian

    2016-01-01

    BACKGROUND & AIMS: Activation of liver macrophages plays a key role in liver and systemic inflammation and may be involved in development and prognosis of acute-on-chronic liver failure (ACLF). We therefore measured the circulating macrophage activation markers soluble sCD163 and mannose receptor......-C ACLF and CLIF-C AD scores. Addition of the macrophage markers to the clinical scores improved the prognostic efficacy: In ACLF patients sCD163 improved prediction of short-term mortality (C-index: 0.74 (0.67-0.80)) and in patients without ACLF sMR improved prediction of long-term mortality (C-index: 0.......80 (0.76-0.85)). CONCLUSIONS: The severity related increase in sCD163 and sMR and close association with mortality suggest a primary importance of inflammatory activation of liver macrophages in the emergence and course of ACLF. Accordingly, supplementation of the macrophage biomarkers to the platform...

  11. Hair cortisol as a marker of hypothalamic-pituitary-adrenal Axis activity in female patients with major depressive disorder.

    Science.gov (United States)

    Pochigaeva, Ksenia; Druzhkova, Tatiana; Yakovlev, Alexander; Onufriev, Mikhail; Grishkina, Maria; Chepelev, Aleksey; Guekht, Alla; Gulyaeva, Natalia

    2017-04-01

    Hair cortisol is regarded as a promising marker of hypothalamic-pituitary-adrenal axis (HPAA) activity alterations due to stress, somatic and mental health conditions. Hair cortisol was previously reported to be elevated in patients with depression, however the data related to remission and recurrent depressive episodes are different. In this study, levels of hair cortisol were assessed in female patients with major depressive disorder (MDD) and the validity of hair cortisol as a marker of HPAA activity in this condition was evaluated. Hair cortisol was measured in 1 cm hair segments of 21 female patients with MDD and 22 female age-matched controls using enzyme-immunoassay analysis. Concurrently, serum cortisol was assessed and psychological status was evaluated using 17-item Hamilton Depression Rating Scale (HAMD-17), Beck Depression Inventory (BDI) and the Spielberger state trait anxiety inventory (STAI). The levels of hair cortisol were significantly lower in the MDD group, while serum cortisol levels were significantly higher in patients, as compared with controls. A significant negative correlation was found between HAMD-17 scores and hair cortisol. Decreased hair cortisol found in female patients with MDD as compared to controls suggests downregulation of HPAA activity during the preceding month. Further studies are needed to investigate the profiles of hair cortisol at different stages of depressive disorder to establish this parameter as a handy clinical tool.

  12. T regulatory cells are markers of disease activity in multiple sclerosis patients.

    Directory of Open Access Journals (Sweden)

    Dacia Dalla Libera

    Full Text Available FoxP3⁺ Treg cells are believed to play a role in the occurrence of autoimmunity and in the determination of clinical recurrences. Contradictory reports are, however, available describing frequency and function of Treg cells during autoimmune diseases. We examined, by both polychromatic flow cytometry, and real-time RT-PCR, several Treg markers in peripheral blood mononuclear cells from patients with multiple sclerosis (MS, an autoimmune disease affecting the central nervous system. We found that Tregs, as defined by CD25, CD39, FoxP3, CTLA4, and GITR expression, were significantly decreased in stable MS patients as compared to healthy donors, but, surprisingly, restored to normal levels during an acute clinical attack. We conclude that Treg cells are not involved in causing clinical relapses, but rather react to inflammation in the attempt to restore homeostasis.

  13. Autonomic markers of emotional processing: skin sympathetic nerve activity in humans during exposure to emotionally charged images.

    Science.gov (United States)

    Brown, Rachael; James, Cheree; Henderson, Luke A; Macefield, Vaughan G

    2012-01-01

    The sympathetic innervation of the skin primarily subserves thermoregulation, but the system has also been commandeered as a means of expressing emotion. While it is known that the level of skin sympathetic nerve activity (SSNA) is affected by anxiety, the majority of emotional studies have utilized the galvanic skin response as a means of inferring increases in SSNA. The purpose of the present study was to characterize the changes in SSNA when showing subjects neutral or emotionally charged images from the International Affective Picture System (IAPS). SSNA was recorded via tungsten microelectrodes inserted into cutaneous fascicles of the common peroneal nerve in ten subjects. Neutral images, positively charged images (erotica) or negatively charged images (mutilation) were presented in blocks of fifteen images of a specific type, each block lasting 2 min. Images of erotica or mutilation were presented in a quasi-random fashion, each block following a block of neutral images. Both images of erotica or images of mutilation caused significant increases in SSNA, but the increases in SSNA were greater for mutilation. The increases in SSNA were often coupled with sweat release and cutaneous vasoconstriction; however, these markers were not always consistent with the SSNA increases. We conclude that SSNA, comprising cutaneous vasoconstrictor and sudomotor activity, increases with both positively charged and negatively charged emotional images. Measurement of SSNA provides a more comprehensive assessment of sympathetic outflow to the skin than does the use of sweat release alone as a marker of emotional processing.

  14. The macrophage activation marker sCD163 combined with markers of the Enhanced Liver Fibrosis (ELF) score predicts clinically significant portal hypertension in patients with cirrhosis

    DEFF Research Database (Denmark)

    Sandahl, T D; McGrail, R; Møller, H J

    2016-01-01

    BACKGROUND: Noninvasive identification of significant portal hypertension in patients with cirrhosis is needed in hepatology practice. AIM: To investigate whether the combination of sCD163 as a hepatic inflammation marker and the fibrosis markers of the Enhanced Liver Fibrosis score (ELF) can...... predict portal hypertension in patients with cirrhosis. METHODS: We measured sCD163 and the ELF components (hyaluronic acid, tissue inhibitor of metalloproteinase-1 and procollagen-III aminopeptide) in two separate cohorts of cirrhosis patients that underwent hepatic vein catheterisation. To test...... the predictive accuracy we developed a CD163-fibrosis portal hypertension score in an estimation cohort (n = 80) and validated the score in an independent cohort (n = 80). A HVPG ≥10 mmHg was considered clinically significant. RESULTS: Both sCD163 and the ELF components increased in a stepwise manner...

  15. Macrophage activation marker soluble CD163 and non-alcoholic fatty liver disease in morbidly obese patients undergoing bariatric surgery

    DEFF Research Database (Denmark)

    Kazankov, Konstantin; Tordjman, Joan; Møller, Holger Jon

    2015-01-01

    BACKGROUND AND AIMS: Macrophages play an important role in non-alcoholic fatty liver disease (NAFLD). Soluble CD163 (sCD163) is a specific marker of macrophage activation. We aimed to measure sCD163 in morbidly obese patients with varying degrees of NAFLD before and after bariatric surgery (BS...... (NAS), Kleiner fibrosis score, and the fatty liver inhibition of progression (FLIP) algorithm. In a subset, CD163 immunohistochemistry and real-time quantitative polymerase chain reaction for CD163 mRNA were performed. RESULTS: sCD163 was higher in patients with NAS ≥ 5 compared with those with NAS ...). METHODS: Demographic, clinical, and biochemical data, and plasma sCD163 measured by enzyme-linked immunosorbent assay, of 196 patients were collected preoperatively and 3, 6, and 12 months after BS leading to significant weight loss. Peroperative liver biopsies were assessed for the NAFLD Activity Score...

  16. Discovery and Validation of a Six-Marker Serum Protein Signature for the Diagnosis of Active Pulmonary Tuberculosis.

    Science.gov (United States)

    De Groote, Mary A; Sterling, David G; Hraha, Thomas; Russell, Theresa M; Green, Louis S; Wall, Kirsten; Kraemer, Stephan; Ostroff, Rachel; Janjic, Nebojsa; Ochsner, Urs A

    2017-10-01

    New non-sputum biomarker tests for active tuberculosis (TB) diagnostics are of the highest priority for global TB control. We performed in-depth proteomic analysis using the 4,000-plex SOMAscan assay on 1,470 serum samples from seven countries where TB is endemic. All samples were from patients with symptoms and signs suggestive of active pulmonary TB that were systematically confirmed or ruled out for TB by culture and clinical follow-up. HIV coinfection was present in 34% of samples, and 25% were sputum smear negative. Serum protein biomarkers were identified by stability selection using L1-regularized logistic regression and by Kolmogorov-Smirnov (KS) statistics. A naive Bayes classifier using six host response markers (HR6 model), including SYWC, kallistatin, complement C9, gelsolin, testican-2, and aldolase C, performed well in a training set (area under the sensitivity-specificity curve [AUC] of 0.94) and in a blinded verification set (AUC of 0.92) to distinguish TB and non-TB samples. Differential expression was also highly significant ( P CA6 (carbonic anhydrase 6). Target product profiles (TPPs) for a non-sputum biomarker test to diagnose active TB for treatment initiation (TPP#1) and for a community-based triage or referral test (TPP#2) have been published by the WHO. With 90% sensitivity and 80% specificity, the HR6 model fell short of TPP#1 but reached TPP#2 performance criteria. In conclusion, we identified and validated a six-marker signature for active TB that warrants diagnostic development on a patient-near platform. Copyright © 2017 De Groote et al.

  17. Spectroscopic detection of fluorescent protein marker gene activity in genetically modified plants

    Science.gov (United States)

    Liew, O. W.; Chong, Jenny P. C.; Asundi, Anand K.

    2005-04-01

    This work focuses on developing a portable fibre optic fluorescence analyser for rapid identification of genetically modified plants tagged with a fluorescent marker gene. Independent transgenic tobacco plant lines expressing the enhanced green fluorescence protein (EGFP) gene were regenerated following Agrobacterium-mediated gene transfer. Molecular characterisation of these plant lines was carried out at the DNA level by PCR screening to confirm their transgenic status. Conventional transgene expression analysis was then carried out at the RNA level by RT-PCR and at the protein level by Western blotting using anti-GFP rabbit antiserum. The amount of plant-expressed EGFP on a Western blot was quantified against known amounts of purified EGFP by scanning densitometry. The expression level of EGFP in transformed plants was found to range from 0.1 - 0.6% of total extractable protein. A comparison between conventional western analysis of transformants and direct spectroscopic quantification using the fibre optic fluorescence analyser was made. The results showed that spectroscopic measurements of fluorescence emission from strong EGFP expressors correlated positively with Western blot data. However, the fluorescence analyser was also able to identify weakly expressing plant transformants below the detection limit of colorimetric Western blotting.

  18. Altered monocyte activation markers in Tourette’s syndrome: a case–control study

    Directory of Open Access Journals (Sweden)

    Matz Judith

    2012-05-01

    Full Text Available Abstract Background Infections and immunological processes are likely to be involved in the pathogenesis of Tourette’s syndrome (TS. To determine possible common underlying immunological mechanisms, we focused on innate immunity and studied markers of inflammation, monocytes, and monocyte-derived cytokines. Methods In a cross-sectional study, we used current methods to determine the number of monocytes and levels of C-reactive protein (CRP in 46 children, adolescents, and adult patients suffering from TS and in 43 healthy controls matched for age and sex. Tumor necrosis factor alpha (TNF-alpha, interleukin 6 (IL-6, soluble CD14 (sCD14, IL1-receptor antagonist (IL1-ra, and serum neopterin were detected by immunoassays. Results We found that CRP and neopterin levels and the number of monocytes were significantly higher in TS patients than in healthy controls. Serum concentrations of TNF-alpha, sIL1-ra, and sCD14 were significantly lower in TS patients. All measured values were within normal ranges and often close to detection limits. Conclusions The present results point to a monocyte dysregulation in TS. This possible dysbalance in innate immunity could predispose to infections or autoimmune reactions.

  19. beta-carotene does not change markers of enzymatic and nonenzymatic antioxidant activity in human blood

    DEFF Research Database (Denmark)

    Castenmiller, J.J.M.; Lauridsen, Søren T.; Dragsted, Lars O.

    1999-01-01

    and erythrocyte enzyme activities were assessed, and differences among experimental groups were tested. Consumption of spinach resulted in greater (P catalase activity and serum alpha-tocopherol concentration compared...... to an increased carotenoid (lutein and zeaxanthin) intake, but beta-carotene is unlikely to be a causative factor. Lower erythrocyte catalase activity after intervention with spinach products may be related to other constituents in spinach such as flavonoids....

  20. Neutrophil activation and nucleosomes as markers of systemic inflammation in paroxysmal nocturnal hemoglobinuria: effects of eculizumab

    NARCIS (Netherlands)

    Bijnen, S.T. van; Wouters, D.; Mierlo, G.J. van; Muus, P.; Zeerleder, S.

    2015-01-01

    BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by complement-mediated hemolysis and a high risk of life-threatening venous and arterial thrombosis. Uncontrolled complement activation and the release of cell-free heme may result in systemic inflammation, neutrophil activation,

  1. Neutrophil activation and nucleosomes as markers of systemic inflammation in paroxysmal nocturnal hemoglobinuria: effects of eculizumab

    NARCIS (Netherlands)

    van Bijnen, S. T. A.; Wouters, D.; van Mierlo, G. J.; Muus, P.; Zeerleder, S.

    2015-01-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by complement-mediated hemolysis and a high risk of life-threatening venous and arterial thrombosis. Uncontrolled complement activation and the release of cell-free heme may result in systemic inflammation, neutrophil activation, and the

  2. Amygdala activation as a marker for selective attention toward neutral faces in a chronic traumatic brain injury population.

    Science.gov (United States)

    Young, Leanne R; Yu, Weikei; Holloway, Michael; Rodgers, Barry N; Chapman, Sandra B; Krawczyk, Daniel C

    2017-09-01

    There has been great interest in characterizing the response of the amygdala to emotional faces, especially in the context of social cognition. Although amygdala activation is most often associated with fearful or angry stimuli, there is considerable evidence that the response of the amygdala to neutral faces is both robust and reliable. This characteristic of amygdala function is of particular interest in the context of assessing populations with executive function deficits, such as traumatic brain injuries, which can be evaluated using fMRI attention modulation tasks that evaluate prefrontal control over representations, notably faces. The current study tested the hypothesis that the amygdala may serve as a marker of selective attention to neutral faces. Using fMRI, we gathered data within a chronic traumatic brain injury population. Blood Oxygenation Level Dependent (BOLD) signal change within the left and right amygdalae and fusiform face areas was measured while participants viewed neutral faces and scenes, under conditions requiring participants to (1) categorize pictures of faces and scenes, (2) selectively attend to either faces or scenes, or (3) attend to both faces and scenes. Findings revealed that the amygdala is an effective marker for selective attention to neutral faces and, furthermore, it was more face-specific than the fusiform face area. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Blood Monocyte Subsets and Selected Cardiovascular Risk Markers in Rheumatoid Arthritis of Short Duration in relation to Disease Activity

    Directory of Open Access Journals (Sweden)

    Ewa Klimek

    2014-01-01

    Full Text Available Objectives. To evaluate blood monocyte subsets and functional monocyte properties in patients with rheumatoid arthritis (RA of short duration in the context of cardiovascular (CV risk and disease activity. Methods. We studied conventional markers of CV risk, intima media thickness (IMT, and blood monocyte subsets in 27 patients aged 41 ± 10 years with RA of short duration (median 12 months and 22 healthy controls. The RA subjects were divided into low (DAS28: 2.6–5.1 and high (DAS28 > 5.1 disease activity. Results. RA patients exhibited increased levels of intermediate (CD14++CD16+ monocytes with decreased CD45RA expression compared to controls, increased counts of classical (CD14++CD16− monocytes, and decreased percentages of nonclassical (CD14+CD16++ monocytes. Patients with high disease activity had lower HLA DR expression on classical monocytes compared to low disease activity patients. There were no differences in monocyte subsets between subjects with DAS > 5.1 and DAS ≤ 5.1. There were no significant intergroup differences in IMT and the majority of classical CV risk factors. Conclusions. Patients with RA of short duration show alteration in peripheral blood monocyte subsets despite the fact that there is no evidence of subclinical atherosclerosis. Disease activity assessed with DAS28 was associated with impaired functional properties but not with a shift in monocyte subpopulations.

  4. Effects of deuterated water upon specific activity of some marker enzymes for cytosol and plasmatic membrane

    International Nuclear Information System (INIS)

    Buzgariu, Wanda; Coroiu, Viorica; Moldovan, Lucia; Titescu, G.; Stefanescu, I.

    2004-01-01

    Recently, numerous studies were devoted to the effects of an increased environmental deuterium concentration on physiological characteristics of various biological systems, from monocellular organisms up to mammals. Within these preoccupations the experiments on enzyme activity and parameters are of special interest since they throw light upon the mechanisms in metabolic biochemical reactions (glycolysis, photosynthesis, transport across membranes, etc). The present work concerns the effects of heavy water upon the activity of some enzymes (dehydrogenase-LDH lactate and 5' nucleotidase) implied in different metabolic pathways, serving as functional indicators for some cellular compartments such as the cytosols and cellular membranes. Enzyme activity was determined by growing for 6 days the cells (Hep 2, CHO, fibroblasts) in deuterated culture media at different concentration levels (20%, 40%, 65% si 90%), as well as in a reaction medium deuterated at 99.96%. In case of the first experimental run the LDH activity was monitored for the three cellular lines (Hep 2, CHO, fibroblasts) for different time intervals (1 d, 3 d and 6 d). After the first 24 h of cells' exposure the activity values were similar regardless of the heavy water concentration in the medium. Exposing the cells for longer time (6 days) led to modifications of LDH activity. In contrast to the case of media with relatively moderate D 2 O content, cell growing in conditions of intense deuteration 65% and 90 % D 2 O) led to an increase of cytosolic enzyme activity of about 50%. In case of 5' nucleotidase after 6 days of cell cultivation in deuteration conditions the activity decreased to 50% and 70% from the value corresponding to normal conditions for cell growth. This diminution of the activity was characteristic for the media with 65% and 90% D 2 O. In the second experimental run the activities of dehydrogenase lactate and 5' nucleotidase from the cellular homogenate obtained from cells grown in

  5. Patterns of frontoparietal activation as a marker for unsuccessful visuospatial processing in healthy aging.

    Science.gov (United States)

    Drag, Lauren L; Light, Sharee N; Langenecker, Scott A; Hazlett, Kathleen E; Wilde, Elisabeth A; Welsh, Robert; Steinberg, Brett A; Bieliauskas, Linas A

    2016-09-01

    Visuospatial abilities are sensitive to age-related decline, although the neural basis for this decline (and its everyday behavioral correlates) is as yet poorly understood. fMRI was employed to examine age-related differences in patterns of functional activation that underlie changes in visuospatial processing. All participants completed a brief neuropsychological battery and also a figure ground task (FGT) assessing visuospatial processing while fMRI was recorded. Participants included 16 healthy older adults (OA; aged 69-82 years) and 16 healthy younger adults (YA; aged 20-35 years). We examined age-related differences in behavioral performance on the FGT in relation to patterns of fMRI activation. OA demonstrated reduced performance on the FGT task and showed increased activation of supramarginal parietal cortex as well as increased activation of frontal and temporal regions compared to their younger counterparts. Performance on the FGT related to increased supramarginal gyrus activity and increased medial prefrontal activity in OAs, but not YAs. Our results are consistent with an anterior-posterior compensation model. Successful FGT performance requires the perception and integration of multiple stimuli and thus it is plausible that healthy aging may be accompanied by changes in visuospatial processing that mimic a subtle form of dorsal simultanagnosia. Overall, decreased visuospatial processing in OA relates to an altered frontoparietal neurobiological signature that may contribute to the general phenomenon of increasingly fragmented execution of behavior associated with normal aging.

  6. Humoral markers of active Epstein-Barr virus infection associate with anti-extractable nuclear antigen autoantibodies and plasma galectin-3 binding protein in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Rasmussen, N S; Nielsen, C T; Houen, G

    2016-01-01

    We investigated if signs of active Epstein-Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein-Barr virus early antigen diffuse...... and cytomegalovirus pp52 were applied as humoral markers of ongoing/recently active Epstein-Barr virus and cytomegalovirus infections, respectively. Plasma galectin-3 binding protein served as a surrogate marker of type I interferon activity. The measurements were conducted in 57 systemic lupus erythematosus patients...... concentrations were significantly higher in systemic lupus erythematosus patients (P = 0.009) and associated positively with Epstein-Barr virus early antigen diffuse-directed antibodies and the presence of autoantibodies against extractable nuclear antigens in adjusted linear regressions (B = 2.02 and 2.02, P...

  7. Serum prolidase enzyme activity in obese subjects and its relationship with oxidative stress markers.

    Science.gov (United States)

    Aslan, Mehmet; Duzenli, Ufuk; Esen, Ramazan; Soyoral, Yasemin Usul

    2017-10-01

    The relationship between increased serum enzyme activity of prolidase and increased rate of collagen turnover in the arterial wall has been asserted in previous studies. Collagen reflects much of the strength to the connective tissue involved in the arterial wall. Atherosclerosis is very common vessel disease and oxidative stress plays a pivotal role in the etiopathogenesis. Our objective was to examine the serum enzyme activity of prolidase and its possible relationships with oxidative stress parameters in obese subjects. Our present study was conducted 27 obese subjects and 26 age-matched healthy control subjects. The serum enzyme activity of prolidase in all study population was evaluated spectrophotometrically. Oxidative stress levels in obese subjects were analyzed with total antioxidant capacity (TAC) and total oxidant status (TOS) as well as oxidative stress index (OSI). Obese subjects have higher serum TOS and OSI indicators as well as prolidase activity than those in control subjects (for all; pstress levels in obese subjects. The significantly correlation between increased oxidative stress and increased prolidase activity may play a pivotal role in etiopathogenesis of atherosclerotic cardiovascular diseases in obese subjects. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Abnormal fronto-striatal activation as a marker of threshold and subthreshold Bulimia Nervosa.

    Science.gov (United States)

    Cyr, Marilyn; Yang, Xiao; Horga, Guillermo; Marsh, Rachel

    2018-04-01

    This study aimed to determine whether functional disturbances in fronto-striatal control circuits characterize adolescents with Bulimia Nervosa (BN) spectrum eating disorders regardless of clinical severity. FMRI was used to assess conflict-related brain activations during performance of a Simon task in two samples of adolescents with BN symptoms compared with healthy adolescents. The BN samples differed in the severity of their clinical presentation, illness duration and age. Multi-voxel pattern analyses (MVPAs) based on machine learning were used to determine whether patterns of fronto-striatal activation characterized adolescents with BN spectrum disorders regardless of clinical severity, and whether accurate classification of less symptomatic adolescents (subthreshold BN; SBN) could be achieved based on patterns of activation in adolescents who met DSM5 criteria for BN. MVPA classification analyses revealed that both BN and SBN adolescents could be accurately discriminated from healthy adolescents based on fronto-striatal activation. Notably, the patterns detected in more severely ill BN compared with healthy adolescents accurately discriminated less symptomatic SBN from healthy adolescents. Deficient activation of fronto-striatal circuits can characterize BN early in its course, when clinical presentations are less severe, perhaps pointing to circuit-based disturbances as useful biomarker or risk factor for the disorder, and a tool for understanding its developmental trajectory, as well as the development of early interventions. © 2018 Wiley Periodicals, Inc.

  9. The feed gas composition determines the degree of physical plasma-induced platelet activation for blood coagulation

    Science.gov (United States)

    Bekeschus, Sander; Brüggemeier, Janik; Hackbarth, Christine; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Partecke, Lars-Ivo; van der Linde, Julia

    2018-03-01

    Cold atmospheric (physical) plasma has long been suggested to be a useful tool for blood coagulation. However, the clinical applicability of this approach has not been addressed sufficiently. We have previously demonstrated the ability of a clinically accepted atmospheric pressure argon plasma jet (kINPen® MED) to coagulate liver incisions in mice with similar performance compared to the gold standard electrocauterization. We could show that plasma-mediated blood coagulation was dependent on platelet activation. In the present work, we extended on this by investigating kINPen®-mediated platelet activation in anticoagulated human donor blood ex vivo. With focus on establishing high-throughput, multi-parametric platelet activation assays and performing argon feed gas parameter studies we achieved the following results: (i) plasma activated platelets in heparinized but not in EDTA-anticoagulated blood; (ii) plasma decreased total platelet counts but increased numbers of microparticles; (iii) plasma elevated the expression of several surface activation markers on platelets (CD62P, CD63, CD69, and CD41/61); (iv) in platelet activation, wet and dry argon plasma outperformed feed gas admixtures with oxygen and/or nitrogen; (v) plasma-mediated platelet activation was accompanied by platelet aggregation. Platelet aggregation is a necessary requirement for blood clot formation. These findings are important to further elucidate molecular details and clinical feasibility of cold physical plasma-mediated blood coagulation.

  10. Intracellular activity of clinical concentrations of phenothiazines including thioridiazine against phagocytosed Staphylococcus aureus.

    Science.gov (United States)

    Ordway, Diane; Viveiros, Miguel; Leandro, Clara; Arroz, Maria Jorge; Amaral, Leonard

    2002-07-01

    The effect of thioridazine (TZ) was studied on the killing activity of human peripheral blood monocyte derived macrophages (HPBMDM) and of human macrophage cell line THP-1 at extracellular concentrations below those achievable clinically. These macrophages have nominal killing activity against bacteria and therefore, would not influence any activity that the compounds may have against intracellular localised Staphylococcus aureus. The results indicated that whereas TZ has an in vitro minimum inhibitory concentration (MIC) against the strains of S. aureus of 18, 0.1 mg/l of TZ in the medium completely inhibits the growth of S. aureus that has been phagocytosed by macrophages. The latter concentration was non-toxic to macrophages, did not cause cellular expression of activation marker CD69 nor induction of CD3+ T cell production of IFN-gamma, but blocked cellular proliferation and down-regulated the production of T cell-derived cytokines (IFN-gamma, IL-5). These results suggest that TZ induces intracellular bactericidal activities independent of the capacity to generate Type 1 responses against S. aureus.

  11. Xeno-oestrogenic activity in serum as marker of occupational pesticide exposure

    DEFF Research Database (Denmark)

    Andersen, Helle Raun; Nielsen, Flemming; Nielsen, Jesper Bo

    2007-01-01

    -oestrogenic activity in serum was statistically significant for women who had been at work within the last week, while no association was observed for women who had not been at work during the most recent week. Conclusions: The study illustrates the usefulness of this biomarker for qualitative assessment...... with oestrogen-like properties in an occupational setting. Methods: Serum samples were obtained from two separate cohorts representing non-pregnant and pregnant female greenhouse workers in Denmark. Serum samples from 270 non-pregnant women and 173 pregnant women were analysed for xeno-oestrogenic activity......, medium or high based on information collected by detailed interviews of the women and the employers. Results: In both cohorts, an exposure-associated increase in the xeno-oestrogenic activity in serum was demonstrated. Among the pregnant women, the association between pesticide exposure and xeno...

  12. Soluble glycoprotein VI, a specific marker of platelet activation is increased in the plasma of subjects with seropositive rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    John R Stack

    Full Text Available Anti-citrullinated protein antibodies (ACPA have been shown to cause platelet activation in vitro, through the low-affinity immunoglobulin G (IgG receptor (FcγRIIa on platelets. Platelet activation via engagement of FcγRIIa results in proteolytic cleavage and shedding of platelet specific glycoprotein VI (GPVI which can be detected in the plasma as soluble GPVI (sGPVI. We hypothesized that plasma levels of sGPVI would be increased among patients with seropositive RA as a consequence of antibody-induced platelet activation and GPVI shedding.Samples from 84 patients with RA (65 seropositive and 19 seronegative and 67 healthy controls were collected prospectively and analysed for sGPVI using a standardised ELISA.Patients with seropositive RA had significantly higher levels of sGPVI compared to seronegative RA and controls. Median (IQR sGPVI levels were 4.2 ng/ml (3.2, 8.0 in seropositve RA, 2.2 ng/ml (1.5, 3.5 in seronegative RA and 2.2 ng/ml (1.6, 3.4 in controls (p<0.0001. sGPVI levels correlated with ACPA titres (r = 0.32, p = 0.0026 and with RF titres (r = 0.48, p<0.0001.Plasma sGPVI, a specific marker of platelet activation is increased among patients with seropositive RA.

  13. Sorting Nexin 2 (SNX2): a potential marker of active thyrocytes in normal and hyperfunctioning thyroid disorders.

    Science.gov (United States)

    Kanzawa, Maki; Hara, Shigeo; Semba, Shuho; Yokozaki, Hiroshi; Hirokawa, Mitsuyoshi; Itoh, Tomoo

    2014-04-01

    Sorting nexins (SNXs) are a large, diverse group of cytoplasmic and membrane-associated proteins that function in a variety of cellular processes, including endocytosis, protein trafficking, and the retrieval of transmembrane proteins. In this study, we demonstrated that SNX2 is expressed in columnar and active thyroid follicular cells but not in flattened inactive thyrocytes. Morphometric analysis revealed a significant correlation between SNX2 positivity and columnar cell morphology. Immunohistochemical staining of serial sections of the thyroid tissue indicated that SNX2 localization was similar to sortilin, a protein expressed by active thyrocytes. Expression of SNX2 in thyrocytes is particularly marked and extensive in most hyperstimulated thyroid disorders, including Graves disease (diffusely SNX2 positive in 73.3% patients) and functioning nodules (93.8% patients). SNX2 immunolocalization in hyperstimulated follicular epithelial cells was specific among the SNXs family members examined. These results support the utility of SNX2 as a novel marker of active thyrocytes and reflect the endosomal trafficking activity in these cells.

  14. Cadmium exposure is associated with soluble urokinase plasminogen activator receptor, a circulating marker of inflammation and future cardiovascular disease

    International Nuclear Information System (INIS)

    Fagerberg, Björn; Borné, Yan; Barregard, Lars; Sallsten, Gerd; Forsgard, Niklas; Hedblad, Bo; Persson, Margaretha; Engström, Gunnar

    2017-01-01

    Background: Diet and smoking are the main sources of cadmium exposure in the general population. Cadmium increases the risk of cardiovascular diseases, and experimental studies show that it induces inflammation. Blood cadmium levels are associated with macrophages in human atherosclerotic plaques. Soluble urokinase-type plasminogen activator receptor (suPAR) is an emerging biomarker for cardiovascular events related to inflammation and atherosclerotic plaques. The aim was to examine whether blood cadmium levels are associated with circulating suPAR and other markers of inflammation. Methods: A population sample of 4648 Swedish middle-aged women and men was examined cross-sectionally in 1991–1994. Plasma suPAR was assessed by ELISA, leukocytes were measured by standard methods, and blood cadmium was analysed by inductively coupled plasma mass spectrometry. Prevalent cardiovascular disease, ultrasound-assessed carotid plaque occurrence, and several possible confounding factors were recorded. Results: After full adjustment for risk factors and confounding variables, a 3-fold increase in blood cadmium was associated with an 10.9% increase in suPAR concentration (p<0.001). In never-smokers, a 3-fold increase in blood cadmium was associated with a 3.7% increase in suPAR concentration (p<0.01) after full adjustment. Blood cadmium was not associated with C-reactive protein, white blood cell count and Lp-PLA2 but with neutrophil/lymphocyte ratio in one of two statistical models. Conclusions: Exposure to cadmium was associated with increased plasma suPAR in the general population, independently of smoking and cardiovascular disease. These results imply that cadmium is a possible cause for raised levels of this inflammatory marker. - Highlights: • Cadmium is a toxic proinflammatory, proatherosclerotic metal. • Soluble urokinase-type plasminogen activator receptor (suPAR) in plasma is a promising proinflammatory marker of atherosclerosis. • Blood cadmium and plasma su

  15. Cadmium exposure is associated with soluble urokinase plasminogen activator receptor, a circulating marker of inflammation and future cardiovascular disease

    Energy Technology Data Exchange (ETDEWEB)

    Fagerberg, Björn, E-mail: bjorn.fagerberg@wlab.gu.se [Department of Molecular and Clinical Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45 Gothenburg (Sweden); Borné, Yan [Department of Clinical Sciences in Malmö, Cardiovascular Epidemiology, CRC, Jan Waldenströms gata 35, Lund University, Skåne University Hospital, Malmö, SE-205 02 Malmö (Sweden); Barregard, Lars; Sallsten, Gerd [Occupational and Environmental Medicine, Sahlgrenska University Hospital and University of Gothenburg, SE-413 45 Gothenburg (Sweden); Forsgard, Niklas [Department of Clinical Chemistry, Sahlgrenska University Hospital, SE-413 45 Gothenburg (Sweden); Hedblad, Bo; Persson, Margaretha; Engström, Gunnar [Department of Clinical Sciences in Malmö, Cardiovascular Epidemiology, CRC, Jan Waldenströms gata 35, Lund University, Skåne University Hospital, Malmö, SE-205 02 Malmö (Sweden)

    2017-01-15

    Background: Diet and smoking are the main sources of cadmium exposure in the general population. Cadmium increases the risk of cardiovascular diseases, and experimental studies show that it induces inflammation. Blood cadmium levels are associated with macrophages in human atherosclerotic plaques. Soluble urokinase-type plasminogen activator receptor (suPAR) is an emerging biomarker for cardiovascular events related to inflammation and atherosclerotic plaques. The aim was to examine whether blood cadmium levels are associated with circulating suPAR and other markers of inflammation. Methods: A population sample of 4648 Swedish middle-aged women and men was examined cross-sectionally in 1991–1994. Plasma suPAR was assessed by ELISA, leukocytes were measured by standard methods, and blood cadmium was analysed by inductively coupled plasma mass spectrometry. Prevalent cardiovascular disease, ultrasound-assessed carotid plaque occurrence, and several possible confounding factors were recorded. Results: After full adjustment for risk factors and confounding variables, a 3-fold increase in blood cadmium was associated with an 10.9% increase in suPAR concentration (p<0.001). In never-smokers, a 3-fold increase in blood cadmium was associated with a 3.7% increase in suPAR concentration (p<0.01) after full adjustment. Blood cadmium was not associated with C-reactive protein, white blood cell count and Lp-PLA2 but with neutrophil/lymphocyte ratio in one of two statistical models. Conclusions: Exposure to cadmium was associated with increased plasma suPAR in the general population, independently of smoking and cardiovascular disease. These results imply that cadmium is a possible cause for raised levels of this inflammatory marker. - Highlights: • Cadmium is a toxic proinflammatory, proatherosclerotic metal. • Soluble urokinase-type plasminogen activator receptor (suPAR) in plasma is a promising proinflammatory marker of atherosclerosis. • Blood cadmium and plasma su

  16. Transcriptome Analysis Reveals Markers of Aberrantly Activated Innate Immunity in Vitiligo Lesional and Non-Lesional Skin

    Science.gov (United States)

    Huang, Yuanshen; Wang, Yang; Yu, Jie; Gao, Min; Levings, Megan; Wei, Shencai; Zhang, Shengquan; Xu, Aie; Su, Mingwan; Dutz, Jan; Zhang, Xuejun; Zhou, Youwen

    2012-01-01

    Background Vitiligo is characterized by the death of melanocytes in the skin. This is associated with the presence of T cell infiltrates in the lesional borders. However, at present, there is no detailed and systematic characterization on whether additional cellular or molecular changes are present inside vitiligo lesions. Further, it is unknown if the normal appearing non-lesional skin of vitiligo patients is in fact normal. The purpose of this study is to systematically characterize the molecular and cellular characteristics of the lesional and non-lesional skin of vitiligo patients. Methods and Materials Paired lesional and non-lesional skin biopsies from twenty-three vitiligo patients and normal skin biopsies from sixteen healthy volunteers were obtained with informed consent. The following aspects were analyzed: (1) transcriptome changes present in vitiligo skin using DNA microarrays and qRT-PCR; (2) abnormal cellular infiltrates in vitiligo skin explant cultures using flow cytometry; and (3) distribution of the abnormal cellular infiltrates in vitiligo skin using immunofluorescence microscopy. Results Compared with normal skin, vitiligo lesional skin contained 17 genes (mostly melanocyte-specific genes) whose expression was decreased or absent. In contrast, the relative expression of 13 genes was up-regulated. The up-regulated genes point to aberrant activity of the innate immune system, especially natural killer cells in vitiligo. Strikingly, the markers of heightened innate immune responses were also found to be up-regulated in the non-lesional skin of vitiligo patients. Conclusions and Clinical Implications As the first systematic transcriptome characterization of the skin in vitiligo patients, this study revealed previously unknown molecular markers that strongly suggest aberrant innate immune activation in the microenvironment of vitiligo skin. Since these changes involve both lesional and non-lesional skin, our results suggest that therapies targeting

  17. Soluble receptors for tumor necrosis factor as markers of disease activity in visceral leishmaniasis

    NARCIS (Netherlands)

    Zijlstra, E. E.; van der Poll, T.; Mevissen, M.

    1995-01-01

    Serum concentrations of soluble receptors for tumor necrosis factor (sTNFRs) were measured before and after antimony therapy in 25 Sudanese patients with active visceral leishmaniasis (VL). Both sTNFR types I and II were significantly elevated in patients with VL compared with healthy controls from

  18. Platelet adenylyl cyclase activity as a biochemical trait marker for predisposition to alcoholism.

    NARCIS (Netherlands)

    Ratsma, J.E.; Gunning, W.B.; Leurs, R.; Schoffelmeer, A.N.M.

    1999-01-01

    Previous studies demonstrated a reduced G(s)-protein stimulated adenylyl cyclase activity in the brain and blood cells of alcoholics. We investigated this phenomenon in platelets of children of alcoholics (COA), i.e., of children at high risk for the acquisition of alcoholism and (as yet) not

  19. Total pepsin activity and gastrin in sera as markers of eradication of Helicobacter pylori

    NARCIS (Netherlands)

    Khoshkholgh, M.; Saberi-Firoozi, M.; Fattahi, M.; Siavoshi, F.; Khatibian, M.; Vahedi, H.; Mikaeli, J.; Ansari, R.; Alizadeh, B.; Malekzadeh, R.; Massarrat, S.

    1994-01-01

    The measurement of total pepsin activity by colorimetry, and gastrin by radioimmunoassay method was performed on the sera of 100 patients (80 with duodenal ulcer and 20 with non-ulcer dyspepsia) before and 4 weeks after the end of antibacterial treatment for eradication of Helicobacter pylori. While

  20. Markers for vulnerability to psychopathology: Temperament traits associated with platelet MAO activity

    International Nuclear Information System (INIS)

    Schalling, D.; Aasberg, M.; Edman, G.; Oreland, L.

    1987-01-01

    The functional linkage between platelet MAO activity and psychopathology was explored by analyzing temperamental correlates in 40 male subjects by means of scales from the Eysenck Personality Questionnaire (EPQ), the Zuckerman Sensation Seeking Inventory, and the Karolinska Scales of Personality (KSP). Linear correlation were found with two sensation seeking scales, replicating earlier findings. However, nonlinear correlations predominated. Subjects with intemediate platelet MAO activity had higher scores in conformity scales and lower scores in anxiety and hostility scales than low and high MAO subgroups. Low MAO subjects showed a pattern of higher scores in KSP Impulsiveness, EPQ Neuroticism, and KSP Somatic Anxiety and Irritability and lower scores in KSP Socialization, in line with personality profiles found in alcoholics, phychopaths, and suicide attempters who also tend to have low platelet MAO activity. High MAO subject scored lower in sensation seeking and conformity scales and higher in KSP Phychasthenia, Muscular Tension and Suspicion scales, consistent with clinical links between high platelet MAO activity and anxiety and paranoia. (author)

  1. Mitochondrial Fragmentation in Aspergillus fumigatus as Early Marker of Granulocyte Killing Activity

    Science.gov (United States)

    Ruf, Dominik; Brantl, Victor; Wagener, Johannes

    2018-01-01

    The host's defense against invasive mold infections relies on diverse antimicrobial activities of innate immune cells. However, studying these mechanisms in vitro is complicated by the filamentous nature of such pathogens that typically form long, branched, multinucleated and compartmentalized hyphae. Here we describe a novel method that allows for the visualization and quantification of the antifungal killing activity exerted by human granulocytes against hyphae of the opportunistic pathogen Aspergillus fumigatus. The approach relies on the distinct impact of fungal cell death on the morphology of mitochondria that were visualized with green fluorescent protein (GFP). We show that oxidative stress induces complete fragmentation of the tubular mitochondrial network which correlates with cell death of affected hyphae. Live cell microscopy revealed a similar and non-reversible disruption of the mitochondrial morphology followed by fading of fluorescence in Aspergillus hyphae that were killed by human granulocytes. Quantitative microscopic analysis of fixed samples was subsequently used to estimate the antifungal activity. By utilizing this assay, we demonstrate that lipopolysaccharides as well as human serum significantly increase the killing efficacy of the granulocytes. Our results demonstrate that evaluation of the mitochondrial morphology can be utilized to assess the fungicidal activity of granulocytes against A. fumigatus hyphae. PMID:29868488

  2. Increased serum YKL-40 in patients with pulmonary sarcoidosis—a potential marker of disease activity?

    DEFF Research Database (Denmark)

    Johansen, JS; Milman, N; Hansen, M

    2005-01-01

    macrophages and giant cells in the granulomatous sarcoid lesions of patients with pulmonary sarcoidosis produce YKL-40 and to determine whether serum YKL-40 in these patients were associated with disease activity. Methods: Serum YKL-40 was determined by radioimmunoassay in 27 patients with a histological...

  3. Soluble urokinase plasminogen activator receptor as a prognostic marker in men participating in prostate cancer screening

    DEFF Research Database (Denmark)

    Kjellman, A; Akre, O; Gustafsson, O

    2011-01-01

    BACKGROUND: The urokinase plasminogen activator (uPA) system is involved in tissue remodelling processes and is up-regulated in many types of malignancies. We investigated whether serum levels of different forms of soluble uPA receptor (suPAR) are associated with survival and in particular with p...

  4. Association of markers of bacterial translocation with immune activation in decompensated cirrhosis

    DEFF Research Database (Denmark)

    Mortensen, Christian; Jensen, Jørgen Skov; Hobolth, Lise

    2014-01-01

    -reactive protein, tumour necrosis factor-α, soluble urokinase plasminogen activating receptor, interleukin-6, interleukin 8, interferon-γ inducible protein-10 and vascular endothelial growth factor in plasma and ascites were measured by multiplex cytokine and ELISA assays. RESULTS: In patients without signs of SBP...

  5. Soluble urokinase-type plasminogen activator receptor forms in plasma as markers of atherosclerotic plaque vulnerability

    DEFF Research Database (Denmark)

    Olson, Fredrik J; Thurison, Tine; Ryndel, Mikael

    2009-01-01

    OBJECTIVES:: To test if circulating forms of the soluble urokinase-type plasminogen activator receptor (suPAR) are potential biomarkers of plaque vulnerability. DESIGN AND METHODS:: Plasma concentrations of suPAR(I-III), suPAR(II-III) and uPAR(I) were measured by time-resolved fluorescence immuno...

  6. Platelet-rich plasma stimulated by pulse electric fields: Platelet activation, procoagulant markers, growth factor release and cell proliferation.

    Science.gov (United States)

    Frelinger, A L; Torres, A S; Caiafa, A; Morton, C A; Berny-Lang, M A; Gerrits, A J; Carmichael, S L; Neculaes, V B; Michelson, A D

    2016-01-01

    Therapeutic use of activated platelet-rich plasma (PRP) has been explored for wound healing, hemostasis and antimicrobial wound applications. Pulse electric field (PEF) stimulation may provide more consistent platelet activation and avoid complications associated with the addition of bovine thrombin, the current state of the art ex vivo activator of therapeutic PRP. The aim of this study was to compare the ability of PEF, bovine thrombin and thrombin receptor activating peptide (TRAP) to activate human PRP, release growth factors and induce cell proliferation in vitro. Human PRP was prepared in the Harvest SmartPreP2 System and treated with vehicle, PEF, bovine thrombin, TRAP or Triton X-100. Platelet activation and procoagulant markers and microparticle generation were measured by flow cytometry. Released growth factors were measured by ELISA. The releasates were tested for their ability to stimulate proliferation of human epithelial cells in culture. PEF produced more platelet-derived microparticles, P-selectin-positive particles and procoagulant annexin V-positive particles than bovine thrombin or TRAP. These differences were associated with higher levels of released epidermal growth factor after PEF than after bovine thrombin or TRAP but similar levels of platelet-derived, vascular-endothelial, and basic fibroblast growth factors, and platelet factor 4. Supernatant from PEF-treated platelets significantly increased cell proliferation compared to plasma. In conclusion, PEF treatment of fresh PRP results in generation of microparticles, exposure of prothrombotic platelet surfaces, differential release of growth factors compared to bovine thrombin and TRAP and significant cell proliferation. These results, together with PEF's inherent advantages, suggest that PEF may be a superior alternative to bovine thrombin activation of PRP for therapeutic applications.

  7. Translocator protein as an imaging marker of macrophage and stromal activation in RA pannus.

    Science.gov (United States)

    Narayan, Nehal; Owen, David; Mandhair, Harpreet; Smyth, Erica; Carlucci, Francesco; Saleem, Azeem; Gunn, Roger; Rabiner, Eugenii Ilan A; Wells, Lisa; Dakin, Stephanie; Sabokbar, Afsie; Taylor, Peter

    2018-01-04

    Positron Emission Tomography (PET) radioligands targeted to Translocator protein (TSPO), offer a highly sensitive and specific means of imaging joint inflammation in rheumatoid arthritis (RA). Through high expression of TSPO on activated macrophages, TSPO PET has been widely reported in several studies of RA as a means of imaging synovial macrophages in vivo. However, this premise does not take into account the ubiquitous expression of TSPO. This study aimed to investigate TSPO expression in major cellular constituents of RA pannus; monocytes, macrophages, fibroblast-like synoviocytes (FLS) and CD4+ T lymphocytes, to more accurately interpret TSPO PET signal from RA synovium. Methods: 3 RA patients and 3 healthy volunteers underwent PET both knees using the TSPO radioligand 11 C-PBR28. Through synovial tissue 3H-PBR28 autoradiography and immunostaining of 6 RA patients and 6 healthy volunteers, cellular expression of TSPO in synovial tissue was evaluated. TSPO mRNA expression and 3H-PBR28 radioligand binding was assessed using in vitro monocytes, macrophages, FLS and CD4+ T-lymphocytes. Results: 11 C-PBR28 PET signal was significantly higher in RA compared to healthy joints (average SUV 0.82± 0.12 compared to 0.03± 0.004 respectively, p<0.01). Further, 3H-PBR28 specific binding in synovial tissue was approximately 10-fold higher in RA compared to healthy controls. Immunofluorescence revealed TSPO expression on macrophages, FLS and CD4+ T cells. In vitro study demonstrated highest TSPO mRNA expression and 3H-PBR28 specific binding, in activated FLS, non-activated and activated 'M2' reparative macrophages, with least TSPO expression in activated and non-activated CD4+ T lymphocytes. Conclusion: This study is the first evaluation of cellular TSPO expression in synovium, finding highest TSPO expression and PBR28 binding on activated synovial FLS and M2 phenotype macrophages. TSPO targeted PET may therefore have unique sensitivity to detect FLS and macrophage

  8. Kinetics of T cell-activation molecules in response to Mycobacterium tuberculosis antigens

    Directory of Open Access Journals (Sweden)

    Antas Paulo RZ

    2002-01-01

    Full Text Available The phenotypic features acquired subsequent to antigen-specific stimulation in vitro were evaluated by means of the kinetic expressions of CD69 and CD25 activation molecules on T lymphocytes and assayed by flow cytometry in response to PPD, Ag85B, and ferritin in PPD-positive healthy control individuals. In response to PHA, CD69 staining on both CD4+ and CD8+ T cells became initially marked after 4 h, peaked at 24 h, and quickly decreased after 120 h. For CD25, a latter expression was detected around 8 h, having increased after 96 h. As expected, the response rate to the mycobacterial antigens was much lower than that to the mitogen. Positive staining was high after 96 h for CD25 and after 24 h for CD69. CD69 expression was significantly enhanced (p < 0.05 on CD8+ as compared to CD4+ T cells. High levels were also found between 96-120 h. Regarding Ag85B, CD25+ cells were mostly CD4+ instead of CD8+ T cells. Moreover, in response to ferritin, a lower CD25 expression was noted. The present data will allow further characterization of the immune response to new mycobacterial-specific antigens and their evaluation for possible inclusion in developing new diagnostic techniques for tuberculosis as well in a new vaccine to prevent the disease.

  9. Oncogene activation and surface markers in mouse lymphomas induced by radiation and nitrosomethylurea

    Energy Technology Data Exchange (ETDEWEB)

    Guerrero, I.; Villasante, A.; Diamond, L.; Berman, J.W.; Newcomb, E.W.; Steinberg, J.J.; Lake, R.; Pellicer, A.

    1986-01-01

    Thymic lymphomas have been induced by ..gamma..-radiation and treatment with the chemical nitrosomethylurea in different mice strains. As indicated by the NIH 3T3 focus forming assay, a significant percentage of the tumors contain activated oncogenes of the ras family (K or N). Cloning and sequencing has enabled us to identify single base mutations as the only significant alteration present in the activated oncogenes. These alterations result in the substitution of amino-acid 12 or 61 of the p21 product of the ras genes. With the use of synthetic oligonucleotides it has been found that the tumors do not all contain the same mutation and in one case so far the normal allele is absent.

  10. Increased serum YKL-40 in patients with pulmonary sarcoidosis--a potential marker of disease activity?

    DEFF Research Database (Denmark)

    Johansen, Julia S; Milman, Nils; Hansen, Michael

    2005-01-01

    YKL-40, a growth factor for fibroblasts and vascular endothelial cells, is secreted by macrophages and neutrophils. Elevated serum YKL-40 is found in patients with diseases characterized by inflammation, tissue remodelling and ongoing fibrosis. The aim was to evaluate whether macrophages and giant...... cells in the granulomatous sarcoid lesions of patients with pulmonary sarcoidosis produce YKL-40 and to determine whether serum YKL-40 in these patients were associated with disease activity....

  11. Neural markers of loss aversion in resting-state brain activity.

    Science.gov (United States)

    Canessa, Nicola; Crespi, Chiara; Baud-Bovy, Gabriel; Dodich, Alessandra; Falini, Andrea; Antonellis, Giulia; Cappa, Stefano F

    2017-02-01

    Neural responses in striatal, limbic and somatosensory brain regions track individual differences in loss aversion, i.e. the higher sensitivity to potential losses compared with equivalent gains in decision-making under risk. The engagement of structures involved in the processing of aversive stimuli and experiences raises a further question, i.e. whether the tendency to avoid losses rather than acquire gains represents a transient fearful overreaction elicited by choice-related information, or rather a stable component of one's own preference function, reflecting a specific pattern of neural activity. We tested the latter hypothesis by assessing in 57 healthy human subjects whether the relationship between behavioral and neural loss aversion holds at rest, i.e. when the BOLD signal is collected during 5minutes of cross-fixation in the absence of an explicit task. Within the resting-state networks highlighted by a spatial group Independent Component Analysis (gICA), we found a significant correlation between strength of activity and behavioral loss aversion in the left ventral striatum and right posterior insula/supramarginal gyrus, i.e. the very same regions displaying a pattern of neural loss aversion during explicit choices. Cross-study analyses confirmed that this correlation holds when voxels identified by gICA are used as regions of interest in task-related activity and vice versa. These results suggest that the individual degree of (neural) loss aversion represents a stable dimension of decision-making, which reflects in specific metrics of intrinsic brain activity at rest possibly modulating cortical excitability at choice. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Evaluation of serum prolidase activity and oxidative stress markers in men with BPH and prostate cancer.

    Science.gov (United States)

    Kucukdurmaz, Faruk; Efe, Erkan; Çelik, Ahmet; Dagli, Hasan; Kılınc, Metin; Resim, Sefa

    2017-12-12

    Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are diseases of elderly men and are related to increased oxidative stress (OS). Although prolidase has a role in collagen metabolism, it is also used to evaluate OS in many diseases. However, there is a lack of data about serum prolidase activity (SPA) in prostate cancer. The aim of this study was to evaluate and compare SPA levels in males with BPH and PCa. Evaluation was made of a total of 81 men who underwent transrectal ultrasound guided prostate biopsy for a definitive diagnosis due to high PSA levels. Patients were separated into 2 groups as BPH and PCa patients. Pre-biopsy malondialdehyde (MDA), superoxide dismutase (SOD), PSA levels and serum prolidase activities (SPA) were compared between the groups and the correlations of SPA with the other parameters were also investigated in both groups. BPH was diagnosed in 51 patients and PCa in 30. The mean age of patients was similar in both groups as 63.25 ± 5.81 years in the BPH group 65.30 ± 7.35 years in the PCa group(p:0.081). The median MDA and SOD levels were insignificantly increased in the PCa patients. SPA values were similar in BPH and PCa patients. SPA did not correlate with age, PSA, MDA or SOD levels in either group. Our study results revealed that serum prolidase activity is similar in BPH and PCa cases and is not correlated with MDA, SOD or PSA levels.

  13. Physical activity reduces systemic blood pressure and improves early markers of atherosclerosis in pre-pubertal obese children.

    Science.gov (United States)

    Farpour-Lambert, Nathalie J; Aggoun, Yacine; Marchand, Laetitia M; Martin, Xavier E; Herrmann, François R; Beghetti, Maurice

    2009-12-15

    The aim of this study was to determine the effects of physical activity on systemic blood pressure (BP) and early markers of atherosclerosis in pre-pubertal obese children. Hypertension and endothelial dysfunction are premature complications of obesity. We performed a 3-month randomized controlled trial with a modified crossover design: 44 pre-pubertal obese children (age 8.9 + or - 1.5 years) were randomly assigned (1:1) to an exercise (n = 22) or a control group (n = 22). We recruited 22 lean children (age 8.5 + or - 1.5 years) for baseline comparison. The exercise group trained 60 min 3 times/week during 3 months, whereas control subjects remained relatively inactive. Then, both groups trained twice/week during 3 months. We assessed changes at 3 and 6 months in office and 24-h BP, arterial intima-media thickness (IMT) and stiffness, endothelial function (flow-mediated dilation), body mass index (BMI), body fat, cardiorespiratory fitness (maximal oxygen consumption [VO(2)max]), physical activity, and biological markers. Obese children had higher BP, arterial stiffness, body weight, BMI, abdominal fat, insulin resistance indexes, and C-reactive protein levels, and lower flow-mediated dilation, VO(2)max, physical activity, and high-density lipoprotein cholesterol levels than lean subjects. At 3 months, we observed significant changes in 24-h systolic BP (exercise -6.9 + or - 13.5 mm Hg vs. control 3.8 + or - 7.9 mm Hg, -0.8 + or - 1.5 standard deviation score [SDS] vs. 0.4 + or - 0.8 SDS), diastolic BP (-0.5 + or - 1.0 SDS vs. 0 + or - 1.4 SDS), hypertension rate (-12% vs. -1%), office BP, BMI z-score, abdominal fat, and VO(2)max. At 6 months, change differences in arterial stiffness and IMT were significant. A regular physical activity program reduces BP, arterial stiffness, and abdominal fat; increases cardiorespiratory fitness; and delays arterial wall remodeling in pre-pubertal obese children. (Effects of Aerobic Exercise Training on Arterial Function and

  14. Alternate radiolabeled markers for detecting metabolic activity of Mycobacterium leprae residing in murine macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, H.K.; Hastings, R.C.

    1985-05-01

    This study demonstrated the utility of using 4% NaOH as a murine macrophage cell-solubilizing agent to discriminate between host macrophage metabolism and that of intracellular Mycobacterium leprae. A 4% concentration of NaOH had no deleterious effect on labeled mycobacteria. Thereby, alternate radiolabeled indicators of the metabolic activity of intracellular M. leprae could be experimented with. Significant incorporation of /sup 14/C-amino acid mixture, (/sup 14/C)leucine, (/sup 14/C)uridine, and carrier-free /sup 32/P was observed in cultures containing freshly extracted (''live'') strains of M. leprae as compared with control cultures containing autoclaved bacilli.

  15. Alternate radiolabeled markers for detecting metabolic activity of Mycobacterium leprae residing in murine macrophages

    International Nuclear Information System (INIS)

    Prasad, H.K.; Hastings, R.C.

    1985-01-01

    This study demonstrated the utility of using 4% NaOH as a murine macrophage cell-solubilizing agent to discriminate between host macrophage metabolism and that of intracellular Mycobacterium leprae. A 4% concentration of NaOH had no deleterious effect on labeled mycobacteria. Thereby, alternate radiolabeled indicators of the metabolic activity of intracellular M. leprae could be experimented with. Significant incorporation of 14 C-amino acid mixture, [ 14 C]leucine, [ 14 C]uridine, and carrier-free 32 P was observed in cultures containing freshly extracted (''live'') strains of M. leprae as compared with control cultures containing autoclaved bacilli

  16. Oxidized lipoproteins are associated with markers of inflammation and immune activation in HIV-1 infection

    Science.gov (United States)

    Kelesidis, T; Jackson, N; McComsey, GA; Wang, X; Elashoff, D; Dube, MP; Brown, TT; Yang, OO; Stein, JH; Currier, JS

    2016-01-01

    Objective The pathogenesis of immune dysfunction in chronic HIV-1 infection is unclear, and a potential role for oxidized lipids has been suggested. We hypothesize that both oxidized low- and high-density lipoproteins (HDLox, LDLox) contribute to HIV-1 related immune dysfunction. Study In the AIDS Clinical Trials Group (ACTG) A5260, 234 HIV-infected antiretroviral therapy (ART)-naïve participants were randomized to receive tenofovir-emtricitabine plus protease inhibitors or raltegravir and had HIV-1 RNA lipoproteins may contribute to persistent immune activation on ART. PMID:27603288

  17. Chronic Alcohol Ingestion Delays T Cell Activation and Effector Function in Sepsis.

    Directory of Open Access Journals (Sweden)

    Lindsay M Margoles

    Full Text Available Sepsis is the leading cause of death in intensive care units in the US, and it is known that chronic alcohol use is associated with higher incidence of sepsis, longer ICU stays, and higher mortality from sepsis. Both sepsis and chronic alcohol use are associated with immune deficits such as decreased lymphocyte numbers, impaired innate immunity, delayed-type hypersensitivity reactions, and susceptibility to infections; however, understanding of specific pathways of interaction or synergy between these two states of immune dysregulation is lacking. This study therefore sought to elucidate mechanisms underlying the immune dysregulation observed during sepsis in the setting of chronic alcohol exposure. Using a murine model of chronic ethanol ingestion followed by sepsis induction via cecal ligation and puncture, we determined that while CD4+ and CD8+ T cells isolated from alcohol fed mice eventually expressed the same cellular activation markers (CD44, CD69, and CD43 and effector molecules (IFN-γ, TNF as their water fed counterparts, there was an overall delay in the acquisition of these phenotypes. This early lag in T cell activation was associated with significantly reduced IL-2 production at a later timepoint in both the CD4+ and CD8+ T cell compartments in alcohol sepsis, as well as with a reduced accumulation of CD8dim activated effectors. Taken together, these data suggest that delayed T cell activation may result in qualitative differences in the immune response to sepsis in the setting of chronic alcohol ingestion.

  18. Chronic Alcohol Ingestion Delays T Cell Activation and Effector Function in Sepsis.

    Science.gov (United States)

    Margoles, Lindsay M; Mittal, Rohit; Klingensmith, Nathan J; Lyons, John D; Liang, Zhe; Serbanescu, Mara A; Wagener, Maylene E; Coopersmith, Craig M; Ford, Mandy L

    2016-01-01

    Sepsis is the leading cause of death in intensive care units in the US, and it is known that chronic alcohol use is associated with higher incidence of sepsis, longer ICU stays, and higher mortality from sepsis. Both sepsis and chronic alcohol use are associated with immune deficits such as decreased lymphocyte numbers, impaired innate immunity, delayed-type hypersensitivity reactions, and susceptibility to infections; however, understanding of specific pathways of interaction or synergy between these two states of immune dysregulation is lacking. This study therefore sought to elucidate mechanisms underlying the immune dysregulation observed during sepsis in the setting of chronic alcohol exposure. Using a murine model of chronic ethanol ingestion followed by sepsis induction via cecal ligation and puncture, we determined that while CD4+ and CD8+ T cells isolated from alcohol fed mice eventually expressed the same cellular activation markers (CD44, CD69, and CD43) and effector molecules (IFN-γ, TNF) as their water fed counterparts, there was an overall delay in the acquisition of these phenotypes. This early lag in T cell activation was associated with significantly reduced IL-2 production at a later timepoint in both the CD4+ and CD8+ T cell compartments in alcohol sepsis, as well as with a reduced accumulation of CD8dim activated effectors. Taken together, these data suggest that delayed T cell activation may result in qualitative differences in the immune response to sepsis in the setting of chronic alcohol ingestion.

  19. Course of chronic hilar sarcoidosis in relation to markers of granulomatous activity

    International Nuclear Information System (INIS)

    Israel, H.L.; Sperber, M.; Steiner, R.M.

    1983-01-01

    Studies of the course of sarcoidosis have emphasized that patients with hilar or mediastinal adenopathy usually recover within several years or develop dissemination to the lungs. Chronic hilar and mediastinal adenopathy persisting with little or no change for many decades is an important subgroup that has not received adequate attention. Twelve such patients have been studied. Seven remained asymptomatic, despite persistent adenopathy, for a mean period of 16 years; two with disfiguring facial sarcoids received corticosteroids for 18 and 27 years, respectively, and three patients after ten years of stable adenopathy developed pulmonary infiltrates. Tests performed on patients with hilar adenopathy to evaluate cellular activity after a mean interval of over 16 years included Kveim reaction (positive in nine of ten), serum angiotensin converting enzyme (elevated in eight of 12), and gallium-67 scanning (hilar uptake in all eight tested). Results were similar for patients who remained well and for those who had symptomatic or progressive disease, indicating that these parameters of granulomatous activity do not reflect the duration of the disease, its outcome, or the need for treatment

  20. α-smooth muscle actin is not a marker of fibrogenic cell activity in skeletal muscle fibrosis.

    Directory of Open Access Journals (Sweden)

    Wanming Zhao

    Full Text Available α-Smooth muscle actin (α-SMA is used as a marker for a subset of activated fibrogenic cells, myofibroblasts, which are regarded as important effector cells of tissue fibrogenesis. We address whether α-SMA-expressing myofibroblasts are detectable in fibrotic muscles of mdx5cv mice, a mouse model for Duchenne muscular dystrophy (DMD, and whether the α-SMA expression correlates with the fibrogenic function of intramuscular fibrogenic cells. α-SMA immunostaining signal was not detected in collagen I (GFP-expressing cells in fibrotic muscles of ColI-GFP/mdx5cv mice, but it was readily detected in smooth muscle cells lining intramuscular blood vessel walls. α-SMA expression was detected by quantitative RT-PCR and Western blot in fibrogenic cells sorted from diaphragm and quadriceps muscles of the ColI-GFP/mdx5cv mice. Consistent with the more severe fibrosis in the ColI-GFP/mdx5cv diaphragm, the fibrogenic cells in the diaphragm exerted a stronger fibrogenic function than the fibrogenic cells in the quadriceps as gauged by their extracellular matrix gene expression. However, both gene and protein expression of α-SMA was lower in the diaphragm fibrogenic cells than in the quadriceps fibrogenic cells in the ColI-GFP/mdx5cv mice. We conclude that myofibroblasts are present in fibrotic skeletal muscles, but their expression of α-SMA is not detectable by immunostaining. The level of α-SMA expression by intramuscular fibrogenic cells does not correlate positively with the level of collagen gene expression or the severity of skeletal muscle fibrosis in the mdx5cv mice. α-SMA is not a functional marker of fibrogenic cells in skeletal muscle fibrosis associated with muscular dystrophy.

  1. Preterm labour detection by use of a biophysical marker: the uterine electrical activity.

    Science.gov (United States)

    Marque, Catherine K; Terrien, Jérémy; Rihana, Sandy; Germain, Guy

    2007-06-01

    The electrical activity of the uterine muscle is representative of uterine contractility. Its characterization may be used to detect a potential risk of preterm delivery in women, even at an early gestational stage. We have investigated the effect of the recording electrode position on the spectral content of the signal by using a mathematical model of the women's abdomen. We have then compared the simulated results to actual recordings. On signals with noise reduced with a dedicated algorithm, we have characterized the main frequency components of the signal spectrum in order to compute parameters indicative of different situations: preterm contractions resulting nonetheless in term delivery (i.e. normal contractions) and preterm contractions leading to preterm delivery (i.e. high-risk contractions). A diagnosis system permitted us to discriminate between these different categories of contractions. As the position of the placenta seems to affect the frequency content of electrical activity, we have also investigated in monkeys, with internal electrodes attached on the uterus, the effect of the placenta on the spectral content of the electrical signals. In women, the best electrode position was the median vertical axis of the abdomen. The discrimination between high risk and normal contractions showed that it was possible to detect a risk of preterm labour as early as at the 27th week of pregnancy (Misclassification Rate range: 11-19.5%). Placental influence on electrical signals was evidenced in animal recordings, with higher energy content in high frequency bands, for signals recorded away from the placenta when compared to signals recorded above the placental insertion. However, we noticed, from pregnancy to labour, a similar evolution of the frequency content of the signal towards high frequencies, whatever the relative position of electrodes and placenta. On human recordings, this study has proved that it is possible to detect, by non-invasive abdominal

  2. Preterm labour detection by use of a biophysical marker: the uterine electrical activity

    Directory of Open Access Journals (Sweden)

    Germain Guy

    2007-06-01

    Full Text Available Abstract Background The electrical activity of the uterine muscle is representative of uterine contractility. Its characterization may be used to detect a potential risk of preterm delivery in women, even at an early gestational stage. Methods We have investigated the effect of the recording electrode position on the spectral content of the signal by using a mathematical model of the women's abdomen. We have then compared the simulated results to actual recordings. On signals with noise reduced with a dedicated algorithm, we have characterized the main frequency components of the signal spectrum in order to compute parameters indicative of different situations: preterm contractions resulting nonetheless in term delivery (i.e. normal contractions and preterm contractions leading to preterm delivery (i.e. high-risk contractions. A diagnosis system permitted us to discriminate between these different categories of contractions. As the position of the placenta seems to affect the frequency content of electrical activity, we have also investigated in monkeys, with internal electrodes attached on the uterus, the effect of the placenta on the spectral content of the electrical signals. Results In women, the best electrode position was the median vertical axis of the abdomen. The discrimination between high risk and normal contractions showed that it was possible to detect a risk of preterm labour as early as at the 27th week of pregnancy (Misclassification Rate range: 11–19.5%. Placental influence on electrical signals was evidenced in animal recordings, with higher energy content in high frequency bands, for signals recorded away from the placenta when compared to signals recorded above the placental insertion. However, we noticed, from pregnancy to labour, a similar evolution of the frequency content of the signal towards high frequencies, whatever the relative position of electrodes and placenta. Conclusion On human recordings, this study has

  3. Improved Preparation of Beta-D-ManNAc-(1-4)-D-Glc and Beta-d-TalNAc-(1-4)-D-Glc Disaccharides and Evaluation of Their Activating Properties on the Natural Killer Cells NKR-P1 and CD69 Receptors

    Czech Academy of Sciences Publication Activity Database

    Attolino, E.; Bonaccorsi, F.; Catelani, G.; D'Andrea, F.; Křenek, Karel; Bezouška, Karel; Křen, Vladimír

    2008-01-01

    Roč. 27, č. 3 (2008), s. 156-171 ISSN 0732-8303 R&D Projects: GA AV ČR IAA400200503; GA MŠk(CZ) LC06010; GA MŠk OC 136 Grant - others:GA MŠk(CZ) COST D34 Institutional research plan: CEZ:AV0Z50200510 Keywords : reductions * nkr-p1 receptor * nk cells Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.114, year: 2008

  4. Synthesis of (2-[{sup 11}C]Methoxy)rotenone, a marker of mitochondrial complex I activity

    Energy Technology Data Exchange (ETDEWEB)

    Charalambous, A; Mangner, T J; Kilbourn, M R

    1995-01-01

    Recent studies suggest that defects in the function of the complexes of the electron transport chain might be involved in the pathology of neurological diseases such as mitochondrial encephalopathies, Parkinson's Huntington's and Alzheimer's disease. Rotenone is a potent reversible competitive inhibitor of complex I (NADH-CoQ reductase). To study the possible involvement of complex I in such diseases, we synthesized (2-[{sup 11}C]methoxy)rotenone by [{sup 11}C]alkylation of 2-O-desmethyl rotenone methyl enol ether followed by hydrolysis of the enol ether to the ketone using aqueous trifluoroacetic acid. (2-[{sup 11}C]Methoxy)rotenone was purified by high pressure liquid chromatography (silica gel) and was obtained in 7-10% yields decay corrected to end of bombardment in synthesis times typically shorter than 48 min. Radiochemical purities were over 95% and specific activities averaged 1000 Ci/mmol at end of synthesis.

  5. Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation.

    Science.gov (United States)

    Irwin, Michael R; Wang, Minge; Campomayor, Capella O; Collado-Hidalgo, Alicia; Cole, Steve

    2006-09-18

    Inflammation is associated with increased risk of cardiovascular disorders, arthritis, diabetes mellitus, and mortality. The effects of sleep loss on the cellular and genomic mechanisms that contribute to inflammatory cytokine activity are not known. In 30 healthy adults, monocyte intracellular proinflammatory cytokine production was repeatedly assessed during the day across 3 baseline periods and after partial sleep deprivation (awake from 11 pm to 3 am). We analyzed the impact of sleep loss on transcription of proinflammatory cytokine genes and used DNA microarray analyses to characterize candidate transcription-control pathways that might mediate the effects of sleep loss on leukocyte gene expression. In the morning after a night of sleep loss, monocyte production of interleukin 6 and tumor necrosis factor alpha was significantly greater compared with morning levels following uninterrupted sleep. In addition, sleep loss induced a more than 3-fold increase in transcription of interleukin 6 messenger RNA and a 2-fold increase in tumor necrosis factor alpha messenger RNA. Bioinformatics analyses suggested that the inflammatory response was mediated by the nuclear factor kappaB inflammatory signaling system as well as through classic hormone and growth factor response pathways. Sleep loss induces a functional alteration of the monocyte proinflammatory cytokine response. A modest amount of sleep loss also alters molecular processes that drive cellular immune activation and induce inflammatory cytokines; mapping the dynamics of sleep loss on molecular signaling pathways has implications for understanding the role of sleep in altering immune cell physiologic characteristics. Interventions that target sleep might constitute new strategies to constrain inflammation with effects on inflammatory disease risk.

  6. Activity of serum angiotensin-converting enzyme as a tumour marker of hepatocellular carcinoma.

    Science.gov (United States)

    Kardum, D; Huskic, J; Fabijanic, D; Banic, M; Buljevac, M; Kujundzic, M; Loncar, B

    1999-11-01

    Previous studies have pointed to the changes of serum angiotensin-converting enzyme (SACE) values in patients with liver disease and cancer located in different sites. The aim of this study was to determine the changes in SACE values in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. The study comprised 30 patients with HCC (22 men and eight women) of average age 48.6 +/- 9.0 years and 30 patients with liver cirrhosis (21 men, nine women) of average age 49.1 +/- 9.5 years. The control group consisted of 30 healthy volunteers with matching anthropometric characteristics. SACE activity was determined by a spectrophotometric method using synthetic hippuryl-glycyl-glycine as substrate. The mean SACE value was considerably lower in patients with HCC, 22.8 U/ml (95% CI, 22.5-23.9), both those in whom HCC developed in cirrhotic liver (n = 23), 23.7 (22.9-24.5) as well as those with HCC without cirrhosis (n = 7), 21.8 (21.0-22.6), with regard to patients with liver cirrhosis, 37.2 (36.6-37.8) (P SACE value was increased in accordance with the severity of the disease expressed by Child's classification; however, at each stage SACE values were considerably lower in patients with HCC in cirrhotic liver (Child A, 35.8 vs 22.1; Child B, 38.7 vs 24.2; Child C, 40.0 vs 28.3) (P SACE activity. The SACE value was also significantly decreased in patients with HCC whose AFP were not altered. The study has shown that SACE values are low in patients with advanced HCC. It may be helpful in detecting HCC in patients with cirrhosis, where it can be difficult to differentiate between small HCC tumours and regeneration nodules.

  7. Persistence of Activated and Adaptive-Like NK Cells in HIV+ Individuals despite 2 Years of Suppressive Combination Antiretroviral Therapy

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    Anna C. Hearps

    2017-06-01

    Full Text Available Innate immune dysfunction persists in HIV+ individuals despite effective combination antiretroviral therapy (cART. We recently demonstrated that an adaptive-like CD56dim NK cell population lacking the signal transducing protein FcRγ is expanded in HIV+ individuals. Here, we analyzed a cohort of HIV+ men who have sex with men (MSM, n = 20 at baseline and following 6, 12, and 24 months of cART and compared them with uninfected MSM (n = 15 to investigate the impact of cART on NK cell dysfunction. Proportions of NK cells expressing markers of early (CD69+ and late (HLA-DR+/CD38+ activation were elevated in cART-naïve HIV+ MSM (p = 0.004 and 0.015, respectively, as were FcRγ− NK cells (p = 0.003. Using latent growth curve modeling, we show that cART did not reduce levels of FcRγ− NK cells (p = 0.115 or activated HLA-DR+/CD38+ NK cells (p = 0.129 but did reduce T cell and monocyte activation (p < 0.001 for all. Proportions of FcRγ− NK cells were not associated with NK cell, T cell, or monocyte activation, suggesting different factors drive CD56dim FcRγ− NK cell expansion and immune activation in HIV+ individuals. While proportions of activated CD69+ NK cells declined significantly on cART (p = 0.003, the rate was significantly slower than the decline of T cell and monocyte activation, indicating a reduced potency of cART against NK cell activation. Our findings indicate that 2 years of suppressive cART have no impact on CD56dim FcRγ− NK cell expansion and that NK cell activation persists after normalization of other immune parameters. This may have implications for the development of malignancies and co-morbidities in HIV+ individuals on cART.

  8. A controlled clinical trial to evaluate the effect of GanedenBC(30) on immunological markers.

    Science.gov (United States)

    Kimmel, M; Keller, D; Farmer, S; Warrino, D E

    2010-03-01

    GanedenBC(30), a probiotic, has been shown to significantly increase T-cell production of TNF-alpha after ex vivo exposure to a strain of adenovirus (AdenoVI) or influenza A (H3N2 Texas strain [FluTex]). The current controlled study was designed to further evaluate the effect of GanedenBC(30) on immunological marker levels following viral exposure. Ten healthy subjects' baseline immunological marker levels were analyzed. Subjects consumed 1 capsule/day of GanedenBC(30) for 28 days and returned for post-treatment immunological marker evaluation. Subjects' baseline measurements served as their own control. All subjects completed the study with no adverse events; however, one subject was excluded from the final analysis based on a reasonable consideration as an outlier. CD3+CD69+ cells, IL-6, IL-8, interferon-gamma (IFN-gamma) and TNF-alpha levels were increased after exposure to AdenoVI and FluTex. IL-1beta levels also increased after exposure to AdenoVI but were decreased after ex vivo exposure to FluTex. CD3+CD69+ cells increased significantly (P = 0.023) after exposure to both viral strains. Differences in IL-8 levels after FluTex exposure achieved statistical significance (P = 0.039) as did IFN-gamma levels after AdenoVI exposure (P = 0.039). A regimen of one capsule per day containing 500 million CFU of GanedenBC30 may be a safe and effective option for enhancing the immunological response to common viral respiratory tract infections. 2010 Prous Science, S.A.U. or its licensors. All rights reserved.

  9. Comparison of the Serum Tumor Markers S100 and Melanoma-inhibitory Activity (MIA) in the Monitoring of Patients with Metastatic Melanoma Receiving Vaccination Immunotherapy with Dendritic Cells.

    Science.gov (United States)

    Uslu, Ugur; Schliep, Stefan; Schliep, Klaus; Erdmann, Michael; Koch, Hans-Uwe; Parsch, Hans; Rosenheinrich, Stina; Anzengruber, Doris; Bosserhoff, Anja Katrin; Schuler, Gerold; Schuler-Thurner, Beatrice

    2017-09-01

    In patients with melanoma, early dissemination via lymphatic and hematogenous routes is frequently seen. Thus, besides clinical follow-up examination and imaging, reliable melanoma-specific serological tumor markers are needed. We retrospectively compared two serum markers for melanoma, S100 and melanoma-inhibitory activity (MIA), for monitoring of patients with metastatic melanoma under either adjuvant or therapeutic vaccination immunotherapy with dendritic cells (DC). Serum was obtained from a total of 100 patients (28 patients in stage III and 72 patients in stage IV, according to the American Joint Committee on Cancer 2002) at regular intervals during therapy, accompanied by follow-up imaging. When relapse was detected, both markers often remained within normal range. In contrast, in patients with metastatic measurable disease receiving therapeutic and not adjuvant DC vaccination, an increase of both markers was a strong indicator for disease progression. When comparing both markers in the whole study population, MIA showed a superior sensitivity to detect disease progression. S100 and MIA are highly sensitive tumor markers for monitoring of patients with melanoma with current metastases, but less sensitive for monitoring of tumor-free patients. In the current study, MIA had a slightly superior sensitivity to detect progressive disease compared to S100 and seems to be more useful in monitoring of patients with metastatic melanoma receiving immunotherapy. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  10. Markers of Microbial Translocation and Immune Activation Predict Cognitive Processing Speed in Heavy-Drinking Men Living with HIV

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    Mollie A. Monnig

    2017-09-01

    Full Text Available HIV infection and alcohol use disorder are associated with deficits in neurocognitive function. Emerging evidence points to pro-inflammatory perturbations of the gut-brain axis as potentially contributing to neurocognitive impairment in the context of HIV and chronic heavy alcohol use. This study examined whether plasma markers of microbial translocation (LPS from the gastrointestinal tract and related immune activation (sCD14, EndoCAb were associated with neurocognition in 21 men living with HIV who were virally suppressed on antiretroviral therapy. All participants met federal criteria for heavy drinking and were enrolled in a randomized controlled trial (RCT of a brief alcohol intervention. This secondary analysis utilized blood samples and cognitive scores (learning, memory, executive function, verbal fluency, and processing speed obtained at baseline and three-month follow-up of the RCT. In generalized estimating equation models, LPS, sCD14, and EndoCAb individually were significant predictors of processing speed. In a model with all biomarkers, higher LPS and sCD14 both remained significant predictors of lower processing speed. These preliminary findings suggest that inflammation stemming from HIV and/or alcohol could have negative effects on the gut-brain axis, manifested as diminished processing speed. Associations of microbial translocation and immune activation with processing speed in heavy-drinking PLWH warrant further investigation in larger-scale studies.

  11. Identification of BDNF sensitive electrophysiological markers of synaptic activity and their structural correlates in healthy subjects using a genetic approach utilizing the functional BDNF Val66Met polymorphism.

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    Fruzsina Soltész

    Full Text Available Increasing evidence suggests that synaptic dysfunction is a core pathophysiological hallmark of neurodegenerative disorders. Brain-derived neurotropic factor (BDNF is key synaptogenic molecule and targeting synaptic repair through modulation of BDNF signalling has been suggested as a potential drug discovery strategy. The development of such "synaptogenic" therapies depend on the availability of BDNF sensitive markers of synaptic function that could be utilized as biomarkers for examining target engagement or drug efficacy in humans. Here we have utilized the BDNF Val66Met genetic polymorphism to examine the effect of the polymorphism and genetic load (i.e. Met allele load on electrophysiological (EEG markers of synaptic activity and their structural (MRI correlates. Sixty healthy adults were prospectively recruited into the three genetic groups (Val/Val, Val/Met, Met/Met. Subjects also underwent fMRI, tDCS/TMS, and cognitive assessments as part of a larger study. Overall, some of the EEG markers of synaptic activity and brain structure measured with MRI were the most sensitive markers of the polymorphism. Met carriers showed decreased oscillatory activity and synchrony in the neural network subserving error-processing, as measured during a flanker task (ERN; and showed increased slow-wave activity during resting. There was no evidence for a Met load effect on the EEG measures and the polymorphism had no effects on MMN and P300. Met carriers also showed reduced grey matter volume in the anterior cingulate and in the (left prefrontal cortex. Furthermore, anterior cingulate grey matter volume, and oscillatory EEG power during the flanker task predicted subsequent behavioural adaptation, indicating a BDNF dependent link between brain structure, function and behaviour associated with error processing and monitoring. These findings suggest that EEG markers such as ERN and resting EEG could be used as BDNF sensitive functional markers in early

  12. Effects of a Physical Activity Program on Markers of Endothelial Dysfunction, Oxidative Stress, and Metabolic Status in Adolescents with Metabolic Syndrome

    Science.gov (United States)

    Camarillo-Romero, Eneida; Dominguez-Garcia, Ma Victoria; Amaya-Chavez, Araceli; Camarillo-Romero, Maria del Socorro; Talavera-Piña, Juan; Huitron-Bravo, Gerardo; Majluf-Cruz, Abraham

    2012-01-01

    The metabolic syndrome (MetS) is a precursor of diabetes. Physical activity (PA) improves endothelial dysfunction and may benefit patients with MetS. Aims. To evaluate the effect of a physical activity (PA) program on markers of endothelial dysfunction and oxidative stress in adolescents with (MetS). Methods. We carried out a cohort study of 38 adolescents with and without MetS (18 females and 20 males). All participants completed a 3-month PA program. All variables of the MetS as well as markers of endothelial dysfunction and oxidative stress tests were evaluated. Results. Females with and without MetS showed significant differences for almost all components of the MetS, whereas males were significantly different in half of the components. After the PA program, components of the MetS were not different from baseline values except for HDL-C levels. Some baseline endothelial dysfunction markers were significantly different among adolescents with and without MetS; however, after the PA program, most of these markers significantly improved in subjects with and without MetS. Conclusion. PA improves the markers of endothelial dysfunction in adolescents with MetS although other changes in the components of the MetS were not observed. Perhaps the benefits of PA on all components of MetS would appear after a PA program with a longer duration. PMID:22888450

  13. Vitamin D status is associated with cardiometabolic markers in 8-11-year-old children, independently of body fat and physical activity

    DEFF Research Database (Denmark)

    Petersen, Rikke A.; Dalskov, Stine-Mathilde; Sørensen, Louise B.

    2015-01-01

    Vitamin D status has been associated with cardiometabolic markers even in children, but the associations may be confounded by fat mass and physical activity behaviour. This study investigated associations between vitamin D status and cardiometabolic risk profile, as well as the impact of fat mass...

  14. Effects of gastric bypass followed by a randomized study of physical training on markers of coagulation activation, fibrin clot properties, and fibrinolysis

    DEFF Research Database (Denmark)

    Stolberg, Charlotte Røn; Mundbjerg, Lene Hymøller; Funch-Jensen, Peter

    2018-01-01

    disease risk markers within coagulation activation, fibrin clot properties, and fibrinolysis. Setting: Bariatric center, Hospital of Southwest Jutland, Denmark. Methods: Sixty obese patients underwent RYGB and 6 months after RYGB were randomized to 26 weeks of physical training or a control group...

  15. Oral candidiasis as a clinical marker of highly active antiretroviral treatment failure in HIV-infected patients

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    Sandra Lopez-Verdin

    Full Text Available Introduction: Oral candidiasis is an opportunistic infection that is readily detectable in the clinic. It has been used to assess the immune status of HIV patients as well as the effectiveness of highly active antiretroviral therapy. Objective: To determine the frequency of oral candidiasis infection among various indicators associated with antiretroviral therapy effectiveness. Material and methods: Cross-sectional and analytical study, in which groups were initially created based on the use or not of antiretroviral therapy. Participants were subjected to questions on factors related to Candida infection, salivary flow measurements and a clinical examination of the oral cavity to determine the frequency of candidiasis Results: The difference in the frequency of oral candidiasis between groups with and without antiretroviral therapy was significant (OR 2.6 IC95% 1.5-4.4. There were also a significant association with decreased number of CD4 lymphocytes.. Discussion: Resistance to anti-retroviral therapy constitutes one of the fundamental barriers to a successful treatment in patients infected with the human immunodeficiency virus, as do toxicities and adherence problems. Clinical markers such oral candidiasis is an easily and accesible parameter for the early detection of treatment failure.

  16. Endothelial activation markers (VCAM-1, vWF in patients with chronic hepatitis C and insulin resistance

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    T. V. Antonova

    2012-01-01

    Full Text Available Blood markers of endothelial activation (sVCAM-1, vWF: Ag in patients with chronic hepatitis C in the presence of insulin resistance, metabolic syndrome and its components had been evaluated. The study included 69 patients with chronic hepatitis C with oligosymptomatic the disease. In one third of cases of chronic hepatitis C (33.3% showed improvement in the blood content of sVCAM-1 and / or vWF: Ag. In patients with chronic hepatitis C with insulin resistance, metabolic syndrome significantly more often found signs adhesion of endothelial dysfunction (increased blood concentrations of sVCAM-1 than in patients without these disorders. Found that in patients with severe hepatic fibrosis in patients with chronic hepatitis C blood concentration sVCAM-1 is significantly higher compared to patients with early stages of fibrosis (F0-F2, including those in patients without insulin resistance. These data suggest the multivariate development of endothelial dysfunction in chronic hepatitis C.

  17. Floral markers of cornflower (Centaurea cyanus) honey and its peroxide antibacterial activity for an alternative treatment of digital dermatitis.

    Science.gov (United States)

    Oelschlaegel, Stefanie; Pieper, Laura; Staufenbiel, Rudolf; Gruner, Margit; Zeippert, Linda; Pieper, Bernd; Koelling-Speer, Isabelle; Speer, Karl

    2012-11-28

    Cornflower (Centaurea cyanus) honey can be characterized by a greenish yellow color and an intense flavor with a bitter aftertaste. Because cornflower honey contains only a limited amount of pollen for the verification of its floral origin, one objective was the characterization of its polyphenol and norisoprenoid contents to assign floral markers. Here, lumichrome (18.8-43.5 mg/kg), 7-carboxylumichrome, (Z/E)-3-oxo-retro-α-ionol, and 3-oxo-α-ionol appeared to be quite suitable for distinguishing cornflower honey from other unifloral honeys. Additionally, due to its comparably high hydrogen peroxide content (0.5-0.9 mM/h) and the associated antibacterial activity, cornflower honey was used as an alternative treatment of digital dermatitis on an organic dairy farm. Cows affected by this hoof disease often show severe lameness and a subsequent decline in milk yield and loss of body condition. The cows' hooves treated with cornflower honey showed significantly faster healing than the control group without any treatment.

  18. LAG-3 Represents a Marker of CD4+ T Cells with Regulatory Activity in Patients with Bone Fracture.

    Science.gov (United States)

    Wang, Jun; Ti, Yunfan; Wang, Yicun; Guo, Guodong; Jiang, Hui; Chang, Menghan; Qian, Hongbo; Zhao, Jianning; Sun, Guojing

    2018-04-19

    The lymphocyte activation gene 3 (LAG-3) is a CD4 homolog with binding affinity to MHC class II molecules. It is thought that LAG-3 exerts a bimodal function, such that co-ligation of LAG-3 and CD3 could deliver an inhibitory signal in conventional T cells, whereas, on regulatory T cells, LAG-3 expression could promote their inhibitory function. In this study, we investigated the role of LAG-3 expression on CD4 + T cells in patients with long bone fracture. We found that LAG-3 + cells represented approximately 13% of peripheral blood CD4 + T cells on average. Compared to LAG-3 - CD4 + T cells, LAG-3 + CD4 + T cells presented significantly higher Foxp3 and CTLA-4 expression. Directly ex vivo or with TCR stimulation, LAG-3 + CD4 + T cells expressed significantly higher levels of IL-10 and TGF-β than LAG-3 - CD4 + T cells. Interestingly, blocking the LAG-3-MHC class II interaction actually increased the IL-10 expression by LAG-3 + CD4 + T cells. The frequency of LAG-3 + CD4 + T cell was positively correlated with restoration of healthy bone function in long bone fracture patients. These results together suggested that LAG-3 is a marker of CD4 + T cells with regulatory function; at the same time, LAG-3 might have limited the full suppressive potential of Treg cells.

  19. Effects of 28 days of resistance exercise and consuming a commercially available pre-workout supplement, NO-Shotgun®, on body composition, muscle strength and mass, markers of satellite cell activation, and clinical safety markers in males

    Directory of Open Access Journals (Sweden)

    Leutholtz Brian

    2009-08-01

    Full Text Available Abstract Purpose This study determined the effects of 28 days of heavy resistance exercise combined with the nutritional supplement, NO-Shotgun®, on body composition, muscle strength and mass, markers of satellite cell activation, and clinical safety markers. Methods Eighteen non-resistance-trained males participated in a resistance training program (3 × 10-RM 4 times/wk for 28 days while also ingesting 27 g/day of placebo (PL or NO-Shotgun® (NO 30 min prior to exercise. Data were analyzed with separate 2 × 2 ANOVA and t-tests (p Results Total body mass was increased in both groups (p = 0.001, but without any significant increases in total body water (p = 0.77. No significant changes occurred with fat mass (p = 0.62; however fat-free mass did increase with training (p = 0.001, and NO was significantly greater than PL (p = 0.001. Bench press strength for NO was significantly greater than PL (p = 0.003. Myofibrillar protein increased with training (p = 0.001, with NO being significantly greater than PL (p = 0.019. Serum IGF-1 (p = 0.046 and HGF (p = 0.06 were significantly increased with training and for NO HGF was greater than PL (p = 0.002. Muscle phosphorylated c-met was increased with training for both groups (p = 0.019. Total DNA was increased in both groups (p = 0.006, while NO was significantly greater than PL (p = 0.038. For DNA/protein, PL was decreased and NO was not changed (p = 0.014. All of the myogenic regulatory factors were increased with training; however, NO was shown to be significantly greater than PL for Myo-D (p = 0.008 and MRF-4 (p = 0.022. No significant differences were located for any of the whole blood and serum clinical chemistry markers (p > 0.05. Conclusion When combined with heavy resistance training for 28 days, NO-Shotgun® is not associated with any negative side effects, nor does it abnormally impact any of the clinical chemistry markers. Rather, NO-Shotgun® effectively increases muscle strength and mass

  20. PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Vowinckel, E; Reutens, D; Becher, B

    1997-01-01

    Activated glial cells are implicated in regulating and effecting the immune response that occurs within the CNS as part of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). The peripheral benzodiazepine receptor (PBR) is expressed in glial cells. We...... examined the utility of using in vitro and in vivo ligand binding to the PBR as a measure of lesion activity in autoimmune CNS demyelinating diseases. Applying a combined autoradiography and immunohistochemical approach to spinal cord and brain tissues from mice with EAE, we found a correlation at sites...... of inflammatory lesions between [3H]-PK11195 binding and immunoreactivity for the activated microglial/macrophage marker Mac-1/CD11b. In MS tissues, [3H]-PK11195 binding correlated with sites of immunoreactivity for the microglial/macrophage marker CD68, at the edges of chronic active plaques. Positron emission...

  1. THE EFFECT OF PHYSICAL ACTIVITY ON INFLAMMATORY MARKERS.THE RISK OF NEW CORONARY EVENT IN CORONARY HEART DISEASE PATIENTS

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    Todorka Savic

    2007-12-01

    Full Text Available Inflammation is an important factor in the pathogenesis of atherosclerosis, and several markers of inflammation have been associated with an increased risk of cardiovascular events. Physical activity may lower the risk of coronary heart disease(CHD by mitigating inflammation. The aim of the study was to investigate the effects of aerobic exercise training on systemic inflammatory response in patients with stabile coronary artery disease participating in a cardiovascular rehabilitation exercise program. Male (n=29 and female (n=23 patients with stable coronary heart disease were recruited for this study. All patients were divided into two groups: group with regular aerobic physical training during cardiovascular rehabilitation program phase II along 3 weeks in rehabilitation center and 3 weeks after that in home of patients and sedentary lifestyle group. There were no significant differences in gender distribution among analyzed groups. Student’s t test showed no significant difference in mean age, waist circumference (OS and waist/hip ratio (WHR. Degree of obesity was measured by BMI, and there was a significant improvement in BMI in patients who underwent the six-week physical training compared to control group (p<0.05.Physical training during 6 weeks did not show any effects on leukocyte count and ICAM-1 levels compared to control group. The exercise training induced reduction in plasma CRP levels by 23.72%, p<0.001, and reduction in plasma VCAM-1 levels by Moderate aerobic exercise training resulted in a significant reduction of inflammatory state by decreasing CRP and VCAM-1 levels without significant body mass and visceral obesity reduction. The obtained results indicate that regular physical activity is clinically attractive in primary and secondary prevention of coronary heart diseases.

  2. ENZYME MARKERS ACTIVITY AND BILE FORMATION FUNCTION OF LIVER IN CASES OF TUBERCULOSTATICS AND HEXAVALENT CHROMIUM COMPOUNDS AFFECTION IN RATS

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    N. I. Burmas

    2016-05-01

    Full Text Available Background. Currently, the growing incidence of toxic lesions of the liver is associated with industrial chemicalization and uncontrolled use of hepatotoxic drugs in everyday life. There are about one thousand drugs with high or low hepatotoxicity, such as anti-TB drugs. Objective. In this research we studied the intracellular enzymes activity and bile formation function of the liver in rats of different ages in cases of tuberculostatic (isoniazid and rifampicin affection and chromium (potassium dichromate intoxication. Methods. The experimental affection of rats of different ages was performed by combined injection of hexavalent chromium compounds (a solution of potassium dichromate, 3 mg/kg, isoniazid (0.05 g/kg and rifampicin (0.25 g/kg. On the 7th and 14th days the rats were injected with enterosorbent Sorbex (150 mg/kg. Enzyme markers activity of the liver was evaluated due to alanine and aspartate aminotransferases (ALT and AST and alkaline phosphatase (ALP rates. Bile formation function of the liver was evaluated by total bilirubin and bile acids content in blood. Results. The disorders in hepatocytes plasma membranes permeability were defined by the increased rates of ALT, AST and alkaline phosphatase in blood serum which were decreased in the liver. It was determined that total bilirubin and bile acids content in blood serum of the affected animals increased. It influenced hepatocytes excretion in bile capillaries and caused cholestasis and revenues decrease in bile. Conclusions. The most significant metabolic disorders in cases of chrome-isoniazid-rifampicin affection were defined in immature and senior animals in comparison with mature animals.

  3. Modulation of inhibitory activity markers by intermittent theta-burst stimulation in rat cortex is NMDA-receptor dependent.

    Science.gov (United States)

    Labedi, Adnan; Benali, Alia; Mix, Annika; Neubacher, Ute; Funke, Klaus

    2014-01-01

    Intermittent theta-burst stimulation (iTBS) applied via transcranial magnetic stimulation has been shown to increase cortical excitability in humans. In the rat brain it strongly reduced the number of neurons expressing the 67-kD isoform of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD67) and those expressing the calcium-binding proteins parvalbumin (PV) and calbindin (CB), specific markers of fast-spiking (FS) and non-FS inhibitory interneurons, respectively, an indication of modified cortical inhibition. Since iTBS effects in humans have been shown to be NMDA receptor sensitive, we wondered whether the iTBS-induced changes in the molecular phenotype of interneurons may be also sensitive to glutamatergic synaptic transmission mediated by NMDA receptors. In a sham-controlled fashion, five iTBS-blocks of 600 stimuli were applied to rats either lightly anesthetized by only urethane or by an additional low (subnarcotic) or high dose of the NMDA receptor antagonist ketamine before immunohistochemical analysis. iTBS reduced the number of neurons expressing GAD67, PV and CB. Except for CB, a low dose of ketamine partially prevented these effects while a higher dose almost completely abolished the iTBS effects. Our findings indicate that iTBS modulates the molecular, and likely also the electric, activity of cortical inhibitory interneurons and that the modulation of FS-type but less that of non-FS-type neurons is mediated by NMDA receptors. A combination of iTBS with pharmacological interventions affecting distinct receptor subtypes may thus offer options to enhance its selectivity in modulating the activity of distinct cell types and preventing others from being modulated. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Developmental heterogeneity in DNA packaging patterns influences T-cell activation and transmigration.

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    Soumya Gupta

    Full Text Available Cellular differentiation programs are accompanied by large-scale changes in nuclear organization and gene expression. In this context, accompanying transitions in chromatin assembly that facilitates changes in gene expression and cell behavior in a developmental system are poorly understood. Here, we address this gap and map structural changes in chromatin organization during murine T-cell development, to describe an unusual heterogeneity in chromatin organization and associated functional correlates in T-cell lineage. Confocal imaging of DNA assembly in cells isolated from bone marrow, thymus and spleen reveal the emergence of heterogeneous patterns in DNA organization in mature T-cells following their exit from the thymus. The central DNA pattern dominated in immature precursor cells in the thymus whereas both central and peripheral DNA patterns were observed in naïve and memory cells in circulation. Naïve T-cells with central DNA patterns exhibited higher mechanical pliability in response to compressive loads in vitro and transmigration assays in vivo, and demonstrated accelerated expression of activation-induced marker CD69. T-cell activation was characterized by marked redistribution of DNA assembly to a central DNA pattern and increased nuclear size. Notably, heterogeneity in DNA patterns recovered in cells induced into quiescence in culture, suggesting an internal regulatory mechanism for chromatin reorganization. Taken together, our results uncover an important component of plasticity in nuclear organization, reflected in chromatin assembly, during T-cell development, differentiation and transmigration.

  5. Expression pattern of pluripotent markers in different embryonic developmental stages of buffalo (Bubalus bubalis) embryos and putative embryonic stem cells generated by parthenogenetic activation.

    Science.gov (United States)

    Singh, Karn P; Kaushik, Ramakant; Garg, Veena; Sharma, Ruchi; George, Aman; Singh, Manoj K; Manik, Radhey S; Palta, Prabhat; Singla, Suresh K; Chauhan, Manmohan S

    2012-12-01

    In this study, we describe the production of buffalo parthenogenetic blastocysts and subsequent isolation of parthenogenetic embryonic stem cell (PGESC)-like cells. PGESC colonies exhibited dome-shaped morphology and were clearly distinguishable from the feeder layer cells. Different stages of development of parthenogenetic embryos and derived embryonic stem cell (ESC)-like cells expressed key ESC-specific markers, including OCT-4, NANOG, SOX-2, FOXD3, REX-1, STAT-3, TELOMERASE, NUCLEOSTEMIN, and cMYC. Immunofluorescence-based studies revealed that the PGESCs were positive for surface-based pluripotent markers, viz., SSEA-3, SSEA-4, TRA 1-80, TRA 1-60, CD-9, and CD-90 and exhibited high alkaline phosphatase (ALP) activity. PGEC cell-like cells formed embryoid body (EB)-like structures in hanging drop cultures and when cultured for extended period of time spontaneously differentiated into derivatives of three embryonic germ layers as confirmed by RT-PCR for ectodermal (CYTOKERATIN8, NF-68), mesodermal (MSX1, BMP-4, ASA), and endodermal markers (AFP, HNF-4, GATA-4). Differentiation of PGESCs toward the neuronal lineage was successfully directed by supplementation of serum-containing media with retinoic acid. Our results indicate that the isolated ESC-like cells from parthenogenetic blastocyst hold properties of ESCs and express markers of pluripotency. The pluripotency markers were also expressed by early cleavage-stage of buffalo embryos.

  6. Tumors markers

    International Nuclear Information System (INIS)

    Yamaguchi-Mizumoto, N.H.

    1989-01-01

    In order to study blood and cell components alterations (named tumor markers) that may indicate the presence of a tumor, several methods are presented. Aspects as diagnostic, prognostic, therapeutic value and clinical evaluation are discussed. (M.A.C.)

  7. Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients.

    Directory of Open Access Journals (Sweden)

    Petronela Ancuta

    2008-06-01

    Full Text Available Elevated plasma lipopolysaccharide (LPS, an indicator of microbial translocation from the gut, is a likely cause of systemic immune activation in chronic HIV infection. LPS induces monocyte activation and trafficking into brain, which are key mechanisms in the pathogenesis of HIV-associated dementia (HAD. To determine whether high LPS levels are associated with increased monocyte activation and HAD, we obtained peripheral blood samples from AIDS patients and examined plasma LPS by Limulus amebocyte lysate (LAL assay, peripheral blood monocytes by FACS, and soluble markers of monocyte activation by ELISA. Purified monocytes were isolated by FACS sorting, and HIV DNA and RNA levels were quantified by real time PCR. Circulating monocytes expressed high levels of the activation markers CD69 and HLA-DR, and harbored low levels of HIV compared to CD4(+ T-cells. High plasma LPS levels were associated with increased plasma sCD14 and LPS-binding protein (LBP levels, and low endotoxin core antibody levels. LPS levels were higher in HAD patients compared to control groups, and were associated with HAD independently of plasma viral load and CD4 counts. LPS levels were higher in AIDS patients using intravenous heroin and/or ethanol, or with Hepatitis C virus (HCV co-infection, compared to control groups. These results suggest a role for elevated LPS levels in driving monocyte activation in AIDS, thereby contributing to the pathogenesis of HAD, and provide evidence that cofactors linked to substance abuse and HCV co-infection influence these processes.

  8. Physical activity and inflammatory markers over 10 years: follow-up in men and women from the Whitehall II cohort study.

    Science.gov (United States)

    Hamer, Mark; Sabia, Severine; Batty, G David; Shipley, Martin J; Tabák, Adam G; Singh-Manoux, Archana; Kivimaki, Mika

    2012-08-21

    Inflammatory processes are putative mechanisms underlying the cardioprotective effects of physical activity. An inverse association between physical activity and inflammation has been demonstrated, but no long-term prospective data are available. We therefore examined the association between physical activity and inflammatory markers over a 10-year follow-up period. Participants were 4289 men and women (mean age, 49.2 years) from the Whitehall II cohort study. Self-reported physical activity and inflammatory markers (serum high-sensitivity C-reactive protein and interleukin-6) were measured at baseline (1991) and follow-up (2002). Forty-nine percent of the participants adhered to standard physical activity recommendations for cardiovascular health (2.5 h/wk moderate to vigorous physical activity) across all assessments. Physically active participants at baseline had lower C-reactive protein and interleukin-6 levels, and this difference remained stable over time. Compared with participants who rarely adhered to physical activity guidelines over the 10-year follow-up, the high-adherence group displayed lower log(e) C-reactive protein (β=-0.07; 95% confidence interval, -0.12 to -0.02) and log(e) interleukin-6 (β=-0.07; 95% confidence interval, -0.10 to -0.03) at follow-up after adjustment for a range of covariates. Compared with participants who remained stable, those who reported an increase in physical activity of at least 2.5 h/wk displayed lower log(e) C-reactive protein (β coefficient=-0.05; 95% confidence interval, -0.10 to -0.001) and log(e) interleukin-6 (β coefficient=-0.06; 95% confidence interval, -0.09 to -0.03) at follow-up. Regular physical activity is associated with lower markers of inflammation over 10 years of follow-up and thus may be important in preventing the proinflammatory state seen with aging.

  9. Circulating activated innate lymphoid cells and mucosal-associated invariant T cells are associated with airflow limitation in patients with asthma.

    Science.gov (United States)

    Ishimori, Ayako; Harada, Norihiro; Chiba, Asako; Harada, Sonoko; Matsuno, Kei; Makino, Fumihiko; Ito, Jun; Ohta, Shoichiro; Ono, Junya; Atsuta, Ryo; Izuhara, Kenji; Takahashi, Kazuhisa; Miyake, Sachiko

    2017-04-01

    A variety of innate subsets of lymphoid cells such as natural killer (NK) cells, several populations of innate lymphoid cells (ILCs), and mucosal-associated invariant T (MAIT) cells as innate-like T lymphocytes are involved in asthma and may have important effector functions in asthmatic immune responses. In the present study, we investigated whether NK cells, ILCs, and MAIT cells in the peripheral blood of patients with asthma would be associated with clinical asthma parameters. We recruited 75 adult patients with mild to severe asthma. The peripheral blood mononuclear cells in peripheral venous blood samples from the patients were purified and stained with different combinations of appropriate antibodies. The cells were analyzed by flow cytometry. The percentage of activated (i.e., CD69 + ) NK cells in the total NK cell population was negatively correlated with FEV 1 % which is calculated by the forced expiratory volume in 1 s (FEV 1 )/the forced vital capacity (FVC). The percentages of CD69 + ILC1s and ILC2s were negatively correlated with FEV 1 % and %FEV 1 . The percentage of CD69 + ILC3s was positively correlated with BMI, and the percentage of CD69 + MAIT cells was negatively correlated with FEV 1 %. Moreover, the percentage of CD69 + NK cells, ILC1s, ILC2s, ILC3s, and MAIT cells were positively correlated with each other. For the first time, our data showed that activated NK cells, ILC1s, ILC2s, ILC3s, and MAIT cells were positively correlated with each other and may be associated with airflow limitation in patients with asthma. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  10. Elevated Serum ADA Activity as a Marker for Diagnosis and Prognosis of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis in Indian Patients

    Science.gov (United States)

    Vijayamahantesh; Amit, Ajay; Dikhit, Manas R.; Pandey, Raj K.; Singh, Kuljit; Mishra, Ritesh; Das, V. N. R; Das, Pradeep; Bimal, Sanjiva

    2016-01-01

    Serum adenosine deaminase (ADA) activity increases in diseases where cellular immunity is involved. Since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ADA activity in different pathological conditions. Adenosine deaminase was determined in sera of active visceral leishmaniasis (VL) patients (n = 39), active postkala-azar dermal leishmaniasis (PKDL) cases (n = 34) at the point of diagnosis and after treatment stages along with healthy controls (n = 30), endemic healthy subjects (n = 34) and endemic asymptomatic subjects (n = 34).Our in-vitro result revealed that monocytes secrete significant ADA level in response to Leishmania donovani (L.donovani) stimulation. The serum ADA activity in active VL and PKDL subjects were found to be significantly higher than that of respective treated cases and healthy controls. We also observed a marginal number (17.6%) of endemic asymptomatic subjects showed elevated serum ADA activity. Further, the ADA activity in PKDL was found to be decreased gradually during the different phases of treatment. Interestingly, 2 out of 32 treated VL cases found to have high serum ADA activity during follow up period were relapsed within few days. These results suggest the possibility of ADA as a marker of clinical pathogenesis and can be used as a surrogate marker in the diagnosis and prognosis of VL and PKDL. PMID:27186641

  11. Elevated Serum ADA Activity as a Marker for Diagnosis and Prognosis of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis in Indian Patients.

    Science.gov (United States)

    Vijayamahantesh; Amit, Ajay; Dikhit, Manas R; Pandey, Raj K; Singh, Kuljit; Mishra, Ritesh; Das, V N R; Das, Pradeep; Bimal, Sanjiva

    2016-01-01

    Serum adenosine deaminase (ADA) activity increases in diseases where cellular immunity is involved. Since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ADA activity in different pathological conditions. Adenosine deaminase was determined in sera of active visceral leishmaniasis (VL) patients (n = 39), active postkala-azar dermal leishmaniasis (PKDL) cases (n = 34) at the point of diagnosis and after treatment stages along with healthy controls (n = 30), endemic healthy subjects (n = 34) and endemic asymptomatic subjects (n = 34).Our in-vitro result revealed that monocytes secrete significant ADA level in response to Leishmania donovani (L.donovani) stimulation. The serum ADA activity in active VL and PKDL subjects were found to be significantly higher than that of respective treated cases and healthy controls. We also observed a marginal number (17.6%) of endemic asymptomatic subjects showed elevated serum ADA activity. Further, the ADA activity in PKDL was found to be decreased gradually during the different phases of treatment. Interestingly, 2 out of 32 treated VL cases found to have high serum ADA activity during follow up period were relapsed within few days. These results suggest the possibility of ADA as a marker of clinical pathogenesis and can be used as a surrogate marker in the diagnosis and prognosis of VL and PKDL.

  12. Chronic Exposure to Malaria Is Associated with Inhibitory and Activation Markers on Atypical Memory B Cells and Marginal Zone-Like B Cells

    Directory of Open Access Journals (Sweden)

    Itziar Ubillos

    2017-08-01

    Full Text Available In persistent infections that are accompanied by chronic immune activation, such as human immunodeficiency virus, hepatitis C virus, and malaria, there is an increased frequency of a phenotypically distinct subset of memory B cells lacking the classic memory marker CD27 and showing a reduced capacity to produce antibodies. However, critical knowledge gaps remain on specific B cell changes and immune adaptation in chronic infections. We hypothesized that expansion of atypical memory B cells (aMBCs and reduction of activated peripheral marginal zone (MZ-like B cells in constantly exposed individuals might be accompanied by phenotypic changes that would confer a tolerogenic profile, helping to establish tolerance to infections. To better understand malaria-associated phenotypic abnormalities on B cells, we analyzed peripheral blood mononuclear cells from 55 pregnant women living in a malaria-endemic area of Papua Nueva Guinea and 9 Spanish malaria-naïve individuals using four 11-color flow cytometry panels. We assessed the expression of markers of B cell specificity (IgG and IgM, activation (CD40, CD80, CD86, b220, TACI, and CD150, inhibition (PD1, CD95, and CD71, and migration (CCR3, CXCR3, and CD62l. We found higher frequencies of active and resting aMBC and marked reduction of MZ-like B cells, although changes in absolute cell counts could not be assessed. Highly exposed women had higher PD1+-, CD95+-, CD40+-, CD71+-, and CD80+-activated aMBC frequencies than non-exposed subjects. Malaria exposure increased frequencies of b220 and proapoptotic markers PD1 and CD95, and decreased expression of the activation marker TACI on MZ-like B cells. The increased frequencies of inhibitory and apoptotic markers on activated aMBCs and MZ-like B cells in malaria-exposed adults suggest an immune-homeostatic mechanism for maintaining B cell development and function while simultaneously downregulating hyperreactive B cells. This mechanism would keep the B cell

  13. Distinct activation phenotype of a highly conserved novel HLA-B57-restricted epitope during dengue virus infection.

    Science.gov (United States)

    Townsley, Elizabeth; Woda, Marcia; Thomas, Stephen J; Kalayanarooj, Siripen; Gibbons, Robert V; Nisalak, Ananda; Srikiatkhachorn, Anon; Green, Sharone; Stephens, Henry A F; Rothman, Alan L; Mathew, Anuja

    2014-01-01

    Variation in the sequence of T-cell epitopes between dengue virus (DENV) serotypes is believed to alter memory T-cell responses during second heterologous infections. We identified a highly conserved, novel, HLA-B57-restricted epitope on the DENV NS1 protein. We predicted higher frequencies of B57-NS1(26-34) -specific CD8(+) T cells in peripheral blood mononuclear cells from individuals undergoing secondary rather than primary DENV infection. However, high tetramer-positive T-cell frequencies during acute infection were seen in only one of nine subjects with secondary infection. B57-NS1(26-34) -specific and other DENV epitope-specific CD8(+) T cells, as well as total CD8(+) T cells, expressed an activated phenotype (CD69(+) and/or CD38(+)) during acute infection. In contrast, expression of CD71 was largely limited to DENV epitope-specific CD8(+) T cells. In vitro stimulation of cell lines indicated that CD71 expression was differentially sensitive to stimulation by homologous and heterologous variant peptides. CD71 may represent a useful marker of antigen-specific T-cell activation. © 2013 John Wiley & Sons Ltd.

  14. Unique ζ-chain motifs mediate a direct TCR-actin linkage critical for immunological synapse formation and T-cell activation.

    Science.gov (United States)

    Klieger, Yair; Almogi-Hazan, Osnat; Ish-Shalom, Eliran; Pato, Aviad; Pauker, Maor H; Barda-Saad, Mira; Wang, Lynn; Baniyash, Michal

    2014-01-01

    TCR-mediated activation induces receptor microclusters that evolve to a defined immune synapse (IS). Many studies showed that actin polymerization and remodeling, which create a scaffold critical to IS formation and stabilization, are TCR mediated. However, the mechanisms controlling simultaneous TCR and actin dynamic rearrangement in the IS are yet not fully understood. Herein, we identify two novel TCR ζ-chain motifs, mediating the TCR's direct interaction with actin and inducing actin bundling. While T cells expressing the ζ-chain mutated in these motifs lack cytoskeleton (actin) associated (cska)-TCRs, they express normal levels of non-cska and surface TCRs as cells expressing wild-type ζ-chain. However, such mutant cells are unable to display activation-dependent TCR clustering, IS formation, expression of CD25/CD69 activation markers, or produce/secrete cytokine, effects also seen in the corresponding APCs. We are the first to show a direct TCR-actin linkage, providing the missing gap linking between TCR-mediated Ag recognition, specific cytoskeleton orientation toward the T-cell-APC interacting pole and long-lived IS maintenance. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Measurement of Circulating Cytokines and Immune-Activation Markers by Multiplex Technology in the Clinical Setting: What Are We Really Measuring?

    Science.gov (United States)

    Aziz, Najib

    2015-01-01

    Measurement of circulating cytokine levels can provide important information in the study of the pathogenesis of disease. John L. Fahey was a pioneer in the measurement of circulating cytokines and immune-activation markers and a leader in the quality assessment/control of assays for measurement of circulating cytokines. Insights into the measurement of circulating cytokines, including consideration of multiplex assays, are presented here.

  16. Effect of different intensities of physical activity on cardiometabolic markers and vascular and cardiac function in adult rats fed with a high-fat high-carbohydrate diet

    OpenAIRE

    Romeo B. Batacan, Jr; Mitch J. Duncan; Vincent J. Dalbo; Geraldine L. Buitrago; Andrew S. Fenning

    2018-01-01

    Background: Physical activity (PA) and diet are 2 lifestyle factors that affect cardiometabolic risk. However, data on how a high-fat high-carbohydrate (HFHC) diet influences the effect of different intensities of PA on cardiometabolic health and cardiovascular function in a controlled setting are yet to be fully established. This study investigated the effect of sedentary behavior, light-intensity training (LIT), and high-intensity interval training (HIIT) on cardiometabolic markers and vasc...

  17. (SSR) markers

    African Journals Online (AJOL)

    acer

    2013-06-26

    Jun 26, 2013 ... analysis was in general agreement with PCoA in discrimi- nating the cultivars. Conclusions. Estimation of morphological diversity may provide addi- tional information on the present finding. Nonetheless, the 29 SSR markers provided considerable genetic reso- lution and this genetic diversity analysis ...

  18. (SSR) markers

    African Journals Online (AJOL)

    SAM

    2014-07-30

    Jul 30, 2014 ... India and the country is currently the leading producer, consumer and exporter of ... registration with the competent authority for plant variety protection. Conventionally ... detection of duplicates, parental verification in crosses, gene tagging in .... allelic patterns as revealed by the current set of SSR markers.

  19. Use of DNA markers in forest tree improvement research

    Science.gov (United States)

    D.B. Neale; M.E. Devey; K.D. Jermstad; M.R. Ahuja; M.C. Alosi; K.A. Marshall

    1992-01-01

    DNA markers are rapidly being developed for forest trees. The most important markers are restriction fragment length polymorphisms (RFLPs), polymerase chain reaction- (PCR) based markers such as random amplified polymorphic DNA (RAPD), and fingerprinting markers. DNA markers can supplement isozyme markers for monitoring tree improvement activities such as; estimating...

  20. Exercise restores decreased physical activity levels and increases markers of autophagy and oxidative capacity in myostatin/activin-blocked mdx mice.

    Science.gov (United States)

    Hulmi, Juha J; Oliveira, Bernardo M; Silvennoinen, Mika; Hoogaars, Willem M H; Pasternack, Arja; Kainulainen, Heikki; Ritvos, Olli

    2013-07-15

    The importance of adequate levels of muscle size and function and physical activity is widely recognized. Myostatin/activin blocking increases skeletal muscle mass but may decrease muscle oxidative capacity and can thus be hypothesized to affect voluntary physical activity. Soluble activin receptor IIB (sActRIIB-Fc) was produced to block myostatin/activins. Modestly dystrophic mdx mice were injected with sActRIIB-Fc or PBS with or without voluntary wheel running exercise for 7 wk. Healthy mice served as controls. Running for 7 wk attenuated the sActRIIB-Fc-induced increase in body mass by decreasing fat mass. Running also enhanced/restored the markers of muscle oxidative capacity and autophagy in mdx mice to or above the levels of healthy mice. Voluntary running activity was decreased by sActRIIB-Fc during the first 3-4 wk correlating with increased body mass. Home cage physical activity of mice, quantified from the force plate signal, was decreased by sActRIIB-Fc the whole 7-wk treatment in sedentary mice. To understand what happens during the first weeks after sActRIIB-Fc administration, when mice are less active, healthy mice were injected with sActRIIB-Fc or PBS for 2 wk. During the sActRIIB-Fc-induced rapid 2-wk muscle growth period, oxidative capacity and autophagy were reduced, which may possibly explain the decreased running activity. These results show that increased muscle size and decreased markers of oxidative capacity and autophagy during the first weeks of myostatin/activin blocking are associated with decreased voluntary activity levels. Voluntary exercise in dystrophic mice enhances the markers of oxidative capacity and autophagy to or above the levels of healthy mice.

  1. Human immunodeficiency virus-like particles activate multiple types of immune cells

    International Nuclear Information System (INIS)

    Sailaja, Gangadhara; Skountzou, Ioanna; Quan, Fu-Shi; Compans, Richard W.; Kang, Sang-Moo

    2007-01-01

    The rapid spread of human immunodeficiency virus (HIV) worldwide makes it a high priority to develop an effective vaccine. Since live attenuated or inactivated HIV is not likely to be approved as a vaccine due to safety concerns, HIV virus like particles (VLPs) offer an attractive alternative because they are safe due to the lack of a viral genome. Although HIV VLPs have been shown to induce humoral and cellular immune responses, it is important to understand the mechanisms by which they induce such responses and to improve their immunogenicity. We generated HIV VLPs, and VLPs containing Flt3 ligand (FL), a dendritic cell growth factor, to target VLPs to dendritic cells, and investigated the roles of these VLPs in the initiation of adaptive immune responses in vitro and in vivo. We found that HIV-1 VLPs induced maturation of dendritic cells and monocyte/macrophage populations in vitro and in vivo, with enhanced expression of maturation markers and cytokines. Dendritic cells pulsed with VLPs induced activation of splenocytes resulting in increased production of cytokines. VLPs containing FL were found to increase dendritic cells and monocyte/macrophage populations in the spleen when administered to mice. Administration of VLPs induced acute activation of multiple types of cells including T and B cells as indicated by enhanced expression of the early activation marker CD69 and down-regulation of the homing receptor CD62L. VLPs containing FL were an effective form of antigen in activating immune cells via dendritic cells, and immunization with HIV VLPs containing FL resulted in enhanced T helper type 2-like immune responses

  2. Humoral markers of active Epstein-Barr virus infection associate with anti-extractable nuclear antigen autoantibodies and plasma galectin-3 binding protein in systemic lupus erythematosus.

    Science.gov (United States)

    Rasmussen, N S; Nielsen, C T; Houen, G; Jacobsen, S

    2016-12-01

    We investigated if signs of active Epstein-Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein-Barr virus early antigen diffuse and cytomegalovirus pp52 were applied as humoral markers of ongoing/recently active Epstein-Barr virus and cytomegalovirus infections, respectively. Plasma galectin-3 binding protein served as a surrogate marker of type I interferon activity. The measurements were conducted in 57 systemic lupus erythematosus patients and 29 healthy controls using ELISAs. Regression analyses and univariate comparisons were performed for associative evaluation between virus serology, plasma galectin-3 binding protein and autoantibodies, along with other clinical and demographic parameters. Plasma galectin-3 binding protein concentrations were significantly higher in systemic lupus erythematosus patients (P = 0.009) and associated positively with Epstein-Barr virus early antigen diffuse-directed antibodies and the presence of autoantibodies against extractable nuclear antigens in adjusted linear regressions (B = 2.02 and 2.02, P = 0.02 and P = 0.002, respectively). Furthermore, systemic lupus erythematosus patients with anti-extractable nuclear antigens had significantly higher antibody levels against Epstein-Barr virus early antigen diffuse (P = 0.02). Our study supports a link between active Epstein-Barr virus infections, positivity for anti-extractable nuclear antigens and increased plasma galectin-3 binding protein concentrations/type I interferon activity in systemic lupus erythematosus patients. © The Author(s) 2016.

  3. Vitamin D status is associated with cardiometabolic markers in 8-11-year-old children, independently of body fat and physical activity

    DEFF Research Database (Denmark)

    Petersen, Rikke A.; Dalskov, Stine-Mathilde; Sørensen, Louise B.

    2015-01-01

    )D) and measured blood pressure, fasting plasma glucose, homoeostasis model of assessment-insulin resistance, plasma lipids, inflammatory markers, anthropometry and fat mass by dual-energy X-ray absorptiometry, and physical activity by 7 d accelerometry during August-November. Mean serum 25(OH)D was 60·8 (sd 18...... lipids) and lower metabolic syndrome (MetS) score (P=0·01). Adjustment for fat mass index did not change the associations, but the association with blood pressure became borderline significant after adjustment for physical activity (P=0·06). In conclusion, vitamin D status was negatively associated...... should be investigated in randomised controlled trials....

  4. Circulatory Immune Cells in Cushing Syndrome: Bystanders or Active Contributors to Atherometabolic Injury? A Study of Adhesion and Activation of Cell Surface Markers

    Directory of Open Access Journals (Sweden)

    Gloria Aranda

    2017-01-01

    Full Text Available Glucocorticoids (GC induce cardiometabolic risk while atherosclerosis is a chronic inflammation involving immunity. GC are immune suppressors, and the adrenocorticotrophic hormone (ACTH has immune modulator activities. Both may act in atherothrombotic inflammation involving immune cells (IMNC. Aim. To investigate adhesion and activation surface cell markers (CDs of peripheral IMNC in endogenous Cushing syndrome (CS and the immune modulator role of ACTH. Material and Methods. 16 ACTH-dependent CS (ACTH-D, 10 ACTH-independent (ACTH-ID CS, and 16 healthy controls (C were included. Leukocytes (Leuc, monocytes (MN, lymphocytes (Lym, and neutrophils (N were analyzed by flow cytometry for atherosclerosis previously associated with CDs. Results. Leuc, N, and MN correlated with CS (p<0.05, WC (p<0.001, WHR (p=0.003, BMI (p<0.001, and hs-CRP (p<0.001. CD14++CD16+ (p=0.047; CD14+CD16++ (p=0.053 MN; CD15+ (p=0.027; CD15+CD16+ (p=0.008 N; and NK-Lym (p=0.019 were higher in CS. CD14+CD16++ MN were higher in ACTH-ID (8.9 ± 3.5% versus ACTH-D CS (4.2 ± 1.9% versus C (4.9 ± 2.3%. NK-Lym correlated with c-LDL (r = 0.433, p=0.039 and CD15+ N with hs-CRP (r = 0.446, p=0.037. In multivariate analysis, Leuc, N, and MN depended on BMI (p=0.021, WC (p=0.002, and WHR (p=0.014, while CD15+ and CD15+CD16+ N on hypercortisolism and CS (p=0.035. Conclusion. In CS, IMNC present changes in activation and adhesion CDs implicated in atherothrombotic inflammation. ACTH-IDCS presents a particular IMNC phenotype, possibly due to the absence of the immune modulator effect of ACTH.

  5. Marker lamps

    International Nuclear Information System (INIS)

    Watkins, D.V.

    1980-01-01

    A marker lamp is described which consists of a block of transparent plastics material encapsulated in which is a radioactive light source. These lights comprise a small sealed glass capsule, the hollow inside surface of which is coated with phosphor and which contains tritium or similar radioactive gas. The use of such lamps for identification marking of routes, for example roads, and for identification of underwater oil pipelines is envisaged. (U.K.)

  6. Cucurbitacin IIb exhibits anti-inflammatory activity through modulating multiple cellular behaviors of mouse lymphocytes.

    Directory of Open Access Journals (Sweden)

    Yao Wang

    Full Text Available Cucurbitacin IIb (CuIIb is one of the major active compounds in Hemsleyadine tablets which have been used for clinical treatment of bacillary dysentery, enteritis and acute tonsilitis. However, its action mechanism has not been completely understood. This study aimed to explore the anti-inflammatory activity of CuIIb and its underlying mechanism in mitogen-activated lymphocytes isolated from mouse mesenteric lymph nodes. The results showed that CuIIb inhibited the proliferation of concanavalin A (Con A-activated lymphocytes in a time- and dose-dependent manner. CuIIb treatment arrested their cell cycle in S and G2/M phases probably due to the disruption of the actin cytoskeleton and the modulation of p27(Kip1 and cyclin levels. Moreover, the surface expression of activation markers CD69 and CD25 on Con A-activated CD3(+ T lymphocytes was suppressed by CuIIb treatment. Both Con A- and phorbol ester plus ionomycin-induced expression of TNF-α, IFN-γ and IL-6 proteins was attenuated upon exposure to CuIIb. Mechanistically, CuIIb treatment suppressed the phosphorylation of JNK and Erk1/2 but not p38 in Con A-activated lymphocytes. Although CuIIb unexpectedly enhanced the phosphorylation of IκB and NF-κB (p65, it blocked the nuclear translocation of NF-κB (p65. In support of this, CuIIb significantly decreased the mRNA levels of IκBα and TNF-α, two target genes of NF-κB, in Con A-activated lymphocytes. In addition, CuIIb downregulated Con A-induced STAT3 phosphorylation and increased cell apoptosis. Collectively, these results suggest that CuIIb exhibits its anti-inflammatory activity through modulating multiple cellular behaviors and signaling pathways, leading to the suppression of the adaptive immune response.

  7. Effects of 6-month soccer and traditional physical activity programmes on body composition, cardiometabolic risk factors, inflammatory, oxidative stress markers and cardiorespiratory fitness in obese boys.

    Science.gov (United States)

    Seabra, André; Katzmarzyk, Peter; Carvalho, Maria José; Seabra, Ana; Coelho-E-Silva, Manuel; Abreu, Sandra; Vale, Susana; Póvoas, Susana; Nascimento, Henrique; Belo, Luís; Torres, Sandra; Oliveira, José; Mota, Jorge; Santos-Silva, Alice; Rêgo, Carla; Malina, Robert M

    2016-10-01

    Physical activity is important in obesity prevention, but the effectiveness of different physical activity modalities remains to be determined among children. The main purpose of this study was to compare the effects of a 6-month soccer programme and a traditional physical activity programme on changes in body composition, cardiometabolic risk factors, inflammatory and oxidative markers, cardiorespiratory fitness and perceived psychological status in obese boys. Eighty-eight boys (8-12 years; BMI > +2 standard deviations of WHO reference values) participated in one of three groups: soccer, traditional activity and control. Soccer and traditional activity programmes involved 3 sessions per week for 60-90 min at an average intensity of 70-80% of maximal heart rate. Control group participated in activities of normal daily living. All boys participated in school physical education, two sessions per week of 45-90-min. Measurements were taken at baseline and after 6 months, and included body size and composition, cardiometabolic risk factors, inflammatory and oxidative markers, cardiorespiratory fitness and perceived psychological status. Physical activity and dietary intake were assessed before and immediately following the intervention. The three groups had similar characteristics at baseline. After 6 months, both intervention groups had significantly lower relative fatness (% fat), waist circumference and total cholesterol, and higher cardiorespiratory fitness, self-esteem, perceived physical competence and attraction to physical activity compared with control group. In conclusion, physical activity interventions over 6 months positively influenced several indicators of health status among obese boys. The results also suggested that soccer has the potential as an effective tool for the prevention and reduction of childhood obesity and associated consequences.

  8. Clinical significance of the changes of serum levels of the rheumatoid activity markers IL-2, sIL-2R, HA and VEGF

    International Nuclear Information System (INIS)

    Bao Yong; Long Wubin; Yu Ke; Zeng Ying; Liu Deying

    2004-01-01

    Objective: To explore the relationship between rheumatoid activity and serum levels of the cytokines interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R), hyaluronic acid (HA), vascular endothelial growth factor (VEGF) in patients with rheumatoid arthritis. Methods: Serum IL-2, HA(with RIA) and sIL-2R, VEGF (with ELISA) levels were determined in 30 controls, 30 patients with active rheumatoid arthritis and 30 patients with rheumatoid arthritis in remission. Sensitivity and specificity for each marker were analyzed. Results: In patients with active rheumatoid arthritis, the serum levels of sIL-2R, HA, VEGF were significantly higher and serum levels of IL-2 significantly lower than those in patients in remission and controls (p<0.01). Determination of VEGF levels possessed the highest specificity (93.3%) and also a high sensitivity (93.3% as well). Conclusion: Determination of the serum levels of any of these markers was valuable for monitoring the activity of the rheumatoid process. It is more desirable to take measurements of VEGF levels due to its highest specificity

  9. Association of serial biochemical markers with acute ischemic stroke: the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator Stroke Study.

    Science.gov (United States)

    Jauch, Edward C; Lindsell, Christopher; Broderick, Joseph; Fagan, Susan C; Tilley, Barbara C; Levine, Steven R

    2006-10-01

    Biochemical markers of acute neuronal injury may aid in the diagnosis and management of acute ischemic stroke. Serum samples from the National Institute for Neurological Disorders and Stroke (NINDS) recombinant tissue plasminogen activator Stroke Study were analyzed for the presence of 4 biochemical markers of neuronal, glial, and endothelial cell injury. These biochemical markers, myelin basic protein (MBP), neuron-specific enolase (NSE), S100beta, and soluble thrombomodulin, were studied for an association with initial stroke severity, infarct volume, and functional outcome. In the original NINDS study, serum samples were drawn from all patients on presentation to the Emergency Department and at approximately 2 and 24 hours after initiation of study therapy. In this analysis, stored serum samples were available for 359 patients; 107 patients had samples for all 3 time points. Serum marker concentrations were measured by ELISA techniques. We examined the relation between serum concentrations of each marker and the degree of baseline neurological deficit, functional outcome, and infarct size on computed tomography at 24 hours and the effect of fibrinolytic therapy. Higher 24-hour peak concentrations of MBP, NSE, and S100beta were associated with higher National Institutes of Health Stroke Scale baseline scores (r=0.186, P<0.0001; r=0.117, P=0.032; and r=0.263, P<0.0001, respectively). Higher peak concentrations of MBP and S100beta (r=0.209, P<0.0001; r=0.239, P<0.0001) were associated with larger computed tomography lesion volumes. Patients with favorable outcomes had smaller changes in MBP and S100beta (P<0.05) concentrations in the first 24 hours. Soluble thrombomodulin was not associated with any severity or outcome measure. This study corroborates previous work demonstrating correlations of MBP, NSE, and S100beta with clinical and radiographic features in acute stroke. Despite significantly better outcomes in the tissue plasminogen activator-treated group, we

  10. Molecular markers in glioma.

    Science.gov (United States)

    Ludwig, Kirsten; Kornblum, Harley I

    2017-09-01

    Gliomas are the most malignant and aggressive form of brain tumors, and account for the majority of brain cancer related deaths. Malignant gliomas, including glioblastoma are treated with radiation and temozolomide, with only a minor benefit in survival time. A number of advances have been made in understanding glioma biology, including the discovery of cancer stem cells, termed glioma stem cells (GSC). Some of these advances include the delineation of molecular heterogeneity both between tumors from different patients as well as within tumors from the same patient. Such research highlights the importance of identifying and validating molecular markers in glioma. This review, intended as a practical resource for both clinical and basic investigators, summarizes some of the more well-known molecular markers (MGMT, 1p/19q, IDH, EGFR, p53, PI3K, Rb, and RAF), discusses how they are identified, and what, if any, clinical relevance they may have, in addition to discussing some of the specific biology for these markers. Additionally, we discuss identification methods for studying putative GSC's (CD133, CD15, A2B5, nestin, ALDH1, proteasome activity, ABC transporters, and label-retention). While much research has been done on these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature. Furthermore, it is unlikely that the investigator will be able to utilize one single marker to prospectively identify and isolate GSC from all, or possibly, any gliomas.

  11. Biological and Chemical Removal of Primary Cilia Affects Mechanical Activation of Chondrogenesis Markers in Chondroprogenitors and Hypertrophic Chondrocytes.

    Science.gov (United States)

    Deren, Matthew E; Yang, Xu; Guan, Yingjie; Chen, Qian

    2016-02-04

    Chondroprogenitors and hypertrophic chondrocytes, which are the first and last stages of the chondrocyte differentiation process, respectively, are sensitive to mechanical signals. We hypothesize that the mechanical sensitivity of these cells depends on the cell surface primary cilia. To test this hypothesis, we removed the primary cilia by biological means with transfection with intraflagellar transport protein 88 (IFT88) siRNA or by chemical means with chloral hydrate treatment. Transfection of IFT88 siRNA significantly reduced the percentage of ciliated cells in both chondroprogenitor ATDC5 cells as well as primary hypertrophic chondrocytes. Cyclic loading (1 Hz, 10% matrix deformation) of ATDC5 cells in three-dimensional (3D) culture stimulates the mRNA levels of chondrogenesis marker Type II collagen (Col II), hypertrophic chondrocyte marker Type X collagen (Col X), and a molecular regulator of chondrogenesis and chondrocyte hypertrophy bone morphogenetic protein 2 (BMP-2). The reduction of ciliated chondroprogenitors abolishes mechanical stimulation of Col II, Col X, and BMP-2. In contrast, cyclic loading stimulates Col X mRNA levels in hypertrophic chondrocytes, but not those of Col II and BMP-2. Both biological and chemical reduction of ciliated hypertrophic chondrocytes reduced but failed to abolish mechanical stimulation of Col X mRNA levels. Thus, primary cilia play a major role in mechanical stimulation of chondrogenesis and chondrocyte hypertrophy in chondroprogenitor cells and at least a partial role in hypertrophic chondrocytes.

  12. Biological and Chemical Removal of Primary Cilia Affects Mechanical Activation of Chondrogenesis Markers in Chondroprogenitors and Hypertrophic Chondrocytes

    Directory of Open Access Journals (Sweden)

    Matthew E. Deren

    2016-02-01

    Full Text Available Chondroprogenitors and hypertrophic chondrocytes, which are the first and last stages of the chondrocyte differentiation process, respectively, are sensitive to mechanical signals. We hypothesize that the mechanical sensitivity of these cells depends on the cell surface primary cilia. To test this hypothesis, we removed the primary cilia by biological means with transfection with intraflagellar transport protein 88 (IFT88 siRNA or by chemical means with chloral hydrate treatment. Transfection of IFT88 siRNA significantly reduced the percentage of ciliated cells in both chondroprogenitor ATDC5 cells as well as primary hypertrophic chondrocytes. Cyclic loading (1 Hz, 10% matrix deformation of ATDC5 cells in three-dimensional (3D culture stimulates the mRNA levels of chondrogenesis marker Type II collagen (Col II, hypertrophic chondrocyte marker Type X collagen (Col X, and a molecular regulator of chondrogenesis and chondrocyte hypertrophy bone morphogenetic protein 2 (BMP-2. The reduction of ciliated chondroprogenitors abolishes mechanical stimulation of Col II, Col X, and BMP-2. In contrast, cyclic loading stimulates Col X mRNA levels in hypertrophic chondrocytes, but not those of Col II and BMP-2. Both biological and chemical reduction of ciliated hypertrophic chondrocytes reduced but failed to abolish mechanical stimulation of Col X mRNA levels. Thus, primary cilia play a major role in mechanical stimulation of chondrogenesis and chondrocyte hypertrophy in chondroprogenitor cells and at least a partial role in hypertrophic chondrocytes.

  13. Contribution for new genetic markers of rheumatoid arthritis activity and severity: sequencing of the tumor necrosis factor-alpha gene promoter.

    Science.gov (United States)

    Fonseca, João Eurico; Cavaleiro, João; Teles, José; Sousa, Elsa; Andreozzi, Valeska L; Antunes, Marília; Amaral-Turkman, Maria A; Canhão, Helena; Mourão, Ana F; Lopes, Joana; Caetano-Lopes, Joana; Weinmann, Pamela; Sobral, Marta; Nero, Patrícia; Saavedra, Maria J; Malcata, Armando; Cruz, Margarida; Melo, Rui; Braña, Araceli; Miranda, Luis; Patto, José V; Barcelos, Anabela; da Silva, José Canas; Santos, Luís M; Figueiredo, Guilherme; Rodrigues, Mário; Jesus, Herberto; Quintal, Alberto; Carvalho, Teresa; da Silva, José A Pereira; Branco, Jaime; Queiroz, Mário Viana

    2007-01-01

    The objective of this study was to assess whether clinical measures of rheumatoid arthritis activity and severity were influenced by tumor necrosis factor-alpha (TNF-alpha) promoter genotype/haplotype markers. Each patient's disease activity was assessed by the disease activity score using 28 joint counts (DAS28) and functional capacity by the Health Assessment Questionnaire (HAQ) score. Systemic manifestations, radiological damage evaluated by the Sharp/van der Heijde (SvdH) score, disease-modifying anti-rheumatic drug use, joint surgeries, and work disability were also assessed. The promoter region of the TNF-alpha gene, between nucleotides -1,318 and +49, was sequenced using an automated platform. Five hundred fifty-four patients were evaluated and genotyped for 10 single-nucleotide polymorphism (SNP) markers, but 5 of these markers were excluded due to failure to fall within Hardy-Weinberg equilibrium or to monomorphism. Patients with more than 10 years of disease duration (DD) presented significant associations between the -857 SNP and systemic manifestations, as well as joint surgeries. Associations were also found between the -308 SNP and work disability in patients with more than 2 years of DD and radiological damage in patients with less than 10 years of DD. A borderline effect was found between the -238 SNP and HAQ score and radiological damage in patients with 2 to 10 years of DD. An association was also found between haplotypes and the SvdH score for those with more than 10 years of DD. An association was found between some TNF-alpha promoter SNPs and systemic manifestations, radiological progression, HAQ score, work disability, and joint surgeries, particularly in some classes of DD and between haplotypes and radiological progression for those with more than 10 years of DD.

  14. Increased plasma levels of advanced oxidation protein products (AOPP) as a marker for oxidative stress in patients with active ulcerative colitis.

    Science.gov (United States)

    Alagozlu, Hakan; Gorgul, Ahmet; Bilgihan, Ayse; Tuncer, Candan; Unal, Selahattin

    2013-02-01

    After NADPH oxidase mediated radical formation, hypochloric acid (HOCl) is formed when Cl is used as a substrate by the myeloperoxidase enzyme. Myeloperoxidase is secreted from H2O2 activated leukocytes with polymorphic nuclei. The generation of HOCl also causes the formation of advanced oxidation protein products (AOPP) through damage to normal tissue and protein oxidation. AOPP has been identified as a marker of inflammation in many diseases. However, AOPP has not been investigated in ulcerative colitis. As a result of mucosal inflammation in ulcerative colitis, oxidative stress can occur. We aimed to determine whether plasma AOPP and oxidative stress markers are detectable in active ulcerative colitis. The patient group consisted of 59 patients who were diagnosed with ulcerative colitis in the clinic by histology and endoscopy. The patients were hospitalised and treated in the Gastroenterology Department of Gazi University Medical Facility. The 59 patients were separated into active and inactive groups according to the endoscopic activation index (EAI). Group I consisted of 33 active ulcerative colitis patients, Group II consisted of 26 inactive ulcerative colitis patients and Group III consisted of healthy control subjects. The disease activity of these patients were measured using the Rachmilewitz EAI based on rectosigmoidoscopic or colonoscopic findings. Patients with EAI scores greater than 4 were scored as having active disease (Group I). Patients with EAI0.05). The EAI value was 8.84±0.31 in Group I and 2.76±0.08 in Group II. There were statistically significant differences for EAI between groups (P<0.05). The correlation between AOPP and EAI in all patients with ulcerative colitis were statistically significant (P<0.05, r=0.61). The regression model in this correlation was statistically significant (y=49.68+10.75x, P<0.05). Based on our results, we suggest that AOPP could be used as a non invasive activation marker for ulcerative colitis patients

  15. The immune marker soluble urokinase plasminogen activator receptor is associated with new-onset diabetes in non-smoking women and men

    DEFF Research Database (Denmark)

    Haugaard, S B; Andersen, O; Hansen, T W

    2012-01-01

    Aim: To explore the putative association of new-onset diabetes and the soluble urokinase plasminogen activator receptor (suPAR), which is a new and stable plasma marker of immune function and low-grade inflammation. This association has been previously suggested by using the less sensitive...... International Classification of Disease system to detect incident diabetes in the Danish MONICA 10 cohort. Methods: The Danish National Diabetes Register enabled more accurate identification of incident diabetes during a median follow-up of 13.8 years in the Danish MONICA 10 cohort (n = 2353 generally healthy......-onset diabetes (P...

  16. Diagnostic value of cerebrospinal fluid cytology in comparison with tumor marker activity in central nervous system metastases secondary to breast cancer

    DEFF Research Database (Denmark)

    Bach, F; Bjerregaard, B; Sölétormos, G

    1993-01-01

    : Cytology and activity of the tumor markers tissue polypeptide antigen (TPA) and creatine kinase-BB isoenzyme (CK-BB) were evaluated in the cerebrospinal fluid (CSF) in 71 consecutive patients with breast cancer suspected for CNS metastases. RESULTS: Forty-three patients had no CNS metastases, 12 patients...... (Spearmans-Rho, 0.49; P Cytologic evaluation of CSF obtained by lumbar punctures is a reliable procedure. In CSF from ICV reservoirs, cytologic evaluation is of limited use, but CK-BB and TPA is of potential value....

  17. FOXQ1, a novel target of the Wnt pathway and a new marker for activation of Wnt signaling in solid tumors.

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    Jon Christensen

    Full Text Available BACKGROUND: The forkhead box transcription factor FOXQ1 has been shown to be upregulated in colorectal cancer (CRC and metastatic breast cancer and involved in tumor development, epithelial-mesenchymal transition and chemoresistance. Yet, its transcriptional regulation is still unknown. METHODS: FOXQ1 mRNA and protein expression were analysed in a panel of CRC cell lines, and laser micro-dissected human biopsy samples by qRT-PCR, microarray GeneChip® U133 Plus 2.0 and western blots. FOXQ1 regulation was assayed by chromatin immunoprecipitation and luciferase reporter assays. RESULTS: FOXQ1 was robustly induced in CRC compared to other tumors, but had no predictive value with regards to grade, metastasis and survival in CRC. Prototype-based gene coexpression and gene set enrichment analysis showed a significant association between FOXQ1 and the Wnt pathway in tumors and cancer cell lines from different tissues. In vitro experiments confirmed, on a molecular level, FOXQ1 as a direct Wnt target. Analysis of known Wnt targets identified FOXQ1 as the most suitable marker for canonical Wnt activation across a wide panel of cell lines derived from different tissues. CONCLUSIONS: Our data show that FOXQ1 is one of the most over-expressed genes in CRC and a direct target of the canonical Wnt pathway. It is a potential new marker for detection of early CRC and Wnt activation in tumors of different origins.

  18. Isovitexin as marker and bioactive compound in the antinociceptive activity of the Brazilian crude drug extracts of Echinodorus scaber and E. grandiflorus

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    Claudia Lea Strada

    Full Text Available Abstract Echinodorus scaber Rataj and Echinodorus grandiflorus (Cham. & Schltdl. Micheli, Alismataceae, are popularly used to relieve inflammatory complaints and as diuretic. A study on the antinociceptive effect and selected marker compounds in eleven extracts from different locations was undertaken and their antinociceptive effect was assessed. The fingerprints were compared by HPLC-DAD and the content of vitexin, isovitexin, isoorientin and vitexin-2-O-rhamnoside were determined. All samples presented antinociceptive activity reducing the writhes by 36.4-62.5% and 47.4-79.8% at 10 and 50 mg/kg, respectively; indomethacin (5 mg/kg reduced writhes by 82.6-90.1%. The content of the flavonoids C-glycosides, however, presented a strong variation. Isovitexin and isoorientin were found in all the samples, with content ranging from traces to 14.70 µg/mg and 2.12-84.27 µg/mg extract, respectively, while vitexin-2-O-rhamnoside occurred in quantifiable amounts only in 3 out of 11 samples ranging from 5.43 to 33.13 µg/mg extract; vitexin was not detected at all or detected in trace amounts. According to the fingerprints, the samples could be arranged in four main groups. All eleven extracts showed antinociceptive activity. Isovitexin was the only flavonoid present in all samples and can be regarded, acting in synergy with the other compounds or not, as the responsible for the antinociceptive activity. Therefore, isovitexin is a good choice as chemical marker when the antinociceptive activity of E. scaber and E. grandiflorus is investigated.

  19. Augmented telomerase activity, reduced telomere length and the presence of alternative lengthening of telomere in renal cell carcinoma: plausible predictive and diagnostic markers.

    Science.gov (United States)

    Pal, Deeksha; Sharma, Ujjawal; Khajuria, Ragini; Singh, Shrawan Kumar; Kakkar, Nandita; Prasad, Rajendra

    2015-05-15

    In this study, we analyzed 100 cases of renal cell carcinoma (RCC) for telomerase activity, telomere length and alternative lengthening of telomeres (ALT) using the TRAP assay, TeloTTAGGG assay kit and immunohistochemical analysis of ALT associated promyelocytic leukemia (PML) bodies respectively. A significantly higher (P=0.000) telomerase activity was observed in 81 cases of RCC which was correlated with clinicopathological features of tumor for instance, stage (P=0.008) and grades (P=0.000) but not with the subtypes of RCC (P = 0.355). Notwithstanding, no correlation was found between telomerase activity and subtypes of RCC. Strikingly, the telomere length was found to be significantly shorter in RCC (P=0.000) to that of corresponding normal renal tissues and it is well correlated with grades (P=0.016) but not with stages (P=0.202) and subtypes (P=0.669) of RCC. In this study, telomere length was also negatively correlated with the age of patients (r(2)=0.528; P=0.000) which supports the notion that it could be used as a marker for biological aging. ALT associated PML bodies containing PML protein was found in telomerase negative cases of RCC. It suggests the presence of an ALT pathway mechanism to maintain the telomere length in telomerase negative RCC tissues which was associated with high stages of RCC, suggesting a prevalent mechanism for telomere maintenance in high stages. In conclusion, the telomerase activity and telomere length can be used as a diagnostic as well as a predictive marker in RCC. The prevalence of ALT mechanism in high stages of RCC is warranted for the development of anti-ALT inhibitors along with telomerase inhibitor against RCC as a therapeutic approach. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Inhibitory Effects of Standardized Extracts of Phyllanthus amarus and Phyllanthus urinaria and Their Marker Compounds on Phagocytic Activity of Human Neutrophils

    Directory of Open Access Journals (Sweden)

    Yuandani

    2013-01-01

    Full Text Available The standardized methanol extracts of Phyllanthus amarus and P. urinaria, collected from Malaysia and Indonesia, and their isolated chemical markers, phyllanthin and hypophyllanthin, were evaluated for their effects on the chemotaxis, phagocytosis and chemiluminescence of human phagocytes. All the plant extracts strongly inhibited the migration of polymorphonuclear leukocytes (PMNs with the Malaysian P. amarus showing the strongest inhibitory activity (IC50 value, 1.1 µg/mL. There was moderate inhibition by the extracts of the bacteria engulfment by the phagocytes with the Malaysian P. amarus exhibiting the highest inhibition (50.8% of phagocytizing cells. The Malaysian P. amarus and P. urinaria showed strong reactive oxygen species (ROS inhibitory activity, with both extracts exhibiting IC50 value of 0.7 µg/mL. Phyllanthin and hypophyllanthin exhibited relatively strong activity against PMNs chemotaxis, with IC50 values slightly lower than that of ibuprofen (1.4 µg/mL. Phyllanthin exhibited strong inhibitory activity on the oxidative burst with an IC50 value comparable to that of aspirin (1.9 µg/mL. Phyllanthin exhibited strong engulfment inhibitory activity with percentage of phagocytizing cells of 14.2 and 27.1% for neutrophils and monocytes, respectively. The strong inhibitory activity of the extracts was due to the presence of high amounts of phyllanthin and hypophyllanthin although other constituents may also contribute.

  1. Serum levels of parathyroid hormone and markers of bone metabolism in patients with rheumatoid arthritis. Relationship to disease activity and glucocorticoid treatment

    DEFF Research Database (Denmark)

    Jensen, Tonny Joran; Hansen, M; Madsen, J C

    2001-01-01

    OBJECTIVE: To evaluate the influence of inflammatory activity and glucocorticoid (GC) treatment on serum parathyroid hormone (s-PTH) and bone metabolism in patients with rheumatoid arthritis (RA). Furthermore, in patients with active RA, to examine the PTH secretion and Ca2+ set point before and ....... The increased levels of markers of type I collagen metabolism (s-ICTP, Pyr) and s-AlbCorrCa2+ in patients with active disease and patients treated with GC may be a result of increased degradation in synovium, cartilage and bone due to the inflammatory process.......OBJECTIVE: To evaluate the influence of inflammatory activity and glucocorticoid (GC) treatment on serum parathyroid hormone (s-PTH) and bone metabolism in patients with rheumatoid arthritis (RA). Furthermore, in patients with active RA, to examine the PTH secretion and Ca2+ set point before...... groups. The levels of urine pyridinoline (Pyr) and s-albumin-corrected calcium (s-AlbCorrCa2+) were elevated in patients with active disease and patients treated with GC. S-PTH and s-phosphate were within normal ranges. S-TAP, s-ICTP, Pyr and s-AlbCorrCa2+ correlated positively with indices of disease...

  2. Cellular Profile and Expression of Immunologic Markers in Chronic Apical Periodontitis from HIV-infected Patients Undergoing Highly Active Antiretroviral Therapy.

    Science.gov (United States)

    Gama, Túlio Gustavo Veiga; Pires, Fabio Ramoa; Armada, Luciana; Gonçalves, Lucio Souza

    2016-06-01

    This study tested the hypothesis that the inflammatory cell profile (CD3-, CD4-, CD8-, CD20-, and CD68-positive cells) and the expression of immunologic markers (tumor necrosis factor α, interferon-γ, interleukin-6, and interleukin-18) in chronic apical periodontitis are the same between non-HIV-infected patients and HIV-infected patients undergoing highly active antiretroviral therapy (HAART). Thirty-four surgically excised chronic apical periodontitis lesions were sampled from 34 patients (17 HIV-infected and 17 non-HIV-infected). The lesions were extracted from teeth with no previous endodontic treatment. All HIV-infected patients were undergoing HAART. The specimens were submitted to histopathologic and immunohistochemical analyses by using an optical microscope. Immunoexpression was graded into 2 levels, focal to weak and moderate to strong. The χ(2), Fisher exact, and Mann-Whitney tests were used to analyze all significant differences between groups. Periapical cysts represented 70.6% and 52.9% of the lesions in the HIV-infected and non-HIV-infected groups, respectively; however, no statistically significant difference was observed (P = .481). There were no statistically significant differences between groups for the inflammatory cell profile and for any of the immunologic markers (P > .05). There are no statistically significant differences of the cellular profile and expression of immunologic markers in chronic apical periodontitis between non-HIV-infected patients and HIV-infected patients undergoing HAART. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  3. Does physical activity during pregnancy adversely influence markers of the metabolic syndrome in adult offspring? A prospective study over two decades.

    Science.gov (United States)

    Danielsen, Inge; Granström, Charlotta; Rytter, Dorte; Hammer Bech, Bodil; Brink Henriksen, Tine; Vaag, Allan Arthur; Olsen, Sjurdur Frodi

    2013-08-01

    It is unknown whether physical activity during pregnancy (PA) has long-term impact on the metabolic profile of the offspring. We investigated associations of PA with markers of the metabolic syndrome (MS) in 20y old offspring. Longitudinal study where 965 pregnant women during 1988-1989 had four dimensions of PA assessed by questionnaires in gestation week 30: PA at work; leisure time PA, daily amount of walking-biking and sport participation. The following MS markers were assessed in the offspring (n=439): body mass index (BMI), waist circumference, blood pressure, homeostasis model assessment insulin resistance as well as fasting plasma glucose, triglycerides, cholesterol (high-density lipoprotein (HDL), low-density lipoprotein and total cholesterol), insulin and leptin levels. Walking-biking PA in pregnancy is associated with unchanged or subtle, adverse changes of distinct MS markers among offspring including lower levels of HDL cholesterol (ratio 0.95 (95% CI 0.92 to 0.98) per 1 h increment in walking-biking), a higher diastolic blood pressure (difference 1.12 (95% CI 0.03 to 2.20) mm Hg/1 h increment) and a higher BMI (ratio 1.03 (95% CI 1.01 to 1.05) per 1 h increment). In separate analyses in males, these associations persisted and additional adverse associations were found for triglycerides, systolic blood pressure, waist circumference and leptin. No associations were detected with other measures of PA. The study did not substantiate any protective effects of PA in pregnancy. In contrast, data suggested that high amounts of daily walking-biking in pregnancy may have adverse effects on levels of HDL cholesterol, diastolic blood pressure and BMI in young adult offspring.

  4. Relation between serum xenobiotic induced receptor activities and sperm DNA damage and sperm apoptotic markers in European and Inuit populations

    DEFF Research Database (Denmark)

    Long, Manhai; Stronati, Alessanda; Bizzaro, Davide

    2007-01-01

    Persistent organic pollutants (POPs) can interfere with hormone activities and are suspected as endocrine disrupters involved in disorders, e.g. reproductive disorders. We investigated the possible relation between the actual integrated serum xenoestrogenic, xenoandrogenic and aryl hydrocarbon......, but higher xenoandrogenic activity. In contrast, in the European groups, xenobiotic-induced receptor activities were found to be positively correlated with the DNA damage. Further research must elucidate whether altered receptor activities in concerted action with genetic and/or nutrient factors may have...... protecting effect on sperm DNA damage of the Inuit population....

  5. The ROCK inhibitor Y-27632 improves recovery of human embryonic stem cells after fluorescence-activated cell sorting with multiple cell surface markers.

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    Nil Emre

    Full Text Available BACKGROUND: Due to the inherent sensitivity of human embryonic stem cells (hESCs to manipulations, the recovery and survival of hESCs after fluorescence-activated cell sorting (FACS can be low. Additionally, a well characterized and robust methodology for performing FACS on hESCs using multiple-cell surface markers has not been described. The p160-Rho-associated coiled kinase (ROCK inhibitor, Y-27632, previously has been identified as enhancing survival of hESCs upon single-cell dissociation, as well as enhancing recovery from cryopreservation. Here we examined the application of Y-27632 to hESCs after FACS to improve survival in both feeder-dependent and feeder-independent growth conditions. METHODOLOGY/PRINCIPAL FINDINGS: HESCs were sorted using markers for SSEA-3, TRA-1-81, and SSEA-1. Cells were plated after sorting for 24 hours in either the presence or the absence of Y-27632. In both feeder-dependent and feeder-independent conditions, cell survival was greater when Y-27632 was applied to the hESCs after sort. Specifically, treatment of cells with Y-27632 improved post-sort recovery up to four fold. To determine the long-term effects of sorting with and without the application of Y-27632, hESCs were further analyzed. Specifically, hESCs sorted with and without the addition of Y-27632 retained normal morphology, expressed hESC-specific markers as measured by immunocytochemistry and flow cytometry, and maintained a stable karyotype. In addition, the hESCs could differentiate into three germ layers in vitro and in vivo in both feeder-dependent and feeder-independent growth conditions. CONCLUSIONS/SIGNIFICANCE: The application of Y-27632 to hESCs after cell sorting improves cell recovery with no observed effect on pluripotency, and enables the consistent recovery of hESCs by FACS using multiple surface markers. This improved methodology for cell sorting of hESCs will aid many applications such as removal of hESCs from secondary cell types

  6. Alpha-Fetoprotein, Identified as a Novel Marker for the Antioxidant Effect of Placental Extract, Exhibits Synergistic Antioxidant Activity in the Presence of Estradiol

    Science.gov (United States)

    Choi, Hye Yeon; Kim, Seung Woo; Kim, BongWoo; Lee, Hae Na; Kim, Su-Jeong; Song, Minjung; Kim, Sol; Kim, Jungho; Kim, Young Bong; Kim, Jin-Hoi; Cho, Ssang-Goo

    2014-01-01

    Placenta, as a reservoir of nutrients, has been widely used in medical and cosmetic materials. Here, we focused on the antioxidant properties of placental extract and attempted to isolate and identify the main antioxidant factors. Porcine placental extracts were prepared through homogenization or acid hydrolysis, and their antioxidant activity was investigated in the human keratinocyte HaCaT cell line. Treatment with homogenized placental extract (H-PE) increased the cell viability of H2O2-treated HaCaT cells more than two-fold. H-PE treatment suppressed H2O2-induced apoptotic and necrotic cell death and decreased intracellular ROS levels in H2O2-treated HaCaT cells. The antioxidant factors in H-PE were found to be thermo-unstable and were thus expected to include proteins. The candidate antioxidant proteins were fractionated with cation-exchange, anion-exchange, and size-exclusion chromatography, and the antioxidant properties of the chromatographic fractions were investigated. We obtained specific antioxidant fractions that suppressed ROS generation and ROS-induced DNA strand breaks. From silver staining and MALDI-TOF analyses, alpha-fetoprotein (AFP) precursor was identified as a main marker for the antioxidant effect of H-PE. Purified AFP or ectopically expressed AFP exhibited synergistic antioxidant activity in the presence of estradiol. Taken together, our data suggest that AFP, a serum glycoprotein produced at high levels during fetal development, is a novel marker protein for the antioxidant effect of the placenta that exhibits synergistic antioxidant activity in the presence of estradiol. PMID:24922551

  7. Alpha-fetoprotein, identified as a novel marker for the antioxidant effect of placental extract, exhibits synergistic antioxidant activity in the presence of estradiol.

    Directory of Open Access Journals (Sweden)

    Hye Yeon Choi

    Full Text Available Placenta, as a reservoir of nutrients, has been widely used in medical and cosmetic materials. Here, we focused on the antioxidant properties of placental extract and attempted to isolate and identify the main antioxidant factors. Porcine placental extracts were prepared through homogenization or acid hydrolysis, and their antioxidant activity was investigated in the human keratinocyte HaCaT cell line. Treatment with homogenized placental extract (H-PE increased the cell viability of H2O2-treated HaCaT cells more than two-fold. H-PE treatment suppressed H2O2-induced apoptotic and necrotic cell death and decreased intracellular ROS levels in H2O2-treated HaCaT cells. The antioxidant factors in H-PE were found to be thermo-unstable and were thus expected to include proteins. The candidate antioxidant proteins were fractionated with cation-exchange, anion-exchange, and size-exclusion chromatography, and the antioxidant properties of the chromatographic fractions were investigated. We obtained specific antioxidant fractions that suppressed ROS generation and ROS-induced DNA strand breaks. From silver staining and MALDI-TOF analyses, alpha-fetoprotein (AFP precursor was identified as a main marker for the antioxidant effect of H-PE. Purified AFP or ectopically expressed AFP exhibited synergistic antioxidant activity in the presence of estradiol. Taken together, our data suggest that AFP, a serum glycoprotein produced at high levels during fetal development, is a novel marker protein for the antioxidant effect of the placenta that exhibits synergistic antioxidant activity in the presence of estradiol.

  8. Dynamics of immune reconstitution and activation markers in HIV+ treatment-naïve patients treated with raltegravir, tenofovir disoproxil fumarate and emtricitabine.

    Directory of Open Access Journals (Sweden)

    Nicholas T Funderburg

    Full Text Available The dynamics of CD4+ T cell reconstitution and changes in immune activation and inflammation in HIV-1 disease following initiation of antiretroviral therapy (ART are incompletely defined and their underlying mechanisms poorly understood.Thirty-nine treatment-naïve patients were treated with raltegravir, tenofovir DF and emtricitabine. Immunologic and inflammatory indices were examined in persons with sustained virologic control during 48 weeks of therapy.Initiation of ART increased CD4+ T cell numbers and decreased activation and cell cycle entry among CD4+ and CD8+ T cell subsets, and attenuated markers of coagulation (D-dimer levels and inflammation (IL-6 and TNFr1. These indices decayed at different rates and almost all remained elevated above levels measured in HIV-seronegatives through 48 weeks of viral control. Greater first and second phase CD4+ T cell restoration was related to lower T cell activation and cell cycling at baseline, to their decay with treatment, and to baseline levels of selected inflammatory indices, but less so to their changes on therapy.ART initiation results in dynamic changes in viral replication, T cell restoration, and indices of immune activation, inflammation, and coagulation. These findings suggest that determinants of T cell activation/cycling and inflammation/coagulation may have distinguishable impact on immune homeostasis.Clinicaltrials.gov NCT00660972.

  9. Endovascular treatment of chronic cerebro spinal venous insufficiency in patients with multiple sclerosis modifies circulating markers of endothelial dysfunction and coagulation activation: a prospective study.

    Science.gov (United States)

    Napolitano, Mariasanta; Bruno, Aldo; Mastrangelo, Diego; De Vizia, Marcella; Bernardo, Benedetto; Rosa, Buonagura; De Lucia, Domenico

    2014-10-01

    We performed a monocentric observational prospective study to evaluate coagulation activation and endothelial dysfunction parameters in patients with multiple sclerosis undergoing endovascular treatment for cerebro-spinal-venous insufficiency. Between February 2011 and July 2012, 144 endovascular procedures in 110 patients with multiple sclerosis and chronical cerebro-spinal venous insufficiency were performed and they were prospectively analyzed. Each patient was included in the study according to previously published criteria, assessed by the investigators before enrollment. Endothelial dysfunction and coagulation activation parameters were determined before the procedure and during follow-up at 1, 3, 6, 9, 12, 15 and 18 months after treatment, respectively. After the endovascular procedure, patients were treated with standard therapies, with the addition of mesoglycan. Fifty-five percent of patients experienced a favorable outcome of multiple sclerosis within 1 month after treatment, 25% regressed in the following 3 months, 24.9% did not experience any benefit. In only 0.1% patients, acute recurrence was observed and it was treated with high-dose immunosuppressive therapy. No major complications were observed. Coagulation activation and endothelial dysfunction parameters were shown to be reduced at 1 month and stable up to 12-month follow-up, and they were furthermore associated with a good clinical outcome. Endovascular procedures performed by a qualified staff are well tolerated; they can be associated with other currently adopted treatments. Correlations between inflammation, coagulation activation and neurodegenerative disorders are here supported by the observed variations in plasma levels of markers of coagulation activation and endothelial dysfunction.

  10. Blockades of mitogen-activated protein kinase and calcineurin both change fibre-type markers in skeletal muscle culture

    DEFF Research Database (Denmark)

    Higginson, James; Wackerhage, Henning; Woods, Niall

    2002-01-01

    A and mitogen-activated protein kinase kinase (MEK1/2) blockade with U0126 upon myosin heavy chain (MHC) isoform mRNA levels and activities of metabolic enzymes after 1 day, 3 days and 7 days of treatment in primary cultures of spontaneously twitching rat skeletal muscle. U0126 treatment significantly decreased......Activation of either the calcineurin or the extracellular signal-regulated kinase (ERK1/2) pathway increases the percentage of slow fibres in vivo suggesting that both pathways can regulate fibre phenotypes in skeletal muscle. We investigated the effect of calcineurin blockade with cyclosporin...

  11. Identification of Glial Activation Markers by Comparison of Transcriptome Changes between Astrocytes and Microglia following Innate Immune Stimulation.

    Science.gov (United States)

    Madeddu, Silvia; Woods, Tyson A; Mukherjee, Piyali; Sturdevant, Dan; Butchi, Niranjan B; Peterson, Karin E

    2015-01-01

    The activation of astrocytes and microglia is often associated with diseases of the central nervous system (CNS). Understanding how activation alters the transcriptome of these cells may offer valuable insight regarding how activation of these cells mediate neurological damage. Furthermore, identifying common and unique pathways of gene expression during activation may provide new insight into the distinct roles these cells have in the CNS during infection and inflammation. Since recent studies indicate that TLR7 recognizes not only viral RNA but also microRNAs that are released by damaged neurons and elevated during neurological diseases, we first examined the response of glial cells to TLR7 stimulation using microarray analysis. Microglia were found to generate a much stronger response to TLR7 activation than astrocytes, both in the number of genes induced as well as fold induction. Although the primary pathways induced by both cell types were directly linked to immune responses, microglia also induced pathways associated with cellular proliferation, while astrocytes did not. Targeted analysis of a subset of the upregulated genes identified unique mRNA, including Ifi202b which was only upregulated by microglia and was found to be induced during both retroviral and bunyavirus infections in the CNS. In addition, other genes including Birc3 and Gpr84 as well as two expressed sequences AW112010 and BC023105 were found to be induced in both microglia and astrocytes and were upregulated in the CNS following virus infection. Thus, expression of these genes may a useful measurement of glial activation during insult or injury to the CNS.

  12. Identification of Glial Activation Markers by Comparison of Transcriptome Changes between Astrocytes and Microglia following Innate Immune Stimulation.

    Directory of Open Access Journals (Sweden)

    Silvia Madeddu

    Full Text Available The activation of astrocytes and microglia is often associated with diseases of the central nervous system (CNS. Understanding how activation alters the transcriptome of these cells may offer valuable insight regarding how activation of these cells mediate neurological damage. Furthermore, identifying common and unique pathways of gene expression during activation may provide new insight into the distinct roles these cells have in the CNS during infection and inflammation. Since recent studies indicate that TLR7 recognizes not only viral RNA but also microRNAs that are released by damaged neurons and elevated during neurological diseases, we first examined the response of glial cells to TLR7 stimulation using microarray analysis. Microglia were found to generate a much stronger response to TLR7 activation than astrocytes, both in the number of genes induced as well as fold induction. Although the primary pathways induced by both cell types were directly linked to immune responses, microglia also induced pathways associated with cellular proliferation, while astrocytes did not. Targeted analysis of a subset of the upregulated genes identified unique mRNA, including Ifi202b which was only upregulated by microglia and was found to be induced during both retroviral and bunyavirus infections in the CNS. In addition, other genes including Birc3 and Gpr84 as well as two expressed sequences AW112010 and BC023105 were found to be induced in both microglia and astrocytes and were upregulated in the CNS following virus infection. Thus, expression of these genes may a useful measurement of glial activation during insult or injury to the CNS.

  13. The biochemical effects of occupational exposure to lead and cadmium on markers of oxidative stress and antioxidant enzymes activity in the blood of glazers in tile industry.

    Science.gov (United States)

    Hormozi, Maryam; Mirzaei, Ramazan; Nakhaee, Alireza; Izadi, Shahrokh; Dehghan Haghighi, Javid

    2018-01-01

    The aim of the present study was to evaluate the effects of occupational exposure to lead (Pb) and cadmium (Cd) on markers of oxidative stress in glazers in tile industries. Total antioxidant capacity (TAC), malondialdehyde (MDA), and the activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined in the blood of 80 subjects, including 40 glazers and 40 nonexposed subjects. Mean levels of blood Cd (8.90 ± 2.80 µg/L) and blood Pb (62.90 ± 38.10 µg/L) of glazers showed a significant increase compared with the control group. In the serum of glazers, the level of MDA was significantly higher and the level of TAC was significantly lower than the control group. We have noted a disturbance in the levels of antioxidants by a significant increase in the CAT activity and a significant decrease in the activities of SOD and GPx in the serum of glazers compared with the controls. Correlation analysis demonstrated that the serum MDA level and CAT activity were positively associated with the blood levels of Pb and Cd. Also, GPx and SOD were negatively correlated with blood Cd levels. The study clearly indicated that co-exposure to Cd and Pb can induce oxidative stress in glazers, resulting in increased lipid peroxidation and altered antioxidant enzymes.

  14. In Silico and In Vitro Anticancer Activity of Isolated Novel Marker Compound from Chemically Modified Bioactive Fraction from Curcuma longa (NCCL).

    Science.gov (United States)

    Naqvi, Arshi; Malasoni, Richa; Gupta, Swati; Srivastava, Akansha; Pandey, Rishi R; Dwivedi, Anil Kumar

    2017-10-01

    Turmeric ( Curcuma longa ) is reported to possess wide array of biological activities. Herbal Medicament (HM) is a standardized hexane-soluble fraction of C. longa and is well known for its neuroprotective effect. In this study, we attempted to synthesize a novel chemically modified bioactive fraction from HM (NCCL) along with isolation and characterization of a novel marker compound (I). NCCL was prepared from HM. The chemical structure of the marker compound isolated from NCCL was determined from 1D/2D nuclear magnetic resonance, mass spectroscopy, and Fourier transform infrared. The compound so isolated was subjected to in silico and in vitro screenings to test its inhibitory effect on estrogen receptors. Molecular docking studies revealed that the binding poses of the compound I was energetically favorable. Among NCCL and compound I taken for in vitro studies, NCCL had exhibited good anti-cancer activity over compound I against MCF-7, MDA-MB-231, DU-145, and PC-3 cells. This is the first study about the synthesis of a chemically modified bioactive fraction which used a standardized extract since the preparation of the HM. It may be concluded that NCCL fraction having residual components induce more cell death than compound I alone. Thus, NCCL may be used as a potent therapeutic drug. In the present paper, a standardized hexane soluble fraction of Curcuma longa (HM) was chemically modified to give a novel bioactive fraction (NCCL). A novel marker compound was isolated from NCCL and was characerized using various spectral techniques. The compound so isolated was investigated for in-silico screenings. NCCL and isolated compound was subjected to in-vitro anti-cancer screenings against MCF 7, MDA MB 231 (breast adenocarcinoma) and DU 145 and PC 3 cell lines (androgen independent human prostate cancer cells). The virtual screenings reveals that isolated compound has shown favourable drug like properties. NCCL fraction having residual components induces more cell

  15. Effects of exercise on markers of oxidative stress: an Ancillary analysis of the Alberta Physical Activity and Breast Cancer Prevention Trial

    Science.gov (United States)

    Friedenreich, Christine M; Pialoux, Vincent; Wang, Qinggang; Shaw, Eileen; Brenner, Darren R; Waltz, Xavier; Conroy, Shannon M; Johnson, Rhys; Woolcott, Christy G; Poulin, Marc J; Courneya, Kerry S

    2016-01-01

    Background Oxidative stress may contribute to cancer aetiology through several mechanisms involving damage to DNA, proteins and lipids leading to genetic mutations and genomic instability. The objective of this study was to determine the effects of aerobic exercise on markers of oxidative damage and antioxidant enzymes in postmenopausal women. Methods The Alberta Physical Activity and Breast Cancer Prevention Trial (ALPHA) was a two-centre, two-armed randomised trial of 320 inactive, healthy, postmenopausal women aged 50–74 years. Participants were randomly assigned to a year-long exercise intervention (225 min/week) or a control group while being asked to maintain a normal diet. Fasting blood samples were obtained and plasma concentrations of two oxidative damage markers (8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-isoprostaglandin F2α (8-Iso-PGF2α)) and two antioxidant enzymes (superoxide dismutase and catalase) were measured at baseline, 6 months and 12 months. Intention-to-treat (ITT) and per-protocol analyses were performed using linear mixed models adjusted for baseline biomarker concentrations. A further exercise adherence analysis, based on mean minutes of exercise per week, was also performed. Results In the ITT and per-protocol analyses, the exercise intervention did not have any statistically significant effect on either oxidative damage biomarkers or antioxidant enzyme activity. Conclusions A year-long aerobic exercise intervention did not have a significant impact on oxidative stress in healthy, postmenopausal women. Trial registration number NCT00522262. PMID:27900199

  16. Circulating intercellular adhesion molecule-1 (ICAM-1) as an early and sensitive marker for virus-induced T cell activation

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Johansen, J; Marker, O

    1995-01-01

    mice, clearly demonstrating that T cells were mandatory. Analysis of MHC class I and MHC class II-deficient mice revealed that either CD4+ or CD8+ T cells alone are sufficient, despite a markedly reduced inflammatory exudate in the former animals. These results indicate that virus-activated T cells......The effect of systemic virus infection on the level of circulating ICAM-1 (cICAM-1) in serum, and the role of virus-activated T cells in this context, were studied using the murine lymphocytic choriomeningitis virus infection as primary model system. A marked virus-induced elevation in cICAM-1...... in serum was revealed, the presence of which coincided with the phase of virus-induced T cell activation. However, high levels of cICAM-1 in serum were observed well before maximal T cell activation could be demonstrated. No increase in cICAM-1 was observed in the serum of infected T cell-deficient nude...

  17. Markers of immune activation and apoptosis in endomyocardial biopsies of individuals with recent-onset dilated cardiomyopathy

    Czech Academy of Sciences Publication Activity Database

    Kubánek, M.; Sramko, M.; Malušková, J.; Chudíčková, Milada; Holáň, Vladimír; Kautzner, J.

    2013-01-01

    Roč. 34, č. 1 (2013), s. 211-211 ISSN 0195-668X. [Congress of the European-Society-of- Cardiology (ESC). 31.08.2013-,04.09.2013, Amsterdam] Institutional support: RVO:68378041 Keywords : dilated cardiomyopathy * immune activation and apoptosis Subject RIV: EC - Immunology

  18. Evaluating Soluble EMMPRIN as a Marker of Disease Activity in Multiple Sclerosis: Studies of Serum and Cerebrospinal Fluid.

    Directory of Open Access Journals (Sweden)

    Deepak K Kaushik

    Full Text Available Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147 is an inducer of matrix metalloproteinases and has roles in leukocyte activation and migration. We reported previously that in MS and its animal model, experimental autoimmune encephalomyelitis, cell surface-associated EMMPRIN was significantly elevated in leukocytes around inflammatory perivascular cuffs in the CNS. In this study we report that activated T-cells can secrete soluble form of EMMPRIN (sEMMPRIN upon activation. As sEMMPRIN is also present in biological fluids, we determined whether sEMMPRIN is altered in the CSF and sera of MS subjects. Sera from individuals without neurological conditions served as controls, while CSFs collected from subjects undergoing discectomy, and without evidence of CNS pathology, were used as a comparator group. We found that serum levels of sEMMPRIN from clinically stable MS patients or other inflammatory conditions did not differ from control subjects. Paired serum and CSF samples demonstrated poor correlation of sEMMPRIN. Interestingly, sEMMPRIN levels were approximately 60% higher in CSFs compared to sera. sEMMPRIN CSF levels were significantly higher in secondary progressive compared to primary progressive subjects. Thus we conclude that measurement of sEMMPRIN in serum is not informative for disease activity in MS. The differential expression of sEMMPRIN in the CSF of primary and secondary progressive MS invites hypotheses of the still undefined roles of EMMPRIN in the CNS.

  19. Evaluating Soluble EMMPRIN as a Marker of Disease Activity in Multiple Sclerosis: Studies of Serum and Cerebrospinal Fluid.

    Science.gov (United States)

    Kaushik, Deepak K; Yong, Heather Y F; Hahn, Jennifer N; Silva, Claudia; Casha, Steven; Hurlbert, R John; Jacques, Francois H; Lisak, Robert; Khan, Omar; Ionete, Carolina; Larochelle, Catherine; Prat, Alex; Bar-Or, Amit; Yong, V Wee

    2016-01-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is an inducer of matrix metalloproteinases and has roles in leukocyte activation and migration. We reported previously that in MS and its animal model, experimental autoimmune encephalomyelitis, cell surface-associated EMMPRIN was significantly elevated in leukocytes around inflammatory perivascular cuffs in the CNS. In this study we report that activated T-cells can secrete soluble form of EMMPRIN (sEMMPRIN) upon activation. As sEMMPRIN is also present in biological fluids, we determined whether sEMMPRIN is altered in the CSF and sera of MS subjects. Sera from individuals without neurological conditions served as controls, while CSFs collected from subjects undergoing discectomy, and without evidence of CNS pathology, were used as a comparator group. We found that serum levels of sEMMPRIN from clinically stable MS patients or other inflammatory conditions did not differ from control subjects. Paired serum and CSF samples demonstrated poor correlation of sEMMPRIN. Interestingly, sEMMPRIN levels were approximately 60% higher in CSFs compared to sera. sEMMPRIN CSF levels were significantly higher in secondary progressive compared to primary progressive subjects. Thus we conclude that measurement of sEMMPRIN in serum is not informative for disease activity in MS. The differential expression of sEMMPRIN in the CSF of primary and secondary progressive MS invites hypotheses of the still undefined roles of EMMPRIN in the CNS.

  20. Dietary program and physical activity impact on biochemical markers in patients with type 2 diabetes: A systematic review.

    Science.gov (United States)

    Barreira, Eduarda; Novo, André; Vaz, Josiana A; Pereira, Ana M G

    2017-10-21

    Evaluate the effectiveness of the implementation of independently or combined dietary and physical activity programs on the blood glucose values and lipid profile in patients with type 2 diabetes, including participants aged 60 years and over. Systematic review. PubMed/Medline database, with language restrictions. Papers published between 2010 and 2016 were included. A total of 30 randomised controlled trials were included that focused on physical activity and dietary interventions in patients with type 2 diabetes mellitus and include participants aged 60 years and over. The selected articles have shown that the implementation of physical activity programs (aerobic, resistance, flexibility and combined exercises), and programs based on a higher intake of vegetables, grains, legumes, fruits, unsaturated fatty acids, as well as consumption of foods with low glycaemic index, calorie restriction, intake of probiotics, vitamin D supplementation and educational sessions about diabetes improves blood glucose levels, as well as the lipid profile, in patients with type 2 diabetes. Physical activity and dietary programs are fundamental in the treatment and metabolic control of type 2 diabetes mellitus. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  1. Vitamin D status is associated with cardiometabolic markers in 8-11-year-old children, independently of body fat and physical activity.

    Science.gov (United States)

    Petersen, Rikke A; Dalskov, Stine-Mathilde; Sørensen, Louise B; Hjorth, Mads F; Andersen, Rikke; Tetens, Inge; Krarup, Henrik; Ritz, Christian; Astrup, Arne; Michaelsen, Kim F; Mølgaard, Christian; Damsgaard, Camilla T

    2015-11-28

    Vitamin D status has been associated with cardiometabolic markers even in children, but the associations may be confounded by fat mass and physical activity behaviour. This study investigated associations between vitamin D status and cardiometabolic risk profile, as well as the impact of fat mass and physical activity in Danish 8-11-year-old children, using baseline data from 782 children participating in the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study. We assessed vitamin D status as serum 25-hydroxyvitamin D (25(OH)D) and measured blood pressure, fasting plasma glucose, homoeostasis model of assessment-insulin resistance, plasma lipids, inflammatory markers, anthropometry and fat mass by dual-energy X-ray absorptiometry, and physical activity by 7 d accelerometry during August-November. Mean serum 25(OH)D was 60·8 (sd 18·7) nmol/l. Each 10 mmol/l 25(OH)D increase was associated with lower diastolic blood pressure (-0·3 mmHg, 95 % CI -0·6, -0·0) (P=0·02), total cholesterol (-0·07 mmol/l, 95 % CI -0·10, -0·05), LDL-cholesterol (-0·05 mmol/l, 95 % CI -0·08, -0·03), TAG (-0·02 mmol/l, 95 % CI -0·03, -0·01) (P≤0·001 for all lipids) and lower metabolic syndrome (MetS) score (P=0·01). Adjustment for fat mass index did not change the associations, but the association with blood pressure became borderline significant after adjustment for physical activity (P=0·06). In conclusion, vitamin D status was negatively associated with blood pressure, plasma lipids and a MetS score in Danish school children with low prevalence of vitamin D deficiency, and apart from blood pressure the associations were independent of body fat and physical activity. The potential underlying cause-effect relationship and possible long-term implications should be investigated in randomised controlled trials.

  2. The Fc Receptor Polymorphisms and Expression of Neutrophil Activation Markers in Patients with Sickle Cell Disease from Western India

    Directory of Open Access Journals (Sweden)

    Harshada K. Kangne

    2013-01-01

    Full Text Available Objective. Sickle cell disease has variable clinical manifestations. Activation of neutrophils plays an important role in the initiation and propagation of vaso occlusive crises which can be analysed by determining the expression of neutrophil antigens such as CD16, CD32, and CD62L. The common FcγR polymorphisms (FcγRIIA and FcγRIIIB are considered to influence clinical presentation. This study focuses on distribution of FcγR polymorphisms and their association with neutrophil activity among the patients from western India. Methods. In this paper 127 sickle cell anemia patients and 58 patients with sickle-β-thalassemia (median age 12±8.58 years with variable clinical phenotypes along with 175 normals were investigated. FcγRs polymorphisms were analysed by RFLP and AS-PCR. Activation of neutrophils was measured by flow cytometry. Results. The genotypic frequency of the H/R genotype of FcγRIIA and the NA1/NA1 genotype of FcγRIIIB was significantly decreased in patients compared to normals (P-0.0074, P-0.0471, resp.. We found a significant difference in the expression of CD32 and CD62L among the patients as against normals. A significantly higher expression of CD32 was seen in the milder patients with the H/H genotype (P-0.0231, whereas the expression of CD16 was higher in severe patients with the NA2/NA2 genotype (P-0.0312. Conclusion. The two FcγR polymorphisms had significant association with variable phenotypes of sickle cell disease. The expression of CD62L decreased in our patients indicating activation of neutrophils.

  3. Inactivated probiotic Bacillus coagulans GBI-30 induces complex immune activating, anti-inflammatory, and regenerative markers in vitro

    OpenAIRE

    Jensen, Gitte S; Cash, Howard A; Farmer, Sean; Keller, David

    2017-01-01

    Gitte S Jensen,1 Howard A Cash,2 Sean Farmer,2 David Keller2 1NIS Labs, Esplanade, Klamath Falls, OR, USA, 2Ganeden Biotech Inc., Landerbrook Drive Suite, Mayfield Heights, OH, USA Objective: The aim of this study was to document the immune activating and anti-inflammatory effects of inactivated probiotic Bacillus coagulans GBI-30, 6086 (Staimune™) cells on human immune cells in vitro.Methods: In vitro cultures of human peripheral blood mononuclear cells (PBMC) from healthy blood do...

  4. ENZYME MARKERS ACTIVITY AND BILE FORMATION FUNCTION OF LIVER IN CASES OF TUBERCULOSTATICS AND HEXAVALENT CHROMIUM COMPOUNDS AFFECTION IN RATS

    OpenAIRE

    N. I. Burmas; L. S. Fira; P. H. Lyhackyy

    2016-01-01

    Background. Currently, the growing incidence of toxic lesions of the liver is associated with industrial chemicalization and uncontrolled use of hepatotoxic drugs in everyday life. There are about one thousand drugs with high or low hepatotoxicity, such as anti-TB drugs. Objective. In this research we studied the intracellular enzymes activity and bile formation function of the liver in rats of different ages in cases of tuberculostatic (isoniazid and rifampicin) affection and chromium (p...

  5. [Activity of antioxidative enzymes and concentration of malondialdehyde as oxidative status markers in women with non-autoimmunological subclinical hyperthyroidism].

    Science.gov (United States)

    Rybus-Kalinowska, Barbara; Zwirska-Korczala, Krystyna; Kalinowski, Mariusz; Kukla, Michał; Birkner, Ewa; Jochem, Jerzy

    2009-01-01

    The recent investigations point out the significant role of oxidative stress in the development of thyroid gland disease. The present study was designed to investigate the variation of oxidative stae in women with non-autoimmunological subclinical hyperthyroidism. The study was conducted on 20 females with non-autoimmunological subclinical hyperthyroidism and 15 healthy women. Manganase-containing superoxide dismutase (Mn-SOD) and extracellular superoxide dismutase (EC-SOD) plasma activity, and malondialdehyde (MDA) plasma concentration were measured. EC-SOD plasma activity was significantly higher in women with subclinical hyperthyroidism when compared with the control group (13.3 +/- 2.1 vs. 10.9 +/- 1.4 NU/ml; p < 0.05), unlike Mn-SOD (4.2 +/- 0.5 vs. 4.0 +/- 1.0 NU/ml). MDA plasma concentration increased significantly in women with subclinical hyperthyroidism (3.5 +/- 1.2 vs. 2.0 +/- 0.6 micromol/l; p < 0.05). The increased EC-SOD plasma activity may reflect disturbances of oxidative state in subclinical hyperthyroidism. Parallel increase of MDA plasma concentration may indicate enhancement of lipid peroxidationin in patients with subclinical hyperthyroidism.

  6. Scleraxis is a transcriptional activator that regulates the expression of Tenomodulin, a marker of mature tenocytes and ligamentocytes.

    Science.gov (United States)

    Shukunami, Chisa; Takimoto, Aki; Nishizaki, Yuriko; Yoshimoto, Yuki; Tanaka, Seima; Miura, Shigenori; Watanabe, Hitomi; Sakuma, Tetsushi; Yamamoto, Takashi; Kondoh, Gen; Hiraki, Yuji

    2018-02-16

    Tenomodulin (Tnmd) is a type II transmembrane glycoprotein predominantly expressed in tendons and ligaments. We found that scleraxis (Scx), a member of the Twist-family of basic helix-loop-helix transcription factors, is a transcriptional activator of Tnmd expression in tenocytes. During embryonic development, Scx expression preceded that of Tnmd. Tnmd expression was nearly absent in tendons and ligaments of Scx-deficient mice generated by transcription activator-like effector nucleases-mediated gene disruption. Tnmd mRNA levels were dramatically decreased during serial passages of rat tenocytes. Scx silencing by small interfering RNA significantly suppressed endogenous Tnmd mRNA levels in tenocytes. Mouse Tnmd contains five E-box sites in the ~1-kb 5'-flanking region. A 174-base pair genomic fragment containing a TATA box drives transcription in tenocytes. Enhancer activity was increased in the upstream region (-1030 to -295) of Tnmd in tenocytes, but not in NIH3T3 and C3H10T1/2 cells. Preferential binding of both Scx and Twist1 as a heterodimer with E12 or E47 to CAGATG or CATCTG and transactivation of the 5'-flanking region were confirmed by electrophoresis mobility shift and dual luciferase assays, respectively. Scx directly transactivates Tnmd via these E-boxes to positively regulate tenocyte differentiation and maturation.

  7. The Brain Activity in Brodmann Area 17: A Potential Bio-Marker to Predict Patient Responses to Antiepileptic Drugs.

    Directory of Open Access Journals (Sweden)

    Yida Hu

    Full Text Available In this study, we aimed to predict newly diagnosed patient responses to antiepileptic drugs (AEDs using resting-state functional magnetic resonance imaging tools to explore changes in spontaneous brain activity. We recruited 21 newly diagnosed epileptic patients, 8 drug-resistant (DR patients, 11 well-healed (WH patients, and 13 healthy controls. After a 12-month follow-up, 11 newly diagnosed epileptic patients who showed a poor response to AEDs were placed into the seizures uncontrolled (SUC group, while 10 patients were enrolled in the seizure-controlled (SC group. By calculating the amplitude of fractional low-frequency fluctuations (fALFF of blood oxygen level-dependent signals to measure brain activity during rest, we found that the SUC patients showed increased activity in the bilateral occipital lobe, particularly in the cuneus and lingual gyrus compared with the SC group and healthy controls. Interestingly, DR patients also showed increased activity in the identical cuneus and lingual gyrus regions, which comprise Brodmann's area 17 (BA17, compared with the SUC patients; however, these abnormalities were not observed in SC and WH patients. The receiver operating characteristic (ROC curves indicated that the fALFF value of BA17 could differentiate SUC patients from SC patients and healthy controls with sufficient sensitivity and specificity prior to the administration of medication. Functional connectivity analysis was subsequently performed to evaluate the difference in connectivity between BA17 and other brain regions in the SUC, SC and control groups. Regions nearby the cuneus and lingual gyrus were found positive connectivity increased changes or positive connectivity changes with BA17 in the SUC patients, while remarkably negative connectivity increased changes or positive connectivity decreased changes were found in the SC patients. Additionally, default mode network (DMN regions showed negative connectivity increased changes or

  8. Macrophage activation marker sCD163 correlates with accelerated lipolysis following LPS exposure: a human-randomised clinical trial

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    Nikolaj Rittig

    2018-01-01

    Full Text Available Background: Macrophage activation determined by levels of soluble sCD163 is associated with obesity, insulin resistance, diabetes mellitus type 2 (DM2 and non-alcoholic fatty liver disease (NAFLD. This suggests that macrophage activation is involved in the pathogenesis of conditions is characterised by adaptions in the lipid metabolism. Since sCD163 is shed to serum by inflammatory signals including lipopolysaccharides (LPS, endotoxin, we investigated sCD163 and correlations with lipid metabolism following LPS exposure. Methods: Eight healthy male subjects were investigated on two separate occasions: (i following an LPS exposure and (ii following saline exposure. Each study day consisted of a four-hour non-insulin-stimulated period followed by a two-hour hyperinsulinemic euglycemic clamp period. A 3H-palmitate tracer was used to calculate the rate of appearance (Rapalmitate. Blood samples were consecutively obtained throughout each study day. Abdominal subcutaneous adipose tissue was obtained for western blotting. Results: We observed a significant two-fold increase in plasma sCD163 levels following LPS exposure (P < 0.001, and sCD163 concentrations correlated positively with the plasma concentration of free fatty acids, Rapalmitate, lipid oxidation rates and phosphorylation of the hormone-sensitive lipase at serine 660 in adipose tissue (P < 0.05, all. Furthermore, sCD163 concentrations correlated positively with plasma concentrations of cortisol, glucagon, tumour necrosis factor (TNF-α, interleukin (IL-6 and IL-10 (P < 0.05, all. Conclusion: We observed a strong correlation between sCD163 and stimulation of lipolysis and fat oxidation following LPS exposure. These findings support preexisting theory that inflammation and macrophage activation play a significant role in lipid metabolic adaptions under conditions such as obesity, DM2 and NAFLD.

  9. Mild episodes of tourniquet-induced forearm ischaemia-reperfusion injury results in leukocyte activation and changes in inflammatory and coagulation markers

    Directory of Open Access Journals (Sweden)

    Bastawrous Salah S

    2007-05-01

    Full Text Available Abstract Background Monocytes and neutrophils are examples of phagocytic leukocytes, with neutrophils being considered as the 'chief' phagocytic leukocyte. Both monocytes and neutrophils have been implicated to play a key role in the development of ischaemia-reperfusion injury, where they are intrinsically involved in leukocyte-endothelial cell interactions. In this pilot study we hypothesised that mild episodes of tourniquet induced forearm ischaemia-reperfusion injury results in leukocyte activation and changes in inflammatory and coagulation markers. Methods Ten healthy human volunteers were recruited after informed consent. None had any history of cardiovascular disease with each subject volunteer participating in the study for a 24 hour period. Six venous blood samples were collected from each subject volunteer at baseline, 10 minutes ischaemia, 5, 15, 30, 60 minutes and 24 hours reperfusion, by means of a cannula from the ante-cubital fossa. Monocyte and neutrophil leukocyte sub-populations were isolated by density gradient centrifugation techniques. Leukocyte trapping was investigated by measuring the concentration of leukocytes in venous blood leaving the arm. The cell surface expression of CD62L (L-selectin, CD11b and the intracellular production of hydrogen peroxide (H2O2 were measured via flow cytometry. C-reactive protein (CRP was measured using a clinical chemistry analyser. Plasma concentrations of D-dimer and von Willebrand factor (vWF were measured using enzyme-linked fluorescent assays (ELFA. Results During ischaemia-reperfusion injury, there was a decrease in CD62L and an increase in CD11b cell surface expression for both monocytes and neutrophils, with changes in the measured parameters reaching statistical significance (p =2O2 production by leukocyte sub-populations, which was measured as a marker of leukocyte activation. Intracellular production of H2O2 in monocytes during ischaemia-reperfusion injury reached statistical

  10. The liberated domain I of urokinase plasminogen activator receptor--a new tumour marker in small cell lung cancer

    DEFF Research Database (Denmark)

    Almasi, Charlotte E; Drivsholm, Lars; Pappot, Helle

    2013-01-01

    The prognosis of small cell lung cancer (SCLC) remains poor with a 5-year survival rate of 4-6%. In non-small cell lung cancer (NSCLC), high levels of intact and cleaved forms of the receptor for urokinase plasminogen activator (uPAR) are significantly associated with short overall survival. Our...... measured using time-resolved fluorescence immunoassays (TR-FIA 1-3). Assessment of association of the uPAR forms to overall survival (OS) was done using Cox regression analysis adjusted for clinical covariates [age, gender, stage, lactate dehydrogenase (LDH), WHO performance status (PS)]. Multivariate...

  11. High plasma homocyst(e)ine levels in elderly Japanese patients are associated with increased cardiovascular disease risk independently from markers of coagulation activation and endothelial cell damage.

    Science.gov (United States)

    Kario, K; Duell, P B; Matsuo, T; Sakata, T; Kato, H; Shimada, K; Miyata, T

    2001-08-01

    Elevated plasma homocyst(e)ine is a risk factor for cardiovascular disease (CVD) in many populations, but the relationship between homocyst(e)ine and CVD in Japanese subjects has been unclear. It has been hypothesized that the link between homocyst(e)ine and CVD may be mediated in part by activation of coagulation and endothelial cell injury in the elderly Japanese subjects. To further evaluate this hypothesis, the present cross-sectional study was designed to assess the relationships among plasma homocyst(e)ine concentrations, risk of CVD, and markers of coagulation (fibrinogen, FVII, F1+2, FVIIa and FXIIa) and endothelial cell damage (vWF and thrombomodulin) in 146 elderly Japanese subjects (79 healthy controls and 67 patients with CVD). The geometric mean (range) of plasma homocyst(e)ine concentrations was 10.2 (3.2--33) micromol/l in 79 Japanese healthy elderly subjects. As expected, healthy female and male elderly subjects had homocyst(e)ine levels that were 2.5 and 5.3 micromol/; higher, respectively, compared to healthy young control subjects (n=62). Healthy young and elderly men had homocyst(e)ine levels that were 1.7 and 4.5 micromol/l higher, respectively, compared to values in women. This higher plasma homocyst(e)ine levels in the elderly subjects were negatively correlated with levels of folic acid, albumin and total cholesterol, but were not significantly related to markers of coagulation or endothelial cell-damage. The results of multiple logistic regression analyses suggested that high homocyst(e)ine levels were independently related to CVD risk. In addition, levels of FVIIa, and F1+2 were significantly higher in elderly Japanese patients with CVD compared to elderly subjects without CVD, but were unrelated to plasma homocyst(e)ine concentrations. In summary, elevated plasma concentrations of homocyst(e)ine, FVIIa, and F1+2 were associated with increased risk of CVD in elderly male and female Japanese subjects, but the association between homocyst

  12. One-step synthesis of redox-active polymer/AU nanocomposites for electrochemical immunoassay of multiplexed tumor markers.

    Science.gov (United States)

    Liu, Zhimin; Rong, Qinfeng; Ma, Zhanfang; Han, Hongliang

    2015-03-15

    In this work, a simple and sensitive multiplexed immunoassay protocol for simultaneous electrochemical determination of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) was designed using redox-active nanocomposites. As the redox-active species, the poly(o-phenylenediamine) (POPD)/Au nanocomposite and poly(vinyl ferrocene-2-aminothiophenol) (poly(VFc-ATP))/Au nanocomposite were obtained by one-step method which HAuCl4 was used as the oxidant. With Au nanoparticles (AuNPs), the nanocomposites were successful to immobilize labeled anti-CEA and anti-AFP as the immunosensing probes. The proposed electrochemical immunoassay enabled the simultaneous monitoring of AFP and CEA in a wide range of 0.01-100ngmL(-1). The detection limits was 0.006ngmL(-1) for CEA and 0.003ngmL(-1) for AFP (S/N=3). The assay results of serum samples with the proposed method were well consistent with the reference values from standard ELISA method. And the negligible cross-reactivity between the two analytes makes it possesses potential promise in clinical diagnosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. The adipose renin-angiotensin system modulates sysemic markers of insulin sensitivity activates the intrarenal renin-angiotensin system

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Suyeon [University of Tennessee, Knoxville (UTK); Soltani-Bejnood, Morvarid [University of Tennessee, Knoxville (UTK); Quignard-Boulange, Annie [Centre Biomedical des Cordeliers, Paris, France; Massiera, Florence [Centre de Biochimie, Nice, France; Teboul, Michele [Centre de Biochimie, Nice, France; Ailhaud, Gerard [Centre de Biochimie, Nice, France; Kim, Jung [University of Tennessee, Knoxville (UTK); Moustaid-Moussa, Naima [University of Tennessee, Knoxville (UTK); Voy, Brynn H [ORNL

    2006-07-01

    BACKGROUND: A growing body of data provides increasing evidence that the adipose tissue renin-angiotensin system (RAS) contributes to regulation of fat mass. Beyond its paracrine actions within adipose tissue, adipocyte-derived angiotensin II (Ang II) may also impact systemic functions such as blood pressure and metabolism. METHODS AND RESULTS: We used a genetic approach to manipulate adipose RAS activity in mice and then study the consequences on metabolic parameters and on feedback regulation of the RAS. The models included deletion of the angiotensinogen (Agt) gene (Agt-KO), its expression solely in adipose tissue under the control of an adipocyte-specific promoter (aP2-Agt/ Agt-KO), and overexpression in adipose tissue of wild type mice (aP2-Agt). Total body weight, epididymal fat pad weight, and circulating levels of leptin, insulin and resistin were significantly decreased in Agt-KO mice, while plasma adiponectin levels were increased. Overexpression of Agt in adipose tissue resulted in increased adiposity and plasma leptin and insulin levels compared to wild type (WT) controls. Angiotensinogen and type I Ang II receptor protein levels were also markedly elevated in kidney of aP2-Agt mice, suggesting that hypertension in these animals may be in part due to stimulation of the intrarenal RAS. CONCLUSIONS: Taken together, the results from this study demonstrate that alterations in adipose RAS activity significantly alter both local and systemic physiology in a way that may contribute to the detrimental health effects of obesity.

  14. Identification of Mx gene nucleotide dimorphism (G/A as genetic marker for antiviral activity in Egyptian chickens

    Directory of Open Access Journals (Sweden)

    Mohamed S. Hassanane

    2018-06-01

    Full Text Available Egyptian chickens, representing 2 breeds and 7 strains, were genotyped using the PCR-RFLP and sequencing techniques for detection of a non-synonymous dimorphism (G/A in exon 14 of chicken Myxovirus resistance (Mx gene. This dimorphic position is responsible for altering Mx protein’s antiviral activity. Polymerase Chain reactions were performed using Egyptian chickens DNA and specific primer set to amplify Mx DNA fragments of 299 or 301 bp, containing the dimorphic position. Amplicons were cut with restriction enzyme Hpy81. Genotype and allele frequencies for the resistant allele A and sensitive allele G were calculated in all the tested chickens. Results of PCR-RFLP were confirmed by sequencing. The three genotypes AA, AG, GG at the target nucleotide position in Mx gene were represented in all the studied Egyptian chicken breeds and strains except Baladi strain which showed only one genotype AA. The average allele frequency of the resistant A allele in the tested birds (0.67 was higher than the sensitive G allele average frequency in the same birds (0.33. Appling PCR-RFLP technique in the breeding program can be used to select chickens carrying the A allele with high frequencies. This will help in improving poultry breeding in Egypt by producing infectious disease-resistant chickens. Keywords: Egyptian chickens, Antiviral activity, Mx gene, Genotyping, PCR-RFLP

  15. Evaluation of 12-Lipoxygenase (12-LOX and Plasminogen Activator Inhibitor 1 (PAI-1 as Prognostic Markers in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Tomasz Gondek

    2014-01-01

    Full Text Available In carcinoma of prostate, a causative role of platelet 12-lipoxygenase (12-LOX and plasminogen activator inhibitor 1 (PAI-1 for tumor progression has been firmly established in tumor and/or adjacent tissue. Our goal was to investigate if 12-LOX and/or PAI-1 in patient’s plasma could be used to predict outcome of the disease. The study comprised 149 patients (age 70±9 divided into two groups: a study group with carcinoma confirmed by positive biopsy of prostate (n=116 and a reference group (n=33 with benign prostatic hyperplasia (BPH. The following parameters were determined by the laboratory test in plasma or platelet-rich plasma: protein level of 12-LOX, PAI-1, thromboglobulin (TGB, prostate specific antigen (PSA, C-reactive protein (CRP, hemoglobin (HGB, and hematocrit (HCT, as well as red (RBC and white blood cells (WBC, number of platelets (PLT, international normalized ratio of blood clotting (INR, and activated partial thromboplastin time (APTT. The only difference of significance was noticed in the concentration of 12-LOX in platelet rich plasma, which was lower in cancer than in BPH group. Standardization to TGB and platelet count increases the sensitivity of the test that might be used as a biomarker to assess risk for prostate cancer in periodically monitored patients.

  16. Increased ventral-striatal activity during monetary decision making is a marker of problem poker gambling severity.

    Science.gov (United States)

    Brevers, Damien; Noël, Xavier; He, Qinghua; Melrose, James A; Bechara, Antoine

    2016-05-01

    The aim of this study was to examine the impact of different neural systems on monetary decision making in frequent poker gamblers, who vary in their degree of problem gambling. Fifteen frequent poker players, ranging from non-problem to high-problem gambling, and 15 non-gambler controls were scanned using functional magnetic resonance imaging (fMRI) while performing the Iowa Gambling Task (IGT). During IGT deck selection, between-group fMRI analyses showed that frequent poker gamblers exhibited higher ventral-striatal but lower dorsolateral prefrontal and orbitofrontal activations as compared with controls. Moreover, using functional connectivity analyses, we observed higher ventral-striatal connectivity in poker players, and in regions involved in attentional/motor control (posterior cingulate), visual (occipital gyrus) and auditory (temporal gyrus) processing. In poker gamblers, scores of problem gambling severity were positively associated with ventral-striatal activations and with the connectivity between the ventral-striatum seed and the occipital fusiform gyrus and the middle temporal gyrus. Present results are consistent with findings from recent brain imaging studies showing that gambling disorder is associated with heightened motivational-reward processes during monetary decision making, which may hamper one's ability to moderate his level of monetary risk taking. © 2015 Society for the Study of Addiction.

  17. Frameworking memory and serotonergic markers.

    Science.gov (United States)

    Meneses, Alfredo

    2017-07-26

    The evidence for neural markers and memory is continuously being revised, and as evidence continues to accumulate, herein, we frame earlier and new evidence. Hence, in this work, the aim is to provide an appropriate conceptual framework of serotonergic markers associated with neural activity and memory. Serotonin (5-hydroxytryptamine [5-HT]) has multiple pharmacological tools, well-characterized downstream signaling in mammals' species, and established 5-HT neural markers showing new insights about memory functions and dysfunctions, including receptors (5-HT1A/1B/1D, 5-HT2A/2B/2C, and 5-HT3-7), transporter (serotonin transporter [SERT]) and volume transmission present in brain areas involved in memory. Bidirectional influence occurs between 5-HT markers and memory/amnesia. A growing number of researchers report that memory, amnesia, or forgetting modifies neural markers. Diverse approaches support the translatability of using neural markers and cerebral functions/dysfunctions, including memory formation and amnesia. At least, 5-HT1A, 5-HT4, 5-HT6, and 5-HT7 receptors and SERT seem to be useful neural markers and therapeutic targets. Hence, several mechanisms cooperate to achieve synaptic plasticity or memory, including changes in the expression of neurotransmitter receptors and transporters.

  18. Serum markers of macrophage activation in pre-eclampsia: no predictive value of soluble CD163 and neopterin

    DEFF Research Database (Denmark)

    Kronborg, Camilla S; Knudsen, Ulla Breth; Moestrup, Søren K

    2007-01-01

    BACKGROUND: Alternatively activated macrophages expressing the CD163 and CD206 surface receptors are the dominant immune-cell type found in the placenta. The placental number and distribution of macrophages is altered in pre-eclampsia, and the generalised inflammatory reaction associated with pre-eclampsia...... might lead to shedding of soluble CD163 into the circulation. METHODS: Serum samples from 18 women with pre-eclampsia and 90 normal pregnancies were obtained from a longitudinal study of 955 pregnant women at Randers County Hospital, Denmark. sCD163 and Neopterin were measured by ELISA on samples....... Neopterin increased throughout pregnancy in both healthy (from median 5.4 to 6.7 nmol/l, ppre-eclampsia...

  19. 6-sulfatoxymelatonin levels in pregnant women during workplace and nonworkplace stresses: a potential biologic marker of sympathetic activity.

    Science.gov (United States)

    Katz, V L; Ekstrom, R D; Mason, G A; Golden, R N

    1995-07-01

    Melatonin production is regulated by both catecholamines and sympathetic activity. Urine levels of the major metabolite of melatonin, 6-sulfatoxymelatonin, correlate well with serum melatonin levels and have been used to evaluate sympathetic output. We tested the hypothesis that urinary levels of 6-sulfatoxymelatonin would reflect the change in adrenergic activity on working days compared with nonworking days during pregnancy. Twenty-three healthy pregnant women, employed in a variety of occupations, including physicians, nurses, secretaries, salespeople, and laboratory workers were recruited from the clinics of the University of North Carolina School of Medicine. We measured 6-sulfatoxymelatonin levels in first morning voids and for the subsequent 10 hours at 24, 28, 32, and 36 weeks' gestation. Urine was collected in sets during working days and during nonworking days. 6-Sulfatoxymelatonin was measured by radioimmunoassay. In 11 women we also measured urine catecholamines by high-performance liquid chromatography. Levels of 6-sulfatoxymelatonin output did not change across gestation, although they tended to drift down as pregnancy progressed. Median levels at first morning void were 6.3 micrograms on workdays and 4.6 micrograms on nonworkdays. Although all values were skewed toward work being greater than nonwork, there were large interindividual variations. We therefore compared subjects against themselves and compared work levels for each subject to the corresponding gestational age-matched nonwork value. Among the 23 women, median 6-sulfatoxymelatonin levels were 81% greater during work than nonwork (p < 0.0002) when first morning collections were compared. Daytime urinary excretion of 6-sulfatoxymelatonin on workdays was 38% (p < 0.005) greater than during nonworkdays.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Epidermal growth factor-like domain 7 is a marker of the endothelial lineage and active angiogenesis.

    Science.gov (United States)

    Bambino, Kathryn; Lacko, Lauretta A; Hajjar, Katherine A; Stuhlmann, Heidi

    2014-07-01

    Epidermal growth factor-like domain 7 (Egfl7) expression in the developing embryo is largely restricted to sites of mesodermal progenitors of angioblasts/hemangioblasts and the vascular endothelium. We hypothesize that Egfl7 marks the endothelial lineage during embryonic development, and can be used to define the emergence of endothelial progenitor cells, as well as to visualize newly-forming vasculature in the embryo and during the processes of physiologic and pathologic angiogenesis in the adult. We have generated a transgenic mouse strain that expresses enhanced green fluorescent protein (eGFP) under the control of a minimal Egfl7 regulatory sequence (Egfl7:eGFP). Expression of the transgene recapitulated that of endogenous Egfl7 at sites of vasculogenesis and angiogenesis in the allantois, yolk sac, and in the embryo proper. The transgene was not expressed in the quiescent endothelium of most adult organs. However, the uterus and ovary, which undergo vascular growth and remodeling throughout the estrus cycle, expressed high levels of Egfl7:eGFP. Importantly, expression of the Egfl7:eGFP transgene was induced in adult neovasculature. We also found that increased Egfl7 expression contributed to pathologic revascularization in the mouse retina. To our knowledge, this is the first mouse model that enables monitoring of endothelial cells at sites of active vasculogenesis and angiogenesis. This model also facilitated the isolation and characterization of EGFL7(+) endothelial cell populations by fluorescence activated cell sorting (FACS). Together, our results demonstrate that the Egfl7:eGFP reporter mouse is a valuable tool that can be used to elucidate the mechanisms by which blood vessels form during development and under pathologic circumstances. © 2014 Wiley Periodicals, Inc.

  1. Time-gated luminescence assay using nonmetal probes for determination of protein kinase activity-based disease markers.

    Science.gov (United States)

    Kasari, Marje; Padrik, Peeter; Vaasa, Angela; Saar, Kristi; Leppik, Krista; Soplepmann, Jaan; Uri, Asko

    2012-03-15

    A novel nonmetal optical probe ARC-1063 whose long-lifetime luminescence is induced by association with the target protein kinase is used for the measurement of the concentration of catalytic subunit of protein kinase A (PKAc) in complicated biological solutions. High affinity (K(D) = 10 pM toward PKAc) and unique optical properties of the probe enable its application for the measurement of picomolar concentrations of PKAc in the presence of high concentrations of other proteins. The described assay is applicable in the high-throughput format with the instrument setups designed for lanthanide-based time-gated (time-resolved) luminescence methods. The assay is used for demonstration that extracellular PKAc (ECPKA) is present in plasma samples of all healthy persons and cancer patients but great care must be taken for procedures of treatment of blood samples to avoid disruption, damage, or activation of platelets in the course of plasma (or serum) preparation and conservation. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Urinary gonadotrophins: a useful non-invasive marker of activation of the hypothalamic pituitary-gonadal axis

    Directory of Open Access Journals (Sweden)

    McNeilly Jane D

    2012-05-01

    Full Text Available Abstract Background Non-invasive screening investigations are rarely used for assessing the activation and progression of the hypothalamic-pituitary gonadal axis through puberty. This study aimed to establish a normal range for urinary gonadotrophins in children progressing through puberty. Methods Urine samples were collected from 161 healthy school children (76 boys, 85 girls aged 4–19 yrs. Height and weight were converted to standard deviation score. Pubertal status, classified by Tanner staging, was determined by self-assessment. Urinary gonadotrophins were measured by chemiluminescent microparticle immunoassay. Results were grouped according to pubertal status (pre-pubertal or pubertal. Results Of the 161 children, 50 were pre-pubertal (28 boys; 22 girls and 111 were pubertal (48 boys; 63 girls. Overall, urinary gonadotrophins concentrations increased with pubertal maturation. All pre-pubertal children had a low urinary LH:Creatinine ratio. LH:Creatinine ratios were significantly higher in pubertal compared to pre-pubertal boys (pp = 0.006. However, LH:FSH ratios were a more consistent discriminant between pre-pubertal and pubertal states in both sexes (Boys 0.45 pubertal vs 0.1 pre-pubertal; girls 0.23 pubertal vs 0.06 pre-pubertal. Conclusion Urinary gonadotrophins analyses could be used as non-invasive integrated measurement of pubertal status which reflects clinical/physical status.

  3. Physical activity and cardiorespiratory fitness as major markers of cardiovascular risk: their independent and interwoven importance to health status.

    Science.gov (United States)

    Myers, Jonathan; McAuley, Paul; Lavie, Carl J; Despres, Jean-Pierre; Arena, Ross; Kokkinos, Peter

    2015-01-01

    The evolution from hunting and gathering to agriculture, followed by industrialization, has had a profound effect on human physical activity (PA) patterns. Current PA patterns are undoubtedly the lowest they have been in human history, with particularly marked declines in recent generations, and future projections indicate further declines around the globe. Non-communicable health problems that afflict current societies are fundamentally attributable to the fact that PA patterns are markedly different than those for which humans were genetically adapted. The advent of modern statistics and epidemiological methods has made it possible to quantify the independent effects of cardiorespiratory fitness (CRF) and PA on health outcomes. Based on more than five decades of epidemiological studies, it is now widely accepted that higher PA patterns and levels of CRF are associated with better health outcomes. This review will discuss the evidence supporting the premise that PA and CRF are independent risk factors for cardiovascular disease (CVD) as well as the interplay between both PA and CRF and other CVD risk factors. A particular focus will be given to the interplay between CRF, metabolic risk and obesity. Published by Elsevier Inc.

  4. Vaginal immunization to elicit primary T-cell activation and dissemination.

    Directory of Open Access Journals (Sweden)

    Elena Pettini

    Full Text Available Primary T-cell activation at mucosal sites is of utmost importance for the development of vaccination strategies. T-cell priming after vaginal immunization, with ovalbumin and CpG oligodeoxynucleotide adjuvant as model vaccine formulation, was studied in vivo in hormone-synchronized mice and compared to the one induced by the nasal route. Twenty-four hours after both vaginal or nasal immunization, antigen-loaded dendritic cells were detected within the respective draining lymph nodes. Vaginal immunization elicited a strong recruitment of antigen-specific CD4(+ T cells into draining lymph nodes that was more rapid than the one observed following nasal immunization. T-cell clonal expansion was first detected in iliac lymph nodes, draining the genital tract, and proliferated T cells disseminated towards distal lymph nodes and spleen similarly to what observed following nasal immunization. T cells were indeed activated by the antigen encounter and acquired homing molecules essential to disseminate towards distal lymphoid organs as confirmed by the modulation of CD45RB, CD69, CD44 and CD62L marker expression. A multi-type Galton Watson branching process, previously used for in vitro analysis of T-cell proliferation, was applied to model in vivo CFSE proliferation data in draining lymph nodes 57 hours following immunization, in order to calculate the probabilistic decision of a cell to enter in division, rest in quiescence or migrate/die. The modelling analysis indicated that the probability of a cell to proliferate was higher following vaginal than nasal immunization. All together these data show that vaginal immunization, despite the absence of an organized mucosal associated inductive site in the genital tract, is very efficient in priming antigen-specific CD4(+ T cells and inducing their dissemination from draining lymph nodes towards distal lymphoid organs.

  5. SCAPIS Pilot Study: Sitness, Fitness and Fatness - Is Sedentary Time Substitution by Physical Activity Equally Important for Everyone's Markers of Glucose Regulation?

    Science.gov (United States)

    Ekblom-Bak, Elin; Ekblom, Örjan; Bolam, Kate A; Ekblom, Björn; Bergström, Göran; Börjesson, Mats

    2016-07-01

    Although moderate-to-vigorous physical activity (MVPA) is mainly recommended for glucose control, light physical activity (LIPA) may also have the potential to induce favorable changes. We investigated sedentary time (SED) substitution with equal time in LIPA and MVPA, and the association with markers of glucose regulation and insulin sensitivity after stratification by waist circumference, fitness and fasting glucose levels. A total of 654 men and women, 50 to 64 years, from the SCAPIS pilot study were included. Daily SED, LIPA and MVPA were assessed using hip-worn accelerometers. Fasting plasma glucose, insulin and HOMA-IR were determined. Substituting 30 min of SED with LIPA was significantly associated with 3.0% lower fasting insulin values and 3.1% lower HOMA-IR values, with even lower levels when substituting SED with MVPA. Participants with lower fitness and participants with high fasting glucose levels benefited significantly more from substituting 30 min of SED with LIPA compared with participants with normal to high fitness levels and participants with normal glucose levels, respectively. LIPA, and not only MVPA, may have beneficial associations with glucose regulation. This is of great clinical and public health importance, not least because it may confer a higher compliance rate to regular PA.

  6. Thrombomodulin, von Willebrand factor and E-selectin as plasma markers of endothelial damage/dysfunction and activation in pregnancy induced hypertension.

    Science.gov (United States)

    Nadar, Sunil K; Al Yemeni, Eman; Blann, Andrew D; Lip, Gregory Y H

    2004-01-01

    Endothelial disturbance (whether activation, dysfunction or damage) is a likely pathogenic mechanism in pre-eclampsia and pregnancy-induced hypertension (PIH). We set out to determine which of three plasma markers of endothelial disturbance, indicating endothelial activation (E-selectin) or damage/dysfunction (von Willebrand factor (vWf), soluble thrombomodulin), would provide the best discriminator of PIH compared to normotensive pregnancy. Cross-sectional study of 36 consecutive women with PIH (age 31+/-6 years) and 36 consecutive women with normotensive pregnancies (age 29+/-5 years) of similar parity. Plasma levels of vWf, E-selectin and thrombomodulin were measured using ELISA. As expected, women with PIH had significantly higher levels of plasma vWf (by 19%, p=0.003), E-selectin (by 40%, p<0.001) and thrombomodulin (by 61%, p=0.01) than normotensive women. However, on stepwise multiple regression analysis, only thrombomodulin was an independent significant predictor of the presence of PIH (p=0.023). We conclude that although vWf, E-selectin and thrombomodulin are all raised in PIH, only thrombomodulin was independently associated with PIH. This molecule could potentially be useful in monitoring and in providing clues in aetiology and pathophysiology, and may have implications for the clinical complications associated with PIH.

  7. Residual viraemia in HIV-1-infected patients with plasma viral load activation markers

    DEFF Research Database (Denmark)

    Ostrowski, S R; Katzenstein, T L; Pedersen, B K

    2008-01-01

    Despite undetectable viral load in conventional assays, probably all human immunodeficiency virus (HIV)-1 infected patients have residual viraemia (RV) detectable by ultra-sensitive assays. To study this issue, this study investigated virologic and immunologic consequences of RV in highly active......-count, CD4+HLA-DR+, CD8+HLA-DR+CD38+, CD4+CD45RA-CD45RO+, CD8+CD45RA-CD45RO+, CD4+CD45RA+CD62L+, CD8+CD45RA+CD62L+ T cells, IgG or IgM. In conclusion, RV was associated with increased blood levels of soluble immune activation markers in HAART-treated HIV-1-infected patients. The finding that RV...... antiretroviral therapy (HAART)-treated HIV-1-infected patients with plasma HIV-1 RNA or=1 episode with TMA-RV whereas 9 patients had undetectable TMA-RV throughout the study-period. Time-points with TMA-RV and PCR-RV were associated with higher circulating sTNFrII (+0.234 ng/ml, P = 0.030) and beta(2...

  8. Long Terminal Repeat Circular DNA as Markers of Active Viral Replication of Human T Lymphotropic Virus-1 in Vivo

    Directory of Open Access Journals (Sweden)

    James M Fox

    2016-03-01

    Full Text Available Clonal expansion of human T-lymphotropic virus type-1 (HTLV-1 infected cells in vivo is well documented. Unlike human immunodeficiency virus type 1 (HIV-1, HTLV-1 plasma RNA is sparse. The contribution of the “mitotic” spread of HTLV-1 compared with infectious spread of the virus to HTLV-1 viral burden in established infection is uncertain. Since extrachromosomal long terminal repeat (LTR DNA circles are indicators of viral replication in HIV-1 carriers with undetectable plasma HIV RNA, we hypothesised that HTLV-1 LTR circles could indicate reverse transcriptase (RT usage and infectious activity. 1LTR and 2LTR DNA circles were measured in HTLV-1 cell lines and peripheral blood mononuclear cells (PBMC of asymptomatic carriers (ACs and patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP or adult T cell leukaemia/lymphoma (ATLL. 1LTR DNA circles were detected in 14/20 patients at a mean of 1.38/100 PBMC but did not differentiate disease status nor correlate with HTLV-1 DNA copies. 2LTR DNA circles were detected in 30/31 patients and at higher concentrations in patients with HTLV-1-associated diseases, independent of HTLV-1 DNA load. In an incident case the 2LTR DNA circle concentration increased 2.1 fold at the onset of HAM/TSP compared to baseline. Detectable and fluctuating levels of HTLV-1 DNA circles in patients indicate viral RT usage and virus replication. Our results indicate HTLV-1 viral replication capacity is maintained in chronic infection and may be associated with disease onset.

  9. Rivastigmine lowers Aβ and increases sAPPα levels, which parallel elevated synaptic markers and metabolic activity in degenerating primary rat neurons.

    Directory of Open Access Journals (Sweden)

    Jason A Bailey

    Full Text Available Overproduction of amyloid-β (Aβ protein in the brain has been hypothesized as the primary toxic insult that, via numerous mechanisms, produces cognitive deficits in Alzheimer's disease (AD. Cholinesterase inhibition is a primary strategy for treatment of AD, and specific compounds of this class have previously been demonstrated to influence Aβ precursor protein (APP processing and Aβ production. However, little information is available on the effects of rivastigmine, a dual acetylcholinesterase and butyrylcholinesterase inhibitor, on APP processing. As this drug is currently used to treat AD, characterization of its various activities is important to optimize its clinical utility. We have previously shown that rivastigmine can preserve or enhance neuronal and synaptic terminal markers in degenerating primary embryonic cerebrocortical cultures. Given previous reports on the effects of APP and Aβ on synapses, regulation of APP processing represents a plausible mechanism for the synaptic effects of rivastigmine. To test this hypothesis, we treated degenerating primary cultures with rivastigmine and measured secreted APP (sAPP and Aβ. Rivastigmine treatment increased metabolic activity in these cultured cells, and elevated APP secretion. Analysis of the two major forms of APP secreted by these cultures, attributed to neurons or glia based on molecular weight showed that rivastigmine treatment significantly increased neuronal relative to glial secreted APP. Furthermore, rivastigmine treatment increased α-secretase cleaved sAPPα and decreased Aβ secretion, suggesting a therapeutic mechanism wherein rivastigmine alters the relative activities of the secretase pathways. Assessment of sAPP levels in rodent CSF following once daily rivastigmine administration for 21 days confirmed that elevated levels of APP in cell culture translated in vivo. Taken together, rivastigmine treatment enhances neuronal sAPP and shifts APP processing toward the

  10. Common γ-chain blocking peptide reduces in vitro immune activation markers in HTLV-1-associated myelopathy/tropical spastic paraparesis.

    Science.gov (United States)

    Massoud, Raya; Enose-Akahata, Yoshimi; Tagaya, Yutaka; Azimi, Nazli; Basheer, Asjad; Jacobson, Steven

    2015-09-01

    Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive inflammatory myelopathy occurring in a subset of HTLV-1-infected individuals. Despite advances in understanding its immunopathogenesis, an effective treatment remains to be found. IL-2 and IL-15, members of the gamma chain (γc) family of cytokines, are prominently deregulated in HAM/TSP and underlie many of the characteristic immune abnormalities, such as spontaneous lymphocyte proliferation (SP), increased STAT5 phosphorylation in the lymphocytes, and increased frequency and cytotoxicity of virus-specific cytotoxic CD8(+) T lymphocytes (CTLs). In this study, we describe a novel immunomodulatory strategy consisting of selective blockade of certain γc family cytokines, including IL-2 and IL-15, with a γc antagonistic peptide. In vitro, a PEGylated form of the peptide, named BNZ132-1-40, reduced multiple immune activation markers such as SP, STAT5 phosphorylation, spontaneous degranulation of CD8(+) T cells, and the frequency of transactivator protein (Tax)-specific CD8(+) CTLs, thought to be major players in the immunopathogenesis of the disease. This strategy is thus a promising therapeutic approach to HAM/TSP with the potential of being more effective than single monoclonal antibodies targeting either IL-2 or IL-15 receptors and safer than inhibitors of downstream signaling molecules such as JAK1 inhibitors. Finally, selective cytokine blockade with antagonistic peptides might be applicable to multiple other conditions in which cytokines are pathogenic.

  11. Microbiota-dependent metabolite and cardiovascular disease marker trimethylamine-N-oxide (TMAO) is associated with monocyte activation but not platelet function in untreated HIV infection

    DEFF Research Database (Denmark)

    Haissman, Judith M; Haugaard, Anna K; Ostrowski, Sisse R

    2017-01-01

    and combination anti-retroviral therapy (cART) HIV infection. METHODS: TMAO and the pre-cursors betaine, choline, and carnitine were quantified by mass-spectrometry in plasma samples from a previously established cross-sectional cohort of 50 untreated and 50 cART treated HIV-infected individuals. Whole...... agonists, or with overall hypo- or hyperreactivity in untreated or treated HIV-infected individuals. In contrast, sCD14 a marker of both monocyte activation and microbial translocation was independently associated with TMAO in untreated HIV-infection (R = 0.381, P = 0.008). Lower levels of carnitine [32.......2 (28.4-36.8) vs. 38.2 (33.6-42.0), P = 0.001] and betaine [33.1 (27.3-43.4) vs.37.4 (31.5-48.7, P = 0.02], but similar TMAO levels [3.8 (2.3-6.1), vs. 2.9 μM (1.9-4.8) P = 0.15] were found in cART treated compared to untreated HIV-infected individuals, resulting in higher ratios of TMAO/carnitine [0...

  12. Short-term effects of air pollution, markers of endothelial activation, and coagulation to predict major adverse cardiovascular events in patients with acute coronary syndrome: insights from AIRACOS study.

    Science.gov (United States)

    Dominguez-Rodriguez, Alberto; Abreu-Gonzalez, Pedro; Rodríguez, Sergio; Avanzas, Pablo; Juarez-Prera, Ruben A

    2017-07-01

    The aim of this study was to determine whether markers of inflammation and coagulation are associated with short-term particulate matter exposure and predict major adverse cardiovascular events at 360 d in patients with acute coronary syndrome (ACS). We included 307 consecutive patients, and assessed the average concentrations of data on atmospheric pollution in ambient air and meteorological variables from 1 d up to 7 d prior to admission. In patients with ACS, the markers of endothelial activation and coagulation, but not black carbon exposure, are associated with major adverse cardiovascular events at one-year follow-up.

  13. Honokiol Increases CD4+ T Cell Activation and Decreases TNF but Fails to Improve Survival Following Sepsis.

    Science.gov (United States)

    Klingensmith, Nathan J; Chen, Ching-Wen; Liang, Zhe; Burd, Eileen M; Farris, Alton B; Arbiser, Jack L; Ford, Mandy L; Coopersmith, Craig M

    2017-10-11

    Honokiol is a biphenolic isolate extracted from the bark of the magnolia tree that has been used in traditional Chinese and Japanese medicine, and has more recently been investigated for its anti-inflammatory and anti-bacterial properties. Honokiol has previously been demonstrated to improve survival in sepsis models that have rapid 100% lethality. The purpose of this study was to determine the impact of Honokiol on the host response in a model of sepsis that more closely approximates human disease. Male and female C57BL/6 mice underwent cecal ligation and puncture (CLP) to induce polymicrobial intraabdominal sepsis. Mice were then randomized to receive an injection of either Honokiol (120 mg/kg/day) or vehicle and were sacrificed after 24 hours for functional studies or followed 7 days for survival. Honokiol treatment after sepsis increased the frequency of CD4 T cells and increased activation of CD4 T cells as measured by the activation marker CD69. Honokiol also increased splenic dendritic cells. Honokiol simultaneously decreased frequency and number of CD8 T cells. Honokiol decreased systemic TNF without impacting other systemic cytokines. Honokiol did not have a detectable effect on kidney function, lung physiology, liver function or intestinal integrity. In contrast to prior studies of Honokiol in a lethal model of sepsis, Honokiol did not alter survival at seven days (70% mortality for Honokiol vs. 60% mortality for vehicle). Honokiol is thus effective in modulating the host immune response and inflammation following a clinically relevant model of sepsis but is not sufficient to alter survival.

  14. High Pre-β1 HDL Concentrations and Low Lecithin: Cholesterol Acyltransferase Activities Are Strong Positive Risk Markers for Ischemic Heart Disease and Independent of HDL-Cholesterol

    Science.gov (United States)

    Sethi, Amar A.; Sampson, Maureen; Warnick, Russell; Muniz, Nehemias; Vaisman, Boris; Nordestgaard, Børge G.; Tybjærg-Hansen, Anne; Remaley, Alan T.

    2016-01-01

    BACKGROUND We hypothesized that patients with high HDL-cholesterol (HDL-C) and ischemic heart disease (IHD) may have dysfunctional HDL or unrecognized nonconventional risk factors. METHODS Individuals with IHD (Copenhagen University Hospital) and either high HDL-C (n = 53; women ≥735 mg/L; men ≥619 mg/L) or low HDL-C (n = 42; women ≤387 mg/L; men ≤341 mg/L) were compared with individuals without IHD (Copenhagen City Heart Study) matched by age, sex, and HDL-C concentrations (n = 110). All participants had concentrations within reference intervals for LDL-C (lecithin:cholesterol acyltransferase (LCAT) activity by using a proteoliposome cholesterol esterification assay. RESULTS Pre-β1 HDL concentrations were 2-fold higher in individuals with IHD vs no IHD in both the high [63 (5.7) vs 35 (2.3) mg/L; P < 0.0001] and low HDL-C [49 (5.0) vs 27 (1.5) mg/L; P = 0.001] groups. Low LCAT activity was also associated with IHD in the high [95.2 (6.7) vs 123.0 (5.3) μmol · L−1 · h−1; P = 0.002] and low [93.4 (8.3) vs 113.5 (4.9) μmol · L−1 · h−1; P = 0.03] HDL-C groups. ROC curves for pre-β1 HDL in the high–HDL-C groups yielded an area under the curve of 0.71 (95% CI: 0.61–0.81) for predicting IHD, which increased to 0.92 (0.87–0.97) when LCAT was included. Similar results were obtained for low HDL-C groups. An inverse correlation between LCAT activity and pre-β1 HDL was observed (r2 = 0.30; P < 0.0001) in IHD participants, which was stronger in the low HDL-C group (r2 = 0.56; P < 0.0001). CONCLUSIONS IHD was associated with high pre-β1 HDL concentrations and low LCAT levels, yielding correct classification in more than 90% of the IHD cases for which both were measured, thus making pre-β1 HDL concentration and LCAT activity level potentially useful diagnostic markers for cardiovascular disease. PMID:20511449

  15. Prehospital resuscitation with hypertonic saline-dextran modulates inflammatory, coagulation and endothelial activation marker profiles in severe traumatic brain injured patients

    Directory of Open Access Journals (Sweden)

    Morrison Laurie J

    2010-01-01

    Full Text Available Abstract Background Traumatic brain injury (TBI initiates interrelated inflammatory and coagulation cascades characterized by wide-spread cellular activation, induction of leukocyte and endothelial cell adhesion molecules and release of soluble pro/antiinflammatory cytokines and thrombotic mediators. Resuscitative care is focused on optimizing cerebral perfusion and reducing secondary injury processes. Hypertonic saline is an effective osmotherapeutic agent for the treatment of intracranial hypertension and has immunomodulatory properties that may confer neuroprotection. This study examined the impact of hypertonic fluids on inflammatory/coagulation cascades in isolated head injury. Methods Using a prospective, randomized controlled trial we investigated the impact of prehospital resuscitation of severe TBI (GCS vs 0.9% normal saline (NS, on selected cellular and soluble inflammatory/coagulation markers. Serial blood samples were drawn from 65 patients (30 HSD, 35 NS at the time of hospital admission and at 12, 24, and 48-h post-resuscitation. Flow cytometry was used to analyze leukocyte cell-surface adhesion (CD62L, CD11b and degranulation (CD63, CD66b molecules. Circulating concentrations of soluble (sL- and sE-selectins (sL-, sE-selectins, vascular and intercellular adhesion molecules (sVCAM-1, sICAM-1, pro/antiinflammatory cytokines [tumor necrosis factor (TNF-α and interleukin (IL-10], tissue factor (sTF, thrombomodulin (sTM and D-dimers (D-D were assessed by enzyme immunoassay. Twenty-five healthy subjects were studied as a control group. Results TBI provoked marked alterations in a majority of the inflammatory/coagulation markers assessed in all patients. Relative to control, NS patients showed up to a 2-fold higher surface expression of CD62L, CD11b and CD66b on polymorphonuclear neutrophils (PMNs and monocytes that persisted for 48-h. HSD blunted the expression of these cell-surface activation/adhesion molecules at all time-points to

  16. Analysis of microRNA expression profiling identifies miR-155 and miR-155* as potential diagnostic markers for active tuberculosis: a preliminary study.

    Science.gov (United States)

    Wu, Jing; Lu, Chanyi; Diao, Ni; Zhang, Shu; Wang, Sen; Wang, Feifei; Gao, Yan; Chen, Jiazhen; Shao, Lingyun; Lu, Jingning; Zhang, Xuelian; Weng, Xinhua; Wang, Honghai; Zhang, Wenhong; Huang, Yuxian

    2012-01-01

    To explore biologic behaviors and disease relevance of microRNAs (miRNAs) in the development of active tuberculosis (ATB), we investigated the expression profile of Mycobacterium tuberculosis (MTB) purified protein derivative (PPD)-induced miRNAs to determine the specific miRNAs involved in the pathogenesis of ATB. The expression profile of miRNA under PPD challenge was first measured using microarray analysis in peripheral blood mononuclear cells isolated from ATB patients and healthy controls (HC). The remarkably reactive miRNAs were then validated in a larger cohort by quantitative real-time polymerase chain reaction (qRT-PCR). The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of the determined PPD-responsive miRNAs. The potential targets for those miRNAs were also predicted by computational programs. Fourteen of 866 human miRNAs exhibited at least 1.8-fold difference in the ratio of expression level before and after stimulation with PPD between the ATB and HC groups. The qRT-PCR study validated the findings from microarray-based screening, in which miR-155 exhibited a fold change of 1.4 in the HC group and 3.7 in the ATB group upon PPD stimulation (p microRNAs exhibited no differences between the ATB and HC groups. miR-155 and miR-155* exhibited characteristic expression by TB-specific antigen, suggesting that they can be potential diagnostic markers under the challenge of specific MTB antigens. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  17. The Association Between Post-traumatic Stress Disorder and Markers of Inflammation and Immune Activation in HIV-Infected Individuals With Controlled Viremia.

    Science.gov (United States)

    Siyahhan Julnes, Peter; Auh, Sungyoung; Krakora, Rebecca; Withers, Keenan; Nora, Diana; Matthews, Lindsay; Steinbach, Sally; Snow, Joseph; Smith, Bryan; Nath, Avindra; Morse, Caryn; Kapetanovic, Suad

    2016-01-01

    Post-traumatic stress disorder (PTSD) may be associated with chronic immune dysregulation and a proinflammatory state. Among HIV-infected individuals, PTSD is associated with greater morbidity and mortality, but the association with immune dysfunction has not been evaluated. This study explores the association between PTSD and selected markers of inflammation and immune activation in a cohort of HIV-infected, virally-suppressed individuals. HIV-infected adults who were virologically controlled on antiretroviral medications were recruited through a screening protocol for studies of HIV-related neurocognitive disorders. Each participant underwent blood draws, urine toxicology screen, and completed the Client Diagnostic Questionnaire, a semistructured psychiatric interview. Of 114 eligible volunteers, 72 (63%) were male, 77 (68%) African American, and 34 (30%) participants met criteria for PTSD. Participants with PTSD were more likely to be current smokers (79%) than those without (60%) (p = 0.05). The PTSD cohort had significantly higher total white blood cell counts (5318 and 6404 cells/uL, p = 0.03), absolute neutrophil count (2767 and 3577 cells/uL, p = 0.02), CD8% (43 and 48, p = 0.05), and memory CD8% (70 and 78%, p = 0.04); lower naïve CD8% (30 and 22%, p = 0.04) and higher rate of high-sensitivity C-reactive protein >3mg/L (29 and 20, p = 0.03). A high prevalence of PTSD was identified in this cohort of HIV-infected adults who were virally suppressed. These results suggest that PTSD may be associated with immune dysregulation even among antiretroviral therapy-adherent HIV-infected individuals. Published by Elsevier Inc.

  18. Screening of specific nucleic acid aptamers binding tumor markers in the serum of the lung cancer patients and identification of their activities.

    Science.gov (United States)

    Li, Kun; Xiu, Chen-Lin; Gao, Li-Ming; Liang, Hua-Gang; Xu, Shu-Feng; Shi, Ming; Li, Jian; Liu, Zhi-Wei

    2017-07-01

    Lung cancer is by far the leading cause of cancer death in the world. Despite the improvements in diagnostic methods, the status of early detection was not achieved. So, a new diagnostic method is needed. The aim of this study is to obtain the highly specific nucleic acid aptamers with strong affinity to tumor markers in the serum of the lung cancer patients for targeting the serum. Aptamers specifically binding to tumor markers in the serum of the lung cancer patients were screened from the random single-stranded DNA library with agarose beads as supports and the serum as a target by target-substituting subtractive SELEX technique and real-time quantitative polymerase chain reaction technique. Subsequently, the secondary single-stranded DNA library obtained by 10 rounds of screening was amplified to double-stranded DNA, followed by high-throughput genome sequence analysis to screen aptamers with specific affinity to tumor markers in the serum of the lung cancer patients. Finally, six aptamers obtained by 10 rounds of screening were identified with high specific affinity to tumor markers in the serum of the lung cancer patients. Compared with other five aptamers, the aptamer 43 was identified both with the highest specificity to bind target molecule and without any obvious affinity to non-specific proteins. The screened aptamers have relatively high specificity to combine tumor markers in the serum of the lung cancer patients, which provides breakthrough points for early diagnosis and treatment of lung cancer.

  19. Stereotactic core needle breast biopsy marker migration: An analysis of factors contributing to immediate marker migration.

    Science.gov (United States)

    Jain, Ashali; Khalid, Maria; Qureshi, Muhammad M; Georgian-Smith, Dianne; Kaplan, Jonah A; Buch, Karen; Grinstaff, Mark W; Hirsch, Ariel E; Hines, Neely L; Anderson, Stephan W; Gallagher, Katherine M; Bates, David D B; Bloch, B Nicolas

    2017-11-01

    To evaluate breast biopsy marker migration in stereotactic core needle biopsy procedures and identify contributing factors. This retrospective study analyzed 268 stereotactic biopsy markers placed in 263 consecutive patients undergoing stereotactic biopsies using 9G vacuum-assisted devices from August 2010-July 2013. Mammograms were reviewed and factors contributing to marker migration were evaluated. Basic descriptive statistics were calculated and comparisons were performed based on radiographically-confirmed marker migration. Of the 268 placed stereotactic biopsy markers, 35 (13.1%) migrated ≥1 cm from their biopsy cavity. Range: 1-6 cm; mean (± SD): 2.35 ± 1.22 cm. Of the 35 migrated biopsy markers, 9 (25.7%) migrated ≥3.5 cm. Patient age, biopsy pathology, number of cores, and left versus right breast were not associated with migration status (P> 0.10). Global fatty breast density (P= 0.025) and biopsy in the inner region of breast (P = 0.031) were associated with marker migration. Superior biopsy approach (P= 0.025), locally heterogeneous breast density, and t-shaped biopsy markers (P= 0.035) were significant for no marker migration. Multiple factors were found to influence marker migration. An overall migration rate of 13% supports endeavors of research groups actively developing new biopsy marker designs for improved resistance to migration. • Breast biopsy marker migration is documented in 13% of 268 procedures. • Marker migration is affected by physical, biological, and pathological factors. • Breast density, marker shape, needle approach etc. affect migration. • Study demonstrates marker migration prevalence; marker design improvements are needed.

  20. Magnetic resonance imaging-determined synovial membrane volume as a marker of disease activity and a predictor of progressive joint destruction in the wrists of patients with rheumatoid arthritis

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Hansen, M; Stoltenberg, M

    1999-01-01

    OBJECTIVE: To evaluate the synovial membrane volume, determined by magnetic resonance imaging (MRI), as a marker of joint disease activity and a predictor of progressive joint destruction in rheumatoid arthritis (RA). METHODS: Twenty-six patients with RA, randomized to receive disease-modifying a......OBJECTIVE: To evaluate the synovial membrane volume, determined by magnetic resonance imaging (MRI), as a marker of joint disease activity and a predictor of progressive joint destruction in rheumatoid arthritis (RA). METHODS: Twenty-six patients with RA, randomized to receive disease......-Pratt analysis). The rate of erosive progression on MRI was highly correlated with baseline scores and, particularly, with area under the curve (AUC) values of synovial membrane volume (Spearman's sigma = 0.69, P

  1. Tumor marker utility and prognostic relevance of cathepsin B, cathepsin L, urokinase-type plasminogen activator, plasminogen activator inhibitor type-1, CEA and CA 19-9 in colorectal cancer

    International Nuclear Information System (INIS)

    Herszényi, László; Farinati, Fabio; Cardin, Romilda; István, Gábor; Molnár, László D; Hritz, István; De Paoli, Massimo; Plebani, Mario; Tulassay, Zsolt

    2008-01-01

    Cathepsin B and L (CATB, CATL), urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 play an important role in colorectal cancer invasion. The tumor marker utility and prognostic relevance of these proteases have not been evaluated in the same experimental setting and compared with that of CEA and CA-19-9. Protease, CEA and CA 19-9 serum or plasma levels were determined in 56 patients with colorectal cancer, 25 patients with ulcerative colitis, 26 patients with colorectal adenomas and 35 tumor-free control patients. Protease, CEA, CA 19-9 levels have been determined by ELISA and electrochemiluminescence immunoassay, respectively; their sensitivity, specificity, diagnostic accuracy have been calculated and correlated with clinicopathological staging. The protease antigen levels were significantly higher in colorectal cancer compared with other groups. Sensitivity of PAI-1 (94%), CATB (82%), uPA (69%), CATL (41%) were higher than those of CEA or CA 19-9 (30% and 18%, respectively). PAI-1, CATB and uPA demonstrated a better accuracy than CEA or CA 19-9. A combination of PAI-1 with CATB or uPA exhibited the highest sensitivity value (98%). High CATB, PAI-1, CEA and CA 19-9 levels correlated with advanced Dukes stages. CATB (P = 0.0004), CATL (P = 0.02), PAI-1 (P = 0.01) and CA 19-9 (P = 0.004) had a significant prognostic impact. PAI-1 (P = 0.001), CATB (P = 0.04) and CA 19-9 (P = 0.02) proved as independent prognostic variables. At the time of clinical detection proteases are more sensitive indicators for colorectal cancer than the commonly used tumor markers. Determinations of CATB, CATL and PAI-1 have a major prognostic impact in patients with colorectal cancer

  2. Efficient activation of T cells by human monocyte-derived dendritic cells (HMDCs pulsed with Coxiella burnetii outer membrane protein Com1 but not by HspB-pulsed HMDCs

    Directory of Open Access Journals (Sweden)

    Wang Xile

    2011-09-01

    Full Text Available Abstract Background Coxiella burnetii is an obligate intracellular bacterium and the etiologic agent of Q fever; both coxiella outer membrane protein 1 (Com1 and heat shock protein B (HspB are its major immunodominant antigens. It is not clear whether Com1 and HspB have the ability to mount immune responses against C. burnetii infection. Results The recombinant proteins Com1 and HspB were applied to pulse human monocyte-derived dendritic cells (HMDCs, and the pulsed HMDCs were used to stimulate isogenic T cells. Com1-pulsed HMDCs expressed substantially higher levels of surface molecules (CD83, CD40, CD80, CD86, CD54, and CD58 and a higher level of interleukin-12 than HspB-pulsed HMDCs. Moreover, Com1-pulsed HMDCs induced high-level proliferation and activation of CD4+ and CD8+ cells, which expressed high levels of T-cell activation marker CD69 and inflammatory cytokines IFN-γ and TNF-α. In contrast, HspB-pulsed HMDCs were unable to induce efficient T-cell proliferation and activation. Conclusions Our results demonstrate that Com1-pulsed HMDCs are able to induce efficient T-cell proliferation and drive T cells toward Th1 and Tc1 polarization; however, HspB-pulsed HMDCs are unable to do so. Unlike HspB, Com1 is a protective antigen, which was demonstrated by the adoptive transfer of Com1-pulsed bone marrow dendritic cells into naive BALB/c mice.

  3. Genetic relationships in Cucurbita pepo (pumpkin, squash, gourd) as viewed with high frequency oligonucleotide–targeting active gene (HFO–TAG) markers

    Science.gov (United States)

    Cucurbita pepo is a highly diverse, economically important member of the Cucurbitaceae. C. pepo encompasses hundreds of cultivars of pumpkins, squash, and gourds. Although C. pepo has been scrutinized with various types of DNA markers, the relationships among the cultivar-groups of C. pepo subsp. p...

  4. Screening bioactive quality control markers of QiShenYiQi dripping pills based on the relationship between the ultra-high performance liquid chromatography fingerprint and vascular protective activity.

    Science.gov (United States)

    Zhuo, Limeng; Peng, Jingjing; Zhao, Yunli; Li, Dongxiang; Xie, Xiuman; Tong, Ling; Yu, Zhiguo

    2017-10-01

    Traditional Chinese medicine consists of complex phytochemical constituents. Selecting appropriate analytical markers of traditional Chinese medicine is a critical step in quality control. Currently, the combination of fingerprinting and efficacy evaluation is considered as a useful method for screening active ingredients in complex mixtures. This study was designed to develop an orthogonal partial least squares model for screening bioactive quality control markers of QishenYiqi dripping pills based on the fingerprint-efficacy relationship. First, the chemical fingerprints of 49 batches of QishenYiqi dripping pill samples were established by ultra-high performance liquid chromatography coupled with a photodiode array detector. Second, ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry was exploited to systematically investigate the 36 copossessing fingerprint components in QishenYiqi dripping pills. The vascular protective activity of QishenYiqi dripping pills was determined by using a cell counting kit-8 assay. Finally, fingerprint-efficacy relationship was established by orthogonal partial least squares model. The results indicated that ten components exhibited strong correlation with vascular protective activity, and these were preliminarily screened as quality control markers. The present study provided a novel idea for the study of the pharmacodynamic material basis and quality evaluation of QishenYiqi dripping pills. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Tantalum markers in radiography

    International Nuclear Information System (INIS)

    Aronson, A.S.; Jonsson, N.; Alberius, P.

    1985-01-01

    The biocompatibility of two types of radiopaque tantalum markers was evaluated histologically. Reactions to pin markers (99.9% purity) and spherical markers (95.2% purity) were investigated after 3-6 weeks in rabbits and 5-48 weeks in children with abnormal growth. Both marker types were firmly attached to bone trabeculae; this was most pronounced in rabbit bone, and no adverse macroscopic reactions were observed. Microscopically, no reactions or only slight fibrosis of bone tissue were detected, while soft tissues only demonstrated a minor inflammatory reaction. Nevertheless, the need for careful preparation and execution of marker implantations is stressed, and particularly avoidance iof the use of emery in sharpening of cannulae. The bioinertness of tantalum was reconfirmed as was its suitability for use as skeletal and soft tissue radiographic markers. (orig.)

  6. PKCθ is required for the activation of human T lymphocytes induced by CD43 engagement

    International Nuclear Information System (INIS)

    Rio, Roxana del; Rincon, Mercedes; Layseca-Espinosa, Esther; Fierro, Nora A.; Rosenstein, Yvonne; Pedraza-Alva, Gustavo

    2004-01-01

    The turnover of phosphoinositides leading to PKC activation constitutes one of the principal axes of intracellular signaling. In T lymphocytes, the enhanced and prolonged PKC activation resulting from the engagement of the TcR and co-receptor molecules ensures a productive T cell response. The CD43 co-receptor promotes activation and proliferation, by inducing IL-2 secretion and CD69 expression. CD43 engagement has been shown to promote phosphoinositide turnover and DAG production. Moreover, PKC activation was found to be required for the activation of the MAP kinase pathway in response to CD43 ligation. Here we show that CD43 engagement led to the membrane translocation and enzymatic activity of specific PKC isoenzymes: cPKC (α/β), nPKC (ε and θ), aPKC (ζ) and PKCμ. We also show that activation of PKCθ resulting from CD43 ligation induced CD69 expression through an ERK-dependent pathway leading to AP-1, NF-κB activation and an ERK independent pathway promoting NFAT activation. Together, these data suggest that PKCθ plays a critical role in the co-stimulatory functions of CD43 in human T cells

  7. Ten polymorphic microsatellite markers characterized for ...

    Indian Academy of Sciences (India)

    MING MING BAO

    development of new microsatellite primers is expensive and time-consuming, whereas ... constructing microsatellite-enriched libraries (Guo et al. 2013). Thirteen markers .... Due to the influence of human activities, stocks of this species have ...

  8. Radiopaque anastomosis marker

    International Nuclear Information System (INIS)

    Elliott, D.P.; Halseth, W.L.

    1977-01-01

    This invention relates to split ring markers fabricated in whole or in part from a radiopaque material, usually metal, having the terminal ends thereof and a medial portion formed to define eyelets by means of which said marker can be sutured to the tissue at the site of an anastomosis to provide a visual indication of its location when examined fluoroscopically

  9. Insulin-like growth factor 1 (IGF1) and its active peptide (1-3)IGF1 enhance the expression of synaptic markers in neuronal circuits through different cellular mechanisms.

    LENUS (Irish Health Repository)

    Corvin, Aiden P

    2012-06-27

    Insulin-like growth factor-1 (IGF1) and its active peptide (1-3)IGF1 modulate brain growth and plasticity and are candidate molecules for treatment of brain disorders. IGF1 N-terminal portion is naturally cleaved to generate the tri-peptide (1-3)IGF1 (glycine-praline-glutamate). IGF1 and (1-3)IGF have been proposed as treatment for neuropathologies, yet their effect on nerve cells has not been directly compared. In this study we examine the effects of IGF1 and (1-3)IGF1 in primary cortical cultures and measure the expression levels of markers for intracellular pathways and synaptic function. We find that both treatments activate the IGF1 receptor and enhance the expression of synaptic markers, however, they activate different intracellular pathways. Furthermore, (1-3)IGF1 administration increases the expression of endogenous IGF1, suggesting a direct interaction between the two molecules. The results show that the two molecules increase the expression of synaptic proteins through activating different cellular mechanisms.

  10. Identification of New Compounds from Sage Flowers (Salvia officinalis L.) as Markers for Quality Control and the Influence of the Manufacturing Technology on the Chemical Composition and Antibacterial Activity of Sage Flower Extracts.

    Science.gov (United States)

    Gericke, Sebastian; Lübken, Tilo; Wolf, Diana; Kaiser, Martin; Hannig, Christian; Speer, Karl

    2018-02-28

    Parts of Salvia species such as its flowers and leaves are currently used as a culinary herb and for some medicinal applications. To distinguish the different sage extracts it is necessary to analyze their individual chemical compositions. Their characteristic compounds might be established as markers to differentiate between sage flowers and leaf extracts or to determine the manufacturing technology and storage conditions. Tri-p-coumaroylspermidine can be detected only in flowers and has been described here for Salvia and Lavandula species for the first time. Markers for oxidation processes are the novel compounds salviquinone A and B, which were generated from carnosol by exposure to oxygen. Caffeic acid ethyl ester was established as an indirect marker for the usage of ethanol as extraction solvent. The compounds were identified by LC-QTOF-HRESIMS, LC-MS, NMR, IR, and single-crystal X-ray diffraction after isolation by semipreparative HPLC. Furthermore, sage flower resin showed interesting antibacterial in vitro activities against Gram-positive and Gram-negative bacteria.

  11. Increased Levels of Oxidative Stress Markers, Soluble CD40 Ligand, and Carotid Intima-Media Thickness Reflect Acceleration of Atherosclerosis in Male Patients with Ankylosing Spondylitis in Active Phase and without the Classical Cardiovascular Risk Factors

    Directory of Open Access Journals (Sweden)

    Agata Stanek

    2017-01-01

    Full Text Available Objective. The primary aim of the study was to assess levels of oxidative stress markers, soluble CD40 ligand (sCD40L, serum pregnancy-associated plasma protein-A (PAPP-A, and placental growth factor (PlGF as well as carotid intima-media thickness (IMT in patients with ankylosing spondylitis (AS with active phase without concomitant classical cardiovascular risk factors. Material and methods. The observational study involved 96 male subjects: 48 AS patients and 48 healthy ones, who did not differ significantly regarding age, BMI, comorbid disorders, and distribution of classical cardiovascular risk factors. In both groups, we estimated levels of oxidative stress markers, lipid profile, and inflammation parameters as well as sCD40L, serum PAPP-A, and PlGF. In addition, we estimated carotid IMT in each subject. Results. The study showed that markers of oxidative stress, lipid profile, and inflammation, as well as sCD40L, PlGF, and IMT, were significantly higher in the AS group compared to the healthy group. Conclusion. Our results demonstrate that ankylosing spondylitis may be associated with increased risk for atherosclerosis.

  12. Apoptotic markers in protozoan parasites

    Directory of Open Access Journals (Sweden)

    Fasel Nicolas

    2010-11-01

    Full Text Available Abstract The execution of the apoptotic death program in metazoans is characterized by a sequence of morphological and biochemical changes that include cell shrinkage, presentation of phosphatidylserine at the cell surface, mitochondrial alterations, chromatin condensation, nuclear fragmentation, membrane blebbing and the formation of apoptotic bodies. Methodologies for measuring apoptosis are based on these markers. Except for membrane blebbing and formation of apoptotic bodies, all other events have been observed in most protozoan parasites undergoing cell death. However, while techniques exist to detect these markers, they are often optimised for metazoan cells and therefore may not pick up subtle differences between the events occurring in unicellular organisms and multi-cellular organisms. In this review we discuss the markers most frequently used to analyze cell death in protozoan parasites, paying special attention to changes in cell morphology, mitochondrial activity, chromatin structure and plasma membrane structure/permeability. Regarding classical regulators/executors of apoptosis, we have reviewed the present knowledge of caspase-like and nuclease activities.

  13. Echinococcus multilocularis vesicular fluid inhibits activation and proliferation of natural killer cells.

    Science.gov (United States)

    Bellanger, Anne-Pauline; Mougey, Valentine; Pallandre, Jean-Rene; Gbaguidi-Haore, Houssein; Godet, Yann; Millon, Laurence

    2017-08-25

    Alveolar echinococcosis is a severe chronic helminthic disease that mimics slow-growing liver cancer. The immune evasion strategy of Echinococcus multilocularis Leuckart, 1863 remains poorly understood. The aim of this study was to investigate in vitro the impact of E. multilocularis vesicular fluid (Em-VF) on peripheral blood mononuclear cells (PBMC) and on natural killer (NK) cells. PBMC and NK cells were exposed to Em-VF (1 µg/ml) during six days. The effect of Em-VF was assessed on CD69, viability and proliferation, and on and transforming growth factor β (TGF-β), interferon γ (IFN-γ), interleukin 17 (IL-17) and interleukin 10, using flow cytometry and ELISA, respectively. Exposure to Em-VF had no bearing on PBMC's viability, proliferation and expression of CD69. In contrast, higher levels of IL-17 at day three and of TGF-β at day six were observed in PBMC supernatant after exposure to Em-VF (p Wilcoxon signed-rank test). Exposure to Em-VF induced a significant decrease of CD69 expression of NK cells at day three and a significant decrease of proliferation of NK cells at day six (p Wilcoxon signed-rank test). In contrast, NK cells viability and levels of cytokines did not vary significantly over Em-VF stimulation. Exposure to Em-VF had a significant bearing on activation and proliferation of NK cells. NK cells may play an important role in the immune response of the host against E. multilocularis.

  14. Multiple marker abundance profiling

    DEFF Research Database (Denmark)

    Hooper, Cornelia M.; Stevens, Tim J.; Saukkonen, Anna

    2017-01-01

    proteins and the scoring accuracy of lower-abundance proteins in Arabidopsis. NPAS was combined with subcellular protein localization data, facilitating quantitative estimations of organelle abundance during routine experimental procedures. A suite of targeted proteomics markers for subcellular compartment...

  15. (DArT) markers

    Indian Academy of Sciences (India)

    2EH Graham Centre for Agricultural Innovation (NSW Department of Industry and Investment and Charles Sturt. University), P. O. Box 588 Wagga Wagga, NSW 2650, Australia. 3Guangxi .... and obtain marker statistics. The exact order of the ...

  16. VT Roadside Historic Markers

    Data.gov (United States)

    Vermont Center for Geographic Information — Roadside Historic Site Marker program has proven an effective way to commemorate Vermont’s many people, events, and places of regional, statewide, or national...

  17. Murine T cell activation is regulated by surfen (bis-2-methyl-4-amino-quinolyl-6-carbamide)

    Energy Technology Data Exchange (ETDEWEB)

    Warford, Jordan, E-mail: jordan.warford@dal.ca [Department of Pathology, Dalhousie University, Tupper Building, 5850 College Street, Halifax, Nova Scotia B3H 4R2 (Canada); Doucette, Carolyn D., E-mail: carolyn.doucette@dal.ca [Department of Microbiology and Immunology, Dalhousie University, Tupper Building, 5850 College Street, Halifax, Nova Scotia B3H 4R2 (Canada); Hoskin, David W., E-mail: d.w.hoskin@dal.ca [Department of Pathology, Dalhousie University, Tupper Building, 5850 College Street, Halifax, Nova Scotia B3H 4R2 (Canada); Department of Microbiology and Immunology, Dalhousie University, Tupper Building, 5850 College Street, Halifax, Nova Scotia B3H 4R2 (Canada); Easton, Alexander S., E-mail: alexander.easton@dal.ca [Department of Pathology, Dalhousie University, Tupper Building, 5850 College Street, Halifax, Nova Scotia B3H 4R2 (Canada); Department of Microbiology and Immunology, Dalhousie University, Tupper Building, 5850 College Street, Halifax, Nova Scotia B3H 4R2 (Canada); Department of Surgery (Neurosurgery), Dalhousie University, Tupper Building, 5850 College Street, Halifax, Nova Scotia B3H 4R2 (Canada)

    2014-01-10

    Highlights: •Surfen is the first inhibitor of glycosaminoglycan function to be studied in murine T cells. •Surfen reduces T cell proliferation stimulated in vitro and in vivo. •Surfen reduces CD25 expression in T cells activated in vivo but not in vitro. •Surfen increases T cell proliferation when T cell receptor activation is bypassed. •Surfen’s effects are blocked by co-administration of heparin sulfate. -- Abstract: Surfen (bis-2-methyl-4-amino-quinolyl-6-carbamide) binds to glycosaminoglycans (GAGs) and has been shown to influence their function, and the function of proteoglycans (complexes of GAGs linked to a core protein). T cells synthesize, secrete and express GAGs and proteoglycans which are involved in several aspects of T cell function. However, there are as yet no studies on the effect of GAG-binding agents such as surfen on T cell function. In this study, surfen was found to influence murine T cell activation. Doses between 2.5 and 20 μM produced a graduated reduction in the proliferation of T cells activated with anti-CD3/CD28 antibody-coated T cell expander beads. Surfen (20 mg/kg) was also administered to mice treated with anti-CD3 antibody to activate T cells in vivo. Lymphocytes from surfen-treated mice also showed reduced proliferation and lymph node cell counts were reduced. Surfen reduced labeling with a cell viability marker (7-ADD) but to a much lower extent than its effect on proliferation. Surfen also reduced CD25 (the α-subunit of the interleukin (IL)-2 receptor) expression with no effect on CD69 expression in T cells treated in vivo but not in vitro. When receptor activation was bypassed by treating T cells in vitro with phorbyl myristate acetate (10 ng/ml) and ionomycin (100 ng/ml), surfen treatment either increased proliferation (10 μM) or had no effect (2.5, 5 and 20 μM). In vitro treatment of T cells with surfen had no effect on IL-2 or interferon-γ synthesis and did not alter proliferation of the IL-2 dependent cell

  18. Whole-Body Cryotherapy Decreases the Levels of Inflammatory, Oxidative Stress, and Atherosclerosis Plaque Markers in Male Patients with Active-Phase Ankylosing Spondylitis in the Absence of Classical Cardiovascular Risk Factors

    Directory of Open Access Journals (Sweden)

    Agata Stanek

    2018-01-01

    Full Text Available Objective. The aim of the study was to estimate the impact of whole-body cryotherapy (WBC on cardiovascular risk factors in patients with ankylosing spondylitis (AS. Material and Methods. We investigated the effect of WBC with subsequent kinesiotherapy on markers of inflammation, oxidative stress, lipid profile, and atherosclerosis plaque in male AS patients (WBC group. To assess the disease activity, the BASDAI and BASFI were also calculated. The results from the WBC group were compared with results from the kinesiotherapy (KT group. Results. The results showed that in the WBC group, the plasma hsCRP level decreased without change to the IL-6 level. The ICAM-1 level showed a decreasing tendency. The CER concentration, as well as the BASDAI and BASFI, decreased in both groups, but the index changes of disease activity were higher in the WBC than KT patients. Additionally, in the WBC group, we observed a decrease in oxidative stress markers, changes in the activity of some antioxidant enzymes and nonenzymatic antioxidant parameters. In both groups, the total cholesterol and LDL cholesterol, triglycerides, sCD40L, PAPP-A, and PLGF levels decreased, but the parameter changes were higher in the WBC group. Conclusion. WBC appears to be a useful method of atherosclerosis prevention in AS patients.

  19. Tumour markers in urology

    International Nuclear Information System (INIS)

    Schmid, L.; Fornara, P.; Fabricius, P.G.

    1988-01-01

    The same applies essentially also for the bladder carcinomas: There is no reliable marker for these cancers which would be useful for clinical purposes. TPA has proven to be too non-specific in malignoma-detection and therefore hardly facilitates clinical decision-making in individual cases. The CEA is not sensitive enough to be recommendable for routine application. However, in advanced stages a CEA examination may be useful if applied within the scope of therapeutic efforts made to evaluate efficacy. In cases of carcinomas of the prostate the sour prostate-specific phosphatase (SPP) and, more recently, especially the prostate-specific antigen (PSA) have proven in follow-up and therapy monitoring, whereby the PSA is superior to the SPP. Nevertheless, both these markers should be employed in therapy monitoring because differences in behaviour will be observed when the desired treatment effect is only achieved in one of the two markers producing tumour cell clonuses. Both markers, but especially the PSA, are quite reliably in agreement with the result of the introduced chemo-/hormone therapy, whereby an increase may be a sure indicator of relapse several months previous to clinical symptoms, imaging procedures, so-called routine laboratory results and subjective complaints. However, none of the 2 markers is appropriate for the purposes of screening or early diagnosis of carcinomas of the prostate. (orig.) [de

  20. [Activation of peripheral T lymphocytes in children with epilepsy and production of cytokines].

    Science.gov (United States)

    Yang, Jie; Hu, Chongkang; Jiang, Xun

    2016-09-01

    Objective To study the state of peripheral T lymphocytes and cytokine levels in children with epilepsy. Methods Twenty children with epilepsy and 20 healthy age-matched children were recruited and their peripheral blood was collected. The activation of T lymphocytes was evaluated by detecting the expressions of CD25, CD69 and cytotoxic T lymphocyte-assicated antigen 4 (CTLA4). The function of T lymphocytes was evaluated by detecting the expressions of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), IL-17A and IL-6. The activation of regulatory T cells (Tregs) was evaluated by detecting the expression of IL-10. Results Children with epilepsy had higher expressions of CD25, CD69 and CTLA-4 in T lymphocytes than the controls did. The expressions of IFN-γ, TNF-α, IL-17A and IL-6 in T lymphocytes of children with epilepsy were higher than those of the controls. Frequency of Tregs producing IL-10 was higher in children with epilepsy as compared with the controls. Conclusion Peripheral T lymphocytes of children with epilepsy are activated and produce cytokines.

  1. The Role of Apoptosis Associated Markers in Pathogenesis of Pulmonary Tuberculosis

    Science.gov (United States)

    2012-08-28

    To Compare the Serum Apoptosis-associated Markers Between Patients With Active TB and Patients With LTBI; To Evaluate the Efficiency of Apoptosis-associated Markers to Differentiate Potential of Active TB From LTBI

  2. The long-term effects of pitavastatin on blood lipids and platelet activation markers in stroke patients: impact of the homocysteine level.

    Directory of Open Access Journals (Sweden)

    Hideki Sugimoto

    Full Text Available To examine the impact of the plasma homocysteine level on the anti-atherosclerotic effects of pitavastatin treatment, we retrospectively examined 59 patients who had a history of stroke and had been prescribed pitavastatin for the treatment of dyslipidemia at the Neurology department of Toho University Ohashi Medical Center Hospital. The patients were classified into two groups according to their homocysteine levels. Carotid artery plaque progression was determined before and after pitavastatin treatment. Plasma levels of high-sensitivity C-reactive protein, platelet molecular markers, and von Willebrand factor were measured. Pitavastatin treatment had beneficial effects on the lipid profiles of these patients and slowed atherosclerosis progression. These effects were observed in both the high and low homocysteine groups. Proactive lipid intervention using pitavastatin may inhibit the progression of atherosclerosis and contribute to secondary prevention of stroke in high-risk patients. We conclude that this statin could inhibit progression at any stage of disease and should therefore be proactively administered to these patient groups, regardless of disease severity.

  3. The Swift Turbidity Marker

    Science.gov (United States)

    Omar, Ahmad Fairuz; MatJafri, Mohd Zubir

    2011-01-01

    The Swift Turbidity Marker is an optical instrument developed to measure the level of water turbidity. The components and configuration selected for the system are based on common turbidity meter design concepts but use a simplified methodology to produce rapid turbidity measurements. This work is aimed at high school physics students and is the…

  4. Paleoreconstruction by biological markers

    Energy Technology Data Exchange (ETDEWEB)

    Seifert, W K; Moldowan, J M

    1981-06-01

    During diagenesis and conversion of the original lipid fraction of biological systems to petroleum hydrocarbons, the following four basic events needed for paleoreconstruction may be monitored by biological markers: (1) sourcing, (2) maturation, (3) migration and (4) biodegradation. Actual cases of applying biological markers to petroleum exploration problems in different parts of the world are demonstrated. Cretaceous- and Phosphoria-sourced oils in the Wyoming Thrust Belt can be distinguished from one another by high quality source fingerprinting of biomarker terpanes using gas chromatography mass spectrometry. Identification of recently discovered biological markers, head-to-head isoprenoids, allows source differentiation between some oils from Sumatra. The degree of crude oil maturation in basins from California, Alaska, Russia, Wyoming and Louisiana can be assessed by specific biomarker ratios (20S/20R sterane epimers). Field evidence from such interpretation is augmented by laboratory pyrolysis of the rock. Extensive migration is documented by biomarkers in several oils. Biological marker results are consistent with the geological setting and add a dimension in assisting the petroleum explorationist towar paleoreconstruction.

  5. Magik Markers Trehvis

    Index Scriptorium Estoniae

    2008-01-01

    Müra-rock'i viljelevast USA duost Magik Markers (ansambel osaleb režissöör Veiko Õunapuu uue mängufilmi "Püha Tõnu kiusamine" võtetel, kontsert 15. nov. Tartus klubis Trehv, vt. www.magikmarkers.audiosport.org.)

  6. Activation of Human Peripheral Blood Eosinophils by Cytokines in a Comparative Time-Course Proteomic/Phosphoproteomic Study.

    Science.gov (United States)

    Soman, Kizhake V; Stafford, Susan J; Pazdrak, Konrad; Wu, Zheng; Luo, Xuemei; White, Wendy I; Wiktorowicz, John E; Calhoun, William J; Kurosky, Alexander

    2017-08-04

    Activated eosinophils contribute to airway dysfunction and tissue remodeling in asthma and thus are considered to be important factors in asthma pathology. We report here comparative proteomic and phosphoproteomic changes upon activation of eosinophils using eight cytokines individually and in selected cytokine combinations in time-course reactions. Differential protein and phosphoprotein expressions were determined by mass spectrometry after 2-dimensional gel electrophoresis (2DGE) and by LC-MS/MS. We found that each cytokine-stimulation produced significantly different changes in the eosinophil proteome and phosphoproteome, with phosphoproteomic changes being more pronounced and having an earlier onset. Furthermore, we observed that IL-5, GM-CSF, and IL-3 showed the greatest change in protein expression and phosphorylation, and this expression differed markedly from those of the other five cytokines evaluated. Comprehensive univariate and multivariate statistical analyses were employed to evaluate the comparative results. We also monitored eosinophil activation using flow cytometry (FC) analysis of CD69. In agreement with our proteomic studies, FC indicated that IL-5, GM-CSF, and IL-3 were more effective than the other five cytokines studied in stimulating a cell surface CD69 increase indicative of eosinophil activation. Moreover, selected combinations of cytokines revealed proteomic patterns with many proteins in common with single cytokine expression patterns but also showed a greater effect of the two cytokines employed, indicating a more complex signaling pathway that was reflective of a more typical inflammatory pathology.

  7. Functional activity of the adrenal glands and abdominal obesity index as markers of dyslipidemia in patients with diabetes mellitus type 2

    Directory of Open Access Journals (Sweden)

    Олеся Вадимівна Корпачева-Зінич

    2015-10-01

    Full Text Available Cortisol and DHEA disbalance that appears in patients with diabetes mellitus type 2 leads to certain metabolic changes especially hyperglycemia, dyslipidemia, accumulation of abdominal fats, increase of proteins decay.Aim. The study of correlations between cortisol/DHEA ratio, constitutional parameters (degree of obesity, character of fat distribution, abdominal obesity index, rates of blood lipid spectrum in patients with diabetes mellitus (DM type 2.Methods. For this aim there were examined 19 patients with DM type 2. There were used general clinical (body mass, height, waist and hips size, body mass and visceral obesity indices, biochemical (glycemia level, blood serum lipid spectrum rates, hormonal (C-peptide, cortisol, dehydroepiandrosterone sulfate and statistical (Student criterion methods of research.Results. There was established that increase of cortisol/DHEA ratio rate is followed with growth of glycemia and glycated hemoglobin ( HbA1c levels and also has a negative influence on blood serum lipid spectrum, that is favors an increase of triglycerindes, atherogenic fractions of cholesterol lipoproteins of the low density (LPLD and lipoproteins of the very low density (LPVLD concentration, decrease of anti-atherogenic lipoproteins of the high density (LPHD content at the stable C-peptide level. The aforesaid negative processes took place simultaneously with the changes of visceral obesity index (VOI that includes both the character of distribution and the function of adipose tissue.Conclusion. Calculation of VOI in patients with diabetes mellitus type 2 as the marker of lipid metabolism disorder and stress/anti-stress corticosteroid disbalance is useful and reasonable

  8. Xanthine Oxidase Activity Is Associated with Risk Factors for Cardiovascular Disease and Inflammatory and Oxidative Status Markers in Metabolic Syndrome: Effects of a Single Exercise Session

    Directory of Open Access Journals (Sweden)

    Ana Maria Pandolfo Feoli

    2014-01-01

    Full Text Available Objective. The main goal of the present study was to investigate the xanthine oxidase (XO activity in metabolic syndrome in subjects submitted to a single exercise session. We also investigated parameters of oxidative and inflammatory status. Materials/Methods. A case-control study (9 healthy and 8 MS volunteers was performed to measure XO, superoxide dismutase (SOD, glutathione peroxidase activities, lipid peroxidation, high-sensitivity C-reactive protein (hsCRP content, glucose levels, and lipid profile. Body mass indices, abdominal circumference, systolic and diastolic blood pressure, and TG levels were also determined. The exercise session consisted of 3 minutes of stretching, 3 minutes of warm-up, 30 minutes at a constant dynamic workload at a moderate intensity, and 3 minutes at a low speed. The blood samples were collected before and 15 minutes after the exercise session. Results. Serum XO activity was higher in MS group compared to control group. SOD activity was lower in MS subjects. XO activity was correlated with SOD, abdominal circumference, body mass indices, and hsCRP. The single exercise session reduced the SOD activity in the control group. Conclusions. Our data support the association between oxidative stress and risk factors for cardiovascular diseases and suggest XO is present in the pathogenesis of metabolic syndrome.

  9. Xanthine oxidase activity is associated with risk factors for cardiovascular disease and inflammatory and oxidative status markers in metabolic syndrome: effects of a single exercise session.

    Science.gov (United States)

    Feoli, Ana Maria Pandolfo; Macagnan, Fabrício Edler; Piovesan, Carla Haas; Bodanese, Luiz Carlos; Siqueira, Ionara Rodrigues

    2014-01-01

    The main goal of the present study was to investigate the xanthine oxidase (XO) activity in metabolic syndrome in subjects submitted to a single exercise session. We also investigated parameters of oxidative and inflammatory status. A case-control study (9 healthy and 8 MS volunteers) was performed to measure XO, superoxide dismutase (SOD), glutathione peroxidase activities, lipid peroxidation, high-sensitivity C-reactive protein (hsCRP) content, glucose levels, and lipid profile. Body mass indices, abdominal circumference, systolic and diastolic blood pressure, and TG levels were also determined. The exercise session consisted of 3 minutes of stretching, 3 minutes of warm-up, 30 minutes at a constant dynamic workload at a moderate intensity, and 3 minutes at a low speed. The blood samples were collected before and 15 minutes after the exercise session. Serum XO activity was higher in MS group compared to control group. SOD activity was lower in MS subjects. XO activity was correlated with SOD, abdominal circumference, body mass indices, and hsCRP. The single exercise session reduced the SOD activity in the control group. Our data support the association between oxidative stress and risk factors for cardiovascular diseases and suggest XO is present in the pathogenesis of metabolic syndrome.

  10. Quality and land use for a sustainable development: bio markers for the soil microbial activity; Calidad y uso del suelo para un desarrollo sostenible: importancia de biomarcadores de la actividad microbiana del suelo

    Energy Technology Data Exchange (ETDEWEB)

    Garcia Izquierdo, C.

    1996-12-01

    Nowadays, to define and assess criteria of soil quality is acquiring an increasingly interest since it will allow to know th influence of different land uses on soil quality. It is so necessary to establish a minimum set of parameters, related with physical, chemical, biological and biochemical properties of soils, which measurement allows us to know the level of quality of a soil. Among the different soil parameters liable to be measured, those which are bio markers of soil microbial activity are, due to their sensitivity, the most useful to know in a quick and effective way the changes brought about in soil quality by soil management. This will help to take decisions on the most sustainable land uses in order to maintain a soil sustainable productivity. (Author) 11 refs.

  11. The urine marker test

    DEFF Research Database (Denmark)

    Elbe, Anne-Marie; Jensen, Stine Nylandsted; Elsborg, Peter

    2016-01-01

    BACKGROUND: Urine sample collection for doping control tests is a key component of the World Anti-Doping Agency's fight against doping in sport. However, a substantial number of athletes experience difficulty when having to urinate under supervision. Furthermore, it cannot always be ensured...... that athletes are actually delivering their own urine. A method that can be used to alleviate the negative impact of a supervised urination procedure and which can also identify urine as coming from a specific athlete is the urine marker test. Monodisperse low molecular weight polyethylene glycols (PEGs......) are given orally prior to urination. Urine samples can be traced to the donor by analysis of the PEGs previously given. OBJECTIVE: The objective of this study was to investigate the use of the urine marker during urine doping control testing. METHODS: Two studies investigated athletes' acceptance...

  12. Immunoliposome-mediated delivery of neomycin phosphotransferase for the lineage-specific selection of differentiated/committed stem cell progenies: potential advantages over transfection with marker genes, fluorescence-activated and magnetic affinity cell-sorting.

    Science.gov (United States)

    Heng, Boon Chin; Cao, Tong

    2005-01-01

    A major challenge in the therapeutic application of stem cells in regenerative medicine is the lineage-specific selection of their committed/differentiated progenies for transplantation. This is necessary to avoid engraftment of undesired lineages at the transplantation site, i.e. fibroblastic scar tissue, as well as to enhance the efficacy of transplantation therapy. Commonly used techniques for lineage-specific selection of committed/differentiated stem cell progenies include marker gene transfection, fluorescence-activated (FACS) and magnetic-affinity (MACS) cell-sorting. Nevertheless, these have their disadvantages for therapeutic applications. Marker gene transfection invariably leads to permanent genetic modification of stem cells, which in turn limits their use in human clinical therapy due to overwhelming ethical and safety concerns. FACS requires expensive instrumentation and highly-skilled personnel, and is unsuited for handling bulk quantities of cells that would almost certainly be required for transplantation therapy. MACS is a cheaper alternative, but the level of purity attained is also reduced. A possible novel approach that has yet to be investigated is immunoliposome-mediated delivery of neomycin phosphotranferase (NPT) for lineage-specific selection of stem cell progenies. This would avoid permanent genetic modification to the cell, unlike recombinant NPT expression linked to activation of specific promoter sequences. Moreover, it could potentially provide a much more practical and cost-effective alternative for handling bulk quantities of cells that would be required for transplantation therapy, as compared to FACS or MACS. As such, this alternative approach needs to be rigorously investigated, in view of its potentially useful applications in stem cell therapeutics.

  13. Prognostic molecular markers in early breast cancer

    International Nuclear Information System (INIS)

    Esteva, Francisco J; Hortobagyi, Gabriel N

    2004-01-01

    A multitude of molecules involved in breast cancer biology have been studied as potential prognostic markers. In the present review we discuss the role of established molecular markers, as well as potential applications of emerging new technologies. Those molecules used routinely to make treatment decisions in patients with early-stage breast cancer include markers of proliferation (e.g. Ki-67), hormone receptors, and the human epidermal growth factor receptor 2. Tumor markers shown to have prognostic value but not used routinely include cyclin D 1 and cyclin E, urokinase-like plasminogen activator/plasminogen activator inhibitor, and cathepsin D. The level of evidence for other molecular markers is lower, in part because most studies were retrospective and not adequately powered, making their findings unsuitable for choosing treatments for individual patients. Gene microarrays have been successfuly used to classify breast cancers into subtypes with specific gene expression profiles and to evaluate prognosis. RT-PCR has also been used to evaluate expression of multiple genes in archival tissue. Proteomics technologies are in development

  14. Time resolved amplified FRET identifies protein kinase B activation state as a marker for poor prognosis in clear cell renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    James Miles

    2017-12-01

    General significance: The quantitative imaging technology based on Amplified-FRET can rapidly analyse protein activation states and molecular interactions. It could be used for prognosis and assess drug function during the early cycles of chemotherapy. It enables evaluation of clinical efficiency of personalised cancer treatment.

  15. From Cocoa to Chocolate: The Impact of Processing on In Vitro Antioxidant Activity and the Effects of Chocolate on Antioxidant Markers In Vivo

    Directory of Open Access Journals (Sweden)

    Carla D. Di Mattia

    2017-09-01

    Full Text Available Chocolate is a product processed from cocoa rich in flavonoids, antioxidant compounds, and bioactive ingredients that have been associated with both its healthy and sensory properties. Chocolate production consists of a multistep process which, starting from cocoa beans, involves fermentation, drying, roasting, nib grinding and refining, conching, and tempering. During cocoa processing, the naturally occurring antioxidants (flavonoids are lost, while others, such as Maillard reaction products, are formed. The final content of antioxidant compounds and the antioxidant activity of chocolate is a function of several variables, some related to the raw material and others related to processing and formulation. The aim of this mini-review is to revise the literature on the impact of full processing on the in vitro antioxidant activity of chocolate, providing a critical analysis of the implications of processing on the evaluation of the antioxidant effect of chocolate in in vivo studies in humans.

  16. From Cocoa to Chocolate: The Impact of Processing on In Vitro Antioxidant Activity and the Effects of Chocolate on Antioxidant Markers In Vivo.

    Science.gov (United States)

    Di Mattia, Carla D; Sacchetti, Giampiero; Mastrocola, Dino; Serafini, Mauro

    2017-01-01

    Chocolate is a product processed from cocoa rich in flavonoids, antioxidant compounds, and bioactive ingredients that have been associated with both its healthy and sensory properties. Chocolate production consists of a multistep process which, starting from cocoa beans, involves fermentation, drying, roasting, nib grinding and refining, conching, and tempering. During cocoa processing, the naturally occurring antioxidants (flavonoids) are lost, while others, such as Maillard reaction products, are formed. The final content of antioxidant compounds and the antioxidant activity of chocolate is a function of several variables, some related to the raw material and others related to processing and formulation. The aim of this mini-review is to revise the literature on the impact of full processing on the in vitro antioxidant activity of chocolate, providing a critical analysis of the implications of processing on the evaluation of the antioxidant effect of chocolate in in vivo studies in humans.

  17. Impact of Combined Prenatal Ethanol and Prenatal Stress Exposures on Markers of Activity-Dependent Synaptic Plasticity in Rat Dentate Gyrus

    OpenAIRE

    Staples, Miranda C.; Porch, Morgan W.; Savage, Daniel D.

    2014-01-01

    Prenatal ethanol exposure and prenatal stress can each cause long-lasting deficits in hippocampal synaptic plasticity and disrupt learning and memory processes. However, the mechanisms underlying these perturbations following a learning event are still poorly understood. We examined the effects of prenatal ethanol exposure and prenatal stress exposure, either alone or in combination, on the cytosolic expression of activity-regulated cytoskeletal (ARC) protein and the synaptosomal expression o...

  18. Restriction on an energy-dense diet improves markers of metabolic health and cellular aging in mice through decreasing hepatic mTOR activity.

    Science.gov (United States)

    Schloesser, Anke; Campbell, Graeme; Glüer, Claus-Christian; Rimbach, Gerald; Huebbe, Patricia

    2015-02-01

    Dietary restriction (DR) on a normal low-fat diet improves metabolic health and may prolong life span. However, it is still uncertain whether restriction of an energy-dense, high-fat diet would also be beneficial and mitigate age-related processes. In the present study, we determined biomarkers of metabolic health, energy metabolism, and cellular aging in obesity-prone mice subjected to 30% DR on a high-fat diet for 6 months. Dietary-restricted mice had significantly lower body weights, less adipose tissue, lower energy expenditure, and altered substrate oxidation compared to their ad libitum-fed counterparts. Hepatic major urinary proteins (Mup) expression, which is linked to glucose and energy metabolism, and biomarkers of metabolic health, including insulin, glucose, cholesterol, and leptin/adiponectin ratio, were likewise reduced in high-fat, dietary-restricted mice. Hallmarks of cellular senescence such as Lamp2a and Hsc70 that mediate chaperone-mediated autophagy were induced and mechanistic target of rapamycin (mTOR) signaling mitigated upon high-fat DR. In contrast to DR applied in low-fat diets, anti-oxidant gene expression, proteasome activity, as well as 5'-adenosine monophosphate-activated protein kinase (AMPK) activation were not changed, suggesting that high-fat DR may attenuate some processes associated with cellular aging without the induction of cellular stress response or energy deprivation.

  19. The non-invasive 13C-methionine breath test detects hepatic mitochondrial dysfunction as a marker of disease activity in non-alcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    Banasch M

    2012-06-01

    Full Text Available Abstract Introduction Mitochondrial dysfunction plays a central role in the general pathogenesis of non-alcoholic fatty liver disease (NAFLD, increasing the risk of developing steatosis and subsequent hepatocellular inflammation. We aimed to assess hepatic mitochondrial function by a non-invasive 13C-methionine breath test (MeBT in patients with histologically proven NAFLD. Methods 118 NAFLD-patients and 18 healthy controls were examined by MeBT. Liver biopsy specimens were evaluated according to the NASH scoring system. Results Higher grades of NASH activity and fibrosis were independently associated with a significant decrease in cumulative 13C-exhalation (expressed as cPDR(%. cPDR1.5h was markedly declined in patients with NASH and NASH cirrhosis compared to patients with simple steatosis or borderline diagnosis (cPDR1.5h: 3.24 ± 1.12% and 1.32 ± 0.94% vs. 6.36 ± 0.56% and 4.80 ± 0.88% respectively; p 13C-exhalation further declined in the presence of advanced fibrosis which was correlated with NASH activity (r = 0.36. The area under the ROC curve (AUROC for NASH diagnosis was estimated to be 0.87 in the total cohort and 0.83 in patients with no or mild fibrosis (F0-1. Conclusion The 13C-methionine breath test indicates mitochondrial dysfunction in non-alcoholic fatty liver disease and predicts higher stages of disease activity. It may, therefore, be a valuable diagnostic addition for longitudinal monitoring of hepatic (mitochondrial function in non-alcoholic fatty liver disease.

  20. Physical activity, sedentary time, and sleep and the association with inflammatory markers and adiponectin in 8- to 11-year-old Danish children

    DEFF Research Database (Denmark)

    Nielsen, Mette Søndergaard; Quist, Jonas Salling; Chaput, Jean-Philippe

    2016-01-01

    the association between accelerometer determined moderate-to-vigorous physical activity (MVPA), sedentary time, and sleep (7 days/8 nights) and fasting C-reactive protein (CRP), interleukin-6 (IL-6), and adiponectin in 806 school children. A sleep variability score was calculated. RESULTS: MVPA was negatively...... associated with adiponectin in boys and girls (Psleep duration, sedentary time, age, fat mass index (FMI), and pubertal status. Sedentary time was positively associated with adiponectin in boys and girls (both Psleep duration...... with adiponectin in boys independent of age, FMI, and pubertal status (PSleep duration variability was positively associated with CRP in girls independent of all covariates (P

  1. Tumor markers in breast cancer- European Group on Tumor Markers recommendations

    DEFF Research Database (Denmark)

    Molina, Rafael; Barak, Vivian; van Dalen, Arie

    2005-01-01

    in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin (trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node...

  2. Neuronal injury external to the retina rapidly activates retinal glia, followed by elevation of markers for cell cycle re-entry and death in retinal ganglion cells.

    Directory of Open Access Journals (Sweden)

    Alba Galan

    Full Text Available Retinal ganglion cells (RGCs are neurons that relay visual signals from the retina to the brain. The RGC cell bodies reside in the retina and their fibers form the optic nerve. Full transection (axotomy of the optic nerve is an extra-retinal injury model of RGC degeneration. Optic nerve transection permits time-kinetic studies of neurodegenerative mechanisms in neurons and resident glia of the retina, the early events of which are reported here. One day after injury, and before atrophy of RGC cell bodies was apparent, glia had increased levels of phospho-Akt, phospho-S6, and phospho-ERK1/2; however, these signals were not detected in injured RGCs. Three days after injury there were increased levels of phospho-Rb and cyclin A proteins detected in RGCs, whereas these signals were not detected in glia. DNA hyperploidy was also detected in RGCs, indicative of cell cycle re-entry by these post-mitotic neurons. These events culminated in RGC death, which is delayed by pharmacological inhibition of the MAPK/ERK pathway. Our data show that a remote injury to RGC axons rapidly conveys a signal that activates retinal glia, followed by RGC cell cycle re-entry, DNA hyperploidy, and neuronal death that is delayed by preventing glial MAPK/ERK activation. These results demonstrate that complex and variable neuro-glia interactions regulate healthy and injured states in the adult mammalian retina.

  3. Metabolic Disturbances in Liver {sup 1}H MR Spectroscopy in HIV and HCV Co-infected Patients as a Potential Marker of Hepatocyte Activation

    Energy Technology Data Exchange (ETDEWEB)

    Tarasow, E.; Wierciska-Drapao, A.; Jaroszewicz, J.; Siergiejczyk, L.; Orzechowska-Bobkiewicz, A.; Prokopowicz, D.; Walecki, J. [Medical Academy Hospital, Bialystok (Poland). Dept. of Radiology

    2004-12-01

    Purpose : To evaluate proton magnetic resonance spectroscopy ({sup 1}H MRS) features in order to assess hepatocellular activation in chronic hepatitis C and human immunodeficiency virus/hepatitis C (HIV/HCV) co-infected patients. Material and Methods : Liver in vivo {sup 1}H MR spectra were obtained in 14 patients with hepatitis C virus infection (HCV), 20 HIV/HCV co-infected individuals, and 24 healthy volunteers. Resonances of lipids, glutamine/glutamate (Glx), phosphomonoesters (PME), glycogen/glucose (Glc) were assessed and metabolite ratios to total lipids (TL) were calculated. Results : A significant increase in Glx/TL and PME/TL was observed in the HCV group as compared to healthy individuals. Patients with HIV and HCV co-infection had a further increase of all metabolite ratios. Changes in metabolite ratios were due to both the increase in particular metabolite contents and to the decrease in lipid levels. HIV/HCV-infected patients treated with highly active anti-retroviral therapy (HAART) showed elevated PME and Glx levels and significantly decreased TL compared to patients not undergoing anti-retroviral treatment. Conclusions : Our findings suggest clinical usefulness of liver {sup 1}H MR spectroscopy in detecting even slight disturbances in liver metabolism.

  4. Metabolic Disturbances in Liver 1H MR Spectroscopy in HIV and HCV Co-infected Patients as a Potential Marker of Hepatocyte Activation

    International Nuclear Information System (INIS)

    Tarasow, E.; Wierciska-Drapao, A.; Jaroszewicz, J.; Siergiejczyk, L.; Orzechowska-Bobkiewicz, A.; Prokopowicz, D.; Walecki, J.

    2004-01-01

    Purpose : To evaluate proton magnetic resonance spectroscopy ( 1 H MRS) features in order to assess hepatocellular activation in chronic hepatitis C and human immunodeficiency virus/hepatitis C (HIV/HCV) co-infected patients. Material and Methods : Liver in vivo 1 H MR spectra were obtained in 14 patients with hepatitis C virus infection (HCV), 20 HIV/HCV co-infected individuals, and 24 healthy volunteers. Resonances of lipids, glutamine/glutamate (Glx), phosphomonoesters (PME), glycogen/glucose (Glc) were assessed and metabolite ratios to total lipids (TL) were calculated. Results : A significant increase in Glx/TL and PME/TL was observed in the HCV group as compared to healthy individuals. Patients with HIV and HCV co-infection had a further increase of all metabolite ratios. Changes in metabolite ratios were due to both the increase in particular metabolite contents and to the decrease in lipid levels. HIV/HCV-infected patients treated with highly active anti-retroviral therapy (HAART) showed elevated PME and Glx levels and significantly decreased TL compared to patients not undergoing anti-retroviral treatment. Conclusions : Our findings suggest clinical usefulness of liver 1 H MR spectroscopy in detecting even slight disturbances in liver metabolism

  5. Excretion of complement proteins and its activation marker C5b-9 in IgA nephropathy in relation to renal function

    Directory of Open Access Journals (Sweden)

    Onda Kisara

    2011-11-01

    Full Text Available Abstract Background Glomerular damage in IgA nephropathy (IgAN is mediated by complement activation via the alternative and lectin pathways. Therefore, we focused on molecules stabilizing and regulating the alternative pathway C3 convertase in urine which might be associated with IgAN pathogenesis. Methods Membrane attack complex (MAC, properdin (P, factor H (fH and Complement receptor type 1 (CR1 were quantified in urine samples from 71 patients with IgAN and 72 healthy controls. Glomerular deposition of C5, fH and P was assessed using an immunofluorescence technique and correlated with histological severity of IgAN and clinical parameters. Fibrotic changes and glomerular sclerosis were evaluated in renal biopsy specimens. Results Immunofluorescence studies revealed glomerular depositions of C5, fH and P in patients with IgAN. Urinary MAC, fH and P levels in IgAN patients were significantly higher than those in healthy controls (p Conclusions Complement activation occurs in the urinary space in IgAN and the measurement of levels of MAC and fH in the urine could be a useful indicator of renal injury in patients with IgAN.

  6. The distinction between chondroma and chondrosarcoma using chemical element mass fractions in tumors determined by neutron activation analysis as diagnostic markers

    International Nuclear Information System (INIS)

    Zaichick, Vladimir; Zaichick, Sofia

    2016-01-01

    The Ca, Cl, Mg, Na, and P content and Ca/P, Ca/Mg, Ca/Na, Cl/Ca, and Cl/Na ratios in tissue of intact bone, chondroma and chondrosarcoma were investigated by neutron activation analysis. It was shown that higher mass fraction of Cl and Na and also Cl/Na mass fraction ratio as well as lower Ca/Cl and Ca/Na mass fraction ratios are typical of the chondrosarcoma tissue compared to chondroma. Finally, it was proposed to use the estimation of such parameters as the Cl mass fraction and the Ca/Cl and Ca/Na mass fraction ratios as an additional test for differential diagnosis between chondroma and chondrosarcoma. (author)

  7. Combined heart rate- and accelerometer-assessed physical activity energy expenditure and associations with glucose homeostasis markers in a population at high risk of developing diabetes

    DEFF Research Database (Denmark)

    Hansen, Anne-Louise Smidt; Carstensen, Bendix; Helge, Jørn Wulff

    2013-01-01

    OBJECTIVE: Regular physical activity (PA) reduces the risk of developing type 2 diabetes, and different subtypes of dysglycemia have shown different associations with PA. To better understand the associations of PA and glucose homeostasis, we examined the association of objectively measured PA...... energy expenditure (PAEE) with detailed measures of glucose homeostasis. RESEARCH DESIGN AND METHODS: In 1,531 men and women, with low to high risk of developing type 2 diabetes, we measured 7 days of PAEE using a combined accelerometry and heart rate monitor (ActiHeart). Measures and indices of glucose...... of PAEE slightly in an entire population at risk for developing type 2 diabetes may be a realistic and worthwhile goal to reach in order to achieve beneficial effect in terms of glucose metabolism....

  8. Emerging Role of Endothelial and Inflammatory Markers in Preeclampsia

    Directory of Open Access Journals (Sweden)

    Menha Swellam

    2009-01-01

    Full Text Available Objectives: Endothelial disturbance and excess inflammatory response are pathogenic mechanisms in pre-eclampsia (PE. Authors determine the clinical diagnostic role for thrombomodulin (TM, plasminogen activator inhibitor-1 (PAI-1 as endothelial markers and C-reactive protein (CRP, and interlukin-6 (IL-6 as inflammatory markers when tested independently or in combinations.

  9. Metabolic markers in sports medicine.

    Science.gov (United States)

    Banfi, Giuseppe; Colombini, Alessandra; Lombardi, Giovanni; Lubkowska, Anna

    2012-01-01

    be interpreted considering the athlete's body-mass index (BMI) and phase of the competitive season; use of cystatin C could be a reliable alternative to creatinine. Exercise and training induce adaptations in glucose metabolism which improve glucose utilization in athletes and are beneficial for reducing insulin insensitivity in nonathletes. Glucose metabolism differs slightly for different sports disciplines, as revealed in laboratory levels. Sport activities induce a blood lipid profile superior to that of sedentary subjects. There are few reports for a definitive conclusion, however. The differences between athletes and sedentary subjects are mainly due to high-density lipoprotein cholesterol (HDLC) concentrations in physically active individuals, although some differences among sport disciplines exist. The effect of sports on serum and urinary markers for bone metabolism is not univocal; further studies are needed to establish the real and effective influence of sport on bone turnover and especially to establish its beneficial effect.

  10. Micrologie de Chris Marker

    Directory of Open Access Journals (Sweden)

    Nicolas Geneix

    2009-10-01

    Full Text Available Abstract (E: Using "micrology", as set out by Adorno in Negative Dialectics, this paper tries to
    characterize a central feature of Chris Marker's approach, as iconographer and writer, namely the way
    in which he explores the echoes of history and culture in the singularity and rarity of the documentary.
    As traveller and photographer he catches and collects microcosmic fragments, tying them up and
    editing them in the various frames of the book, the film or the new media.
    Abstract (F: En s'appuyant sur la "micrologie" proposée par Adorno dans la Dialectique négative,
    cet article tente de caractériser un aspect de la démarche de Chris Marker, iconographe et écrivain.
    C'est en effet dans le singulier et la rareté documentaires que ce cinéaste sonde des échos historiques et
    culturels. Voyageur et photographe, il saisit et collectionne des fragments microcosmiques, les liant et
    les montant dans les cadres divers du livre, du film et des nouveaux médias.

  11. Novel marker for the onset of frontotemporal dementia: early increase in activity-dependent neuroprotective protein (ADNP in the face of Tau mutation.

    Directory of Open Access Journals (Sweden)

    Yulie Schirer

    Full Text Available Tauopathy, a major pathology in Alzheimer's disease, is also found in ~50% of frontotemporal dementias (FTDs. Tau transcript, a product of a single gene, undergoes alternative splicing to yield 6 protein species, each with either 3 or 4 microtubule binding repeat domains (tau 3R or 4R, associated with dynamic and stable microtubules, respectively. While the healthy human brain shows a 1/1 ratio of tau 3R/4R, this ratio may be dramatically changed in the FTD brain. We have previously discovered that activity-dependent neuroprotective protein (ADNP is essential for brain formation in the mouse, with ADNP+/- mice exhibiting tauopathy, age-driven neurodegeneration and behavioral deficits. Here, in transgenic mice overexpressing a mutated tau 4R species, in the cerebral cortex but not in the cerebellum, we showed significantly increased ADNP expression (~3-fold transcripts in the cerebral cortex of young transgenic mice (~disease onset, but not in the cerebellum, as compared to control littermates. The transgene-age-related increased ADNP expression paralleled augmented dynamic tau 3R transcript level compared to control littermates. Blocking mutated tau 4R transgene expression resulted in normalization of ADNP and tau 3R expression. ADNP was previously shown to be a member of the SWItch/Sucrose NonFermentable (SWI/SNF chromatin remodeling complex. Here, Brahma (Brm, a component of the SWI/SNF complex regulating alternative splicing, showed a similar developmental expression pattern to ADNP. Immunoprecipitations further suggested Brm-ADNP interaction coupled to ADNP - polypyrimidine tract-binding protein (PTB-associated splicing factor (PSF-binding, with PSF being a direct regulator of tau transcript splicing. It should be noted that although we have shown a correlation between levels of ADNP and tau isoform expression three months of age, we are not presenting evidence of a direct link between the two. Future research into ADNP/tau relations is

  12. Progressive decline in fractional anisotropy on serial DTI examinations of the corpus callosum: a putative marker of disease activity and progression in SPMS

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Wei; Zhu, Tong; Zhong, Jianhui; Liu, Xiang [University of Rochester Medical Center, Department of Imaging Sciences, Rochester, NY (United States); Rao, Praveen; Segal, Benjamin M. [University of Michigan, Department of Neurology, Holtom-Garrett Program in Neuroimmunology, Ann Arbor, MI (United States); Ekholm, Sven [University of Rochester Medical Center, Department of Imaging Sciences, Rochester, NY (United States); University of Rochester Medical Center, Division of Diagnostic and Interventional Neuroradiology, Rochester, NY (United States)

    2012-04-15

    Clinical trials of secondary progressive multiple sclerosis (SPMS) is lacking reliable biomarkers or outcome measures that reflect tissue injury incurred within a 1- to 2-year observation period. Diffusion tensor imaging (DTI) is sensitive in detecting acute brain tissue damage. We monitored SPMS patients over 12 months for diffusion changes within the corpus callosum (CC). Bimonthly MRI examinations over a 1-year period were performed on 11 SPMS patients. The protocol included postcontrast T1-weighted images and DTI. Based on the appearance of T1 enhancing lesion(s) during the study period, the patients were divided into enhancing (five patients) and nonenhancing (six patients) groups. Fractional anisotropy (FA) and mean diffusivity (MD) of the genu, body, and splenium of the CC were measured and temporal changes in mean FA and MD were evaluated for each group as well as between groups. Immunology data from peripheral blood mononuclear cells were also collected on a monthly basis. The enhancing group showed significant, progressive decrease in FA in body (p = 0.012) and splenium (p = 0.033) of CC, and significantly higher lymphotoxin-{beta} levels. No significant FA changes were seen in the nonenhancing group. Moreover, the FA decline in the enhancing group deviated significantly from the nonenhancing group, which remained essentially stable. Although MD increased slightly in both groups, there was no significant difference between the two groups. Based on the MR and immunology findings, the results of our study suggest that DTI undergo more rapid and longitudinal changes in SPMS patients with inflammatory activity. (orig.)

  13. Effects of ingesting JavaFit Energy Extreme functional coffee on aerobic and anaerobic fitness markers in recreationally-active coffee consumers

    Directory of Open Access Journals (Sweden)

    Kreider Richard B

    2007-12-01

    Full Text Available Abstract The purpose of this study was to examine the effects of ingesting JavaFit™ Energy Extreme (JEE on aerobic and anaerobic performance measures in recreationally-active male and female coffee drinkers. Five male (27.6 ± 4.2 yrs, 93.2 ± 11.7 kg, 181.6 ± 6.9 cm and five female (29 ± 4.6 yrs, 61.5 ± 9.2 kg, 167.6 ± 6.9 cm regular coffee drinkers (i.e., 223.9 ± 62.7 mg·d-1 of caffeine participated in this study. In a cross-over, randomized design, participants performed a baseline (BASELINE graded treadmill test (GXT for peak VO2 assessment and a Wingate test for peak power. Approximately 3–4 d following BASELINE testing, participants returned to the lab for the first trial and ingested 354 ml of either JEE or decaffeinated coffee (DECAF, after which they performed a GXT and Wingate test. Criterion measures during the GXT included an assessment of peakVO2 at maximal exercise, as well as VO2 at 3 minutes and 10 minutes post-exercise. Additionally, time-to-exhaustion (TTE, maximal RPE, mean heart rate (HR, mean systolic pressure (SBP, and mean diastolic blood pressure (DBP were measured during each condition. Criterion measures for the Wingate included mean HR, SBP, DBP, peak power, and time to peak power (TTP. Participants then returned to the lab approximately one week later to perform the second trial under the same conditions as the first, except consuming the remaining coffee. Data were analyzed using a one way ANOVA (p 2 at 3 minutes post-exercise when compared to BASELINE (p = 0.04 and DECAF (p = 0.02 values, which may be beneficial in enhancing post-exercise fat metabolism.

  14. Cancer and tumour markers

    International Nuclear Information System (INIS)

    Osifo, B.

    1999-02-01

    Cancer has been a major cause of death world wide and in Nigeria there are six commonest forms of manifestation of cancer known. Of these prostrate cancer is the highest with 16% occurrence of all known cancers according to a study by the Histopathology Department of the UCH. Many factors, amongst them dietary, environmental, lifestyle, age and sedentary work are possible causes. With the global rise in incidents, the IAEA initiated the Tumour Marker Project as a means of screening cancers in 15 African countries including Nigeria. In Nigeria, 4 groups of the commonest cancers have been chosen for screening. These are prostrate cancer, primary liver cancer, cancer of the GI tract and trophoblastic cancer

  15. Tumor markers in colorectal cancer

    OpenAIRE

    Fernandes, Luís César [UNIFESP; Matos, Delcio [UNIFESP

    2002-01-01

    Colorectal cancer is a clinical entity of a persistent relevance in clinical practice and its early diagnosis is a determinant factor to obtain better therapeutic results. Tumor markers are helpful means for a better approach to individuals with such neoplasm. In the present review, the authors analyze the phases in which surgical-clinical treatment markers must be used: diagnosis, determination of tumor stage, establishment of prognosis and detection of recurrence. Current and future markers...

  16. Serum markers of liver fibrosis

    DEFF Research Database (Denmark)

    Veidal, Sanne Skovgård; Bay-Jensen, Anne-Christine; Tougas, Gervais

    2010-01-01

    -epitopes, may be targeted for novel biochemical marker development in fibrosis. We used the recently proposed BIPED system (Burden of disease, Investigative, Prognostic, Efficacy and Diagnostic) to characterise present serological markers. METHODS: Pubmed was search for keywords; Liver fibrosis, neo......, a systematic use of the neo-epitope approach, i.e. the quantification of peptide epitopes generated from enzymatic cleavage of proteins during extracellular remodeling, may prove productive in the quest to find new markers of liver fibrosis....

  17. Biochemical markers of bone turnover

    International Nuclear Information System (INIS)

    Kim, Deog Yoon

    1999-01-01

    Biochemical markers of bone turnover has received increasing attention over the past few years, because of the need for sensitivity and specific tool in the clinical investigation of osteoporosis. Bone markers should be unique to bone, reflect changes of bone less, and should be correlated with radiocalcium kinetics, histomorphometry, or changes in bone mass. The markers also should be useful in monitoring treatment efficacy. Although no bone marker has been established to meet all these criteria, currently osteocalcin and pyridinium crosslinks are the most efficient markers to assess the level of bone turnover in the menopausal and senile osteoporosis. Recently, N-terminal telopeptide (NTX), C-terminal telopeptide (CTX) and bone specific alkaline phosphatase are considered as new valid markers of bone turnover. Recent data suggest that CTX and free deoxypyridinoline could predict the subsequent risk of hip fracture of elderly women. Treatment of postmenopausal women with estrogen, calcitonin and bisphosphonates demonstrated rapid decrease of the levels of bone markers that correlated with the long-term increase of bone mass. Factors such as circadian rhythms, diet, age, sex, bone mass and renal function affect the results of biochemical markers and should be appropriately adjusted whenever possible. Each biochemical markers of bone turnover may have its own specific advantages and limitations. Recent advances in research will provide more sensitive and specific assays

  18. Alteration of serum thymus and activation-regulated chemokine level during biologic therapy for psoriasis: Possibility as a marker reflecting favorable response to anti-interleukin-17A agents.

    Science.gov (United States)

    Shibuya, Takashi; Honma, Masaru; Iinuma, Shin; Iwasaki, Takeshi; Takahashi, Hidetoshi; Ishida-Yamamoto, Akemi

    2018-06-01

    Biologics show great efficacy in treating psoriasis, a chronic inflammatory skin disease. The high cost and side-effects of biologics, dose-reduction, elongation of administration interval and suspension are possible options. However, there has been no reliable biomarker we can use when we consider these moderations in therapy. This study was conducted to test the possibility of using serum thymus and activation-regulated chemokine (TARC) level as an indicator for step down of biologic therapy. Serum TARC level was measured in 70 psoriatic patients at Asahikawa Medical University, and a correlation of TARC and severity of skin lesions was analyzed. Referring to serum TARC level, psoriatic patients can be divided into two groups. One is a population in which serum TARC level is positively correlated with severity of skin lesions, and the other is a population with low psoriatic severity and high TARC level. Serum TARC level was higher in the group that achieved PASI-clear with biologics than in the group which did not achieve PASI-clear. Among biologics, the group treated with secukinumab, an anti-interleukin (IL)-17A agent, showed significantly higher TARC level compared with the group treated with anti-tumor necrosis factor agents. In certain populations achieving PASI-clear, serum TARC level may be a potent marker reflecting better response to IL-17A inhibitors, and in this case step down of treatment for psoriasis is possible. © 2018 Japanese Dermatological Association.

  19. TLA-marker for wear rate monitoring

    International Nuclear Information System (INIS)

    Stan-Sion, C.; Plostinaru, D.; Ivan, A.; Catana, M.; Roman, M.

    1992-01-01

    A very effective and promising method of wear monitoring in industry is the Thin Layer Activation (TLA) method. The main feature of this technique is the creation of thin radioactive layers on the investigated surface by irradiation of the sample with an accelerated ion beam (protons, deuterons, 3-He). In the present paper we describe an extension of the TLA-Method to produce radioactive markers to be implanted into heavy object which can hardly be transported to an accelerator for direct surface activation. The sensitivity of wear measuring is usually 1% of the actual layer thickness. It is obvious that the TLA technique has a sensitivity about two orders of magnitude higher than the activation in the bulk volume, produced in a nuclear reactor. Controlling the activation depth (80 - 250 microns) we produced different marker sets with sensitivities of 1 - 3 microns. The TLA markers were used to measure the wear rate of railway-car brake disks and of the railroad. The measured data were corroborated with other physical parameters of interest. (Author)

  20. TLA-marker for wear rate monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Stan-Sion, C; Plostinaru, D; Ivan, A [Institute of Atomic Physics, Institute of Physics and Nuclear Engineering, R-76900 Bucharest, P.O.Box MG-6, (Romania); Catana, M; Roman, M [Institute for Research and Design in Transportation, Bucharest, (Romania)

    1992-01-01

    A very effective and promising method of wear monitoring in industry is the Thin Layer Activation (TLA) method. The main feature of this technique is the creation of thin radioactive layers on the investigated surface by irradiation of the sample with an accelerated ion beam (protons, deuterons, 3-He). In the present paper we describe an extension of the TLA-Method to produce radioactive markers to be implanted into heavy object which can hardly be transported to an accelerator for direct surface activation. The sensitivity of wear measuring is usually 1% of the actual layer thickness. It is obvious that the TLA technique has a sensitivity about two orders of magnitude higher than the activation in the bulk volume, produced in a nuclear reactor. Controlling the activation depth (80 - 250 microns) we produced different marker sets with sensitivities of 1 - 3 microns. The TLA markers were used to measure the wear rate of railway-car brake disks and of the railroad. The measured data were corroborated with other physical parameters of interest. (Author).

  1. Tumor markers in clinical oncology

    International Nuclear Information System (INIS)

    Novakovic, S.

    2004-01-01

    The subtle differences between normal and tumor cells are exploited in the detection and treatment of cancer. These differences are designated as tumor markers and can be either qualitative or quantitative in their nature. That means that both the structures that are produced by tumor cells as well as the structures that are produced in excessive amounts by host tissues under the influence of tumor cells can function as tumor markers. Speaking in general, the tumor markers are the specific molecules appearing in the blood or tissues and the occurrence of which is associated with cancer. According to their application, tumor markers can be roughly divided as markers in clinical oncology and markers in pathology. In this review, only tumor markers in clinical oncology are going to be discussed. Current tumor markers in clinical oncology include (i) oncofetal antigens, (ii) placental proteins, (iii) hormones, (iv) enzymes, (v) tumor-associated antigens, (vi) special serum proteins, (vii) catecholamine metabolites, and (viii) miscellaneous markers. As to the literature, an ideal tumor marker should fulfil certain criteria - when using it as a test for detection of cancer disease: (1) positive results should occur in the early stages of the disease, (2) positive results should occur only in the patients with a specific type of malignancy, (3) positive results should occur in all patients with the same malignancy, (4) the measured values should correlate with the stage of the disease, (5) the measured values should correlate to the response to treatment, (6) the marker should be easy to measure. Most tumor markers available today meet several, but not all criteria. As a consequence of that, some criteria were chosen for the validation and proper selection of the most appropriate marker in a particular malignancy, and these are: (1) markers' sensitivity, (2) specificity, and (3) predictive values. Sensitivity expresses the mean probability of determining an elevated tumor

  2. Salivary exoglycosidases as markers of alcohol dependence.

    Science.gov (United States)

    Waszkiewicz, Napoleon; Chojnowska, Sylwia; Zalewska, Anna; Zwierz, Krzysztof; Szulc, Agata; Szajda, Sławomir Dariusz

    2014-01-01

    Some salivary markers of alcohol abuse/dependence have been proposed so far: aminotransferases, gamma-glutamyltransferase, ethanol, ethyl glucuronide, ethyl sulfate, sialic acid, β-hexosaminidase A, oral peroxidase, methanol, diethylene/ethylene glycol, α-amylase, clusterin, haptoglobin, heavy/light chains of immunoglobulins and transferrin. To investigate the effect of chronic alcohol drinking and smoking on the activity (pKat/ml) and output (pKat/min) of salivary lysosomal exoglycosidases: α-fucosidase (FUC), α-mannosidase (MAN), β-galactosidase (GAL), and β-glucuronidase (GLU), and their applicability as markers of alcohol dependence. The activity of FUC, MAN, GAL and GLU was measured colorimetrically in the saliva of healthy social drinkers, alcohol-dependent non-smokers and alcohol-dependent smokers. We observed an increased salivary activity of FUC, GAL, GLU and MAN, as well as an increased output of GAL and GLU, in comparison with controls. The highest increase in the activity/output was found in salivary GLU and MAN (GLU, even 7- to 18-fold), and the least in GAL. We found an excellent sensitivity and specificity and a high accuracy (measured by the area under the ROC curve) for salivary FUC, GLU and MAN activities. The salivary GLU activity positively correlated with the number of days of last alcohol intoxication. Salivary activity of FUC, GAL and MAN, but not GLU, positively correlated with the periodontal parameters such as gingival index and papilla bleeding index. Although we found an excellent sensitivity and specificity as well as a high accuracy for the salivary activity of FUC, GLU and MAN, the GLU activity seems to be mostly applicable as a marker of chronic alcohol drinking (alcohol dependence). © The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  3. GH activity and markers of inflammation

    DEFF Research Database (Denmark)

    Andreassen, Mikkel; Frystyk, Jan; Faber, Jens

    2012-01-01

    The GH/IGF1 axis may modulate inflammatory processes. However, the relationship seems complicated as both pro- and anti-inflammatory effects have been demonstrated.......The GH/IGF1 axis may modulate inflammatory processes. However, the relationship seems complicated as both pro- and anti-inflammatory effects have been demonstrated....

  4. Marker Detection in Aerial Images

    KAUST Repository

    Alharbi, Yazeed

    2017-04-09

    The problem that the thesis is trying to solve is the detection of small markers in high-resolution aerial images. Given a high-resolution image, the goal is to return the pixel coordinates corresponding to the center of the marker in the image. The marker has the shape of two triangles sharing a vertex in the middle, and it occupies no more than 0.01% of the image size. An improvement on the Histogram of Oriented Gradients (HOG) is proposed, eliminating the majority of baseline HOG false positives for marker detection. The improvement is guided by the observation that standard HOG description struggles to separate markers from negatives patches containing an X shape. The proposed method alters intensities with the aim of altering gradients. The intensity-dependent gradient alteration leads to more separation between filled and unfilled shapes. The improvement is used in a two-stage algorithm to achieve high recall and high precision in detection of markers in aerial images. In the first stage, two classifiers are used: one to quickly eliminate most of the uninteresting parts of the image, and one to carefully select the marker among the remaining interesting regions. Interesting regions are selected by scanning the image with a fast classifier trained on the HOG features of markers in all rotations and scales. The next classifier is more precise and uses our method to eliminate the majority of the false positives of standard HOG. In the second stage, detected markers are tracked forward and backward in time. Tracking is needed to detect extremely blurred or distorted markers that are missed by the previous stage. The algorithm achieves 94% recall with minimal user guidance. An average of 30 guesses are given per image; the user verifies for each whether it is a marker or not. The brute force approach would return 100,000 guesses per image.

  5. The Infinitive Marker across Scandinavian

    DEFF Research Database (Denmark)

    Christensen, Ken Ramshøj

    2007-01-01

    In this paper I argue that the base-position of the infinitive marker in the Scandinavian languages and English share a common origin site. It is inserted as the top-most head in the VP-domain. The cross-linguistic variation in the syntactic distribution of the infinitive marker can be accounted...

  6. Prepuberal stimulation of 5-HT7-R by LP-211 in a rat model of hyper-activity and attention-deficit: permanent effects on attention, brain amino acids and synaptic markers in the fronto-striatal interface.

    Directory of Open Access Journals (Sweden)

    Lucia A Ruocco

    Full Text Available The cross-talk at the prefronto-striatal interface involves excitatory amino acids, different receptors, transducers and modulators. We investigated long-term effects of a prepuberal, subchronic 5-HT7-R agonist (LP-211 on adult behaviour, amino acids and synaptic markers in a model for Attention-Deficit/Hyperactivity Disorder (ADHD. Naples High Excitability rats (NHE and their Random Bred controls (NRB were daily treated with LP-211 in the 5th and 6th postnatal week. One month after treatment, these rats were tested for indices of activity, non selective (NSA, selective spatial attention (SSA and emotionality. The quantity of L-Glutamate (L-Glu, L-Aspartate (L-Asp and L-Leucine (L-Leu, dopamine transporter (DAT, NMDAR1 subunit and CAMKIIα, were assessed in prefrontal cortex (PFC, dorsal (DS and ventral striatum (VS, for their role in synaptic transmission, neural plasticity and information processing. Prepuberal LP-211 (at lower dose reduced horizontal activity and (at higher dose increased SSA, only for NHE but not in NRB rats. Prepuberal LP-211 increased, in NHE rats, L-Glu in the PFC and L-Asp in the VS (at 0.250 mg/kg dose, whereas (at 0.125 mg/kg dose it decreased L-Glu and L-Asp in the DS. The L-Glu was decreased, at 0.125 mg/kg, only in the VS of NRB rats. The DAT levels were decreased with the 0.125 mg/kg dose (in the PFC, and increased with the 0.250 mg/kg dose (in the VS, significantly for NHE rats. The basal NMDAR1 level was higher in the PFC of NHE than NRB rats; LP-211 treatment (at 0.125 mg/kg dose decreased NMDAR1 in the VS of NRB rats. This study represents a starting point about the impact of developmental 5-HT7-R activation on neuro-physiology of attentive processes, executive functions and their neural substrates.

  7. C-reactive protein in patients with acute coronary syndrome: association with coronary markers, lipid profile and markers of coagulation

    International Nuclear Information System (INIS)

    Munir, T.A.; Afzal, M.N.

    2010-01-01

    To determine levels of C-reactive protein (CRP) and its association with coronary markers, lipid profile and markers of coagulation in patients of acute coronary syndrome (ACS). The study was conducted at Shifa college of Medicine and Shifa international hospital for a period of one year (November 2005-December 2006). Patients and Methods: Sixty nine age matched controls and 133 consecutive patients of ACS were included in the study. CRP were measured by immunoturbidometric method, MB fraction of creatine kinase (CK-MB) and Troponin-1 by micro-particle enzyme immunoassay, lipid levels by Colorimetric Enzymatic methods, platelets by celldyn and coagulation markers were measured by CA-50 Sysmax. At admission mean CRP levels, cardiac biomarkers, lipid profile and coagulation markers were significantly increased in patients of ACS versus controls. Within the patients of ACS the mean levels of CRP, CK-MB, Trop I, prothrombin time (PT) and activated partial thromboplastin time (Am) were significantly raised in patients with ST - elevation myocardial infarction (STEMI) and non STEMI (NSTEMI) versus patients of unstable angina (VA). Association between CRP levels and coronary markers, coagulation markers and lipid profile was found to be non significant. The CRP levels were increased in patients with ACS as compared to controls. The CRP levels were insignificantly correlated with coronary markers (CK-MB, Trop I), coagulation markers (platelet count, PT, Am), and lipid profile (cholesterol, triglyceride, HDL and LDL cholesterol) in patients with ACS. (author)

  8. Deficits in Processing Case Markers in Individuals with Aphasia

    Directory of Open Access Journals (Sweden)

    Jee Eun Sung

    2015-04-01

    Individuals with aphasia demonstrated greater difficulties in the case marker assignment compared to their normal control group. Furthermore, noncanonical word-order and passive sentences elicited more errors on the task than canonical and active sentences. Passive sentences were the significant predictors for overall aphasia severity. The results suggested that PWA using a verb-final language with well-developed case-marking systems presented deficits in case marker processing. The syntactic structure and canonicity of word order need to be considered as critical linguistic features in testing their performance on dealing with case markers.

  9. Significance Of Immunohistochemical Markers In Diagnostics Of Urinary Bladder Cancer

    Directory of Open Access Journals (Sweden)

    A.V. Medvedeva

    2009-12-01

    Full Text Available On the basis of surgical and biopsy material 106 patients with diseases of urinary bladder have been under study. They received treatment at Scientific Research Institute of Fundamental and Clinical Uronephrology of Saratov State Medical University. 13 immunohistochemical markers have been evaluated: markers of proliferative activity - Ki-67, PCNA, p63, suppressor of tumor growth - p53, markers of apoptosis - Bcl-2, Bax, receptor of epidermal growth factors - EGFR, cytokeratin profile - (CK7, CK8, CK10/13, CK 17, CK18, CK19, as well as their diagnostic significance for identifying the urinary bladder cancer

  10. [Markers of angiogenesis in tumor growth].

    Science.gov (United States)

    Nefedova, N A; Kharlova, O A; Danilova, N V; Malkov, P G; Gaifullin, N M

    2016-01-01

    Angiogenesis is a process of new blood vessels formation. The role of angiogenesis in growth, invasion and metastasis of malignant tumours is nowdays universally recognized. Though, investigation of mechanisms of blood vessels formation and elaboration methods for assessment of tumour angiogenesis are still up-dated. Another important concern are different aspects of usage of immunohistochemical markers of blood vessels endothelium (CD31 and CD34) for assessment of tumour aggressiveness and prognosis. The problems of malignant lymphangiogenesis are also up-to-date. The focus is on methods of immunohistochemical visualization of forming lymphatic vessels, role of podoplanin, the most reliable marker of lymphatic vessels, in their identification, and formulization of the main criteria for lymphangiogenesis estimation, its correlation with metastatic activity and prognostic potential. Studying of angiogenesis and lymph angiogenesis in malignant tumors is important and challenging direction for researching tumour progression and invention of antiangiogenic therapy.

  11. Prenatal Screening Using Maternal Markers

    Directory of Open Access Journals (Sweden)

    Howard Cuckle

    2014-05-01

    Full Text Available Maternal markers are widely used to screen for fetal neural tube defects (NTDs, chromosomal abnormalities and cardiac defects. Some are beginning to broaden prenatal screening to include pregnancy complications such as pre-eclampsia. The methods initially developed for NTDs using a single marker have since been built upon to develop high performance multi-maker tests for chromosomal abnormalities. Although cell-free DNA testing is still too expensive to be considered for routine application in public health settings, it can be cost-effective when used in combination with existing multi-maker marker tests. The established screening methods can be readily applied in the first trimester to identify pregnancies at high risk of pre-eclampsia and offer prevention though aspirin treatment. Prenatal screening for fragile X syndrome might be adopted more widely if the test was to be framed as a form of maternal marker screening.

  12. Fasting enhances TRAIL-mediated liver natural killer cell activity via HSP70 upregulation.

    Directory of Open Access Journals (Sweden)

    Vu T A Dang

    Full Text Available Acute starvation, which is frequently observed in clinical practice, sometimes augments the cytolytic activity of natural killer cells against neoplastic cells. In this study, we investigated the molecular mechanisms underlying the enhancement of natural killer cell function by fasting in mice. The total number of liver resident natural killer cells in a unit weight of liver tissue obtained from C57BL/6J mice did not change after a 3-day fast, while the proportions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL+ and CD69+ natural killer cells were significantly elevated (n = 7, p <0.01, as determined by flow cytometric analysis. Furthermore, we found that TRAIL- natural killer cells that were adoptively transferred into Rag-2-/- γ chain-/- mice could convert into TRAIL+ natural killer cells in fasted mice at a higher proportion than in fed mice. Liver natural killer cells also showed high TRAIL-mediated antitumor function in response to 3-day fasting. Since these fasted mice highly expressed heat shock protein 70 (n = 7, p <0.05 in liver tissues, as determined by western blot, the role of this protein in natural killer cell activation was investigated. Treatment of liver lymphocytes with 50 µg/mL of recombinant heat shock protein 70 led to the upregulation of both TRAIL and CD69 in liver natural killer cells (n = 6, p <0.05. In addition, HSP70 neutralization by intraperitoneally injecting an anti- heat shock protein 70 monoclonal antibody into mice prior to fasting led to the downregulation of TRAIL expression (n = 6, p <0.05. These findings indicate that acute fasting enhances TRAIL-mediated liver natural killer cell activity against neoplastic cells through upregulation of heat shock protein 70.

  13. Criteria for selection and application of molecular markers for clinical studies of osteoarthritis.

    Science.gov (United States)

    Otterness, I G; Swindell, A C

    2003-03-01

    To develop criteria for the selection and application of molecular markers for the study of osteoarthritis (OA). Statistical criteria for marker selection for OA are developed. After studying more than 20 different molecular markers for monitoring OA, procedures for choosing markers for clinical studies have been developed. For a particular study, the process starts with the markers showing 'face-validity' for monitoring OA. They are next required to successfully distinguish OA patients from controls. This necessitates definition of the distribution of marker values in OA patients and controls. So far, they have been consistently log-normal. The difference (Delta) in marker values between OA and controls defines the opportunity for marker improvement. The between-visit standard deviation (S) in patients puts limits on the detection of marker changes. The two variables can be combined to estimate the practicality of a marker using a modified power analysis. The number of patients (N*) required to observe a 50% improvement with an alpha level of P=0.05 and with 80% certainty is estimated as 50(S/Delta)(2). N*, S and Delta should be used to characterize and compare markers. Marker efficiency can be refined by regressing on secondary variables, such as age, sex, BMI, severity, etc. Finally, the use of two or more markers may be required to improve marker prediction of clinical outcome. Correlated markers can be used to reinforce conclusions by essentially adding replicative data. Independent, complementary markers can be used to develop associations with clinical parameters, and perhaps diagnose and monitor disease status, activities that so far have not been possible with single markers.

  14. [Prognostic and predictive molecular markers for urologic cancers].

    Science.gov (United States)

    Hartmann, A; Schlomm, T; Bertz, S; Heinzelmann, J; Hölters, S; Simon, R; Stoehr, R; Junker, K

    2014-04-01

    Molecular prognostic factors and genetic alterations as predictive markers for cancer-specific targeted therapies are used today in the clinic for many malignancies. In recent years, many molecular markers for urogenital cancers have also been identified. However, these markers are not clinically used yet. In prostate cancer, novel next-generation sequencing methods revealed a detailed picture of the molecular changes. There is growing evidence that a combination of classical histopathological and validated molecular markers could lead to a more precise estimation of prognosis, thus, resulting in an increasing number of patients with active surveillance as a possible treatment option. In patients with urothelial carcinoma, histopathological factors but also the proliferation of the tumor, mutations in oncogenes leading to an increasing proliferation rate and changes in genes responsible for invasion and metastasis are important. In addition, gene expression profiles which could distinguish aggressive tumors with high risk of metastasis from nonmetastasizing tumors have been recently identified. In the future, this could potentially allow better selection of patients needing systemic perioperative treatment. In renal cell carcinoma, many molecular markers that are associated with metastasis and survival have been identified. Some of these markers were also validated as independent prognostic markers. Selection of patients with primarily organ-confined tumors and increased risk of metastasis for adjuvant systemic therapy could be clinically relevant in the future.

  15. Intraovarian markers of follicular and oocyte maturation.

    Science.gov (United States)

    Pellicer, A; Diamond, M P; DeCherney, A H; Naftolin, F

    1987-08-01

    The use of ovulation induction for multiple follicular growth in in vitro fertilization (IVF) has introduced the problem of follicular asynchrony. As a consequence of the asynchrony, the parameters most commonly used by IVF groups to assess follicular and oocyte quality within those follicles are not sufficiently sensitive or specific. Thus, each follicle must be considered separately, and specific markers of follicular and/or oocyte maturation must be sought from within the follicle. In this review we analyze previous reports of potential markers of follicular and oocyte maturation. In regards to the follicular fluid constituents, the level of estradiol in follicular fluid correlates with fertilization and pregnancy in stimulated cycles. Other steroids are only helpful when specific stimulation protocols are used. The level of some follicular proteins such as alpha-1-antitrypsin and fibrinogen also correlates with fertilization and pregnancy outcome. Cyclic AMP levels in follicular fluid are significantly reduced in follicles leading to conception. Regulators of oocyte maturation, such as the Oocyte Maturation Inhibitor (OMI) or the Meiosis Inducing Substance (MIS) have also been correlated with IVF outcome, but their exact structure remains still unknown. In addition, other sophisticated parameters, such as chemotactic activity of human leukocytes, or simple methods, such as the presence of intrafollicular echoes, have also been used as successful markers in predicting IVF outcome.

  16. Proton NMR-based metabolite analyses of archived serial paired serum and urine samples from myeloma patients at different stages of disease activity identifies acetylcarnitine as a novel marker of active disease.

    Directory of Open Access Journals (Sweden)

    Alessia Lodi

    Full Text Available BACKGROUND: Biomarker identification is becoming increasingly important for the development of personalized or stratified therapies. Metabolomics yields biomarkers indicative of phenotype that can be used to characterize transitions between health and disease, disease progression and therapeutic responses. The desire to reproducibly detect ever greater numbers of metabolites at ever diminishing levels has naturally nurtured advances in best practice for sample procurement, storage and analysis. Reciprocally, since many of the available extensive clinical archives were established prior to the metabolomics era and were not processed in such an 'ideal' fashion, considerable scepticism has arisen as to their value for metabolomic analysis. Here we have challenged that paradigm. METHODS: We performed proton nuclear magnetic resonance spectroscopy-based metabolomics on blood serum and urine samples from 32 patients representative of a total cohort of 1970 multiple myeloma patients entered into the United Kingdom Medical Research Council Myeloma IX trial. FINDINGS: Using serial paired blood and urine samples we detected metabolite profiles that associated with diagnosis, post-treatment remission and disease progression. These studies identified carnitine and acetylcarnitine as novel potential biomarkers of active disease both at diagnosis and relapse and as a mediator of disease associated pathologies. CONCLUSIONS: These findings show that samples conventionally processed and archived can provide useful metabolomic information that has important implications for understanding the biology of myeloma, discovering new therapies and identifying biomarkers potentially useful in deciding the choice and application of therapy.

  17. [Immunological Markers in Organ Transplantation].

    Science.gov (United States)

    Beckmann, J H; Heits, N; Braun, F; Becker, T

    2017-04-01

    The immunological monitoring in organ transplantation is based mainly on the determination of laboratory parameters as surrogate markers of organ dysfunction. Structural damage, caused by alloreactivity, can only be detected by invasive biopsy of the graft, which is why inevitably rejection episodes are diagnosed at a rather progressive stage. New non-invasive specific markers that enable transplant clinicians to identify rejection episodes at an earlier stage, on the molecular level, are needed. The accurate identification of rejection episodes and the establishment of operational tolerance permit early treatment or, respectively, a controlled cessation of immunosuppression. In addition, new prognostic biological markers are expected to allow a pre-transplant risk stratification thus having an impact on organ allocation and immunosuppressive regimen. New high-throughput screening methods allow simultaneous examination of hundreds of characteristics and the generation of specific biological signatures, which might give concrete information about acute rejection, chronic dysfunction as well as operational tolerance. Even though multiple studies and a variety of publications report about important advances on this subject, almost no new biological marker has been implemented in clinical practice as yet. Nevertheless, new technologies, in particular analysis of the genome, transcriptome, proteome and metabolome will make personalised transplantation medicine possible and will further improve the long-term results and graft survival rates. This article gives a survey of the limitations and possibilities of new immunological markers in organ transplantation. Georg Thieme Verlag KG Stuttgart · New York.

  18. Biological Markers and Salivary Cortisol

    DEFF Research Database (Denmark)

    Hansen, Åse Marie; Gunnarsson, Lars-Gunnar; Harris, Anette

    2011-01-01

    This chapter focuses on salivary cortisol in relation to biological markers. Specifically, associations with conventional cardiovascular risk factors and metabolic abnormalities (body mass index, waist circumference, waist/hip ratio, lipid status, glucose, blood pressure, heart rate and heart rate...... variations and pharmacological interventions were also excluded. After meeting all exclusion criteria, 42 papers remained. In total, 273 associations between salivary cortisol and any of the markers mentioned were studied, comprising 241 associations on metabolic abnormalities, 30 on inflammation, and 2...... on stress hormones. Of the salivary cortisol measures reported for evaluations of all markers tested were 136 (49%) single time points, 100 (37%) deviations, 36 (13%) AUC, and 1 (1%) dexamethasone test. Of these, 72 (26%) were statistically significant, and 201 (74%) indicated non-significant findings...

  19. Connective tissue markers of rheumatoid arthritis

    DEFF Research Database (Denmark)

    Møller, H J

    1998-01-01

    Rheumatoid arthritis (RA) is a common systemic autoimmune disorder of unknown aetiology. The most common outcome of RA is a progressive development of joint destruction and deformity. Early introduction of disease-modifying antirheumatic drugs seems important for prevention of the long term...... of rheumatoid factor contributes to the classification of arthritis as RA, and acute phase reactants are useful for quantifying and comparing the level of inflammatory activity in the course of a given patient. There is, however, a lack of sensitive and specific biochemical markers for RA, and frontline...

  20. A multi-nutrient supplement reduced markers of inflammation and improved physical performance in active individuals of middle to older age: a randomized, double-blind, placebo-controlled study

    Directory of Open Access Journals (Sweden)

    Szivak Tunde K

    2011-09-01

    ± 282 W and grip strength (from 42.1 ± 5.9 to 48.5 ± 4.9 kg. Conclusions A multi-nutrient supplement is effective in improving inflammatory status in both men and women, markers of pain, joint pain, strength, and power in men only, and both anxiety and balance (a risk factor for hip fracture in women. Therefore, a multi-nutrient supplement may help middle-aged individuals to prolong physical function and maintain a healthy, active lifestyle.

  1. PAV markers in Sorghum bicolour

    DEFF Research Database (Denmark)

    Shen, Xin; Liu, Zhiquan; Mocoeur, Anne Raymonde Joelle

    2015-01-01

    Abstract Genic presence/absence variants (PAVs) correlate closely to the phenotypic variation, impacting plant genome sizes and the adaption to the environment. To shed more light on their genome-wide patterns, functions and to test the possibility of using them as molecular markers, we analyzed...... enriched in stress responses and protein modification. We used 325 polymorphic PAVs in two sorghum inbred lines Ji2731 and E-Tian, together with 49 SSR markers, and constructed a genetic map, which consisted of 10 linkage groups corresponding to the 10 chromosomes of sorghum and spanned 1430.3 cM in length...

  2. Mucin-type sialooligosacharides are ligands for human CD69 that induce its expression on natural killer cells (NK) and are involved in cancer immunotherapy

    Czech Academy of Sciences Publication Activity Database

    Pospíšil, Miloslav; Vannucci, L.; Horváth, Ondřej; Fišerová, Anna; Krausová, Kateřina; Bezouška, Karel

    1999-01-01

    Roč. 4, Suppl 1 (1999), s. 244 ISSN 1107-3756. [World Congress on Advances in Oncology /4./. 07.10.1999-09.10.1999, Athens] R&D Projects: GA ČR GV312/98/K034 Institutional research plan: CEZ:A53/98:Z5-020-9ii Subject RIV: EC - Immunology

  3. Body fluid markers to monitor multiple sclerosis: The assays and the challenges

    NARCIS (Netherlands)

    Laman, J.D.; Thompson, E.J.; Kappos, L.

    1998-01-01

    The need for reliable markers of disease activity in multiple sclerosis (MS) to better guide basic research, diagnosis, treatment, and monitoring of therapy is well-recognized. A recent European Charcot Foundation Symposium (Body fluid markers for course and activity of disease in multiple sclerosis

  4. Biochemical Markers for Assessing Aquatic Contamination

    Directory of Open Access Journals (Sweden)

    Zdeňka Svobodová

    2007-11-01

    Full Text Available Biochemical markers, specifically enzymes of the first phase of xenobiotic transformation - cytochrome P450 and ethoxyresorufin-O-deethylase (EROD - were used to determine the quantities of persistent organic pollutants (POPs in fish muscle (PCB, HCB, HCH, OCS, DDT. Eight rivers were monitored (Orlice, Chrudimka, Cidlina, Jizera, Vltava, Ohře and Bílina; and the River Blanice was used as a control. The indicator species selected was the chub (Leuciscus cephalus L.. There were no significant differences in cytochrome P450 content between the locations monitored. The highest concentration of cytochrome P450 in fish liver was in the Vltava (0.241 nmol mg-1 protein, and the lowest was in the Orlice (0.120 nmol mg-1 protein. Analysis of EROD activity showed a significant difference between the Blanice and the Vltava (P< 0.05, and also between the Orlice and the Vltava (P< 0.01, the Orlice and the Bílina (P< 0.01, and the Orlice and the Ohře (P< 0.05. The highest EROD activity in fish liver was in the Vltava (576.4 pmol min-1 mg-1 protein, and the lowest was in the Orlice (63.05 pmol min-1 mg-1 protein. In individual locations, results of chemical monitoring and values of biochemical markers were compared. A significant correlation (P< 0.05 was found between biochemical markers and OCS, and PCB. Among the tributaries studied those that contaminated the Elbe most were the Vltava and the Bílina. These tributaries should not be considered the main sources of industrial contamination of the River Elbe, because the most important contamination sources were along the river Elbe itself.

  5. EasyClone-MarkerFree

    DEFF Research Database (Denmark)

    Fabre, Mathew Malcolm Jessop; Jakociunas, Tadas; Stovicek, Vratislav

    2016-01-01

    Clone-MarkerFree. The integration of linearized expression cassettes into defined genomic loci is facilitated by CRISPR/Cas9. Cas9 is recruited to the chromosomal location by specific guide RNAs (gRNAs) expressed from a set of gRNA helper vectors. Using our genome engineering vector suite, single and triple insertions are obtained...

  6. Tumour markers in gynaecological practice

    International Nuclear Information System (INIS)

    Adewole, I.F.

    1999-02-01

    Gynaecological cancers are fairly common in developing countries and represent about 26 % f all cancers. Application of cervical cytology screening nationally has made cervical cancer one of the most preventable malignant diseases thus eliminating the challenges of advanced cancer management. Tumour markers has played a most crucial role in this respect

  7. Testing theories about ethnic markers

    DEFF Research Database (Denmark)

    Jensen, Niels Holm; Petersen, Michael Bang; Høgh-Olesen, Henrik

    2015-01-01

    In recent years, evolutionary psychologists and anthropologists have debated whether ethnic markers have evolved to solve adaptive problems related to interpersonal coordination or to interpersonal cooperation. In the present study, we add to this debate by exploring how individuals living in a m...

  8. Sympathetic arousal as a marker of chronicity in childhood stuttering.

    Science.gov (United States)

    Zengin-Bolatkale, Hatun; Conture, Edward G; Walden, Tedra A; Jones, Robin M

    2018-01-01

    This study investigated whether sympathetic activity during a stressful speaking task was an early marker for stuttering chronicity. Participants were 9 children with persisting stuttering, 23 children who recovered, and 17 children who do not stutter. Participants performed a stress-inducing picture-naming task and skin conductance was measured across three time points. Findings indicated that at the initial time point, children with persisting stuttering exhibited higher sympathetic arousal during the stressful speaking task than children whose stuttering recovered. Findings are taken to suggest that sympathetic activity may be an early marker of heightened risk for chronic stuttering.

  9. Progress on macrophage's proinflammatory products as markers of acute endometriosis

    Directory of Open Access Journals (Sweden)

    Alicja Ziętek

    2015-08-01

    Full Text Available To provide the review of the macrophage activity products as pathophysiological markers of endometriosis by literature survey (PubMed, Cochrane. Immunoreactive cells and several of their synthesis products concentrations are elevated in the serum and peritoneal fluid in patients with endometriosis. The enhanced reactive proteins contributed to local inflammation and aggregation of endometriotic lesions. Immune response and immune surveillance of tissue play an important role in pathogenesis of endometriosis. Activated macrophages in peritoneal environment secrete immunoreactive cytokines which are responsible for inflammatory cascade of reactions. The immunoreactive cytokines should be a target not only as a disease marker but also as a part of therapeutic protocol.

  10. Biochemical Markers in Neurocritical Care

    Directory of Open Access Journals (Sweden)

    Omidvar Rezae

    2016-07-01

    Full Text Available During the past two decades, a variety of serum or cerebrospinal fluid (CSF biochemical markers in daily clinical practice have been recommended to diagnose and monitor diverse diseases or pathologic situations. It will be essential to develop a panel of biomarkers, to be suitable for evaluation of treatment efficacy, representing distinct phases of injury and recovery and consider the temporal profile of those. Among the possible and different biochemical markers, S100b appeared to fulfill many of optimized criteria of an ideal marker. S100b, a cytosolic low molecular weight dimeric calciumbinding protein from chromosome 21, synthesized in glial cells throughout the CNS, an homodimeric diffusible, belongs to a family of closely related protein, predominantly expressed by astrocytes and Schwann cells and a classic immunohistochemical marker for these cells, is implicated in brain development and neurophysiology. Of the 3 isoforms of S-100, the BB subunit (S100B is present in high concentrations in central and peripheral glial and Schwann cells, Langerhans and anterior pituitary cells, fat, muscle, and bone marrow tissues. The biomarker has shown to be a sensitive marker of clinical and subclinical cerebral damage, such as stroke, traumatic brain injury, and spinal cord injury. Increasing evidence suggests that the biomarker plays a double function as an intracellular regulator and an extracellular signal of the CNS. S100b is found in the cytoplasm in a soluble form and also is associated with intracellular membranes, centrosomes, microtubules, and type III intermediate filaments. Their genomic organization now is known, and many of their target proteins have been identified, although the mechanisms of regulating S100b secretion are not completely understood and appear to be related to many factors, such as the proinflammatory cytokines, tumor necrosis factor alpha (TNF-a, interleukin (IL-1b, and metabolic stress. 

  11. Nuclear medicine markers of tumor oxygenation and radioresistance

    International Nuclear Information System (INIS)

    Chapman, J. Donald; Schneider, R.H.; Stobbe, C.C.; Kim, E.; Engelhardt, E.L.; Coia, L.

    1996-01-01

    Purpose/Objective: The objective of this research project was to synthesize, purify, radiolabel and characterize second-generation nuclear medicine markers of tissue oxygenation with properties superior to iodoazomycin arabinoside (IAZA) and to validate the hypoxia-marking activity of optimal compounds by independent measurements of tumor oxygenation and tumor radioresistance. Materials and Methods: Six hypoxic markers of the iodoazomycin nucleoside class with water solubilities greater than IAZA were synthesized by published procedures. The markers were purified, chemically characterized and labeled with Iodine-125 or Iodine-131. Absolute rates of marker ligation to the macromolecules of hypoxic EMT-6 tumor cells in vitro were determined as a function of marker concentration and used to establish relative marker effectiveness. Hypoxic marking activity in tumors was determined from tumor/blood (T/B) and tumor/muscle (T/M) ratios of radiolabelled marker in EMT-6 tumor-bearing C.B17/Icr scid mice. The optimal marker was administered to R3327-H and R3327-AT tumor-bearing Fischer X Copenhagen rats for estimates of tumor oxygenation by T/B and T/M ratios. Oxygen distributions in the same tumors were obtained with the Eppendorf pO 2 Histograph. The radioresistance of individual tumors was determined from in vitro plating efficiencies of cells released from tumors which had been irradiated in vivo with 20 Gy Cs-137 γ-rays. Results: Of the six iodinated azomycin nucleosides investigated, five were novel markers and all had water solubilities higher than IAZA. Iodinated azomycin xylopyranoside (β-D-IAZXP) was selected as the optimal marker of this class since it 1) exhibited the highest absolute rate of ligation to hypoxic tumor cells in vitro, 2) had the fastest plasma clearance rate in tumor-bearing mice and 3) yielded high T/B ratios in both the mouse and rat tumor models employed in this study. Planar nuclear medicine images of (I-131) β-D-IAZXP in tumor-bearing rats

  12. NABIC marker database: A molecular markers information network of agricultural crops.

    Science.gov (United States)

    Kim, Chang-Kug; Seol, Young-Joo; Lee, Dong-Jun; Jeong, In-Seon; Yoon, Ung-Han; Lee, Gang-Seob; Hahn, Jang-Ho; Park, Dong-Suk

    2013-01-01

    In 2013, National Agricultural Biotechnology Information Center (NABIC) reconstructs a molecular marker database for useful genetic resources. The web-based marker database consists of three major functional categories: map viewer, RSN marker and gene annotation. It provides 7250 marker locations, 3301 RSN marker property, 3280 molecular marker annotation information in agricultural plants. The individual molecular marker provides information such as marker name, expressed sequence tag number, gene definition and general marker information. This updated marker-based database provides useful information through a user-friendly web interface that assisted in tracing any new structures of the chromosomes and gene positional functions using specific molecular markers. The database is available for free at http://nabic.rda.go.kr/gere/rice/molecularMarkers/

  13. Skewed distribution of circulating activated natural killer T (NKT) cells in patients with common variable immunodeficiency disorders (CVID).

    Science.gov (United States)

    Carvalho, Karina I; Melo, Karina M; Bruno, Fernanda R; Snyder-Cappione, Jennifer E; Nixon, Douglas F; Costa-Carvalho, Beatriz T; Kallas, Esper G

    2010-09-09

    Common variable immunodeficiency disorder (CVID) is the commonest cause of primary antibody failure in adults and children, and characterized clinically by recurrent bacterial infections and autoimmune manifestations. Several innate immune defects have been described in CVID, but no study has yet investigated the frequency, phenotype or function of the key regulatory cell population, natural killer T (NKT) cells. We measured the frequencies and subsets of NKT cells in patients with CVID and compared these to healthy controls. Our results show a skewing of NKT cell subsets, with CD4+ NKT cells at higher frequencies, and CD8+ NKT cells at lower frequencies. However, these cells were highly activated and expression CD161. The NKT cells had a higher expression of CCR5 and concomitantly expression of CCR5+CD69+CXCR6 suggesting a compensation of the remaining population of NKT cells for rapid effector action.

  14. [Circadian markers and genes in bipolar disorder].

    Science.gov (United States)

    Yeim, S; Boudebesse, C; Etain, B; Belliviera, F

    2015-09-01

    Bipolar disorder is a severe and complex multifactorial disease, characterized by alternance of acute episodes of depression and mania/hypomania, interspaced by euthymic periods. The etiological determinants of bipolar disorder yet, are still poorly understood. For the last 30 years, chronobiology is an important field of investigation to better understand the pathophysiology of bipolar disorder. We conducted a review using Medline, ISI Database, EMBase, PsyInfo up to January 2015, using the following keywords combinations: "mood disorder", "bipolar disorder", "depression", "unipolar disorder", "major depressive disorder", "affective disorder", for psychiatric conditions; and "circadian rhythms", "circadian markers", "circadian gene", "clock gene", "melatonin" for circadian rhythms. The search critera was presence of word in any field of the article. Quantitative and qualitative circadian abnormalities are associated with bipolar disorders both during acute episodes and euthymic periods, suggesting that these altered circadian rhythms may represent biological trait markers of the disorder. These circadian dysfunctions were assessed by various validated tools including polysomnography, actigraphy, sleep diaries, chronotype assessments and blood melatonin/cortisol measures. Other altered endogenous circadian activities have also been reported in bipolar patients, such as hormones secretion, core body temperature or fibroblasts activity. Moreover, these markers were also altered in healthy relatives of bipolar patients, suggesting a degree of heritability. Several genetic association studies have also showed associations between multiple circadian genes and bipolar disorder, such as CLOCK, ARTNL1, GSK3β, PER3, NPAS2, NR1D1, TIMELESS, RORA, RORB, and CSNK1ε. Thus, these circadian gene variants may contribute to the genetic susceptibility of the disease. Furthermore, the study of the clock system may help to better understand some phenotypic aspects like the

  15. Converging intracranial markers of conscious access.

    Directory of Open Access Journals (Sweden)

    Raphaël Gaillard

    2009-03-01

    Full Text Available We compared conscious and nonconscious processing of briefly flashed words using a visual masking procedure while recording intracranial electroencephalogram (iEEG in ten patients. Nonconscious processing of masked words was observed in multiple cortical areas, mostly within an early time window (<300 ms, accompanied by induced gamma-band activity, but without coherent long-distance neural activity, suggesting a quickly dissipating feedforward wave. In contrast, conscious processing of unmasked words was characterized by the convergence of four distinct neurophysiological markers: sustained voltage changes, particularly in prefrontal cortex, large increases in spectral power in the gamma band, increases in long-distance phase synchrony in the beta range, and increases in long-range Granger causality. We argue that all of those measures provide distinct windows into the same distributed state of conscious processing. These results have a direct impact on current theoretical discussions concerning the neural correlates of conscious access.

  16. Occupational exposure to 50 Hz magnetic fields does not alter responses of inflammatory genes and activation of splenic lymphocytes in mice

    Directory of Open Access Journals (Sweden)

    Xue Luo

    2016-04-01

    Full Text Available Objectives: The objective of the present study was to observe the effects of 50 Hz magnetic fields (MFs on the immune function of splenic lymphocytes in mice. Material and Methods: Twenty male Kunming mice (6 weeks old, weighing 18– 25 g, were randomly divided into sham exposure (N = 10 and 500 μT MFs (N = 10 groups. The mice in the MFs group were exposed to 500 μT MFs for 8 h daily (5 days/week for up to 60 days. In vitro study was carried out to examine the effects of 50 Hz MFs on the expression of inflammatory factor genes and a cluster of differentiation 69 (CD69 in mouse prime splenic lymphocytes activated by para-Methoxyamphetamine (PMA and ionomycin. In the in vitro experiments, lymphocytes were isolated from the spleen of 10 healthy Kunming mice, the cells were cultured in the Roswell Park Memorial Institute 1640 medium (RPMI-1640 and exposed to 0 μT, 250 μT, 500 μT, or 1 mT MFs in an incubator under 5% carbon dioxide (CO2 at 37°C for 6 h. The levels of interleukin-2 (IL-2, IL-4, interferon-gamma (IFN-γ, GATA binding protein 3 (GATA-3 and T cell-specific T-box transcription factor (T-bet were assessed by the real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR, respectively. The expression of CD69 was checked using the flow cytometry. Results: Under our experimental conditions, body weight of the mice exposed to occupational, extremely low frequency- electromagnetic fields (ELF-EMFs significantly decreased on day 20 and day 30. There were no significant changes observed in vivo in spleen weight, splenic coefficient, splenic histology profile and cytokine production in spleen tissues. Our in vitro experiments showed that 50 Hz MFs had no effect on the expression of these genes and CD69 to primary splenic cells. Conclusions: In conclusion, under the applied experimental conditions, occupational exposure to 50 Hz magnetic field did not alter responses of inflammatory genes and activation of splenic

  17. Markers and mapping revisited: finding your gene.

    Science.gov (United States)

    Jones, Neil; Ougham, Helen; Thomas, Howard; Pasakinskiene, Izolda

    2009-01-01

    This paper is an update of our earlier review (Jones et al., 1997, Markers and mapping: we are all geneticists now. New Phytologist 137: 165-177), which dealt with the genetics of mapping, in terms of recombination as the basis of the procedure, and covered some of the first generation of markers, including restriction fragment length polymorphisms (RFLPs), random amplified polymorphic DNA (RAPDs), simple sequence repeats (SSRs) and quantitative trait loci (QTLs). In the intervening decade there have been numerous developments in marker science with many new systems becoming available, which are herein described: cleavage amplification polymorphism (CAP), sequence-specific amplification polymorphism (S-SAP), inter-simple sequence repeat (ISSR), sequence tagged site (STS), sequence characterized amplification region (SCAR), selective amplification of microsatellite polymorphic loci (SAMPL), single nucleotide polymorphism (SNP), expressed sequence tag (EST), sequence-related amplified polymorphism (SRAP), target region amplification polymorphism (TRAP), microarrays, diversity arrays technology (DArT), single-strand conformation polymorphism (SSCP), denaturing gradient gel electrophoresis (DGGE), temperature gradient gel electrophoresis (TGGE) and methylation-sensitive PCR. In addition there has been an explosion of knowledge and databases in the area of genomics and bioinformatics. The number of flowering plant ESTs is c. 19 million and counting, with all the opportunity that this provides for gene-hunting, while the survey of bioinformatics and computer resources points to a rapid growth point for future activities in unravelling and applying the burst of new information on plant genomes. A case study is presented on tracking down a specific gene (stay-green (SGR), a post-transcriptional senescence regulator) using the full suite of mapping tools and comparative mapping resources. We end with a brief speculation on how genome analysis may progress into the future of

  18. Peripheral blood CD161+ T cells from asthmatic patients are activated during asthma attack and predominantly produce IFN-gamma.

    Science.gov (United States)

    González-Hernández, Y; Pedraza-Sánchez, S; Blandón-Vijil, V; del Río-Navarro, B E; Vaughan, G; Moreno-Lafont, M; Escobar-Gutiérrez, A

    2007-04-01

    In humans, T cells expressing the CD161 molecule NKR-P1A constitute around 20% of the circulating CD3(+) cells and are potentially immunoregulatory in several diseases. Their role in asthma is not well known, but they could participate in asthma attacks. To determinate whether activation of CD161(+) T cells and their cytokine production correlate with clinical status of asthma, we analysed blood samples from asthma attack patients (AAP) and stable asthma patients (SAP) in comparison with healthy non-atopic controls (HC). There was a significant higher baseline expression of CD69 on T cells from AAP and the difference was more notorious on CD161(+) T cells; upregulation of CD69 was observed on both CD161(-) and CD161(+) T cells driven by Dermatophagoides pteronyssinus crude extract, whereas polyclonal stimulation with phorbol 12-myristate 13-acetate plus ionomycin predominantly induced IFN-gamma but no IL-4, IL-5 and IL-13 by CD161(+) T cells in all groups; upon polyclonal stimulation, there were more CD161(+) T cells producing IFN-gamma and less CD161(-) T cells producing this cytokine, contrasting with the opposite results observed in SAP and HC groups. Our results indicate that, during asthma attack, CD161(+) T cells are activated and are able to produce predominantly IFN-gamma but no Th2 cytokines. We hypothesize that during an asthma attack, IFN-gamma produced by CD161(+) T cells could help to reestablish the Th1/Th2 equilibrium. These observations may contribute to the understanding of the immune mechanisms involved in asthma attacks.

  19. Increased expression of the regulatory T cell-associated marker CTLA-4 in bovine leukemia virus infection.

    Science.gov (United States)

    Suzuki, Saori; Konnai, Satoru; Okagawa, Tomohiro; Ikebuchi, Ryoyo; Nishimori, Asami; Kohara, Junko; Mingala, Claro N; Murata, Shiro; Ohashi, Kazuhiko

    2015-02-15

    Regulatory T cells (Tregs) play a critical role in the maintenance of the host's immune system. Tregs, particularly CD4(+)CD25(+)Foxp3(+) T cells, have been reported to be involved in the immune evasion mechanism of tumors and several pathogens that cause chronic infections. Recent studies showed that a Treg-associated marker, cytotoxic T-lymphocyte antigen 4 (CTLA-4), is closely associated with the progression of several diseases. We recently reported that the proportion of Foxp3(+)CD4(+) cells was positively correlated with the number of lymphocytes, virus titer, and virus load but inversely correlated with IFN-γ expression in cattle infected with bovine leukemia virus (BLV), which causes chronic infection and lymphoma in its host. Here the kinetics of CTLA-4(+) cells were analyzed in BLV-infected cattle. CTLA-4 mRNA was predominantly expressed in CD4(+) T cells in BLV-infected cattle, and the expression was positively correlated with Foxp3 mRNA expression. To test for differences in the protein expression level of CTLA-4, we measured the proportion of CTLA-4-expressing cells by flow cytometry. In cattle with persistent lymphocytosis (PL), mean fluorescence intensities (MFIs) of CTLA-4 on CD4(+) and CD25(+) T cells were significantly increased compared with that in control and aleukemic (AL) cattle. The percentage of CTLA-4(+) cells in the CD4(+) T cell subpopulation was positively correlated with TGF-β mRNA expression, suggesting that CD4(+)CTLA-4(+) T cells have a potentially immunosuppressive function in BLV infection. In the limited number of cattle that were tested, the anti-CTLA-4 antibody enhanced the expression of CD69, IL-2, and IFN-γ mRNA in anti-programmed death ligand 1 (PD-L1) antibody-treated peripheral blood mononuclear cells from BLV-infected cattle. Together with previous findings, the present results indicate that Tregs may be involved in the inhibition of T cell function during BLV infection. Copyright © 2014 Elsevier B.V. All rights

  20. Endometriosis and possible inflammation markers

    OpenAIRE

    Meng-Hsing Wu; Kuei-Yang Hsiao; Shaw-Jenq Tsai

    2015-01-01

    Inflammation plays an important role in the pathogenesis of endometriosis. Infiltration of peritoneal macrophages and local proinflammatory mediators in the peritoneal microenvironment affect ovarian function and pelvic anatomy leading to the symptoms and signs of endometriosis. The identification of a noninvasive marker for endometriosis will facilitate early diagnosis and treatment of this disease. This review provides an overview of local microenvironmental inflammation and systemic inflam...

  1. Endometriosis and possible inflammation markers

    Directory of Open Access Journals (Sweden)

    Meng-Hsing Wu

    2015-08-01

    Full Text Available Inflammation plays an important role in the pathogenesis of endometriosis. Infiltration of peritoneal macrophages and local proinflammatory mediators in the peritoneal microenvironment affect ovarian function and pelvic anatomy leading to the symptoms and signs of endometriosis. The identification of a noninvasive marker for endometriosis will facilitate early diagnosis and treatment of this disease. This review provides an overview of local microenvironmental inflammation and systemic inflammation biomarkers in endometriosis.

  2. Molecular markers for thyroid cancer

    International Nuclear Information System (INIS)

    Marrero Rodriguez, Maria Teresa; Sinconegui Gomez, Belkys; Cruz Cruz, Anaisa

    2015-01-01

    The importance of the study of the thyroid nodule lies in excluding the possibility of a malignant lesion because the majority of lesions are benign but there is a malignancy risk of 5 to 10%. Most of them are well differentiated carcinomas originating in the follicular epithelium. In spite of the fact that the majority are benign lesions, distinguishing them from carcinomas is crucial to treatment and adequate follow-up. Fine-needle biopsy allows making the diagnosis in most of cases. However, this method is restricted, particularly when diagnosing follicular lesions. In an effort to improve the diagnostic accuracy of biopsy and to provide new diagnosing criteria, a number of molecular markers have been put forward, some of which has wide range of approval whereas others still awaits to be validated for further implementation. This article presented an updated review of molecular markers with higher number of evidence, more accessible and potentially usable from a methodological viewpoint for diagnosis of the thyroid nodule before surgery. The importance of the study of the thyroid nodule lies in excluding the possibility of a malignant lesion because the majority of lesions are benign but there is a malignancy risk of 5 to 10%. Most of them are well differentiated carcinomas originating in the follicular epithelium. In spite of the fact that the majority are benign lesions, distinguishing them from carcinomas is crucial to treatment and adequate follow-up. Fine-needle biopsy allows making the diagnosis in most of cases. However, this method is restricted, particularly when diagnosing follicular lesions. In an effort to improve the diagnostic accuracy of biopsy and to provide new diagnosing criteria, a number of molecular markers have been put forward, some of which has wide range of approval whereas others still awaits to be validated for further implementation. This article presented an updated review of molecular markers with higher number of evidence, more

  3. Serotonin, neural markers and memory

    Directory of Open Access Journals (Sweden)

    Alfredo eMeneses

    2015-07-01

    Full Text Available Diverse neuropsychiatric disorders present dysfunctional memory and no effective treatment exits for them; likely as result of the absence of neural markers associated to memory. Neurotransmitter systems and signaling pathways have been implicated in memory and dysfunctional memory; however, their role is poorly understood. Hence, neural markers and cerebral functions and dysfunctions are revised. To our knowledge no previous systematic works have been published addressing these issues. The interactions among behavioral tasks, control groups and molecular changes and/or pharmacological effects are mentioned. Neurotransmitter receptors and signaling pathways, during normal and abnormally functioning memory with an emphasis on the behavioral aspects of memory are revised. With focus on serotonin, since as it is a well characterized neurotransmitter, with multiple pharmacological tools, and well characterized downstream signaling in mammals’ species. 5-HT1A, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 receptors as well as SERT (serotonin transporter seem to be useful neural markers and/or therapeutic targets. Certainly, if the mentioned evidence is replicated, then the translatability from preclinical and clinical studies to neural changes might be confirmed. Hypothesis and theories might provide appropriate limits and perspectives of evidence

  4. Herbs and spices: characterization and quantitation of biologically-active markers for routine quality control by multiple headspace solid-phase microextraction combined with separative or non-separative analysis.

    Science.gov (United States)

    Sgorbini, Barbara; Bicchi, Carlo; Cagliero, Cecilia; Cordero, Chiara; Liberto, Erica; Rubiolo, Patrizia

    2015-01-09

    Herbs and spices are used worldwide as food flavoring, thus determination of their identity, origin, and quality is mandatory for safe human consumption. An analysis strategy based on separative (HS-SPME-GC-MS) and non-separative (HS-SPME-MS) approaches is proposed for the volatile fraction of herbs and spices, for quality control and to quantify the aromatic markers with a single analysis directly on the plant material as such. Eight-to-ten lots of each of the following herbs/spices were considered: cloves (Syzygium aromaticum (L.) Merr. & Perry), American peppertree (Schinus molle L.), black pepper and white pepper (Piper nigrum L.), rosemary (Rosmarinus officinalis L.), sage (Salvia officinalis L.) and thyme (Thymus vulgaris L.). Homogeneity, origin, and chemotypes of the investigated lots of each herb/spice were defined by fingerprinting, through statistical elaboration with principal component analysis (PCA). Characterizing aromatic markers were directly quantified on the solid matrix through multiple headspace extraction-HS-SPME (MHS-SPME). Reliable results were obtained with both separative and non-separative methods (where the latter were applicable); the two were in full agreement, RSD% ranging from 1.8 to 7.7% for eugenol in cloves, 2.2-18.4% for carvacrol+thymol in thyme, and 3.1-16.8% for thujones in sage. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Preclinical assessment of hypoxic marker specificity and sensitivity

    International Nuclear Information System (INIS)

    Iyer, Renuka V.; Engelhardt, Edward L.; Stobbe, Corinne C.; Schneider, Richard F.; Chapman, J. Donald

    1998-01-01

    Purpose: In the search for a sensitive, accurate, and noninvasive technique for quantifying human tumor hypoxia, our laboratory has synthesized several potential radiodiagnostic agents. The purpose of this study was to assess and compare the hypoxic marking properties of both radioiodinated and Tc-99m labeled markers in appropriate test systems which can predict for in vivo activity. Materials and Methods: Preclinical assessment of hypoxic marker specificity and sensitivity employed three laboratory assays with tumor cells in vitro and in vivo. Radiolabeled marker uptake and/or binding to whole EMT-6 tumor cells under extremely hypoxic and aerobic conditions was measured and their ratio defined hypoxia-specific factor (HSF). Marker specificity to hypoxic tumor tissue was estimated from its selective avidity to two rodent tumors in vivo, whose radiobiologic hypoxic fractions (HF) had been measured. The ratios of % injected dose/gram (%ID/g) of marker at various times in EMT-6 tumor tissue relative to that in the blood and muscle of scid mice were used to quantify hypoxia-specific activity. This tumor in this host exhibited an average radiobiologic HF of ∼35%. As well, nuclear medicine images were acquired from R3327-AT (HF ≅15%) and R3327-H (no measurable HF) prostate carcinomas growing in rats to distinguish between marker avidity due to hypoxia versus perfusion. Results: The HSF for FC-103 and other iodinated markers were higher (5-40) than those for FC-306 and other Tc-99m labeled markers. The latter did not show hypoxia-specific uptake into cells in vitro. Qualitative differences were observed in the biodistribution and clearance kinetics of the iodinated azomycin nucleosides relative to the technetium chelates. The largest tumor/blood (T/B) and tumor/muscle (T/M) ratios were observed for compounds of the azomycin nucleoside class in EMT-6 tumor-bearing scid mice. These markers also showed a 3-4 x higher uptake into R3327-AT tumors relative to the well

  6. The interaction of dendritic cells and γδ T cells promotes the activation of γδ T cells in experimental autoimmune uveitis

    Directory of Open Access Journals (Sweden)

    Beibei Wang

    2017-03-01

    Full Text Available Uveitis is a severe inflammatory disease that can cause visual impairment. Recently, activated γδ T cells were proved to play a central role in the development of experimental autoimmune uveitis (EAU. However, the mechanism underlying γδ T-cell activation in EAU is incompletely known. In this study, we determined the percentage changes in and the phenotypes of γδ T cells and dendritic cells (DCs obtained from the spleens of immunized C57BL/6 (B6 mice, an animal model of EAU. We found that the number of γδ T cells and DCs obviously increased during the inflammation phase of EAU (days 16–20 of our experiment, and that during this time, γδ T cells expressed high levels of CD69 and the integrin lymphocyte function–associated antigen-1 (LFA-1 and secreted high levels of interleukin (IL-17A. Moreover, DCs obtained during this phase expressed high levels of CD80, CD83, CD86, and intracellular cell adhesion molecule-1 (ICAM-1. Furthermore, we studied the interaction between DCs and γδ T cells by using flow cytometry and confocal microscopy in order to determine whether DCs affected γδ T-cell activation in vitro. Co-cultures of the two types of cells showed that DCs induced high levels of CD69, LFA-1, and IL-17A in γδ T cells. Imaging studies revealed contact between the DCs and γδ T cells. This interaction was mediated by the accumulation of ICAM-1 and LFA-1 at the interface of DCs-γδ T cells. Thus, the activation of γδ T cells in EAU was promoted by DCs interacting with γδ T cells.

  7. New approach for isolation of VNTR markers.

    OpenAIRE

    Nakamura, Y; Carlson, M; Krapcho, K; Kanamori, M; White, R

    1988-01-01

    Elsewhere we have reported an efficient method for isolating VNTR (Variable Number of Tandem Repeats) markers. Several of the VNTR markers isolated in those experiments were sequenced, and a DNA sequence of 9 bp (GNNGTGGG) emerged as an apparent consensus sequence for VNTR markers. To confirm this result and to develop more VNTR markers, we synthesized nine different 18-base-long oligonucleotides whose sequences each included GNNGTGGG. When 102 cosmid clones selected by these oligonucleotides...

  8. Bacterial and fungal markers in tobacco smoke

    International Nuclear Information System (INIS)

    Szponar, B.; Pehrson, C.; Larsson, L.

    2012-01-01

    Previous research has demonstrated that cigarette smoke contains bacterial and fungal components including lipopolysaccharide (LPS) and ergosterol. In the present study we used gas chromatography–mass spectrometry to analyze tobacco as well as mainstream and second hand smoke for 3-hydroxy fatty acids (3-OH FAs) of 10 to 18 carbon chain lengths, used as LPS markers, and ergosterol, used as a marker of fungal biomass. The air concentrations of LPS were 0.0017 nmol/m 3 (N = 5) and 0.0007/m 3 (N = 6) in the smoking vs. non-smoking rooms (p = 0.0559) of the studied private houses, and 0.0231 nmol/m 3 (N = 5) vs. 0.0006 nmol/m 3 (N = 5) (p = 0.0173), respectively, at the worksite. The air concentrations of ergosterol were also significantly higher in rooms with ongoing smoking than in rooms without smoking. A positive correlation was found between LPS and ergosterol in rooms with smoking but not in rooms without smoking. 3-OH C14:0 was the main 3-OH FA, followed by 3-OH C12:0, both in mainstream and second hand smoke and in phenol:water smoke extracts prepared in order to purify the LPS. The Limulus activity of the phenolic phase of tobacco was 3900 endotoxin units (EU)/cigarette; the corresponding amount of the smoke, collected on filters from 8 puffs, was 4 EU/cigarette. Tobacco smoking has been associated with a range of inflammatory airway conditions including COPD, asthma, bronchitis, alveolar hypersensitivity etc. Significant levels of LPS and ergosterol were identified in tobacco smoke and these observations support the hypothesis that microbial components of tobacco smoke contribute to inflammation and airway disease. -- Highlights: ► Air concentration of bacterial and fungal markers is significantly higher in rooms with ongoing smoking than without smoking. ► Bacterial LPS correlates with fungal marker in rooms with ongoing smoking but not without smoking. ► LPS from mainstream smoke contains 3-hydroxy 14:0 and 12:0 fatty acids in similar proportion as

  9. Bacterial and fungal markers in tobacco smoke

    Energy Technology Data Exchange (ETDEWEB)

    Szponar, B., E-mail: szponar@iitd.pan.wroc.pl [Lund University, Dept. of Laboratory Medicine, Soelvegatan 23, 223 62 Lund (Sweden); Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wroclaw (Poland); Pehrson, C.; Larsson, L. [Lund University, Dept. of Laboratory Medicine, Soelvegatan 23, 223 62 Lund (Sweden)

    2012-11-01

    Previous research has demonstrated that cigarette smoke contains bacterial and fungal components including lipopolysaccharide (LPS) and ergosterol. In the present study we used gas chromatography-mass spectrometry to analyze tobacco as well as mainstream and second hand smoke for 3-hydroxy fatty acids (3-OH FAs) of 10 to 18 carbon chain lengths, used as LPS markers, and ergosterol, used as a marker of fungal biomass. The air concentrations of LPS were 0.0017 nmol/m{sup 3} (N = 5) and 0.0007/m{sup 3} (N = 6) in the smoking vs. non-smoking rooms (p = 0.0559) of the studied private houses, and 0.0231 nmol/m{sup 3} (N = 5) vs. 0.0006 nmol/m{sup 3} (N = 5) (p = 0.0173), respectively, at the worksite. The air concentrations of ergosterol were also significantly higher in rooms with ongoing smoking than in rooms without smoking. A positive correlation was found between LPS and ergosterol in rooms with smoking but not in rooms without smoking. 3-OH C14:0 was the main 3-OH FA, followed by 3-OH C12:0, both in mainstream and second hand smoke and in phenol:water smoke extracts prepared in order to purify the LPS. The Limulus activity of the phenolic phase of tobacco was 3900 endotoxin units (EU)/cigarette; the corresponding amount of the smoke, collected on filters from 8 puffs, was 4 EU/cigarette. Tobacco smoking has been associated with a range of inflammatory airway conditions including COPD, asthma, bronchitis, alveolar hypersensitivity etc. Significant levels of LPS and ergosterol were identified in tobacco smoke and these observations support the hypothesis that microbial components of tobacco smoke contribute to inflammation and airway disease. -- Highlights: Black-Right-Pointing-Pointer Air concentration of bacterial and fungal markers is significantly higher in rooms with ongoing smoking than without smoking. Black-Right-Pointing-Pointer Bacterial LPS correlates with fungal marker in rooms with ongoing smoking but not without smoking. Black-Right-Pointing-Pointer LPS

  10. Evaluation of liver marker enzymes in diabetic subjects in the ...

    African Journals Online (AJOL)

    The activity levels of the liver marker enzymes; Aspartate and Alanine amino transferases (AST and ALT), Alkaline Phosphatase (ALP) and Gamma glutamyltransferase (GGT) in diabetic and non-diabetic subjects within the ages of 25 to 86 were assayed. This study was for two weeks. The results indicated that the plasma ...

  11. Markers of liver function and inflammatory cytokines modulation by ...

    African Journals Online (AJOL)

    Conclusion: Aerobic exercise training modulates inflammatory cytokine levels and markers of liver function in patients with nonalcoholic ... and is associated with over nutrition and under activity, ... of these subjects with leptin reduced liver fat and liver enzyme ... tissue, muscle-released interleukin-6 inhibition of tumor.

  12. Quercetin reduces markers of oxidative stress and inflammation in sarcoidosis

    NARCIS (Netherlands)

    Boots, Agnes W.; Drent, Marjolein; de Boer, Vincent C. J.; Bast, Aalt; Haenen, Guido R. M. M.

    2011-01-01

    Oxidative stress and low antioxidant levels are implicated in the aetiology of sarcoidosis, an inflammatory disease. Quercetin is a potent dietary antioxidant that also displays anti-inflammatory activities. Consequently, the aim is to examine the effect of quercetin supplementation on markers of

  13. Application of molecular markers in apple breeding

    Directory of Open Access Journals (Sweden)

    Marić Slađana

    2010-01-01

    Full Text Available Apple is economically the most important species of genus Malus Miller. In respect of production, trade and consumption, it ranks first among deciduous fruit and third on a global scale among all fruit species. Apple breeding is carried out on a large scale in several scientific institutes throughout the world. Due to this activity, apple is a fruit species with the highest number of described monogenic traits; 76 genes, encoding morphological traits, pest and disease resistance, as well as 69 genes encoding enzymes. The development of molecular markers (RFLPs, AFLPs, SCARs and SSRs has allowed the mapping of the apple genome and the development of several saturated genetic maps, to which genes controlling important traits are assigned. Markers flanking these genes not only play an important role in selecting parental combinations and seedlings with positive traits, but they are also particularly important in detecting recessive traits, such as seedless fruit. In addition they enable pre-selection for polygenic quantitative traits. In recent years, particular attention has been paid to biochemical and physiological processes involved in the pathway of important traits e.g., ripening and the storage capability of apple fruit.

  14. Identify super quality markers from prototype-based pharmacokinetic markers of Tangzhiqing tablet (TZQ) based on in vitro dissolution/ permeation and in vivo absorption correlations.

    Science.gov (United States)

    Li, Ziqiang; Liu, Jia; Li, Yazhuo; Du, Xi; Li, Yanfen; Wang, Ruihua; Lv, Chunxiao; He, Xin; Wang, Baohe; Huang, Yuhong; Zhang, Deqin

    2018-06-01

    A quality marker (Q-marker) is defined as an inherent chemical compound that is used for the quality control of a drug. Its biological activities are closely related to safety and therapeutic effects. Generally, a multiple-component herbal medicine may have many Q-markers. We therefore proposed a concept of "super Q-marker" satisfying both the criterion of Q-markers and PK-markers to be used in more effective quality control of herbal medicine. The first aim was to find suitable prototype-based PK-markers from Tangzhiqing tablets (TZQ), a Chinese patent medicine. Then super Q-markers were expected to be identified from the prototype-based PK-markers based on an in vitro-in vivo correlation study. Potentially eligible prototype-based PK-markers were identified in a single- and multiple-dose pharmacokinetic study on TZQ in 30 healthy volunteers. The in vitro dissolution and permeation profiles of the prototype-based PK-markers of TZQ were evaluated by the physiologically-based drug dissolution/absorption simulating system (DDASS). An in vitro-in vivo correlation analysis was conducted between the dissolution/permeation behaviors in DDASS and the actual absorption profiles in human to test the transferability and traceability of the promising super Q-markers for TZQ. In human, plasma paeoniflorin and nuciferine as prototype-based PK-markers exhibited the appropriate pharmacokinetic properties, including dose-dependent systemic exposure (AUC, C max ) and a proper elimination half-life (1∼3h). In DDASS, it was predicted that paeoniflorin and nuciferine are highly permeable but the absorption rates are primarily limited by the dissolution rates. Moreover, the established in vitro-in vivo correlations of paeoniflorin and nuciferine were in support of the super Q-markers features. Paeoniflorin and nuciferine are identified as the super Q-markers from the prototype-based PK-markers of TZQ based on findings from a combination of in vitro, in vivo, and in vitro-in vivo

  15. Markers and residual time to AIDS

    NARCIS (Netherlands)

    Geskus, R. B.

    2002-01-01

    The value of immunological and virological markers as predictors of progression to AIDS, or death by AIDS, is a topic of much current interest. Mostly, the influence of markers is investigated in a time-dependent or a baseline proportional hazard model, relating time-varying or baseline marker

  16. From Subordinate Marker to Discourse Marker: que in Andean Spanish

    Directory of Open Access Journals (Sweden)

    Anna María Escobar

    2005-06-01

    Full Text Available This paper proposes an analysis of a redundant use of que ('that' found in Andean Spanish as an expression which has undergone a grammaticalization process. Evidence suggests that the function of que as subordinate marker is much more generalized in this variety than in other dialects of Spanish. que is found to be used as a marker introducing both nominal and adjectival clauses, suggesting that adjectival subordinates behave as nominal subordinates in this variety of Spanish. An intrusive que appears in restricted syntactic and semantic contexts with clauses that have nominal and adjectival functions, and even appears replacing adverbial expressions in some adverbial subordinates (temporal, spatial, and manner. Furthermore, it is found to be sensitive to the degree of the argument’s thematic/semantic function in the subordinate clause. In particular, it seems to occur more often with low-agency arguments in adjectival and nominal contexts, and, in nominal subordinates, tends to appear with a restricted set of epistemic and evidential main verbs (e.g. creer 'to believe', saber 'to know', decir 'to say'. The analysis suggests that que has developed a new function in this variety of Spanish, namely, one of indicating that the information contained in the subordinate clause does not constitute background information (as would be expected in non-contact varieties of Spanish but instead contains information relevant to the discourse.

  17. Oligothiophenes as Fluorescent Markers for Biological Applications

    Directory of Open Access Journals (Sweden)

    Antonio Manetto

    2012-01-01

    Full Text Available This paper summarizes some of our results on the application of oligothiophenes as fluorescent markers for biological studies. The oligomers of thiophene, widely known for their semiconductor properties in organic electronics, are also fluorescent compounds characterized by chemical and optical stability, high absorbance and quantum yield. Their fluorescent emission can be easily modulated via organic synthesis by changing the number of thiophene rings and the nature of side-chains. This review shows how oligothiophenes can be derivatized with active groups such as phosphoramidite, N-hydroxysuccinimidyl and 4-sulfotetrafluorophenyl esters, isothiocyanate and azide by which the (biomolecules of interest can be covalently bound. This paper also describes how molecules such as oligonucleotides, proteins and even nanoparticles, tagged with oligothiophenes, can be used in experiments ranging from hybridization studies to imaging of fixed and living cells. Finally, a few multilabeling experiments are described.

  18. Biological (molecular and cellular) markers of toxicity

    International Nuclear Information System (INIS)

    Shugart, L.R.; D'Surney, S.J.; Gettys-Hull, C.; Greeley, M.S. Jr.

    1991-01-01

    Several molecular and cellular markers of genotoxicity were adapted for measurement in the Medaka (Oryzias latipes), and were used to describe the effects of treatment of the organism with diethylnitrosamine (DEN). NO 6 -ethyl guanine adducts were detected, and a slight statistically significant, increase in DNA strand breaks was observed. These results are consistent with the hypothesis that prolonged exposure to high levels of DEN induced alkyltransferase activity which enzymatically removes any O 6 -ethyl guanine adducts but does not result in strand breaks or hypomethylation of the DNA such as might be expected from excision repair of chemically modified DNA. Following a five week continuous DEN exposure with 100 percent renewal of DEN-water every third day, the F values (DNA double strandedness) increased considerably and to similar extent in fish exposed to 25, 50, and 100 ppM DEN. This has been observed also in medaka exposed to BaP

  19. Potential Audiological and MRI Markers of Tinnitus.

    Science.gov (United States)

    Gopal, Kamakshi V; Thomas, Binu P; Nandy, Rajesh; Mao, Deng; Lu, Hanzhang

    2017-09-01

    Subjective tinnitus, or ringing sensation in the ear, is a common disorder with no accepted objective diagnostic markers. The purpose of this study was to identify possible objective markers of tinnitus by combining audiological and imaging-based techniques. Case-control studies. Twenty adults drawn from our audiology clinic served as participants. The tinnitus group consisted of ten participants with chronic bilateral constant tinnitus, and the control group consisted of ten participants with no history of tinnitus. Each participant with tinnitus was closely matched with a control participant on the basis of age, gender, and hearing thresholds. Data acquisition focused on systematic administration and evaluation of various audiological tests, including auditory-evoked potentials (AEP) and otoacoustic emissions, and magnetic resonance imaging (MRI) tests. A total of 14 objective test measures (predictors) obtained from audiological and MRI tests were subjected to statistical analyses to identify the best predictors of tinnitus group membership. The least absolute shrinkage and selection operator technique for feature extraction, supplemented by the leave-one-out cross-validation technique, were used to extract the best predictors. This approach provided a conservative model that was highly regularized with its error within 1 standard error of the minimum. The model selected increased frontal cortex (FC) functional MRI activity to pure tones matching their respective tinnitus pitch, and augmented AEP wave N₁ amplitude growth in the tinnitus group as the top two predictors of tinnitus group membership. These findings suggest that the amplified responses to acoustic signals and hyperactivity in attention regions of the brain may be a result of overattention among individuals that experience chronic tinnitus. These results suggest that increased functional MRI activity in the FC to sounds and augmented N₁ amplitude growth may potentially be the objective diagnostic

  20. Corneal markers of diabetic neuropathy.

    Science.gov (United States)

    Pritchard, Nicola; Edwards, Katie; Shahidi, Ayda M; Sampson, Geoff P; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

    2011-01-01

    Diabetic neuropathy is a significant clinical problem that currently has no effective therapy, and in advanced cases, leads to foot ulceration and lower limb amputation. The accurate detection, characterization and quantification of this condition are important in order to define at-risk patients, anticipate deterioration, monitor progression, and assess new therapies. This review evaluates novel corneal methods of assessing diabetic neuropathy. Two new noninvasive corneal markers have emerged, and in cross-sectional studies have demonstrated their ability to stratify the severity of this disease. Corneal confocal microscopy allows quantification of corneal nerve parameters and noncontact corneal esthesiometry, the functional correlate of corneal structure, assesses the sensitivity of the cornea. Both these techniques are quick to perform, produce little or no discomfort for the patient, and are suitable for clinical settings. Each has advantages and disadvantages over traditional techniques for assessing diabetic neuropathy. Application of these new corneal markers for longitudinal evaluation of diabetic neuropathy has the potential to reduce dependence on more invasive, costly, and time-consuming assessments, such as skin biopsy.

  1. Molecular Markers for Food Traceability

    Directory of Open Access Journals (Sweden)

    Paula Martins-Lopes

    2013-01-01

    Full Text Available DNA analysis with molecular markers has opened a way to understand complex organism's genome. It is presently being widely applied across different fields, where food takes a preeminent position. Constant outbreaks of foodborne illnesses are increasing consumer's attention towards more detailed information related to what they are consuming. This overview reports on the areas where food traceability has been considered, and the problems that still remain to be bypassed in order to be widely applied. An outline of the most broadly used PCR-based methods for food traceability is described. Applications in the area of detection of genetically modified organisms, protected denomination of origin, allergenic and intolerance reactions are detailed in order to understand the dimension of the performed studies.

  2. Echinococcus metacestode: in search of viability markers.

    Science.gov (United States)

    Gottstein, Bruno; Wang, Junhua; Blagosklonov, Oleg; Grenouillet, Frédéric; Millon, Laurence; Vuitton, Dominique A; Müller, Norbert

    2014-01-01

    Epidemiological studies have demonstrated that most humans infected with Echinococcus spp. exhibit resistance to disease. When infection leads to disease, the parasite is partially controlled by host immunity: in case of immunocompetence, the normal alveolar echinococcosis (AE) or cystic echinococcosis (CE) situation, the metacestode grows slowly, and first clinical signs appear years after infection; in case of impaired immunity (AIDS; other immunodeficiencies), uncontrolled proliferation of the metacestode leads to rapidly progressing disease. Assessing Echinococcus multilocularis viability in vivo following therapeutic interventions in AE patients may be of tremendous benefit when compared with the invasive procedures used to perform biopsies. Current options are F18-fluorodeoxyglucose-positron emission tomography (FDG-PET), which visualizes periparasitic inflammation due to the metabolic activity of the metacestode, and measurement of antibodies against recEm18, a viability-associated protein, that rapidly regresses upon metacestode inactivation. For Echinococcus granulosus, similar prognosis-associated follow-up parameters are still lacking but a few candidates may be listed. Other possible markers include functional and diffusion-weighted Magnetic Resonance Imaging (MRI), and measurement of products from the parasite (circulating antigens or DNA), and from the host (inflammation markers, cytokines, or chemokines). Even though some of them have been promising in pilot studies, none has been properly validated in an appropriate number of patients until now to be recommended for further use in clinical settings. There is therefore still a need to develop reliable tools for improved viability assessment to provide the sufficient information needed to reliably withdraw anti-parasite benzimidazole chemotherapy, and a basis for the development of new alternative therapeutic tools. © B. Gottstein et al., published by EDP Sciences, 2014.

  3. Changes in soluble factor-mediated CD8+ cell-derived antiviral activity in cynomolgus macaques infected with simian immunodeficiency virus SIVmac251: relationship to biological markers of progression.

    Science.gov (United States)

    Dioszeghy, Vincent; Benlhassan-Chahour, Kadija; Delache, Benoit; Dereuddre-Bosquet, Nathalie; Aubenque, Celine; Gras, Gabriel; Le Grand, Roger; Vaslin, Bruno

    2006-01-01

    Cross-sectional studies have shown that the capacity of CD8+ cells from human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV) SIVmac-infected macaques to suppress the replication of human and simian immunodeficiency viruses in vitro depends on the clinical stage of disease, but little is known about changes in this antiviral activity over time in individual HIV-infected patients or SIV-infected macaques. We assessed changes in the soluble factor-mediated noncytolytic antiviral activity of CD8+ cells over time in eight cynomolgus macaques infected with SIVmac251 to determine the pathophysiological role of this activity. CD8+ cell-associated antiviral activity increased rapidly in the first week after viral inoculation and remained detectable during the early phase of infection. The net increase in antiviral activity of CD8+ cells was correlated with plasma viral load throughout the 15 months of follow-up. CD8+ cells gradually lost their antiviral activity over time and acquired virus replication-enhancing capacity. Levels of antiviral activity correlated with CD4+ T-cell counts after viral set point. Concentrations of beta-chemokines and interleukin-16 in CD8+ cell supernatants were not correlated with this antiviral activity, and alpha-defensins were not detected. The soluble factor-mediated antiviral activity of CD8+ cells was neither cytolytic nor restricted to major histocompatibility complex. This longitudinal study strongly suggests that the increase in noncytolytic antiviral activity from baseline and the maintenance of this increase over time in cynomolgus macaques depend on both viral replication and CD4+ T cells.

  4. Changes in Soluble Factor-Mediated CD8+ Cell-Derived Antiviral Activity in Cynomolgus Macaques Infected with Simian Immunodeficiency Virus SIVmac251: Relationship to Biological Markers of Progression†

    Science.gov (United States)

    Dioszeghy, Vincent; Benlhassan-Chahour, Kadija; Delache, Benoit; Dereuddre-Bosquet, Nathalie; Aubenque, Celine; Gras, Gabriel; Le Grand, Roger; Vaslin, Bruno

    2006-01-01

    Cross-sectional studies have shown that the capacity of CD8+ cells from human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV) SIVmac-infected macaques to suppress the replication of human and simian immunodeficiency viruses in vitro depends on the clinical stage of disease, but little is known about changes in this antiviral activity over time in individual HIV-infected patients or SIV-infected macaques. We assessed changes in the soluble factor-mediated noncytolytic antiviral activity of CD8+ cells over time in eight cynomolgus macaques infected with SIVmac251 to determine the pathophysiological role of this activity. CD8+ cell-associated antiviral activity increased rapidly in the first week after viral inoculation and remained detectable during the early phase of infection. The net increase in antiviral activity of CD8+ cells was correlated with plasma viral load throughout the 15 months of follow-up. CD8+ cells gradually lost their antiviral activity over time and acquired virus replication-enhancing capacity. Levels of antiviral activity correlated with CD4+ T-cell counts after viral set point. Concentrations of β-chemokines and interleukin-16 in CD8+ cell supernatants were not correlated with this antiviral activity, and α-defensins were not detected. The soluble factor-mediated antiviral activity of CD8+ cells was neither cytolytic nor restricted to major histocompatibility complex. This longitudinal study strongly suggests that the increase in noncytolytic antiviral activity from baseline and the maintenance of this increase over time in cynomolgus macaques depend on both viral replication and CD4+ T cells. PMID:16352548

  5. Elevated tumour marker: an indication for imaging?

    LENUS (Irish Health Repository)

    McMahon, Colm J

    2012-02-01

    INTRODUCTION: The purpose of this study was to evaluate the utility of imaging examinations in patients with elevated tumour markers when (a) the tumour marker is not validated for as a primary diagnostic test; (b) the patient had no personal history of cancer and (c) the patient had no other imaging indication. MATERIALS AND METHODS: Patients without known cancer who had abnormal carcinoembryonic antigen, CA19-9, CA125 and\\/or CA15-3 serology over a one-year period were included. A retrospective medical record review was performed to assess the number of these cases who underwent imaging because of \\'elevated tumour marker\\' in the absence of a clinical indication for imaging. The number and result of these imaging studies were evaluated. RESULTS: Eight hundred and nineteen patients were included. Of those, 25 patients (mean age: 67.8 [range 41-91] y), were imaged to evaluate: \\'elevated tumour marker\\'. They underwent 29 imaging studies (mean [+\\/-standard deviation (SD)] per patient = 1.2 [+\\/-0.4]), and had 42 elevated tumour marker serology tests (mean [+\\/-SD] per patient = 1.7 [+\\/-0.7]). Four patients had >1 imaging test. No patient had an imaging study which diagnosed a malignancy or explained the elevated tumour marker. CONCLUSION: The non-judicious use of tumour markers can prompt further unnecessary investigations including imaging. In this study, there was no positive diagnostic yield for imaging performed for investigation of \\'elevated tumour marker\\'. \\'Elevated tumour marker\\

  6. Radiographic markers - A reservoir for bacteria?

    International Nuclear Information System (INIS)

    Tugwell, Jenna; Maddison, Adele

    2011-01-01

    Introduction: Amongst the most frequently handled objects in the radiology department are radiographic markers. They are personal accessories used with every patient, and are kept in the radiographers pockets when not utilised. Upon enquiry it was discovered that many radiographers disregarded the potential of these accessories to become a vector for cross-contamination thus never or rarely clean them. The aims of this study were therefore to identify if radiographic markers are a reservoir for bacteria and to establish an effective cleaning method for decontaminating them. Methodology: 25 radiographers/student radiographers were selected for this study. Swabbing of their markers prior and post cleaning took place. The microbiology laboratory subsequently analyzed the results by quantifying and identifying the bacteria present. The participants also completed a closed questionnaire regarding their markers (e.g. frequency of cleaning and type of marker) to help specify the results gained from the swabbing procedure. Results: From the sample swabbed, 92% were contaminated with various organisms including Staphylococcus and Bacillus species, the amount of bacteria present ranged from 0 to >50 CFU. There were no significant differences between disinfectant wipes and alcohol gel in decontaminating the markers. Both successfully reduced their bacterial load, with 80% of the markers post cleaning having 0 CFU. Conclusion: The results indicated that radiographic markers can become highly contaminated with various organisms thus serve as a reservoir for bacteria. In addition, the markers need to be cleaned on a regular basis, with either disinfectant wipes or alcohol gel to reduce their bacterial load.

  7. Identifying genetic marker sets associated with phenotypes via an efficient adaptive score test

    KAUST Repository

    Cai, T.; Lin, X.; Carroll, R. J.

    2012-01-01

    the overall effect of a marker-set have been actively studied in recent years. For example, score tests derived under an Empirical Bayes (EB) framework (Liu and others, 2007. Semiparametric regression of multidimensional genetic pathway data: least

  8. Elimination of ghost markers during dual sensor-based infrared tracking of multiple individual reflective markers

    International Nuclear Information System (INIS)

    Stroian, G.; Falco, T.; Seuntjens, J.P.

    2004-01-01

    The accuracy of dose delivery in radiotherapy is affected by the uncertainty in tumor localization. Motion of internal anatomy due to physiological processes such as respiration may lead to significant displacements which compromise tumor coverage and generate irradiation of healthy tissue. Real-time tracking with infrared-based systems is often used for tracking thoracic motion in radiation therapy. We studied the origin of ghost markers ('crosstalk') which may appear during dual sensor-based infrared tracking of independent reflective markers. Ghost markers occur when two or more reflective markers are coplanar with each other and with the sensors of the two camera-based infrared tracking system. Analysis shows that sensors are not points but they have a finite extent and this extent determines for each marker a 'ghost volume'. If one reflective marker enters the ghost volume of another marker, ghost markers will be reported by the tracking system; if the reflective markers belong to a surface their 'ghost volume' is reduced to a 'ghost surface' (ghost zone). Appearance of ghost markers is predicted for markers taped on the torso of an anthropomorphic phantom. This study illustrates the dependence of the shape, extent, and location of the ghost zones on the shape of the anthropomorphic phantom, the angle of view of the tracking system, and the distance between the tracking system and the anthropomorphic phantom. It is concluded that the appearance of ghost markers can be avoided by positioning the markers outside the ghost zones of the other markers. However, if this is not possible and the initial marker configuration is ghost marker-free, ghost markers can be eliminated during real-time tracking by virtue of the fact that they appear in the coordinate data sequence only temporarily

  9. Cerebrospinal fluid CXCL13 in multiple sclerosis: a suggestive prognostic marker for the disease course

    DEFF Research Database (Denmark)

    Khademi, Mohsen; Kockum, Ingrid; Andersson, Magnus L

    2011-01-01

    Levels of CXCL13, a potent B-cell chemoattractant, are elevated in the cerebrospinal fluid (CSF) during multiple sclerosis (MS) and are associated with markers of MS activity. Levels decrease upon effective treatments.......Levels of CXCL13, a potent B-cell chemoattractant, are elevated in the cerebrospinal fluid (CSF) during multiple sclerosis (MS) and are associated with markers of MS activity. Levels decrease upon effective treatments....

  10. Bladder tumor markers beyond cytology: International Consensus Panel on bladder tumor markers.

    NARCIS (Netherlands)

    Lokeshwar, V.B.; Habuchi, T.; Grossman, H.B.; Murphy, W.M.; Hautmann, S.H.; Hemstreet, G.P.; Bono, A.V.; Getzenberg, R.H.; Goebell, P.; Schmitz-Drager, B.J.; Schalken, J.A.; Fradet, Y.; Marberger, M.; Messing, E.; Droller, M.J.

    2005-01-01

    This is the first of 2 articles that summarize the findings of the International Consensus Panel on cytology and bladder tumor markers. The objectives of our panel were to reach a consensus on the areas where markers are needed, to define the attributes of an ideal tumor marker, and to identify

  11. Tumor markers kits development for use in radioimmunometric assays

    International Nuclear Information System (INIS)

    Ahmed, B.

    1997-01-01

    The immunoassays such as RIA and IRMA are now widely used through the world for the quantitation of a variety of substances in the biological fluid for their high sensibility and specificity which required simple equipments. These techniques are also very used in Algeria for an effective amelioration of public heath The assays kits of RIA/IRMA of thyroid hormones are the most used, followed by peptidic hormones, steroids hormones and IRMA Tumor Markers (T.M) kits. In spite of the important demand, of tumor markers kits for the diagnosis and follow up of cancers their use are always insufficient due to the high cost. The research contract programme proposed by IAEA on the theme 'The Developments of IRMA Tumor Markers Kits' of prostate specific Antigen (PSA) and Tissue Polypeptide Specific Antigen (TPS) will allowed us to produce locally with best quality-price, the main reagents for PSA and TPS IRMA assays kits for diagnosis and follow up the prostate and breast cancers which are very spready in the country. This report include the following points: Generalities on the use of tumor markers in Algeria, programme for the Development of the PSA IRMA assay (schedule of protocols applied for each reagents; annual planning for assessing the programme activities) and conclusion

  12. Development and characterization of microsatellite markers for ...

    Indian Academy of Sciences (India)

    This species is threatened throughout its range in West- ern Ghats as a result of overexploitation and habitat destruc- tion, which have reduced local population sizes and has led many populations to local extinction. In this study, we report the development of microsatellite markers and discuss the utility of these markers in ...

  13. A molecular marker map for roses

    NARCIS (Netherlands)

    Debener, T.; Mattiesch, L.; Vosman, B.

    2001-01-01

    n addition to an existing core map for diploid roses which comprised 305 molecular markers 60 additional markers were mapped to extend the map. As a first application of the information contained in the map, the map position of a resistance gene from roses, Rdr1, was determined by identifying

  14. (SSR) markers for drought tolerance in maize

    African Journals Online (AJOL)

    use

    2011-11-21

    Nov 21, 2011 ... and dominance gene effects in inheritance are included in almost all traits related to drought (Shiri et al., 2010a, b). Identifying the complete-linked molecular markers with target gene and mapping its chromosome locus is an important goal in plant breeding for gene cloning and marker-aided selection.

  15. Marker-Free Human Motion Capture

    DEFF Research Database (Denmark)

    Grest, Daniel

    Human Motion Capture is a widely used technique to obtain motion data for animation of virtual characters. Commercial optical motion capture systems are marker-based. This book is about marker-free motion capture and its possibilities to acquire motion from a single viewing direction. The focus...

  16. germplasm using ISSR markers and their relationships

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-17

    Dec 17, 2008 ... (MAS) is the current trend in 'Modern Agriculture'. These. DNA markers allow the construction of ... are inherited in Mendelian fashion and are scored as dominant markers (Ratnaparkhe et al., 1998) ... ISSR amplified PCR products were resolved on 2% agarose gel in. 1X TBE buffer (89 mM Tris-Hcl, pH 8.3, ...

  17. Chromosomal location of genomic SSR markers associated

    Indian Academy of Sciences (India)

    Among the same earlier tested 230 primers, one SSR marker (Xgwm311) also amplified a fragment which is present in the resistant parent and in the resistant bulks, but absent in the susceptible parent and in the susceptible bulks. To understand the chromosome group location of these diagnostic markers, Xgwm382 and ...

  18. Phosphoproteins in extracellular vesicles as candidate markers for breast cancer

    OpenAIRE

    Chen, I-Hsuan; Xue, Liang; Hsu, Chuan-Chih; Paez, Juan Sebastian Paez; Pan, Li; Andaluz, Hillary; Wendt, Michael K.; Iliuk, Anton B.; Zhu, Jian-Kang; Tao, W. Andy

    2017-01-01

    Protein phosphorylation is a major regulatory mechanism for many cellular functions, but no phosphoprotein in biofluids has been developed for disease diagnosis because of the presence of active phosphatases. This study presents a general strategy to isolate and identify phosphoproteins in extracellular vesicles (EVs) from human plasma as potential markers to differentiate disease from healthy states. We identified close to 10,000 unique phosphopeptides in EVs from small volumes of plasma sam...

  19. Real-time tumor tracking using implanted positron emission markers: Concept and simulation study

    International Nuclear Information System (INIS)

    Xu Tong; Wong, Jerry T.; Shikhaliev, Polad M.; Ducote, Justin L.; Al-Ghazi, Muthana S.; Molloi, Sabee

    2006-01-01

    The delivery accuracy of radiation therapy for pulmonary and abdominal tumors suffers from tumor motion due to respiration. Respiratory gating should be applied to avoid the use of a large target volume margin that results in a substantial dose to the surrounding normal tissue. Precise respiratory gating requires the exact spatial position of the tumor to be determined in real time during treatment. Usually, fiducial markers are implanted inside or next to the tumor to provide both accurate patient setup and real-time tumor tracking. However, current tumor tracking systems require either substantial x-ray exposure to the patient or large fiducial markers that limit the value of their application for pulmonary tumors. We propose a real-time tumor tracking system using implanted positron emission markers (PeTrack). Each marker will be labeled with low activity positron emitting isotopes, such as 124 I, 74 As, or 84 Rb. These isotopes have half-lives comparable to the duration of radiation therapy (from a few days to a few weeks). The size of the proposed PeTrack marker will be 0.5-0.8 mm, which is approximately one-half the size of markers currently employed in other techniques. By detecting annihilation gammas using position-sensitive detectors, multiple positron emission markers can be tracked in real time. A multimarker localization algorithm was developed using an Expectation-Maximization clustering technique. A Monte Carlo simulation model was developed for the PeTrack system. Patient dose, detector sensitivity, and scatter fraction were evaluated. Depending on the isotope, the lifetime dose from a 3.7 MBq PeTrack marker was determined to be 0.7-5.0 Gy at 10 mm from the marker. At the center of the field of view (FOV), the sensitivity of the PeTrack system was 240-320 counts/s per 1 MBq marker activity within a 30 cm thick patient. The sensitivity was reduced by 45% when the marker was near the edge of the FOV. The scatter fraction ranged from 12% ( 124 I, 74 As

  20. The Alcohol Dehydrogenase Isoenzyme as a Potential Marker of Pancreatitis.

    Science.gov (United States)

    Jelski, Wojciech; Piechota, Joanna; Orywal, Karolina; Szmitkowski, Maciej

    2018-05-01

    Human pancreas parenchyma contains various alcohol dehydrogenase (ADH) isoenzymes and also possesses aldehyde dehydrogenase (ALDH) activity. The altered activities of ADH and ALDH in damaged pancreatic tissue in the course of pancreatitis are reflected in the human serum. The aim of this study was to investigate a potential role of ADH and ALDH as markers for acute (AP) and chronic pancreatitis (CP). Serum samples were collected for routine biochemical investigations from 75 patients suffering from acute pancreatitis and 70 patients with chronic pancreatitis. Fluorometric methods were used to measure the activity of class I and II ADH and ALDH activity. The total ADH activity and activity of class III and IV isoenzymes were measured by a photometric method. There was a significant increase in the activity of ADH III isoenzyme (15.06 mU/l and 14.62 mU/l vs. 11.82 mU/l; ppancreatitis or chronic pancreatitis compared to the control. The diagnostic sensitivity for ADH III was about 84%, specificity was 92 %, positive and negative predictive values were 93% and 87% respectively in acute pancreatitis. Area under the Receiver Operating Curve (ROC) curve for ADH III in AP and CP was 0.88 and 0.86 respectively. ADH III has a potential role as a marker of acute and chronic pancreatitis. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. Hands as markers of fragmentation

    Directory of Open Access Journals (Sweden)

    A. Barnard

    2005-07-01

    Full Text Available Margaret Atwood is an internationally read, translated, and critiqued writer whose novels have established her as one of the most esteemed authors in English (McCombs & Palmer, 1991:1. Critical studies of her work deal mainly with notions of identity from psychoanalytical perspectives. This study has identified a gap in current critical studies on Atwood’s works, namely the challenging of textual unity which is paralleled in the challenging of the traditional (single narrative voice. The challenging of textual unity and the single narrative voice brings about the fragmentation of both. This article will focus on the role that hands play as markers of fragmentation in “The Blind Assassin” (2000. In the novel, the writing hand destabilises the narrative voice, since it is not connected to the voice of a single author. If the author of the text – the final signified – is eliminated, the text becomes fragmentary and open, inviting the reader to contribute to the creation of meaning. Hands play a signficant role in foregrounding the narrator’s fragmented identity, and consequently, the fragmentation of the text. We will investigate this concept in the light of Roland Barthes’ notion of the scriptor, whose hand is metaphorically severed from his or her “voice”. Instead of the text being a unified entity, it becomes unstable and it displays the absence of hierarchical textual levels. Based mainly on Barthes’ writings, this article concludes that hands foreground the narrator’s fragmented identity, which is paralleled in the fragmented text.

  2. Markers for nutrition studies: review of criteria for the evaluation of markers.

    Science.gov (United States)

    de Vries, Jan; Antoine, Jean-Michel; Burzykowski, Tomasz; Chiodini, Alessandro; Gibney, Mike; Kuhnle, Gunter; Méheust, Agnès; Pijls, Loek; Rowland, Ian

    2013-10-01

    Markers are important tools to assess the nutrition status and effects of nutrition interventions. There is currently insufficient consensus in nutrition sciences on how to evaluate markers, despite the need for properly evaluating them. To identify the criteria for the evaluation of markers related to nutrition, health and disease and to propose generic criteria for evaluation. The report on "Evaluation of Biomarker and Surrogate Endpoints in Chronic Disease" from the Institute of Medicine was the starting point for the literature search. Additionally, specific search strategies were developed for Pubmed. In nutrition, no set of criteria or systematic approach to evaluate markers is currently available. There is a reliance on the medical area where statistical methods have been developed to quantify the evaluation of markers. Even here, a systematic approach is lacking-markers are still evaluated on a case-by-case basis. The review of publications from the literature search resulted in a database with definitions, criteria for validity and the rationale behind the criteria. It was recognized that, in nutrition, a number of methodological aspects differ from medical research. The following criteria were identified as essential elements in the evaluation of markers: (1) the marker has a causal biological link with the endpoint, (2) there is a significant association between marker and endpoint in the target population, (3) marker changes consistently with the endpoint, e.g., in response to an intervention, and (4) change in the marker explains a substantial proportion of the change in the endpoint in response to the intervention.

  3. Intersection tests for single marker QTL analysis can be more powerful than two marker QTL analysis

    Directory of Open Access Journals (Sweden)

    Doerge RW

    2003-06-01

    Full Text Available Abstract Background It has been reported in the quantitative trait locus (QTL literature that when testing for QTL location and effect, the statistical power supporting methodologies based on two markers and their estimated genetic map is higher than for the genetic map independent methodologies known as single marker analyses. Close examination of these reports reveals that the two marker approaches are more powerful than single marker analyses only in certain cases. Simulation studies are a commonly used tool to determine the behavior of test statistics under known conditions. We conducted a simulation study to assess the general behavior of an intersection test and a two marker test under a variety of conditions. The study was designed to reveal whether two marker tests are always more powerful than intersection tests, or whether there are cases when an intersection test may outperform the two marker approach. We present a reanalysis of a data set from a QTL study of ovariole number in Drosophila melanogaster. Results Our simulation study results show that there are situations where the single marker intersection test equals or outperforms the two marker test. The intersection test and the two marker test identify overlapping regions in the reanalysis of the Drosophila melanogaster data. The region identified is consistent with a regression based interval mapping analysis. Conclusion We find that the intersection test is appropriate for analysis of QTL data. This approach has the advantage of simplicity and for certain situations supplies equivalent or more powerful results than a comparable two marker test.

  4. Markers of Deception in Italian Speech

    Directory of Open Access Journals (Sweden)

    Katelyn eSpence

    2012-10-01

    Full Text Available Lying is a universal activity and the detection of lying a universal concern. Presently, there is great interest in determining objective measures of deception. The examination of speech, in particular, holds promise in this regard; yet, most of what we know about the relationship between speech and lying is based on the assessment of English-speaking participants. Few studies have examined indicators of deception in languages other than English. The world’s languages differ in significant ways, and cross-linguistic studies of deceptive communications are a research imperative. Here we review some of these differences amongst the world’s languages, and provide an overview of a number of recent studies demonstrating that cross-linguistic research is a worthwhile endeavour. In addition, we report the results of an empirical investigation of pitch, response latency, and speech rate as cues to deception in Italian speech. True and false opinions were elicited in an audio-taped interview. A within subjects analysis revealed no significant difference between the average pitch of the two conditions; however, speech rate was significantly slower, while response latency was longer, during deception compared with truth-telling. We explore the implications of these findings and propose directions for future research, with the aim of expanding the cross-linguistic branch of research on markers of deception.

  5. Comparison between low-cost marker-less and high-end marker-based motion capture systems for the computer-aided assessment of working ergonomics.

    Science.gov (United States)

    Patrizi, Alfredo; Pennestrì, Ettore; Valentini, Pier Paolo

    2016-01-01

    The paper deals with the comparison between a high-end marker-based acquisition system and a low-cost marker-less methodology for the assessment of the human posture during working tasks. The low-cost methodology is based on the use of a single Microsoft Kinect V1 device. The high-end acquisition system is the BTS SMART that requires the use of reflective markers to be placed on the subject's body. Three practical working activities involving object lifting and displacement have been investigated. The operational risk has been evaluated according to the lifting equation proposed by the American National Institute for Occupational Safety and Health. The results of the study show that the risk multipliers computed from the two acquisition methodologies are very close for all the analysed activities. In agreement to this outcome, the marker-less methodology based on the Microsoft Kinect V1 device seems very promising to promote the dissemination of computer-aided assessment of ergonomics while maintaining good accuracy and affordable costs. PRACTITIONER’S SUMMARY: The study is motivated by the increasing interest for on-site working ergonomics assessment. We compared a low-cost marker-less methodology with a high-end marker-based system. We tested them on three different working tasks, assessing the working risk of lifting loads. The two methodologies showed comparable precision in all the investigations.

  6. MOLECULAR MARKERS FOR METASTATIC PROSTATE ADENOCARCINOMA

    Directory of Open Access Journals (Sweden)

    I. S. Kunin

    2012-01-01

    Full Text Available The search of molecular markers of metastasing and prognosis in prostate cancer remains an urgent task. In this study, we investigated the relationship of gene expression heparanase-1 (HPSE1 and D-glucuronil C5-epimerase (GLCE with early disease relapse and metastasis of a 2,5−3 years after diagnosis. It was shown that the ratio of the expression levels of genes HPSE1/GLCE > 1 may serve as a prognostic relapse marker and trends of the tumour to metastasis. The data obtained suggest to use this option as a molecular marker for the diagnostics of metastatic process and the disease prognosis.

  7. Immunocytochemistry of the olfactory marker protein.

    Science.gov (United States)

    Monti-Graziadei, G A; Margolis, F L; Harding, J W; Graziadei, P P

    1977-12-01

    The olfactory marker protein has been localized, by means of immunohistochemical techniques in the primary olfactory neurons of mice. The olfactory marker protein is not present in the staminal cells of the olfactory neuroepithelium, and the protein may be regarded as indicative of the functional stage of the neurons. Our data indicate that the olfactory marker protein is present in the synaptic terminals of the olfactory neurons at the level of the olfactory bulb glomeruli. The postsynaptic profiles of both mitral and periglomerular cells are negative.

  8. Stemness-related markers in cancer

    Directory of Open Access Journals (Sweden)

    Wenxiu Zhao

    2017-01-01

    Full Text Available Cancer stem cells (CSCs, with their self-renewal ability and multilineage differentiation potential, are a critical subpopulation of tumor cells that can drive tumor initiation, growth, and resistance to therapy. Like embryonic and adult stem cells, CSCs express markers that are not expressed in normal somatic cells and are thus thought to contribute toward a “stemness” phenotype. This review summarizes the current knowledge of stemness-related markers in human cancers, with a particular focus on important transcription factors, protein surface markers, and signaling pathways.

  9. An in-vitro approach for water quality determination: activation of NF-κB as marker for cancer-related stress responses induced by anthropogenic pollutants of drinking water.

    Science.gov (United States)

    Spitta, Luis F; Diegeler, Sebastian; Baumstark-Khan, Christa; Hellweg, Christine E

    2018-02-01

    Epidemiological studies show that there is a link between urban water pollution and increase in human morbidity and mortality. With the increase in number of new substances arising from the chemical, pharmaceutical, and agricultural industries, there is an urgent need to develop biological test systems for fast evaluation of potential risks to humans and the environmental ecosystems. Here, a combined cellular reporter assay based on the cellular survival and the stress-induced activation of the survival-promoting factor nuclear factor κB (NF-κB) and its use for the detection of cytotoxicity and cancer-related stress responses is presented. A total of 14 chemicals that may be found in trace-amounts in ground water levels are applied and tested with the presented assay. The project is embedded within the joint research project TOX-BOX which aims to develop a harmonized testing strategy for risk management of anthropogenic trace substances in potable water. The assay identified carbendazim as a NF-κB-activating agent in mammalian cells.

  10. Dengue-2 and yellow fever 17DD viruses infect human dendritic cells, resulting in an induction of activation markers, cytokines and chemokines and secretion of different TNF-α and IFN-α profiles

    Directory of Open Access Journals (Sweden)

    Mariana Gandini

    2011-08-01

    Full Text Available Flaviviruses cause severe acute febrile and haemorrhagic infections, including dengue and yellow fever and the pathogenesis of these infections is caused by an exacerbated immune response. Dendritic cells (DCs are targets for dengue virus (DENV and yellow fever virus (YF replication and are the first cell population to interact with these viruses during a natural infection, which leads to an induction of protective immunity in humans. We studied the infectivity of DENV2 (strain 16681, a YF vaccine (YF17DD and a chimeric YF17D/DENV2 vaccine in monocyte-derived DCs in vitro with regard to cell maturation, activation and cytokine production. Higher viral antigen positive cell frequencies were observed for DENV2 when compared with both vaccine viruses. Flavivirus-infected cultures exhibited dendritic cell activation and maturation molecules. CD38 expression on DCs was enhanced for both DENV2 and YF17DD, whereas OX40L expression was decreased as compared to mock-stimulated cells, suggesting that a T helper 1 profile is favoured. Tumor necrosis factor (TNF-α production in cell cultures was significantly higher in DENV2-infected cultures than in cultures infected with YF17DD or YF17D/DENV. In contrast, the vaccines induced higher IFN-α levels than DENV2. The differential cytokine production indicates that DENV2 results in TNF induction, which discriminates it from vaccine viruses that preferentially stimulate interferon expression. These differential response profiles may influence the pathogenic infection outcome.

  11. [A Method for Selecting Self-Adoptive Chromaticity of the Projected Markers].

    Science.gov (United States)

    Zhao, Shou-bo; Zhang, Fu-min; Qu, Xing-hua; Zheng, Shi-wei; Chen, Zhe

    2015-04-01

    The authors designed a self-adaptive projection system which is composed of color camera, projector and PC. In detail, digital micro-mirror device (DMD) as a spatial light modulator for the projector was introduced in the optical path to modulate the illuminant spectrum based on red, green and blue light emitting diodes (LED). However, the color visibility of active markers is affected by the screen which has unknown reflective spectrum as well. Here active markers are projected spot array. And chromaticity feature of markers is sometimes submerged in similar spectral screen. In order to enhance the color visibility of active markers relative to screen, a method for selecting self-adaptive chromaticity of the projected markers in 3D scanning metrology is described. Color camera with 3 channels limits the accuracy of device characterization. For achieving interconversion of device-independent color space and device-dependent color space, high-dimensional linear model of reflective spectrum was built. Prior training samples provide additional constraints to yield high-dimensional linear model with more than three degrees of freedom. Meanwhile, spectral power distribution of ambient light was estimated. Subsequently, markers' chromaticity in CIE color spaces was selected via maximization principle of Euclidean distance. The setting values of RGB were easily estimated via inverse transform. Finally, we implemented a typical experiment to show the performance of the proposed approach. An 24 Munsell Color Checker was used as projective screen. Color difference in the chromaticity coordinates between the active marker and the color patch was utilized to evaluate the color visibility of active markers relative to the screen. The result comparison between self-adaptive projection system and traditional diode-laser light projector was listed and discussed to highlight advantage of our proposed method.

  12. Use of a human chromosome 11 radiation hybrid panel to map markers at 11q13

    International Nuclear Information System (INIS)

    Withers, D.; Richard, C. III; Meeker, T.C.; Maurer, S.; Evans, G.; Myers, R.M.; Cox, D.R.

    1990-01-01

    A human/hamster hybrid cell line containing human chromosome 11 was X-irradiated and 102-independent derivative lines were recovered. These 'radiation hybrids' contain random fragments of human chromosome 11. This radiation hybrid panel was used to score the retention of markers at band 11q13. Statistical analysis of marker co-retention patterns in the radiation hybrid panel permits a preliminary ordering and mapping of the markers used. The best order for six scored markers is: proximal - CD5 - CD20 - PGA - HST - BCL1 - SEA - distal. Additional markers are currently being scored. The six 11q13 markers above are spread over approximately 10-12 mB of DNA. The mapping data has implications for the identification of the bcl-1 gene. bcl-1 is the site of chromosome breakage in translocations associated with B lymphocytic malignancy. bcl-1 markers map at least 4 Mb away from any of four genes previously hypothesized to be activated by such translocations, thereby making them unlikely candidates for activation

  13. Genomic markers for decision making: what is preventing us from using markers?

    Science.gov (United States)

    Coyle, Vicky M; Johnston, Patrick G

    2010-02-01

    The advent of novel genomic technologies that enable the evaluation of genomic alterations on a genome-wide scale has significantly altered the field of genomic marker research in solid tumors. Researchers have moved away from the traditional model of identifying a particular genomic alteration and evaluating the association between this finding and a clinical outcome measure to a new approach involving the identification and measurement of multiple genomic markers simultaneously within clinical studies. This in turn has presented additional challenges in considering the use of genomic markers in oncology, such as clinical study design, reproducibility and interpretation and reporting of results. This Review will explore these challenges, focusing on microarray-based gene-expression profiling, and highlights some common failings in study design that have impacted on the use of putative genomic markers in the clinic. Despite these rapid technological advances there is still a paucity of genomic markers in routine clinical use at present. A rational and focused approach to the evaluation and validation of genomic markers is needed, whereby analytically validated markers are investigated in clinical studies that are adequately powered and have pre-defined patient populations and study endpoints. Furthermore, novel adaptive clinical trial designs, incorporating putative genomic markers into prospective clinical trials, will enable the evaluation of these markers in a rigorous and timely fashion. Such approaches have the potential to facilitate the implementation of such markers into routine clinical practice and consequently enable the rational and tailored use of cancer therapies for individual patients.

  14. Voice analysis as an objective state marker in bipolar disorder

    DEFF Research Database (Denmark)

    Faurholt-Jepsen, M.; Busk, Jonas; Frost, M.

    2016-01-01

    Changes in speech have been suggested as sensitive and valid measures of depression and mania in bipolar disorder. The present study aimed at investigating (1) voice features collected during phone calls as objective markers of affective states in bipolar disorder and (2) if combining voice...... features, automatically generated objective smartphone data on behavioral activities and electronic self-monitored data were collected from 28 outpatients with bipolar disorder in naturalistic settings on a daily basis during a period of 12 weeks. Depressive and manic symptoms were assessed using...... and electronic self-monitored data increased the accuracy, sensitivity and specificity of classification of affective states slightly. Voice features collected in naturalistic settings using smartphones may be used as objective state markers in patients with bipolar disorder....

  15. Biochemical Markers for Osteoarthritis: Is There any Promising Candidate?

    Directory of Open Access Journals (Sweden)

    Elif Aydın

    2016-04-01

    Full Text Available Osteoarthritis (OA is the most common degenerative joint disease. OA affects millions of individuals each year and becoming the most important cause of pain in geriatric population. Progressive destruction of articular cartilage is one of the prominent features of the disease. The diagnosis of OA is generally based on clinical and radiographical findings, which are insufficient to determine early-stage OA and predict disease course. There is a need for biomarkers that help clinicians early diagnose, assess disease activity, predict prognosis and monitor response to therapy. There are a growing number of publications regarding candidate markers in this field. The aim of this paper was to review recent studies on biochemical markers that reflect cartilage, synovial and bone turnover and their clinical use in patients with OA.

  16. SU-G-BRA-10: Marker Free Lung Tumor Motion Tracking by An Active Contour Model On Cone Beam CT Projections for Stereotactic Body Radiation Therapy of Lung Cancer

    International Nuclear Information System (INIS)

    Chao, M; Yuan, Y; Lo, Y; Wei, J

    2016-01-01

    Purpose: To develop a novel strategy to extract the lung tumor motion from cone beam CT (CBCT) projections by an active contour model with interpolated respiration learned from diaphragm motion. Methods: Tumor tracking on CBCT projections was accomplished with the templates derived from planning CT (pCT). There are three major steps in the proposed algorithm: 1) The pCT was modified to form two CT sets: a tumor removed pCT and a tumor only pCT, the respective digitally reconstructed radiographs DRRtr and DRRto following the same geometry of the CBCT projections were generated correspondingly. 2) The DRRtr was rigidly registered with the CBCT projections on the frame-by-frame basis. Difference images between CBCT projections and the registered DRRtr were generated where the tumor visibility was appreciably enhanced. 3) An active contour method was applied to track the tumor motion on the tumor enhanced projections with DRRto as templates to initialize the tumor tracking while the respiratory motion was compensated for by interpolating the diaphragm motion estimated by our novel constrained linear regression approach. CBCT and pCT from five patients undergoing stereotactic body radiotherapy were included in addition to scans from a Quasar phantom programmed with known motion. Manual tumor tracking was performed on CBCT projections and was compared to the automatic tracking to evaluate the algorithm accuracy. Results: The phantom study showed that the error between the automatic tracking and the ground truth was within 0.2mm. For the patients the discrepancy between the calculation and the manual tracking was between 1.4 and 2.2 mm depending on the location and shape of the lung tumor. Similar patterns were observed in the frequency domain. Conclusion: The new algorithm demonstrated the feasibility to track the lung tumor from noisy CBCT projections, providing a potential solution to better motion management for lung radiation therapy.

  17. SU-G-BRA-10: Marker Free Lung Tumor Motion Tracking by An Active Contour Model On Cone Beam CT Projections for Stereotactic Body Radiation Therapy of Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chao, M; Yuan, Y; Lo, Y [The Mount Sinai Medical Center, New York, NY (United States); Wei, J [City College of New York, New York, NY (United States)

    2016-06-15

    Purpose: To develop a novel strategy to extract the lung tumor motion from cone beam CT (CBCT) projections by an active contour model with interpolated respiration learned from diaphragm motion. Methods: Tumor tracking on CBCT projections was accomplished with the templates derived from planning CT (pCT). There are three major steps in the proposed algorithm: 1) The pCT was modified to form two CT sets: a tumor removed pCT and a tumor only pCT, the respective digitally reconstructed radiographs DRRtr and DRRto following the same geometry of the CBCT projections were generated correspondingly. 2) The DRRtr was rigidly registered with the CBCT projections on the frame-by-frame basis. Difference images between CBCT projections and the registered DRRtr were generated where the tumor visibility was appreciably enhanced. 3) An active contour method was applied to track the tumor motion on the tumor enhanced projections with DRRto as templates to initialize the tumor tracking while the respiratory motion was compensated for by interpolating the diaphragm motion estimated by our novel constrained linear regression approach. CBCT and pCT from five patients undergoing stereotactic body radiotherapy were included in addition to scans from a Quasar phantom programmed with known motion. Manual tumor tracking was performed on CBCT projections and was compared to the automatic tracking to evaluate the algorithm accuracy. Results: The phantom study showed that the error between the automatic tracking and the ground truth was within 0.2mm. For the patients the discrepancy between the calculation and the manual tracking was between 1.4 and 2.2 mm depending on the location and shape of the lung tumor. Similar patterns were observed in the frequency domain. Conclusion: The new algorithm demonstrated the feasibility to track the lung tumor from noisy CBCT projections, providing a potential solution to better motion management for lung radiation therapy.

  18. Tumor markers: applications and recommendations. New IZOTOPE products

    International Nuclear Information System (INIS)

    Gyenes, Ana Rosa

    2016-01-01

    At work aspects are discussed: Tumor markers; New products IZOTOP; Measuring principle of IRMA kits for tumor markers; Guidelines and Recommendations for the use of tumor markers. pre-analytical, post-analytical and Quality control recommendations are given

  19. Diagnostic markers for germ cell neoplasms

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, Ewa; Nielsen, John E; Skakkebaek, Niels E

    2015-01-01

    This concise review summarises tissue and serum markers useful for differential diagnosis of germ cell tumours (GCTs), with focus on the most common testicular GCTs (TGCTs). GCTs are characterised by phenotypic heterogeneity due to largely retained embryonic pluripotency and aberrant somatic diff...... of molecular markers, which allow specific diagnosis of various subtypes of GCT and are very useful for early detection at the precursor stage and for monitoring of patients during the follow-up....

  20. Systematic study of the ion beam mixing of oxide markers into alumina

    International Nuclear Information System (INIS)

    Cooper, E.A.; Kung, H.; Nastasi, M.

    1995-01-01

    The study of ion beam mixing of layered compositions is important in two regards: first, there is the potential of alloying the layers into a new functionally different composition and, secondly, from a fundamental aspect, it is important be able to anticipate the potential damage due to degradation of the layer structure that could be caused in these materials due to a radiation environment. The authors have completed a systematic study of ion beam mixing of thin marker layers into amorphous alumina. The degree of mixing was found to be controlled by thermodynamic factors, the nature of the marker (oxidation state), and matrix crystallinity. Ballistic mixing was observed for all markers, but the mixing of some oxide markers exhibits a thermally activated regime at higher temperatures. The experiments were conducted from a low temperature of -170 C to a maximum temperature of 75O C. 210 keV Ar was used to ion beam mix the marker layer at the various temperatures. The marker spreading was analyzed using RBS. The mixing of one marker (Fe 2 O 3 ) into crystalline alumina (sapphire) was compared to that of the amorphous alumina. It was found that the marker mixed asymmetrically into the two matrix materials, with a higher degree of mixing into the amorphous matrix. TEM cross-section results verify that there is a preference for the marker to mix into the amorphous alumina layer preferentially to the crystalline layer. The interest in ion beam mixing of marker layers in ceramic systems is motivated by the fact that layered oxides are technologically important materials for fusion reactor applications

  1. Effect of UV-irradiation on immunological and histochemical markers of Langerhans cells in normal appearing skin of psoriatic patients

    International Nuclear Information System (INIS)

    Tjernlund, U.; Juhlin, L.

    1982-01-01

    A total of 12 patients with moderately severe psoriasis was treated with psoralen baths and/or ultraviolet radiation. Punch biopsies were taken for mimunological markers and shave biopsies for ATPase detection. As immunological marker immunosorbent purified antibodies against Ia antigens and monoclonal antigens against thymocyte antigens were used. The study showed that in the clinical relevant situation PUVA treatment had a more profound effect on the immunological markers of epidermal Langerhans cells than had light treatment without psoralens. With UV treatment without psoralens the ATPase activity of the Langerhans cells seemed to be more influenced than the immunological markers. (orig.)

  2. Oxidative stress markers, cognitive functions, and psychosocial functioning in bipolar disorder: an empirical cross-sectional study.

    Science.gov (United States)

    Aydemir, Ömer; Çubukçuoğlu, Zeynep; Erdin, Soner; Taş, Cumhur; Onur, Ece; Berk, Michael

    2014-01-01

    This study aimed to evaluate the relationship between oxidative stress markers and cognitive functions and domains of psychosocial functioning in bipolar disorder. Oxidative stress markers, cognitive functions, and domains of psychosocial functioning were evaluated in 51 patients with bipolar disorder who were in remission. Correlation analyses between these parameters were calculated with data controlled for duration of illness and number of episodes. There was no statistically significant correlation between oxidative stress markers and cognitive functions. In terms of psychosocial functioning, significant correlations were found between malondialdehyde and sense of stigmatization (r = -0.502); household activities and superoxide dismutase (r = 0.501); participation in social activities and nitric oxide (r = 0.414); hobbies and leisure time activities and total glutathione (r = -0.567), superoxide dismutase (r = 0.667), and neurotrophin 4 (r = 0.450); and taking initiative and self-sufficiency and superoxide dismutase (r = 0.597). There was no correlation between other domains of psychosocial functioning and oxidative stress markers. These results imply that oxidative stress markers do not appear to correlate clearly with cognitive impairment and reduced psychosocial functioning. However, there were some associations between selected oxidative markers and activity-oriented functional markers. This may represent a true negative association, or may be an artifact of oxidative stress being a state rather than a trait marker.

  3. Oxidative stress markers, cognitive functions, and psychosocial functioning in bipolar disorder: an empirical cross-sectional study

    Directory of Open Access Journals (Sweden)

    Ömer Aydemir

    2014-12-01

    Full Text Available Objective: This study aimed to evaluate the relationship between oxidative stress markers and cognitive functions and domains of psychosocial functioning in bipolar disorder. Methods: Oxidative stress markers, cognitive functions, and domains of psychosocial functioning were evaluated in 51 patients with bipolar disorder who were in remission. Correlation analyses between these parameters were calculated with data controlled for duration of illness and number of episodes. Results: There was no statistically significant correlation between oxidative stress markers and cognitive functions. In terms of psychosocial functioning, significant correlations were found between malondialdehyde and sense of stigmatization (r = -0.502; household activities and superoxide dismutase (r = 0.501; participation in social activities and nitric oxide (r = 0.414; hobbies and leisure time activities and total glutathione (r = -0.567, superoxide dismutase (r = 0.667, and neurotrophin 4 (r = 0.450; and taking initiative and self-sufficiency and superoxide dismutase (r = 0.597. There was no correlation between other domains of psychosocial functioning and oxidative stress markers. Conclusion: These results imply that oxidative stress markers do not appear to correlate clearly with cognitive impairment and reduced psychosocial functioning. However, there were some associations between selected oxidative markers and activity-oriented functional markers. This may represent a true negative association, or may be an artifact of oxidative stress being a state rather than a trait marker.

  4. Circulating Markers of Vascular Injury and Angiogenesis in ANCA-Associated Vasculitis

    Science.gov (United States)

    Monach, Paul A; Tomasson, Gunnar; Specks, Ulrich; Stone, John H; Cuthbertson, David; Krischer, Jeffrey; Ding, Linna; Fervenza, Fernando C; Fessler, Barri J; Hoffman, Gary S; Ikle, David; Kallenberg, Cees GM; Langford, Carol A; Mueller, Mark; Seo, Philip; St.Clair, E William; Spiera, Robert; Tchao, Nadia; Ytterberg, Steven R; Gu, Yi-Zhong; Snyder, Ronald D; Merkel, Peter A

    2011-01-01

    Objective To identify biomarkers that distinguish between active ANCA-associated vasculitis (AAV) and remission in a manner superior or complementary to established markers of systemic inflammation. Methods Markers of vascular injury and angiogenesis were measured before and after treatment in a large clinical trial in AAV. 163 subjects enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial were studied. Serum levels of E-selectin, ICAM-3, MMP1, MMP3, MMP9, P-selectin, thrombomodulin, and VEGF were measured at study screening (time of active disease) and at month 6. ESR and CRP levels had been measured at the time of the clinical visit. The primary outcome was the difference in marker level between screening and month 6 among patients in remission (BVAS/WG score of 0) at month 6. Results All subjects had severe active vasculitis (mean BVAS/WG score 8.6 +/− 3.2 SD) at screening. Among the 123 subjects clinically in remission at month 6, levels of all markers except E-selectin showed significant declines. MMP3 levels were also higher among the 23 subjects with active disease at month 6 than among the 123 subjects in remission. MMP3 levels correlated weakly with ESR and CRP. Conclusion Many markers of vascular injury and angiogenesis are elevated in severe active AAV and decline with treatment, but MMP3 appears to distinguish active AAV from remission better than the other markers studied. Further study of MMP3 is warranted to determine its clinical utility in combination with conventional markers of inflammation and ANCA titers. PMID:21953143

  5. Enzyme markers in inbred rat strains: genetics of new markers and strain profiles.

    Science.gov (United States)

    Adams, M; Baverstock, P R; Watts, C H; Gutman, G A

    1984-08-01

    Twenty-six inbred strains of the laboratory rat (Rattus norvegicus) were examined for electrophoretic variation at an estimated 97 genetic loci. In addition to previously documented markers, variation was observed for the enzymes aconitase, aldehyde dehydrogenase, and alkaline phosphatase. The genetic basis of these markers (Acon-1, Ahd-2, and Akp-1) was confirmed. Linkage analysis between 35 pairwise comparisons revealed that the markers Fh-1 and Pep-3 are linked. The strain profiles of the 25 inbred strains at 11 electrophoretic markers are given.

  6. Scaffold protein JLP mediates TCR-initiated CD4+T cell activation and CD154 expression.

    Science.gov (United States)

    Yan, Qi; Yang, Cheng; Fu, Qiang; Chen, Zhaowei; Liu, Shan; Fu, Dou; Rahman, Rahmat N; Nakazato, Ryota; Yoshioka, Katsuji; Kung, Sam K P; Ding, Guohua; Wang, Huiming

    2017-07-01

    CD4 + T-cell activation and its subsequent induction of CD154 (CD40 ligand, CD40L) expression are pivotal in shaping both the humoral and cellular immune responses. Scaffold protein JLP regulates signal transduction pathways and molecular trafficking inside cells, thus represents a critical component in maintaining cellular functions. Its role in regulating CD4 + T-cell activation and CD154 expression, however, is unclear. Here, we demonstrated expression of JLP in mouse tissues of lymph nodes, thymus, spleen, and also CD4 + T cells. Using CD4+ T cells from jlp-deficient and jlp-wild-type mice, we demonstrated that JLP-deficiency impaired T-cell proliferation, IL-2 production, and CD154 induction upon TCR stimulations, but had no impacts on the expression of other surface molecules such as CD25, CD69, and TCR. These observed impaired T-cell functions in the jlp-/- CD4 + T cells were associated with defective NF-AT activation and Ca 2 + influx, but not the MAPK, NF-κB, as well as AP-1 signaling pathways. Our findings indicated that, for the first time, JLP plays a critical role in regulating CD4 + T cells response to TCR stimulation partly by mediating the activation of TCR-initiated Ca 2+ /NF-AT. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. From verbal prefixes to direction/result markers in Romance

    Directory of Open Access Journals (Sweden)

    Patrizia Cordin

    2011-12-01

    Full Text Available In this paper I analyze verb-locative constructions in Romance. Even though not allowed in standard Romance languages, which have maintained and codified the classical Latin prefix system, these constructions are widely attested in non standard varieties, that are scarcely (or not at all regularized. In this paper I deal in particular with a northern Italian variety, Trentino, where locatives, combining with some classes of verbs (unaccusative verbs and transitive activity verbs can express not only concrete direction and metaphorical direction, but also aspect (the result of an activity or the progress of a process; in other words, they can express an abstract, more grammaticalized feature of direction. In fact, Trentino verb-locative constructions can express a specific phase of the development of an event, often the result (end-point of an activity, or the start-point, or the progress, or the intensity of the activity itself. I argue that in Trentino (and in other similar dialectal varieties locatives can function as grammatical markers both for arguments (in combination with motion verbs and for aspect (in combination with verbs involving the feature of an abstract path. In a more general context, I note that locatives in combination of verbs function as goal/result markers in those varieties that tend to spell out markers of functional elements, frequently generating a repetition (doubling of the same feature. Finally, I compare Romance and Germanic constructions, noting that diachronic, grammatical and typological differences (with particular reference to Talmy's distinction between verb-framed languages and satellite languages confirm the independence of Romance verb-locative constructions.

  8. Brief report: benchmarking human pluripotent stem cell markers during differentiation into the three germ layers unveils a striking heterogeneity: all markers are not equal.

    Science.gov (United States)

    Ramirez, Jean-Marie; Gerbal-Chaloin, Sabine; Milhavet, Ollivier; Qiang, Bai; Becker, Fabienne; Assou, Said; Lemaître, Jean-Marc; Hamamah, Samir; De Vos, John

    2011-09-01

    Pluripotent stem cells (PSC) are functionally characterized by their capacity to differentiate into all the cell types from the three germ layers. A wide range of markers, the expression of which is associated with pluripotency, has been used as surrogate evidence of PSC pluripotency, but their respective relevance is poorly documented. Here, we compared by polychromatic flow cytometry the kinetics of loss of expression of eight widely used pluripotency markers (SSEA3, SSEA4, TRA-1-60, TRA-1-81, CD24, OCT4, NANOG, and alkaline phosphatase [AP]) at days 0, 5, 7, and 9 after induction of PSC differentiation into cells representative of the three germ layers. Strikingly, each marker showed a different and specific kinetics of disappearance that was similar in all the PSC lines used and for all the induced differentiation pathways. OCT4, SSEA3, and TRA-1-60 were repeatedly the first markers to be downregulated, and their expression was completely lost at day 9. By contrast, AP activity, CD24, and NANOG proteins were still detectable at day 9. In addition, we show that differentiation markers are coexpressed with pluripotency markers before the latter begin to disappear. These results suggest that OCT4, SSEA3, and TRA-1-60 might be better to trace in vitro the emergence of pluripotent cells during reprogramming. Copyright © 2011 AlphaMed Press.

  9. Marker-assisted selection in forestry species

    International Nuclear Information System (INIS)

    Butcher, P.; Southerton, S.

    2007-01-01

    The primary goal of tree breeding is to increase the quantity and quality of wood products from plantations. Major gains have been achieved using recurrent selection in genetically diverse breeding populations to capture additive variation. However, the long generation times of trees, together with poor juvenile-mature trait correlations, have promoted interest in marker-assisted selection (MAS) to accelerate breeding through early selection. MAS relies on identifying DNA markers, which explain a high proportion of variation in phenotypic traits. Genetic linkage maps have been developed for most commercial tree species and these can be used to locate chromosomal regions where DNA markers co-segregate with quantitative traits (quantitative trait loci, QTL). MAS based on QTL is most likely to be used for within-family selection in a limited number of elite families that can be clonally propagated. Limitations of the approach include the low resolution of marker-trait associations, the small proportion of phenotypic variation explained by QTL and the low success rate in validating QTL in different genetic backgrounds and environments. This has led to a change in research focus towards association mapping to identify variation in the DNA sequence of genes directly controlling phenotypic variation (gene-assisted selection, GAS). The main advantages of GAS are the high resolution of marker-trait associations and the ability to transfer markers across families and even species. Association studies are being used to examine the adaptive significance of variation in genes controlling wood formation and quality, pathogen resistance, cold tolerance and drought tolerance. Single nucleotide polymorphisms (SNPs) in these gene sequences that are significantly associated with trait variation can then be used for early selection. Markers for SNPs can be transferred among individuals regardless of pedigree or family relationship, increasing opportunities for their application in

  10. Voice analysis as an objective state marker in bipolar disorder

    DEFF Research Database (Denmark)

    Faurholt-Jepsen, M.; Busk, Jonas; Frost, M.

    2016-01-01

    features with automatically generated objective smartphone data on behavioral activities (for example, number of text messages and phone calls per day) and electronic self-monitored data (mood) on illness activity would increase the accuracy as a marker of affective states. Using smartphones, voice...... features, automatically generated objective smartphone data on behavioral activities and electronic self-monitored data were collected from 28 outpatients with bipolar disorder in naturalistic settings on a daily basis during a period of 12 weeks. Depressive and manic symptoms were assessed using...... to be more accurate, sensitive and specific in the classification of manic or mixed states with an area under the curve (AUC)=0.89 compared with an AUC=0.78 for the classification of depressive states. Combining voice features with automatically generated objective smartphone data on behavioral activities...

  11. Microglia Induce Neurotoxic IL-17+ γδ T Cells Dependent on TLR2, TLR4, and TLR9 Activation.

    Directory of Open Access Journals (Sweden)

    Katja Derkow

    Full Text Available Interleukin-17 (IL-17 acts as a key regulator in central nervous system (CNS inflammation. γδ T cells are an important innate source of IL-17. Both IL-17+ γδ T cells and microglia, the major resident immune cells of the brain, are involved in various CNS disorders such as multiple sclerosis and stroke. Also, activation of Toll-like receptor (TLR signaling pathways contributes to CNS damage. However, the mechanisms underlying the regulation and interaction of these cellular and molecular components remain unclear.In this study, we investigated the crosstalk between γδ T cells and microglia activated by TLRs in the context of neuronal damage. To this end, co-cultures of IL-17+ γδ T cells, neurons, and microglia were analyzed by immunocytochemistry, flow cytometry, ELISA and multiplex immunoassays.We report here that IL-17+ γδ T cells but not naïve γδ T cells induce a dose- and time-dependent decrease of neuronal viability in vitro. While direct stimulation of γδ T cells with various TLR ligands did not result in up-regulation of CD69, CD25, or in IL-17 secretion, supernatants of microglia stimulated by ligands specific for TLR2, TLR4, TLR7, or TLR9 induced activation of γδ T cells through IL-1β and IL-23, as indicated by up-regulation of CD69 and CD25 and by secretion of vast amounts of IL-17. This effect was dependent on the TLR adaptor myeloid differentiation primary response gene 88 (MyD88 expressed by both γδ T cells and microglia, but did not require the expression of TLRs by γδ T cells. Similarly to cytokine-primed IL-17+ γδ T cells, IL-17+ γδ T cells induced by supernatants derived from TLR-activated microglia also caused neurotoxicity in vitro. While these neurotoxic effects required stimulation of TLR2, TLR4, or TLR9 in microglia, neuronal injury mediated by bone marrow-derived macrophages did not require TLR signaling. Neurotoxicity mediated by IL-17+ γδ T cells required a direct cell-cell contact between T

  12. MOLECULAR GENETIC MARKERS AND METHODS OF THEIR IDENTIFICATION IN MODERN FISH-FARMING

    Directory of Open Access Journals (Sweden)

    I. Hrytsyniak

    2014-03-01

    Full Text Available Purpose. The application of molecular genetic markers has been widely used in modern experimental fish-farming in recent years. This methodology is currently presented by a differentiated approach with individual mechanisms and clearly defined possibilities. Numerous publications in the scientific literature that are dedicated to molecular genetic markers for the most part offer purely practical data. Thus, the synthesis and analysis of existing information on the general principles of action and the limits of the main methods of using molecular genetic markers is an actual problem. In particular, such a description will make it possible to plan more effectively the experiment and to obtain the desired results with high reliability. Findings. The main types of variable parts of DNA that can be used as molecular genetic markers in determining the level of stock hybridization, conducting genetic inventory of population and solving other problems in modern fish-farming are described in this paper. Also, the article provides an overview of principal modern methods that can be used to identify molecular genetic markers. Originality. This work is a generalization of modern ideas about the mechanisms of experiments with molecular genetic markers in fish-farming. Information is provided in the form of consistent presentation of the principles and purpose of each method, as well as significant advances during their practical application. Practical value. The proposed review of classic and modern literature data on molecular genetic markers can be used for planning, modernization and correction of research activity in modern fish-farming.

  13. Grammatical markers switch roles and elicit different electrophysiological responses under shallow and deep semantic requirements.

    Science.gov (United States)

    Soshi, Takahiro; Nakajima, Heizo; Hagiwara, Hiroko

    2016-10-01

    Static knowledge about the grammar of a natural language is represented in the cortico-subcortical system. However, the differences in dynamic verbal processing under different cognitive conditions are unclear. To clarify this, we conducted an electrophysiological experiment involving a semantic priming paradigm in which semantically congruent or incongruent word sequences (prime nouns-target verbs) were randomly presented. We examined the event-related brain potentials that occurred in response to congruent and incongruent target words that were preceded by primes with or without grammatical case markers. The two participant groups performed either the shallow (lexical judgment) or deep (direct semantic judgment) semantic tasks. We hypothesized that, irrespective of the case markers, the congruent targets would reduce centro-posterior N400 activities under the deep semantic condition, which induces selective attention to the semantic relatedness of content words. However, the same congruent targets with correct case markers would reduce lateralized negativity under the shallow semantic condition because grammatical case markers are related to automatic structural integration under semantically unattended conditions. We observed that congruent targets (e.g., 'open') that were preceded by primes with congruent case markers (e.g., 'shutter-object case') reduced lateralized negativity under the shallow semantic condition. In contrast, congruent targets, irrespective of case markers, consistently yielded N400 reductions under the deep semantic condition. To summarize, human neural verbal processing differed in response to the same grammatical markers in the same verbal expressions under semantically attended or unattended conditions.

  14. Grammatical markers switch roles and elicit different electrophysiological responses under shallow and deep semantic requirements

    Directory of Open Access Journals (Sweden)

    Takahiro Soshi

    2016-10-01

    Full Text Available Static knowledge about the grammar of a natural language is represented in the cortico-subcortical system. However, the differences in dynamic verbal processing under different cognitive conditions are unclear. To clarify this, we conducted an electrophysiological experiment involving a semantic priming paradigm in which semantically congruent or incongruent word sequences (prime nouns–target verbs were randomly presented. We examined the event-related brain potentials that occurred in response to congruent and incongruent target words that were preceded by primes with or without grammatical case markers. The two participant groups performed either the shallow (lexical judgment or deep (direct semantic judgment semantic tasks. We hypothesized that, irrespective of the case markers, the congruent targets would reduce centro-posterior N400 activities under the deep semantic condition, which induces selective attention to the semantic relatedness of content words. However, the same congruent targets with correct case markers would reduce lateralized negativity under the shallow semantic condition because grammatical case markers are related to automatic structural integration under semantically unattended conditions. We observed that congruent targets (e.g., ‘open' that were preceded by primes with congruent case markers (e.g., ‘shutter-object case' reduced lateralized negativity under the shallow semantic condition. In con