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Sample records for affect lymphocyte function

  1. Mutant Huntingtin Does Not Affect the Intrinsic Phenotype of Human Huntington's Disease T Lymphocytes.

    Science.gov (United States)

    Miller, James R C; Träger, Ulrike; Andre, Ralph; Tabrizi, Sarah J

    2015-01-01

    Huntington's disease is a fatal neurodegenerative condition caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system is dysregulated in Huntington's disease and may contribute to its pathogenesis. However, it is not clear whether or to what extent the adaptive immune system is also involved. Here, we carry out the first comprehensive investigation of human ex vivo T lymphocytes in Huntington's disease, focusing on the frequency of a range of T lymphocyte subsets, as well as analysis of proliferation, cytokine production and gene transcription. In contrast to the innate immune system, the intrinsic phenotype of T lymphocytes does not appear to be affected by the presence of mutant huntingtin, with Huntington's disease T lymphocytes exhibiting no significant functional differences compared to control cells. The transcriptional profile of T lymphocytes also does not appear to be significantly affected, suggesting that peripheral immune dysfunction in Huntington's disease is likely to be mediated primarily by the innate rather than the adaptive immune system. This study increases our understanding of the effects of Huntington's disease on peripheral tissues, while further demonstrating the differential effects of the mutant protein on different but related cell types. Finally, this study suggests that the potential use of novel therapeutics aimed at modulating the Huntington's disease innate immune system should not be extended to include the adaptive immune system.

  2. Mutant Huntingtin Does Not Affect the Intrinsic Phenotype of Human Huntington's Disease T Lymphocytes.

    Directory of Open Access Journals (Sweden)

    James R C Miller

    Full Text Available Huntington's disease is a fatal neurodegenerative condition caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system is dysregulated in Huntington's disease and may contribute to its pathogenesis. However, it is not clear whether or to what extent the adaptive immune system is also involved. Here, we carry out the first comprehensive investigation of human ex vivo T lymphocytes in Huntington's disease, focusing on the frequency of a range of T lymphocyte subsets, as well as analysis of proliferation, cytokine production and gene transcription. In contrast to the innate immune system, the intrinsic phenotype of T lymphocytes does not appear to be affected by the presence of mutant huntingtin, with Huntington's disease T lymphocytes exhibiting no significant functional differences compared to control cells. The transcriptional profile of T lymphocytes also does not appear to be significantly affected, suggesting that peripheral immune dysfunction in Huntington's disease is likely to be mediated primarily by the innate rather than the adaptive immune system. This study increases our understanding of the effects of Huntington's disease on peripheral tissues, while further demonstrating the differential effects of the mutant protein on different but related cell types. Finally, this study suggests that the potential use of novel therapeutics aimed at modulating the Huntington's disease innate immune system should not be extended to include the adaptive immune system.

  3. Phenotypic and Functional Analysis of Porcine T Lymphocytes

    Institute of Scientific and Technical Information of China (English)

    李华; 陈应华

    2001-01-01

    Porcine and other higher mammals express clusters of differentiation (CD) antigens on the surface of T lymphocytes, such as CD2, CD3, CD4, CD8, etc. However, in porcine, a high percentage of the CD4+ CD8-T lymphocyte subpopulation exist in the peripheral blood and the ratio of the CD4+ and CD8+ T lymphocyte subpopulations is reversed. These differences bring new challenges to better understanding of the phenotype and function of porcine T lymphocytes in antigen recognition and immune response.

  4. Piperine from black pepper inhibits activation-induced proliferation and effector function of T lymphocytes.

    Science.gov (United States)

    Doucette, Carolyn D; Rodgers, Gemma; Liwski, Robert S; Hoskin, David W

    2015-11-01

    Piperine is a major alkaloid component of black pepper (Piper nigrum Linn), which is a widely consumed spice. Here, we investigated the effect of piperine on mouse T lymphocyte activation. Piperine inhibited polyclonal and antigen-specific T lymphocyte proliferation without affecting cell viability. Piperine also suppressed T lymphocyte entry into the S and G2 /M phases of the cell cycle, and decreased expression of G1 -associated cyclin D3, CDK4, and CDK6. In addition, piperine inhibited CD25 expression, synthesis of interferon-γ, interleukin (IL)-2, IL-4, and IL-17A, and the generation of cytotoxic effector cells. The inhibitory effect of piperine on T lymphocytes was associated with hypophosphorylation of Akt, extracellular signal-regulated kinase, and inhibitor of κBα, but not ZAP-70. The ability of piperine to inhibit several key signaling pathways involved in T lymphocyte activation and the acquisition of effector function suggests that piperine might be useful in the management of T lymphocyte-mediated autoimmune and chronic inflammatory disorders.

  5. 50 Hz sinusoidal magnetic fields do not affect human lymphocyte activation and proliferation in vitro

    Science.gov (United States)

    Capri, Miriam; Mesirca, Pietro; Remondini, Daniel; Carosella, Simona; Pasi, Sara; Castellani, Gastone; Franceschi, Claudio; Bersani, Ferdinando

    2004-12-01

    In the last 30 years, an increasing public concern about the possible harmful effects of electromagnetic fields generated by power lines and domestic appliances has pushed the scientific community to search for a correct and comprehensive answer to this problem. In this work the effects of exposure to 50 Hz sinusoidal magnetic fields, with a magnetic flux density of 0.05 mT and 2.5 mT (peak values), were studied on human peripheral blood mononuclear cells (PBMCs) collected from healthy young and elderly donors. Cell activation and proliferation were investigated by using flow cytometry techniques and 3H-TdR incorporation assays, respectively. The results obtained indicated that exposure to the fields altered neither DNA synthesis nor the capacity of lymphocytes to enter the activation phase and progress into the cell cycle. Thus, the conclusions are that two important functional phases of human lymphocytes, such as activation and proliferation, are not affected by exposures to 50 Hz magnetic fields similar to those found under power lines.

  6. FUNCTIONAL AORTIC STIFFNESS:ROLE OF CD4+ T LYMPHOCYTES

    Directory of Open Access Journals (Sweden)

    Beenish A. Majeed

    2015-08-01

    Full Text Available The immune system is suggested to be essential in vascular remodeling and stiffening. To study the dependence upon lymphocytes in vascular stiffening, we compared an angiotensin II-model of vascular stiffening in normal C57BL/6J mice with lymphocyte-deficient RAG 1-/- mice and additionally characterized the component of vascular stiffness due to vasoconstriction versus vascular remodeling. Chronic angiotensin II increased aortic pulse wave velocity, effective wall stiffness, and effective Young’s modulus in C57BL/6J mice by 3-fold but caused no change in the RAG 1-/- mice. These functional measurements were supported by aortic morphometric analysis. Adoptive transfer of CD4+ T helper lymphocytes restored the angiotensin II-mediated aortic stiffening in the RAG 1-/- mice. In order to account for the hydraulic versus material effects of angiotensin II on pulse wave velocity, subcutaneous osmotic pumps were removed after 21 days of angiotensin II-infusion in the WT mice to achieve normotensive values. The pulse wave velocity decreased from 3- to 2-fold above baseline values up to 7 days following pump removal. This study supports the pivotal role of the CD4+ T-lymphocytes in angiotensin II-mediated vascular stiffening and that angiotensin II-mediated aortic stiffening is due to the additive effect of active vascular smooth muscle vasoconstriction and vascular remodeling.

  7. Abnormalities of lymphocyte function and phenotypic pattern in a case of toxic epidermal necrolysis

    DEFF Research Database (Denmark)

    Hagdrup, H; Tønnesen, E; Clemmensen, O

    1992-01-01

    We examined the blood lymphocyte function and phenotypic pattern in a patient with toxic epidermal necrolysis after taking salazopyrin. We studied cell surface markers, natural killer cell activity and mitogen-induced lymphocyte transformation. Our results point to temporary immunosuppression...... as evidenced by lymphopenia with a large "null cell" population, reduced natural killer cell activity, and impaired lymphocyte response to mitogens....

  8. The Study on Morphological and Functional Changes of Thymus, Spleen and T Lymphocytes in Vasectomized Rabbits

    Institute of Scientific and Technical Information of China (English)

    刘睿智; 李璐; 赵丹; 赵雪检; 丛琦; 郑志超; 潘淑琴

    1997-01-01

    The morphology and functional changes of thymus, spleen and T lymphocytes were studied in vasectomlzed rabbits. The results showed that: (t) A significant low weight of thymus and spleen, and a slight or medium atrophy of thymic lobules and shrinked splenic nodules and lymphoid tissues were observed in the rabbits vasectomized for 6 months (VG6 rabbits), (2) Spontaneous-proliferation of thymus could not be affected by vasectomy, (3) The lowest activity of IL 2 was detected in the supernatant of spleen ceil culture of VG6 rabbits.

  9. Flow cytometric analyses of the viability, surface marker expression and function of lymphocytes from children following cryopreservation.

    Science.gov (United States)

    Chen, Xi; Zhang, Hui; Mou, Wenjun; Qi, Zhan; Ren, Xiaoya; Wang, Guoliang; Jiao, Hong; Kong, Xiaohui; Gui, Jingang

    2016-11-01

    Flow cytometric analysis is important for the investigation and clinical preparation of lymphocytes from children. However, the strict requirement of cell freshness and inter‑assay variability limits the application of this methodology for pediatric investigations. Therefore, it is necessary to identify a reliable cryopreservative method capable of maintaining high cell viability and proper cell function in lymphocytes from children. In the present study, eight commonly‑used cell cyropreservative methods were used, and their effects on cell viability, surface marker expression and cell function were examined. In addition, how these methods affect the distribution of T‑cell receptor Vβ subfamilies were also determined. The results of the present study provided valuable experimental evidence, based on which the optimal method for the cryopreservation of lymphocytes from children in pediatric investigations and clinical applications can be selected.

  10. Proliferation capacity of T-lymphocytes is affected transiently after a long-term weight gain in Beagle dogs.

    Science.gov (United States)

    Van de Velde, H; Janssens, G P J; Rochus, K; Duchateau, L; Scharek-Tedin, L; Zentek, J; Nguyen, P; Cox, E; Buyse, J; Biourge, V; Hesta, M

    2013-04-15

    Across species obesity is associated with several disorders but in companion animals little information is available on the impact of chronic obesity on immune competence. The aim of the present study was to investigate whether weight gain and stable obese bodyweight affects the immune cell response. Obesity was induced in eight adult healthy beagle dogs (weight gain group; WGG) by a weight gain period (WGP) of 47 weeks, which was immediately followed by a period (stable period: SP) of stable obesity of 26 weeks. Eight adult healthy beagle dogs were included as a control group (CG) and remained at their ideal bodyweight throughout the entire study. Body composition was measured at five intervening time-points. Concentration of serum leptin and inflammatory cytokines, functionality of lymphocytes and phagocytic activity of neutrophils and monocytes were evaluated at ten intervening time-points. Serum leptin concentration was rising during the WGP in the WGG but went to lower concentrations during the SP. At the end of long-term weight gain, a decreased mitogen-induced proliferation of T-lymphocytes was noted but this alteration seemed to be transient after stabilization of bodyweight. This finding may imply an altered immune response for dogs with different energy balances. However, no systemic low grade inflammation or alteration in other immune cell functions was observed. Consequently it is suggested that the change in energy balance during the onset of obesity (becoming obese versus being obese), evokes an additional obesity-related disorder in dogs, i.e. impaired T-lymphocyte immune function.

  11. Changes in count and function of splenic lymphocytes from patients with portal hypertension

    Institute of Scientific and Technical Information of China (English)

    Zong-Fang Li; Shu Zhang; Gao-Bo Lv; Ying Huang; Wei Zhang; Song Ren; Jun Yang; Shuang-Suo Dang

    2008-01-01

    AIM: To investigate changes in numbers and proliferative function of splenic lymphocytes in patients with hypersplenism due to portal hypertension (PH), to provide evidence for further study of immune status of the spleen during PH.METHODS: Twelve spleens from patients with hypersplenism due to PH served as the PH group, and four spleens from cases of traumatic spleen rupture were regarded as the control group. After weighing the spleen, lymphocytes were separated and counted using a cell counting plate to calculate the lymphocyte count per gram of spleen tissue (relative quantity) and total lymphocyte count in whole spleen (absolute quantity). The immunohistochemical SP method was used to observe the density and distribution of lymphocytes in the spleen. The MTT method was used to observe changes in lymphocyte proliferative function.RESULTS: As compared to the control group, the splenic lymphocytes in the PH group showed that: (1) There was no difference in distribution but a significant decrease in density; (2) the number of lymphocytes per gram of spleen (relative quantity) decreased significantly [(0.822±0.157) × 108 vs (1.174±0.254) × 108, P < 0.01];(3) with the significant increase in the weight of the PH spleen (832.6±278.2 g vs 211.7±85.6 g, P < 0.01),the total quantity of lymphocytes (absolute quantity)increased significantly [(0.685±0.072) × 1011 vs (0.366±0.057) × 1011, P < 0.01]; and (4) the proliferative function of lymphocytes was enhanced: T lymphocytes,(0.022±0.005 vs 0.015±0.003, P < 0.05), and B lymphocytes (0.034±0.006 vs 0.023±0.001, P < 0.01).CONCLUSION: Although lymphocyte density in the spleen decreased in patients with PH, the total quantity of lymphoytes increased because spleen weight increased greatly, along with the proliferating function. With respect to changes in lymphocytes, PH spleens may still have immune function, although it may be disordered. However,complete evaluation of the immune function of the spleenin PH

  12. Regulatory B lymphocyte functions should be considered in chronic lymphocytic leukemia.

    Science.gov (United States)

    Mohr, Audrey; Renaudineau, Yves; Bagacean, Cristina; Pers, Jacques-Olivier; Jamin, Christophe; Bordron, Anne

    2016-05-01

    Chronic lymphocytic leukemia (CLL) is characterized by an abnormal expansion of mature B cells in the bone marrow and their accumulation in blood and secondary lymphoid organs. Tumor CLL cells share expression of various surface molecules with many subsets of B cells and have several common characteristics with regulatory B cells (B regs). However, the identification of B regs and their role in CLL remain elusive. The aim of this review is to summarize recent works regarding the regulatory and phenotypic characteristic of B regs and their associated effects on the immune system. It is also meant to highlight their potential importance with regards to the immunotherapeutic response.

  13. Duodenal intraepithelial T lymphocytes in patients with functional dyspepsia

    Institute of Scientific and Technical Information of China (English)

    Gilles Gargala; Stéphana Lecleire; Arnaud Frangois; Serge Jacquot; Pierre Déchelotte; Jean Jacques Ballet; Loic Favennec; Philippe Ducrotté

    2007-01-01

    AIM:To quantify the intraepithelial lymphocytes (IELs) and to document the membrane expression of CD4,CD8,TCRγδ and adhesion and/or activation-associated molecules (CD103,CD28,CD44,CD69,HLA-DR,CD95/Fas) in the duodenal mucosa of patients with functional dyspepsia (FD) in order to provide arguments for an immunological process in FD.METHODS:Twenty-six FD patients according to Rome Ⅱ criteria (20 were H pylori negative) were studied and compared to 12 healthy adults.IELs were isolated from five duodenal biopsy samples,then quantified by microscopy and flow cytometry while the membrane phenotypes were determined by cytofluorometry.RESULTS:Duodenal histological examination was normal.In H pylori negative patients,the number of IELs was not different from that in healthy controls.Median percentage expression of CD4,CD8,or TCRγδ and CD103,CD44,CD28,CD69 on CD3+ IELs,among the adhesion/activation associated molecules tested,was not different from that in healthy controls.In contrast,the median percentage expression of CD95/Fas [22(9-65) vs 45(19-88),P=0.03] and HLADR expressing CD3+ IELs [4(0-30) vs 13(4-42),P=0.041 was signifcantly lower in the H pylori negative FD group than in healthy controls,respectively.The number of IELs was significantly greater in H pylori positive FD patients than in healthy controls [median ratio for 100 enterocytes 27.5 (6.7-62.5) vs 10.8 (3-33.3), P = 0.02] due to a higher number of CD8+ CD3+ IELs.CONCLUSION: In H pylori negative FD patients, the phenotypic characterization of IELs suggests that we cannot exclude a role of IELs in FD.

  14. Effect of levamisole and methisoprinol on in vitro lymphocyte reactivity in chronically irradiated subjects and patients affected by neoplasias

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    Campo, M.; Chiavaro, I.; Canfarotta, C.; Stivala, F.; Berrardini, A.

    1982-01-01

    The data of this experiment show that Levamisole moderately stimulates T-lymphocyte proliferation and efficiency in vitro and methisoprinol markedly does so when both drugs act in combination with PHA in subjects with severely impaired cell-mediated responsiveness, whereas they do not exert any effect on lymphocytes in normal subjects. B-lymphocyte in vitro responsiveness does not appear to be affected by the immunomodulators, except for some cases of cancer of the stomach wherein B-lymphocyte responsiveness is stimulated in vitro by Levamisole and more evidently by Methisoprinol. These data support the use of Methisoprinol or Levamisole in therapy, and further investigations regarding the mechanisms whereby they might act and the dose-effect relationship which might show to be important for the type of desired immunomodulation would appear appropriate.

  15. Desensitization oft lymphocyte function by CXCR3 ligands in human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yu-Qing Liu; Ronnie T. Poon; Jeremy Hughes; Qin-Yu Li; Wan-Ching Yu; Sheung-Tat Fan

    2005-01-01

    AIM: Despite the presence of lymphocyte infiltration, human hepatocellular carcinoma (HCC) is typically a rapidly progressive disease. The mechanism of regulation of lymphocyte migration is poorly understood. In this study,we investigated various factors regulating T cell migration in HCC patients. We examined serum CXC chemokine levels in HCC patients and demonstrated the production of CXC chemokines by HCC cell lines. We determined the effect of both HCC patient serum and tumor cell conditioned supernatant upon lymphocyte expression of chemokine receptor CXCR3 as well as lymphocyte migration. Lastly,we examined the chemotactic responses of lymphocytes derived from HCC patients.METHODS: The serum chemokines IP-10 (CXCL10) and Mig (CXCL9) levels were measured by cytometric bead array (CBA) and the tumor tissue IP-10 concentration was measured by ELISA. The surface expression of CXCR3 on lymphocytes was determined by flow cytometry. The migratory function of lymphocytes to the corresponding chemokines was assessed using an in vitro chemotactic assay. Phosphorylation of extracellular signal-regulated kinase (ERK) was determined by Western blot analysis.RESULTS: Increased levels of IP-10 and Mig were detected in HCC patient serum and culture supernatants of HCC cell lines. The IP-10 concentration in the tumor was significantly higher than that in the non-involved adjacent liver tissues.HCC cell lines secreted functional chemokines that induced a CXCR3-specific chemotactic response of lymphocytes.Furthermore, tumor-cell-derived chemokines induced initial rapid phosphorylation of lymphocyte ERK followed by later inhibition of ERK phosphorylation. The culture of normal lymphocytes with HCC cell line supernatants or medium containing serum from HCC patients resulted in a significant reduction in the proportion of lymphocytes exhibiting surface expression of CXCR3. The reduction in T cell expression of CXCR3 resulted in reduced migration toward the ligand IP-10, and both

  16. Stress, cortisol, and B lymphocytes: a novel approach to understanding academic stress and immune function.

    Science.gov (United States)

    McGregor, Bonnie A; Murphy, Karly M; Albano, Denise L; Ceballos, Rachel M

    2016-01-01

    Animal and human in vitro models suggest that stress-related B lymphocyte decrements are due to high levels of glucocorticoids which cause apoptosis of pre-B-cells as they emerge from the bone marrow. The present study sought to explore the relationships among distress, salivary cortisol, and human B lymphocytes in vivo. Distress (perceived stress, negative affect, depressive symptoms), lymphocyte phenotype, and salivary cortisol were assessed among first-year graduate students (n = 22) and a community control sample (n = 30) at the start of classes in the fall and the week immediately before spring preliminary exams. Compared to controls, students reported greater distress on all measures at each time point except baseline perceived stress. Hierarchical linear regression with necessary control variables was used to assess the effect of student status on the three measures of distress, the four measures of lymphocyte phenotype, and cortisol AUC and CAR over time (T1-T2). Student status was associated with a significant decrease in CD19 + B lymphocytes and flattened cortisol awakening response (CAR). Change in CAR was associated with the decrease in CD19 + B lymphocytes. Results indicated that there are significant associations among student status, flattening of CAR, and decrements in CD19 + lymphocytes.

  17. Stress, Cortisol, and B-Lymphocytes: A Novel Approach to Understanding Academic Stress and Immune Function

    Science.gov (United States)

    McGregor, Bonnie A; Murphy, Karly Mary; Albano, Denise L; Ceballos, Rachel M

    2016-01-01

    Animal and human in vitro models suggest that stress-related B lymphocyte decrements are due to high levels of glucocorticoids which cause apoptosis of pre-B-cells as they emerge from the bone marrow. The present study sought to explore the relationships among distress, salivary cortisol and human B lymphocytes in vivo. Distress (perceived stress, negative affect, depressive symptoms), lymphocyte phenotype, and salivary cortisol were assessed among first year graduate students (n=22) and a community control sample (n= 30) at the start of classes in the fall and the week immediately before spring preliminary exams. Compared to controls, students reported greater distress on all measures at each time point except baseline perceived stress. Hierarchical linear regression with necessary control variables was used to assess the effect of student status on the three measures of distress, the four measures of lymphocyte phenotype, and cortisol AUC and CAR over time (T1-T2). Student status was associated with a significant decrease in CD19+ B lymphocytes and flattened cortisol awakening response (CAR). Change in CAR was associated with the decrease in CD19+ B lymphocytes. Results indicated that there are significant associations among student status, flattening of CAR, and decrements in CD19+ lymphocytes. PMID:26644211

  18. Diet-induced docosahexaenoic acid non-raft domains and lymphocyte function.

    Science.gov (United States)

    Raza Shaikh, Saame

    2010-01-01

    Docosahexaenoic acid (DHA) is an n-3 polyunsaturated fatty acid (PUFA) that generally suppresses the function of T lymphocytes and antigen presenting cells (APCs). An emerging mechanism by which DHA modifies lymphocyte function is through changes in the organization of sphingolipid/cholesterol lipid raft membrane domains. Two contradictory models have been proposed to explain how DHA exerts its effects through changes in raft organization. The biophysical model, developed in model membranes, shows that DHA-containing phospholipids form unique non-raft membrane domains, that are organizationally distinct from lipid rafts, which serve to alter the conformation and/or lateral organization of lymphocyte proteins. In contrast, the cellular model on DHA and rafts shows that DHA suppresses lymphocyte function, in part, by directly incorporating into lipid rafts and altering protein activity. To reconcile opposing biophysical and cellular viewpoints, a major revision to existing models is presented herein. Based largely on quantitative microscopy data, it is proposed that DHA, consumed through the diet, modifies lymphocyte function, in part, through the formation of nanometer scale DHA-rich domains. These nano-scale domains disrupt the optimal raft-dependent clustering of proteins necessary for initial signaling. The data covered in this review highlights the importance of understanding how dietary n-3 PUFAs modify lymphocyte membranes, which is essential toward developing these fatty acids as therapeutic agents for treating inflammatory diseases.

  19. Sublethal red tide toxin exposure in free-ranging manatees (Trichechus manatus) affects the immune system through reduced lymphocyte proliferation responses, inflammation, and oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, Catherine J., E-mail: cjwalsh@mote.org [Marine Immunology Program, Mote Marine Laboratory, 1600 Ken Thompson Parkway, Sarasota, FL 34236 (United States); Butawan, Matthew, E-mail: mattbutawan@outlook.com [Marine Immunology Program, Mote Marine Laboratory, 1600 Ken Thompson Parkway, Sarasota, FL 34236 (United States); Yordy, Jennifer, E-mail: jennifer.e.balmer@gmail.com [Marine Immunology Program, Mote Marine Laboratory, 1600 Ken Thompson Parkway, Sarasota, FL 34236 (United States); Ball, Ray, E-mail: Ray.Ball@lowryparkzoo.com [Lowry Park Zoo, 1101 W Sligh Ave, Tampa, FL 33604 (United States); Flewelling, Leanne, E-mail: Leanne.Flewelling@MyFWC.com [Fish and Wildlife Research Institute, Florida Fish and Wildlife Conservation Commission, 100 8th Ave SE, St. Petersburg, FL 33701 (United States); Wit, Martine de, E-mail: Martine.deWit@MyFWC.com [Fish and Wildlife Research Institute, Florida Fish and Wildlife Conservation Commission, 100 8th Ave SE, St. Petersburg, FL 33701 (United States); Bonde, Robert K., E-mail: rbonde@usgs.gov [U.S. Geological Survey, Sirenia Project, 7920 NE 71st Street, Gainesville, FL 32653 (United States)

    2015-04-15

    Highlights: • Sublethal brevetoxin exposure affects manatee immune function. • Plasma brevetoxin levels correlate with oxidative stress in rescued manatees. • Brevetoxin exposure affects lymphocyte proliferation in rescued manatees. • Plasma brevetoxin concentrations ranged from 0 to 19 ng PbTx-3 eq/mL. - Abstract: The health of many Florida manatees (Trichechus manatus latirostris) is adversely affected by exposure to blooms of the toxic dinoflagellate, Karenia brevis. K. brevis blooms are common in manatee habitats of Florida’s southwestern coast and produce a group of cyclic polyether toxins collectively referred to as red tide toxins, or brevetoxins. Although a large number of manatees exposed to significant levels of red tide toxins die, several manatees are rescued from sublethal exposure and are successfully treated and returned to the wild. Sublethal brevetoxin exposure may potentially impact the manatee immune system. Lymphocyte proliferative responses and a suite of immune function parameters in the plasma were used to evaluate effects of brevetoxin exposure on health of manatees rescued from natural exposure to red tide toxins in their habitat. Blood samples were collected from rescued manatees at Lowry Park Zoo in Tampa, FL and from healthy, unexposed manatees in Crystal River, FL. Peripheral blood leukocytes (PBL) isolated from whole blood were stimulated with T-cell mitogens, ConA and PHA. A suite of plasma parameters, including plasma protein electrophoresis profiles, lysozyme activity, superoxide dismutase (SOD) activity, and reactive oxygen/nitrogen (ROS/RNS) species, was also used to assess manatee health. Significant decreases (p < 0.05) in lymphocyte proliferation were observed in ConA and PHA stimulated lymphocytes from rescued animals compared to non-exposed animals. Significant correlations were observed between oxidative stress markers (SOD, ROS/RNS) and plasma brevetoxin concentrations. Sublethal exposure to brevetoxins in the

  20. Flat affect and social functioning

    DEFF Research Database (Denmark)

    Simonsen, Erik; Evensen, Julie; Røsberg, Jan Ivar;

    2012-01-01

    , predictors and outcome factors including social functioning. Methods: Three-hundred-and-one patients with FEP were included at baseline, 186 participated in the 10 year follow-up. These were followed on PANSS item N1 (FA) from baseline through 5 follow-up assessments over 10 years. Patients were grouped...... as having never-present, improving, deteriorating, fluctuating or enduring FA. The groups were compared on baseline variables, variables at 10 year follow-up, and social functioning throughout the follow-up period. Results: Twenty nine percent never displayed FA, 66% had improving, deteriorating...... or fluctuating FA, while 5% of patients had enduring FA. Premorbid social function predicted enduring FA. The patients with enduring, fluctuating and deteriorating FA did poorer on all outcome variables, including remission and recovery rates. The enduring FA group did significantly poorer in social functioning...

  1. SERUM HAPTOGLOBIN SUPPRESSES T-LYMPHOCYTE FUNCTIONS FOLLOWING BURNS

    Institute of Scientific and Technical Information of China (English)

    王凤君; 黄文华; 黎鳌

    1996-01-01

    It is well known that serum immunosuppressive factors play an important role in the mechanismi of postburn immunosuppression.This study was intended to investigate the effect of haptoglobin,purified from the serum of burned patients by affinity chromatography,on the proliferation and interleukin-2(IL-2)secretion of normal nurine thymocytes induced by conA and the proliferation of IL-2 dependent cell line (CTLL-2) stimulated by recombinant human IL-2,so as to elucidate the role of serum haptoglobin in postburn T-lymphocyte dysfunction.The results showed that purified haptoglobin,at the level equivalent to the concentration found in serum of burned patients,significantly inhibited the prolifration and IL-2 secretion of normal murine thymocytes as well as CTLL-2 proliferation;wheres it exhibited no immunosuppressive effects at the level equivalent to the concentration found in serum of normal vohmteers.According to the results reported here,it is suggested that extraordinary increase in serum haptoglobin level may be an important factor of impaired T-lymphocyte responses following burns.

  2. Effect of Excessive Iodine on Immune Function of Lymphocytes and Intervention with Selenium

    Institute of Scientific and Technical Information of China (English)

    CHEN Xiaoyi; LIU Liegang; YAO Ping; YU Dong; HAO Liping; SUN Xiufa

    2007-01-01

    In order to study the effect of excessive iodine on immune function of lymphocytes and the role of selenium supplementation with excessive iodine intake, the changes of T lymphocyte number, ratio of subsets, activity of natural killer (NK) cells and lymphocytes proliferation response were investigated. 150 female BALB/C mice were randomly divided into 5 groups in terms of their body weight (n=30 in each group), and 10 of each group were taken as one batch for test. Mice in the 5 groups were orally administrated with iodine 0 (group Ⅰ ), 1500 (group Ⅱ), 3000 (group Ⅲ),6000 μg/L (group Ⅳ), iodine 6000 μg/L plus selenium 0.3 mg/L (group Ⅴ) respectively for 30 days.Lymphocyte proliferation response, CD4+/CD8+, Th1/Th2 and the activity of NK cells were measured. CD4+/CD8+ was significantly lower, while lymphocyte proliferation response stronger, and Th1/Th2 and the activity of NK cells significantly higher in group Ⅳ than in group Ⅰ (P<0.01).There was no significant difference in all indexes between group Ⅴ and group Ⅰ (P>0.05). It was suggested that excessive iodine as exogenous chemical materials can induce disorders of T lymphocyte immune function in mice. 0.3 mg/L selenium supplementation can protect mice against toxicity induced by 6000 μg/L iodine.

  3. Placebo Sleep Affects Cognitive Functioning

    Science.gov (United States)

    Draganich, Christina; Erdal, Kristi

    2014-01-01

    The placebo effect is any outcome that is not attributed to a specific treatment but rather to an individual's mindset (Benson & Friedman, 1996). This phenomenon can extend beyond its typical use in pharmaceutical drugs to involve aspects of everyday life, such as the effect of sleep on cognitive functioning. In 2 studies examining whether…

  4. Tissue Dimensionality Influences the Functional Response of Cytotoxic T Lymphocyte-Mediated Killing of Targets.

    Science.gov (United States)

    Gadhamsetty, Saikrishna; Marée, Athanasius F M; de Boer, Rob J; Beltman, Joost B

    2016-01-01

    Cytotoxic T lymphocyte (CTL)-mediated killing of virus infections and tumors occurs over a wide range of conditions. The spatial environments in which CTLs encounter target cells vary from narrow vessels, to two-dimensional epithelial tissues, to densely populated 3-dimensional (3D) T cell areas within lymphoid tissues. How such spatial environments alter the functional response of CTL-mediated killing, i.e., how the killing efficiency depends on cell densities, is unclear. In this study, we perform cellular Potts model simulations in different spatial configurations to investigate how the dimensionality of the space affects the functional response of CTL-mediated killing. Irrespective of the spatial configuration, the function with separate saturation constants for CTL and for target cell densities that we previously proposed can in all cases describe the response, demonstrating its generality. However, the tissue dimensionality determines at which cell densities the killing rate starts to saturate. We show that saturation in a fully 3D environment is stronger than in a "flat" 3D environment, which is largely due to accompanying differences in the CTL-target encounter rates.

  5. B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction

    Science.gov (United States)

    Zouggari, Yasmine; Ait-Oufella, Hafid; Bonnin, Philippe; Simon, Tabassome; Sage, Andrew P; Guérin, Coralie; Vilar, José; Caligiuri, Giuseppina; Tsiantoulas, Dimitrios; Laurans, Ludivine; Dumeau, Edouard; Kotti, Salma; Bruneval, Patrick; Charo, Israel F; Binder, Christoph J; Danchin, Nicolas; Tedgui, Alain; Tedder, Thomas F; Silvestre, Jean-Sébastien; Mallat, Ziad

    2014-01-01

    Acute myocardial infarction is a severe ischemic disease responsible for heart failure and sudden death. Here, we show that after acute myocardial infarction in mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6Chi monocyte mobilization and recruitment to the heart, leading to enhanced tissue injury and deterioration of myocardial function. Genetic (Baff receptor deficiency) or antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial injury and improved heart function. These effects were recapitulated in mice with B cell–selective Ccl7 deficiency. We also show that high circulating concentrations of CCL7 and BAFF in patients with acute myocardial infarction predict increased risk of death or recurrent myocardial infarction. This work identifies a crucial interaction between mature B lymphocytes and monocytes after acute myocardial ischemia and identifies new therapeutic targets for acute myocardial infarction. PMID:24037091

  6. Phenotypic and functional characteristics of human newborns' B lymphocytes.

    Science.gov (United States)

    Durandy, A; Thuillier, L; Forveille, M; Fischer, A

    1990-01-01

    It has been demonstrated two major facts concerning human newborns' B lymphocytes: 1) they differentiate poorly into Ig-producing cells and 2) they express CD5 and CD1c membrane proteins. We have further analyzed human newborns' B cell characteristics and found that approximately half of them express activation Ag, i.e., 4F2 and IL-2R, both associated in significant proportions with CD23 and Bac-1. These membrane Ag were found both on CD5(+) and CD5(-) B cells. Newborns' B cells do not exhibit other activation markers because they express surface IgD, and because their size, RNA, and DNA contents do not differ from those of adults' B cells, indicating that they are in the G0/G1 cell cycle phase. Newborns' B cell proliferation can be induced by rIL-2, rIL-4, low m.w. B cell growth factor, and by Staphylococcus aureus protein A. It is presently difficult to build a hypothesis accounting for all the specific findings made on newborns' B cells. It is not known for instance whether CD5(+) and (-) B cells belong to distinct subsets as suggested by the fluorescence intensity curve obtained with an anti-CD5 antibody or to distinct stages in a unique pattern of B cell maturation during fetal and newborn life. This may indicate that partially activated B cells actually produce natural polyspecific autoantibodies of the IgM isotype found in newborns' human serum.

  7. Activation Effects of Polysaccharides of Flammulina velutipes Mycorrhizae on the T Lymphocyte Immune Function

    Directory of Open Access Journals (Sweden)

    Zheng-Fei Yan

    2014-01-01

    Full Text Available Flammulina velutipes mycorrhizae have increasingly been produced with increasing of F. velutipes production. A mouse model was thus used to examine potential effect of F. velutipes mycorrhizae on the immune function. Fifty female Wistar mice (5-weeks-old weighed 15–20 g were randomly allocated into five groups. Polysaccharide of F. velutipes mycorrhizae were treated with mice and mice spleen lymphocytes. The levels of CD3+, CD4+, and CD8+ T lymphocyte, interleukin-2 (IL-2, and tumor necrosis factor-a (TNF-α were determined. The results showed that the proportions of CD3+, and CD4+ T lymphocyte, the ratio of CD4+/CD8+, and the levels of IL-2 and TNF-a were significantly increased in polysaccharide of F. velutipes mycorrhizae, while the proportion of CD8+ T lymphocyte was decreased in polysaccharide of F. velutipes mycorrhizae-dose dependent manner. Our findings indicated that a long term exposure of polysaccharide of F. velutipes mycorrhizae could activate the T lymphocyte immune function. Polysaccharide of F. velutipes mycorrhizae was expected to develop into the immune health products.

  8. Activation effects of polysaccharides of Flammulina velutipes mycorrhizae on the T lymphocyte immune function.

    Science.gov (United States)

    Yan, Zheng-Fei; Liu, Nai-Xu; Mao, Xin-Xin; Li, Yu; Li, Chang-Tian

    2014-01-01

    Flammulina velutipes mycorrhizae have increasingly been produced with increasing of F. velutipes production. A mouse model was thus used to examine potential effect of F. velutipes mycorrhizae on the immune function. Fifty female Wistar mice (5-weeks-old) weighed 15-20 g were randomly allocated into five groups. Polysaccharide of F. velutipes mycorrhizae were treated with mice and mice spleen lymphocytes. The levels of CD3(+), CD4(+), and CD8(+) T lymphocyte, interleukin-2 (IL-2), and tumor necrosis factor-a (TNF-α) were determined. The results showed that the proportions of CD3(+), and CD4(+) T lymphocyte, the ratio of CD4(+)/CD8(+), and the levels of IL-2 and TNF-a were significantly increased in polysaccharide of F. velutipes mycorrhizae, while the proportion of CD8(+) T lymphocyte was decreased in polysaccharide of F. velutipes mycorrhizae-dose dependent manner. Our findings indicated that a long term exposure of polysaccharide of F. velutipes mycorrhizae could activate the T lymphocyte immune function. Polysaccharide of F. velutipes mycorrhizae was expected to develop into the immune health products.

  9. Activation Effects of Polysaccharides of Flammulina velutipes Mycorrhizae on the T Lymphocyte Immune Function

    OpenAIRE

    Zheng-Fei Yan; Nai-Xu Liu; Xin-Xin Mao; Yu Li; Chang-Tian Li

    2014-01-01

    Flammulina velutipes mycorrhizae have increasingly been produced with increasing of F. velutipes production. A mouse model was thus used to examine potential effect of F. velutipes mycorrhizae on the immune function. Fifty female Wistar mice (5-weeks-old) weighed 15–20 g were randomly allocated into five groups. Polysaccharide of F. velutipes mycorrhizae were treated with mice and mice spleen lymphocytes. The levels of CD3+, CD4+, and CD8+ T lymphocyte, interleukin-2 (IL-2), and tumor necros...

  10. Altered lymphocyte proliferation and innate immune function in scrapie 139A- and ME7-infected mice.

    Science.gov (United States)

    Cho, In Soo; Spinner, Daryl S; Kascsak, Richard J; Meeker, H Cliff; Kim, Bo Sook; Park, Seung Yong; Schuller-Levis, Georgia; Park, Eunkyue

    2013-06-01

    Lymphoid organs play an important role in prion disease development and progression. While the role of lymphoid organs and changes in immune-related genes have been extensively investigated in scrapie-infected animals, innate immunity has not. Previous studies examined lymphocyte function in scrapie-infected C3H/HeJ mice, which exhibit defects in lipopolysaccharide (LPS) response now known to result from a mutation in Toll-like receptor (TLR) 4. We examined immune function in scrapie-infected CD1 mice, which are LPS responders. Lymphocyte proliferation from CD1 mice infected with either 139A or ME7 scrapie was measured in response to concanavalin (Con) A or LPS at 1 and 3 months after infection. Following LPS exposure, mice infected 3 months with ME7, but not 139A, demonstrated significantly decreased lymphocyte proliferation compared to controls. After Con A exposure, lymphocyte proliferation in scrapie-infected mice did not differ from controls. Gender-specific comparison of lymphocyte proliferation showed significant decreases in mitogenic responses in females infected 3 months with either 139A or ME7, compared to controls. Males infected for 3 months with ME7, but not 139A, showed significantly decreased proliferation after lymphocyte exposure to LPS, but not Con A. Neither gender showed changes in lymphocyte proliferation after 1 month of scrapie infection. Innate immune activation of peritoneal macrophages was determined via production of nitric oxide (NO), IL-6, and TNF-α after exposure to TLR ligands. TNF-α and IL-6 production were reduced in macrophages from females infected with either scrapie strain for 3 months, while NO production after TLR agonist plus IFN-γ exposure was decreased in both females and males infected for 3 months with 139A, compared to ME7. These data demonstrated altered innate immunity, suggesting hormonal and/or other gender-specific regulation may contribute to gender differences in some immune functions. Our data demonstrate

  11. Glutathione and lymphocyte activation: a function of ageing and auto-immune disease.

    Science.gov (United States)

    Fidelus, R K; Tsan, M F

    1987-08-01

    A decline in tissue and serum of glutathione (GSH) content and GSH-metabolizing enzymes with age has been implicated in the increasing susceptibility to carcinogens, disease and drugs which occurs with advanced age. Immunological senescence has been directly associated with increased incidence of cancer and infection with age. The auto-immune diseases of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) demonstrate depressed T-cell function together with B-cell hyperactivity. In addition, RA and SLE are chronic inflammatory conditions which have been associated with low serum and erythrocyte GSH concentrations when compared to normal. We hypothesized that augmentation of intracellular GSH concentrations in lymphocytes may enhance immune function in depressed immune states. Our data, using murine animal models for ageing (C57BL/6J) and the RA/SLE-like auto-immune diseases of the MRL/lpr mouse, indicate that intracellular glutathione of splenic lymphocytes does not decline with age or with a chronic inflammatory auto-immune disease. In contrast, immune responsiveness in splenic lymphocytes does decline. We can, however, augment both intracellular GSH concentrations and the immune response of splenic lymphocytes from animals of all ages as well as in those animals with the SLE-like auto-immune disease.

  12. Local glucocorticoid production in lymphoid organs of mice and birds: Functions in lymphocyte development.

    Science.gov (United States)

    Taves, Matthew D; Hamden, Jordan E; Soma, Kiran K

    2017-02-01

    Circulating glucocorticoids (GCs) are powerful regulators of immunity. Stress-induced GC secretion by the adrenal glands initially enhances and later suppresses the immune response. GC targets include lymphocytes of the adaptive immune system, which are well known for their sensitivity to GCs. Less appreciated, however, is that GCs are locally produced in lymphoid organs, such as the thymus, where GCs play a critical role in selection of the T cell antigen receptor (TCR) repertoire. Here, we review the roles of systemic and locally-produced GCs in T lymphocyte development, which has been studied primarily in laboratory mice. By antagonizing TCR signaling in developing T cells, thymus-derived GCs promote selection of T cells with stronger TCR signaling. This results in increased T cell-mediated immune responses to a range of antigens. We then compare local and systemic GC patterns in mice to those in several bird species. Taken together, these studies suggest that a combination of adrenal and lymphoid GC production might function to adaptively regulate lymphocyte development and selection, and thus antigen-specific immune reactivity, to optimize survival under different environmental conditions. Future studies should examine how lymphoid GC patterns vary across other vertebrates, how GCs function in B lymphocyte development in the bone marrow, spleen, and the avian bursa of Fabricius, and whether GCs adaptively program immunity in free-living animals.

  13. TNF-alpha, leptin, and lymphocyte function in human aging

    DEFF Research Database (Denmark)

    Bruunsgaard, H.; Pedersen, Agnes Nadelmann; Schroll, M.

    2000-01-01

    Aging is associated with increased inflammatory activity and concomitant decreased T cell mediated immune responses. Leptin may provide a link between inflammation and T cell function in aging. The aim of the study was to investigate if plasma levels of tumor necrosis factor (TNF)-alpha were...... associated with leptin, circulating interleukin-2 receptors (sIL-2R), and phytohaemagglutinin (PHA) induced IL-2 production in whole blood in elderly humans. Circulating levels of TNF-alpha and sIL-2R were higher in elderly humans (N=42) compared to a young control group (N=37) whereas...... there was no difference with regard to IL-2 production. Furthermore, there were no age-related differences in serum levels of leptin, However, women had higher levels than men. In the elderly people, serum levels of leptin were correlated with TNF-alpha in univariate regression analysis and in a multiple linear...

  14. Three Consecutive Days of Interval Runs to Exhaustion Affects Lymphocyte Subset Apoptosis and Migration

    Directory of Open Access Journals (Sweden)

    James W. Navalta

    2014-01-01

    Full Text Available This investigation assessed the lymphocyte subset response to three days of intermittent run exercise to exhaustion. Twelve healthy college-aged males (n=8 and females (n=4 (age = 26 ± 4 years; height = 170.2 ± 10 cm; body mass = 75 ± 18 kg completed an exertion test (maximal running speed and VO2max and later performed three consecutive days of an intermittent run protocol to exhaustion (30 sec at maximal running speed and 30 sec at half of the maximal running speed. Blood was collected before exercise (PRE and immediately following the treadmill bout (POST each day. When the absolute change from baseline was evaluated (i. e., Δ baseline, a significant change in CD4+ and CD8+ for CX3CR1 cells was observed by completion of the third day. Significant changes in both apoptosis and migration were observed following two consecutive days in CD19+ lymphocytes, and the influence of apoptosis persisted following the third day. Given these lymphocyte responses, it is recommended that a rest day be incorporated following two consecutive days of a high-intensity intermittent run program to minimize immune cell modulations and reduce potential susceptibility.

  15. Study Of The Existence Of Neoantigens In Affected Hair Follicles Using Lymphocyte Transformation Test In Alopecia Areata And Healthy Persons

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    Saehi Nodeh A

    2004-07-01

    Full Text Available Background: Alopecia areata is a common, inflamatory and chronic disease of hair and nails, which in some cases result in growth inhibition and lose of hairs. Several factors such as genetic factors, autoimmunity, atopy, stress, fear etc, are known as effective factors in induction and severity of the disease, but the ethiology of this disease is not known exactly so far. Some evidences such as presence of an autoantibodies against hair follicules and infiltration of immunocompetent cells in affected areas of the disease lead that most investigators classify alopecia as autoimmune disease. In one investigation in immunology department of Tarbiat Modarres university concerning the humoral immunity in alopecia pathogenesis some evidences were found for the presences of a neoantigen in affected hair follicles. Since various studies indicates that cellular arm of the immune system is more important in alopecia areata pathogenesis, in this investigation we studied the existence of neoantigens in affected hair follicles using lymphocyte transformation test (LTT. Materials and Methods: The proliferation responses of peripheral blood mononuclear cells (MNC from alopecia patients and normal individuals were investigated against the follicular extracts of affected and normal hairs separately. Results: Our results indicate a non significant difference between proliferation responses of MNC’s from alopecia patients and normal controls against follicular extract of normal hairs. These responses were not significantly different against folliclar extracts of affected hairs as well. Regarding our results. Conclusion: We could not show the existence of a neoantigen in alopecia hair follicles, but the obtained results can not completely reject the role of a neoantigen in alopecia pathogenesis as well, because in LTT the responding cells are of memory type and these cells may be very low in peripheral blood. The immune response in this disease may be restricted

  16. Increased micronucleus frequency in peripheral blood lymphocytes contributes to cancer risk in the methyl isocyanate-affected population of Bhopal.

    Science.gov (United States)

    Senthilkumar, Chinnu Sugavanam; Akhter, Sameena; Malla, Tahir Mohiuddin; Sah, Nand Kishore; Ganesh, Narayanan

    2015-01-01

    The Bhopal gas tragedy involving methyl isocyanate (MIC) is one of the most horrific industrial accidents in recent decades. We investigated the genotoxic effects of MIC in long-term survivors and their offspring born after the 1984 occurrence. There are a few cytogenetic reports showing genetic damage in the MIC-exposed survivors, but there is no information about the associated cancer risk. The same is true about offspring. For the first time, we here assessed the micronucleus (MN) frequency using cytokinesis-blocked micronucleus (CBMN) assay to predict cancer risk in the MIC-affected population of Bhopal. A total of 92 healthy volunteers (46 MIC- affected and 46 controls) from Bhopal and various regions of India were studied taking gender and age into consideration. Binucleated lymphocytes with micronuclei (BNMN), total number of micronuclei in lymphocytes (MNL), and nuclear division index (NDI) frequencies and their relationship to age, gender and several lifestyle variabilities (smoking, alcohol consumption and tobacco-chewing) were investigated. Our observations showed relatively higher BNMN and MNL (Pexposure to MIC. Briefly, the observed cytogenetic damage to the MIC-affected could contribute to cancer risk, especially in the EF and FOE.

  17. THE ADAPTABLE CHANGE OF THE FUNCTION OF T LYMPHOCYTES FOR PHYSICAL EXERCISE WITH OXYGEN

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To find out the possible regularity and mechanism of the adaptable change of human being T lymphocytes for physical exercise with oxygen and bring the original data for the Movement of All People Improving their Health. Methods We selected 16 untrained female students in university and let them had the same amount of exercise for 8 weeks. After that, we collected the cycle blood at the time point of before exercise, the end of exercise and 1 hour after exercise at the end of the 0,first,2 nd,4 nd,6 nd and 8 nd week respectively, so as to determine its stimuli index (SI) by MTT method. Results In the different time sect, such as the early stage of exercise, quiet condition,as soon as the end of exercise and 1 hour after exercise, we found that the SI were obviously Iower than that of normal (P<0. 05) ,especially in the time sect of the end of exercise. Continuing to 4 weeks,the function of T lymphocytes restored gradualy and it lasted to the 8 th week, the SI in quiet condition and 1 hour after exercise had restored to normal(P>0.05),but in the end of exercise, it still was Iow,however, the extent of the cases selected was in a condition of acute excitability. Conclusion As the bodies adapting to the exercise, the function of T lymphocytes restored slowly and the rate increased faster and faster.

  18. Changes in lymphocyte function and subsets in dogs with naturally occurring chronic renal failure.

    Science.gov (United States)

    Kralova, Simona; Leva, Lenka; Toman, Miroslav

    2010-04-01

    Chronic renal failure (CRF) causes immunosuppresion in humans and is thought to be one of the causes of noninfectious secondary immunosuppression in dogs. Hematological, biochemical, and immunological examinations were performed on blood samples obtained from dogs in various stages of CRF. The number of dogs with lymphopenia increased with the progression of clinical signs. All main subsets of lymphocytes were decreased, but more considerable reduction was detected in B-cells, Tc-cells, and NK cells. Depressed lymphocyte response to concanavalin A and pokeweed mitogen was found in dogs with severe clinical signs and lymphopenia. Our results, showing impaired immunological functions, are similar to results obtained from uremic humans, suggesting that infection may be an important complication in dogs with CRF.

  19. Effect of Alemtuzumab on Intestinal Intraepithelial Lymphocytes and Intestinal Barrier Function in Cynomolgus Model

    Institute of Scientific and Technical Information of China (English)

    Lin-Lin Qu; Ya-Qing Lyu; Hai-Tao Jiang; Ting Shan; Jing-Bin Zhang; Qiu-Rong Li; Jie-Shou Li

    2015-01-01

    Background:Alemtuzumab has been used in organ transplantation and a variety of hematologic malignancies (especially for the treatment of B-cell chronic lymphocytic leukemia).However,serious infectious complications frequently occur after treatment.The reason for increased infections postalemtuzumab treatment is unknown at this stage.We explore the effect ofalemtuzumab on intestinal intraepithelial lymphocytes (IELs) and intestinal barrier function in cynomolgus model to explain the reason of infection following alemtuzumab treatment.Methods:Twelve male cynomolguses were randomly assigned to either a treatment or control group.The treatment group received alemtuzumab (3 mg/kg,intravenous injection) while the control group received the same volume of physiological saline.Intestinal IELs were isolated from the control group and the treatment group (on day 9,35,and 70 after treatment) for counting and flow cytometric analysis.Moreover,intestinal permeability was monitored by enzymatic spectrophotometric technique and enzyme-linked immunosorbent assay.Results:The numbers of IELs were decreased significantly on day 9 after treatment compared with the control group (0.35 ± 0.07 x 108 and 1.35 ± 0.09 × 108,respectively; P < 0.05) and were not fully restored until day 70 after treatment.There were significant differences among four groups considering IELs subtypes.In addition,the proportion ofapoptotic IELs after alemtuzumab treatment was significantly higher than in the control group (22.01 ± 3.67 and 6.01 ± 1.42,respectively; P < 0.05).Moreover,the concentration of D-lactate and endotoxin was also increased significantly on day 9 after treatment.Conclusions:Alemtuzumab treatment depletes lymphocytes in the peripheral blood and intestine of cynomolgus model.The induction of apoptosis is an important mechanism of lymphocyte depletion after alemtuzumab treatment.Notably,intestinal barrier function may be disrupted after alemtuzumab treatment.

  20. Effect of Alemtuzumab on Intestinal Intraepithelial Lymphocytes and Intestinal Barrier Function in Cynomolgus Model

    Directory of Open Access Journals (Sweden)

    Lin-Lin Qu

    2015-01-01

    Full Text Available Background: Alemtuzumab has been used in organ transplantation and a variety of hematologic malignancies (especially for the treatment of B-cell chronic lymphocytic leukemia. However, serious infectious complications frequently occur after treatment. The reason for increased infections postalemtuzumab treatment is unknown at this stage. We explore the effect of alemtuzumab on intestinal intraepithelial lymphocytes (IELs and intestinal barrier function in cynomolgus model to explain the reason of infection following alemtuzumab treatment. Methods: Twelve male cynomolguses were randomly assigned to either a treatment or control group. The treatment group received alemtuzumab (3 mg/kg, intravenous injection while the control group received the same volume of physiological saline. Intestinal IELs were isolated from the control group and the treatment group (on day 9, 35, and 70 after treatment for counting and flow cytometric analysis. Moreover, intestinal permeability was monitored by enzymatic spectrophotometric technique and enzyme-linked immunosorbent assay. Results: The numbers of IELs were decreased significantly on day 9 after treatment compared with the control group (0.35 ± 0.07 × 10 8 and 1.35 ± 0.09 × 10 8 , respectively; P < 0.05 and were not fully restored until day 70 after treatment. There were significant differences among four groups considering IELs subtypes. In addition, the proportion of apoptotic IELs after alemtuzumab treatment was significantly higher than in the control group (22.01 ± 3.67 and 6.01 ± 1.42, respectively; P < 0.05. Moreover, the concentration of D-lactate and endotoxin was also increased significantly on day 9 after treatment. Conclusions: Alemtuzumab treatment depletes lymphocytes in the peripheral blood and intestine of cynomolgus model. The induction of apoptosis is an important mechanism of lymphocyte depletion after alemtuzumab treatment. Notably, intestinal barrier function may be disrupted after

  1. Lymphocytes as an Indicator for Initial Kidney Function: A Single Center Analysis of Outcome after Alemtuzumab or Basiliximab Induction

    Directory of Open Access Journals (Sweden)

    Annemarie Weissenbacher

    2015-01-01

    Full Text Available Alemtuzumab, an anti-CD52 T-cell and B-cell depleting monoclonal antibody, is established for induction therapy in renal transplantation (KTx. We herein provide a comparative analysis between alemtuzumab and basiliximab induction therapy and correlate lymphocyte depletion and recovery with the clinical course after KTx. This is a single center retrospective analysis of 225 patients/consecutive kidney transplantations treated with alemtuzumab for lymphocyte depletion and 205 recipients treated with basiliximab. Mean lymphocyte counts were 22.8 ± 9.41% before Tx and 2.61 ± 3.11% between week 1 and week 3 in the alemtuzumab group and 23.77 ± 10.42% before Tx and 13.92 ± 8.20% in the basiliximab group. Delayed graft function (DGF, cytomegalovirus (CMV status, and recipient age showed a significant correlation with lymphocyte counts in the alemtuzumab group only. The outcome was read in reference to the velocity of lymphocyte recovery and in comparison to the control group. Lymphocyte counts early after transplantation, following alemtuzumab treatment, could be identified as a predictive factor for kidney function early after transplantation. A detailed analysis of phenotype and function of lymphocytes after alemtuzumab induction together with a correlation with the clinical course is warranted.

  2. Lymphocytes as an Indicator for Initial Kidney Function: A Single Center Analysis of Outcome after Alemtuzumab or Basiliximab Induction.

    Science.gov (United States)

    Weissenbacher, Annemarie; Hautz, Theresa; Kimelman, Michael; Oberhuber, Rupert; Ulmer, Hanno; Bösmüller, Claudia; Maglione, Manuel; Schneeberger, Stefan

    2015-01-01

    Alemtuzumab, an anti-CD52 T-cell and B-cell depleting monoclonal antibody, is established for induction therapy in renal transplantation (KTx). We herein provide a comparative analysis between alemtuzumab and basiliximab induction therapy and correlate lymphocyte depletion and recovery with the clinical course after KTx. This is a single center retrospective analysis of 225 patients/consecutive kidney transplantations treated with alemtuzumab for lymphocyte depletion and 205 recipients treated with basiliximab. Mean lymphocyte counts were 22.8 ± 9.41% before Tx and 2.61 ± 3.11% between week 1 and week 3 in the alemtuzumab group and 23.77 ± 10.42% before Tx and 13.92 ± 8.20% in the basiliximab group. Delayed graft function (DGF), cytomegalovirus (CMV) status, and recipient age showed a significant correlation with lymphocyte counts in the alemtuzumab group only. The outcome was read in reference to the velocity of lymphocyte recovery and in comparison to the control group. Lymphocyte counts early after transplantation, following alemtuzumab treatment, could be identified as a predictive factor for kidney function early after transplantation. A detailed analysis of phenotype and function of lymphocytes after alemtuzumab induction together with a correlation with the clinical course is warranted.

  3. HIV-1-infection of T lymphocytes and macrophages affects their migration via Nef

    Directory of Open Access Journals (Sweden)

    Christel eVérollet

    2015-10-01

    Full Text Available The human immunodeficiency virus (HIV-1 disseminates in the body and is found in several organs and tissues. While HIV-1 mainly targets both CD4+ T lymphocytes and macrophages, it has contrasting effects between these cell populations. HIV-1 infection namely reduces the viability of CD4+ T cells, whereas infected macrophages are long-lived. In addition, the migration of T cells is reduced by the infection, while HIV-1 differentially modulates the migration modes of macrophages. In 2-dimensions (2D assays, infected macrophages are less motile compared to the control counterparts. In 3D environments, macrophages use two migration modes that are dependent on the matrix architecture: amoeboid and mesenchymal migration. HIV-1 infected macrophages exhibit a reduced amoeboid migration but an enhanced mesenchymal migration, via the viral protein Nef. Indeed, the mesenchymal migration involves podosomes, and Nef stabilizes these cell structures through the activation of the tyrosine kinase Hck, which in turn phosphorylates the Wiskott Aldrich Syndrome Protein (WASP. WASP is a key player in actin remodeling and cell migration. The reprogramed motility of infected macrophages observed in vitro correlates in vivo with enhanced macrophage infiltration in experimental tumors in Nef-transgenic mice compared to control mice.In conclusion, HIV infection of host target cells modifies their migration capacity; we infer that HIV-1 enhances virus spreading in confined environments by reducing T cells migration, and facilitates virus dissemination into different organs and tissues of the human body by enhancing macrophage mesenchymal migration.

  4. The role of apoptosis in the development and function of T lymphocytes

    Institute of Scientific and Technical Information of China (English)

    Nu ZHANG; Heather HARTIG; Ivan DZHAGALOV; David DRAPER; You Wen HE

    2005-01-01

    Apoptosis plays an essential role in T cell biology. Thymocytes expressing nonfunctional or autoreactive TCRs are eliminated by apoptosis during development. Apoptosis also leads to the deletion of expanded effector T cells during immune responses. The dysregulation of apoptosis in the immune system results in autoimmunity, tumorogenesis and immunodeficiency. Two major pathways lead to apoptosis: the intrinsic cell death pathway controlled by Bcl-2 family members and the extrinsic cell death pathway controlled by death receptor signaling. These two pathways work together to regulate T lymphocyte development and function.

  5. Age-related changes of the multidrug resistance P-glycoprotein function in normal human peripheral blood T lymphocytes

    Directory of Open Access Journals (Sweden)

    C.G. Machado

    2003-12-01

    Full Text Available The multidrug resistance P-glycoprotein is a transmembrane efflux pump expressed by lymphocytes and is involved in their cytolytic activity. In the present study, we investigated the age-related changes of P-glycoprotein function in normal peripheral blood lymphocytes. Blood samples from 90 normal volunteers (age range, 0 to 86 years were analyzed. P-glycoprotein function was assessed by the flow cytometric rhodamine 123 assay. P-glycoprotein function was highest in cord blood and progressively declined with age in peripheral blood T CD4+ and CD8+ cells. In contrast, P-glycoprotein function did not vary with age in CD19+ B or CD16+CD56+ natural killer cells. These data suggest that the decline in P-glycoprotein function in T CD4+ and CD8+ lymphocytes as a function of age may contribute to the decrease in T cell cytolytic activity with aging.

  6. Does selenium supplementation affect thyroid function?

    DEFF Research Database (Denmark)

    Winther, Kristian Hillert; Bonnema, Steen Joop; Cold, Frederik

    2015-01-01

    OBJECTIVE: Selenium is present in the active site of proteins important for thyroid hormone synthesis and metabolism. The objective of this study is to investigate the effect of selenium supplementation in different doses on thyroid function, under conditions of suboptimal dietary selenium intake....... DESIGN: The Danish PREvention of Cancer by Intervention with SElenium pilot study (DK-PRECISE) is a randomized, double-blinded, placebo-controlled trial. A total of 491 males and females aged 60-74 years were randomized to 100 μg (n=124), 200 μg (n=122), or 300 μg (n=119) selenium-enriched yeast......=0.015), respectively, per 100 μg/day increase, with insignificant differences between 6 months and 5 years. No significant effects were found for FT3 and FT3:FT4 ratio. CONCLUSIONS: In euthyroid subjects, selenium supplementation minutely and dose-dependently affects thyroid function, when compared...

  7. MHC class I phenotype and function of human beta 2-microglobulin transgenic murine lymphocytes

    DEFF Research Database (Denmark)

    Bjerager, L; Pedersen, L O; Bregenholt, S;

    1996-01-01

    Lymphoid cells from beta 2-microglobulin (beta 2m) knockout mice transgenic for human (h) beta 2m (C57BL/10 m beta 2m-/h beta 2m+) were compared with normal mice for their binding to exogenously added h beta 2m, binding to a H-2Db peptide and for functional activity in a one-way allogenic MLC....... Based on data from cellular binding studies, Scatchard analyses and flow cytometry, it is concluded that exogenous h beta 2m does not bind to hybrid MHC class I (MHC-I) molecules composed of mouse heavy chain/h beta 2m molecules expressed on lymphocytes of transgenic mice. Immunoprecipitation and SDS...... binds radiolabelled peptide in the absence of exogenous added h beta 2m suggesting that a stable fraction of hybrid H-2Db molecules is empty or contain peptides with very low affinity. In a one-way allogenic mixed lymphocyte culture, transgenic splenocytes were found to be far less stimulatory than...

  8. Pulmonary Function Affects Language Performance in Aging

    Directory of Open Access Journals (Sweden)

    Lewina O Lee

    2014-04-01

    associated with better ES performance (B = 6.64, SE = 2.43, p = .01. Higher FVC and FEV1 were related to better MN performance, but this did not reach statistical significance (FVC: B = 3.68, SE = 2.16, p = .09; FEV1: B = 4.92, SE = 2.64, p = .06. Higher FVC (B = 3.98, SE = 1.44, p = .01 and FEV1 (B = 4.79, SE = 1.75, p = .01 were associated with better ANT performance. The positive association between PF and BNT performance was marginally significant (FVC: B = 4.19, SE = 2.18, p = .06; FEV1: B = 3.51, SE = 2.66, p = .10. Discussion and Conclusion Better PF was associated with higher accuracy on sentence processing and naming-based lexical retrieval tasks, consistent with the conclusion that pulmonary function affects older adults’ language performance. Our findings support the emerging thesis that language changes in aging are influenced by health-related physiological and neural mechanisms (e.g., Albert et al., 2009; Cahana-Amitay et al., 2013. From a clinical perspective, these findings highlight the promise of targeting PF as an intervention for improving language abilities among the elderly.

  9. Assessing T lymphocyte function and differentiation by genetically encoded reporter systems.

    Science.gov (United States)

    Hoekstra, Mirjam E; Dijkgraaf, Feline E; Schumacher, Ton N; Rohr, Jan C

    2015-07-01

    Upon infection, antigen-specific T lymphocytes become activated, proliferate, differentiate, and acquire various effector functions. Much of our understanding of the molecular mechanisms underlying these processes derives from studies leveraging gene deletion, RNAi, and overexpression approaches. However, these perturbations do not inform on the regulation of gene activity under physiological conditions. Genetic reporter systems that couple biological events to detectable output signals are capable of providing this information. Here, we review the reporter approaches being currently used to investigate various aspects of T cell behavior, and discuss advantages and disadvantages inherent to different designs. We outline emerging applications based on recent advances in other fields, and highlight the potential of synthetic biology and genome engineering to address open questions in the field.

  10. Functional capabilities of marmoset T and B lymphocytes in primary in vitro antibody formation

    Energy Technology Data Exchange (ETDEWEB)

    Nickerson, D.A.; Gengozian, N.

    1981-01-15

    In vitro tests of T- and B-lymphocyte function of two marmoset species, Saguinus fuscicollis and Saguinus oedipus, were examined to explore the lower immune response profile previously reported for S. o. oedipus. Experiments with trinitrophenyl-lipopolysaccharide (TNP-LPS) revealed peripheral blood leukocytes (PBL) from both species capable of antibody formation. This response was both T cell and monocyte independent; indeed, removal of T cells led to an enhanced response, indicating a regulatory role for this cell in each species. Studies with the nonmitogenic form of TNP-LPS, trinitrophenyl-base-hydrolyzed-lipopolysaccharide, revealed that plaque-forming cells could be obtained from S. fuscicollis PBL while S. o. oedipus PBL were unresponsive. This report also demonstrates that hemopoietic chimerism, a feature common to all marmosets, has a negative influence on antibody-forming capabilities.

  11. CD152 (CTLA-4) regulates effector functions of CD8+ T lymphocytes by repressing Eomesodermin.

    Science.gov (United States)

    Hegel, Johannes K; Knieke, Karin; Kolar, Paula; Reiner, Steven L; Brunner-Weinzierl, Monika C

    2009-03-01

    CD8(+) T lymphocytes are required for effective host defense against pathogens and also for mediating effector responses against uncontrolled proliferating self-tissues. In this study, we determine that individual CD8(+) T cells are tightly controlled in their effector functions by CD152 (CTLA-4). We demonstrate that signals induced by CD152 reduce the frequency of IFN-gamma and granzyme B expressing CD8(+) T cells independently of the transcription factors T-bet or cKrox by selectively inhibiting accumulation of Eomesodermin mRNA and protein. Ectopic expression of Eomesodermin reversed the CD152-mediated inhibition of effector molecule production. Additionally, enhanced cytotoxicity of individual CD8(+) T cells differentiated in the absence of CD152 signaling was determined in vivo. These novel insights extend our understanding of how immune responses of CD8(+) T cells are selectively modulated.

  12. SOCS5 is expressed in primary B and T lymphoid cells but is dispensable for lymphocyte production and function

    DEFF Research Database (Denmark)

    Brender, Christine; Columbus, Ruth; Metcalf, Donald

    2004-01-01

    Suppressors of cytokine signaling (SOCSs) are key regulators of cytokine-induced responses in hematopoietic as well as nonhematopoietic cells. SOCS1 and SOCS3 have been shown to modulate T-cell responses, whereas the roles of other SOCS family members in the regulation of lymphocyte function...... are less clear. Here, we report the generation of mice with a targeted disruption of the Socs5 gene. Socs5(-/-) mice were born in a normal Mendelian ratio and were healthy and fertile. We found that SOCS5 is expressed in primary B and T cells in wild-type mice. However, no abnormalities in the lymphocyte...... to be dispensable for the regulation of lymphocyte function....

  13. Sublethal red tide toxin exposure in free-ranging manatees (Trichechus manatus) affects the immune system through reduced lymphocyte proliferation responses, inflammation, and oxidative stress.

    Science.gov (United States)

    Walsh, Catherine J; Butawan, Matthew; Yordy, Jennifer; Ball, Ray; Flewelling, Leanne; de Wit, Martine; Bonde, Robert K

    2015-04-01

    The health of many Florida manatees (Trichechus manatus latirostris) is adversely affected by exposure to blooms of the toxic dinoflagellate, Karenia brevis. K. brevis blooms are common in manatee habitats of Florida's southwestern coast and produce a group of cyclic polyether toxins collectively referred to as red tide toxins, or brevetoxins. Although a large number of manatees exposed to significant levels of red tide toxins die, several manatees are rescued from sublethal exposure and are successfully treated and returned to the wild. Sublethal brevetoxin exposure may potentially impact the manatee immune system. Lymphocyte proliferative responses and a suite of immune function parameters in the plasma were used to evaluate effects of brevetoxin exposure on health of manatees rescued from natural exposure to red tide toxins in their habitat. Blood samples were collected from rescued manatees at Lowry Park Zoo in Tampa, FL and from healthy, unexposed manatees in Crystal River, FL. Peripheral blood leukocytes (PBL) isolated from whole blood were stimulated with T-cell mitogens, ConA and PHA. A suite of plasma parameters, including plasma protein electrophoresis profiles, lysozyme activity, superoxide dismutase (SOD) activity, and reactive oxygen/nitrogen (ROS/RNS) species, was also used to assess manatee health. Significant decreases (pimmune function components, and thus, overall health, in the Florida manatee.

  14. IL-10 is excluded from the functional cytokine memory of human CD4+ memory T lymphocytes.

    Science.gov (United States)

    Dong, Jun; Ivascu, Claudia; Chang, Hyun-Dong; Wu, Peihua; Angeli, Roberta; Maggi, Laura; Eckhardt, Florian; Tykocinski, Lars; Haefliger, Carolina; Möwes, Beate; Sieper, Jochen; Radbruch, Andreas; Annunziato, Francesco; Thiel, Andreas

    2007-08-15

    Epigenetic modifications, including DNA methylation, profoundly influence gene expression of CD4(+) Th-specific cells thereby shaping memory Th cell function. We demonstrate here a correlation between a lacking fixed potential of human memory Th cells to re-express the immunoregulatory cytokine gene IL10 and its DNA methylation status. Memory Th cells secreting IL-10 or IFN-gamma were directly isolated ex vivo from peripheral blood of healthy volunteers, and the DNA methylation status of IL10 and IFNG was assessed. Limited difference in methylation was found for the IL10 gene locus in IL-10-secreting Th cells, as compared with Th cells not secreting IL-10 isolated directly ex vivo or from in vitro-established human Th1 and Th2 clones. In contrast, in IFN-gamma(+) memory Th cells the promoter of the IFNG gene was hypomethylated, as compared with IFN-gamma-nonsecreting memory Th cells. In accordance with the lack of epigenetic memory, almost 90% of ex vivo-isolated IL-10-secreting Th cells lacked a functional memory for IL-10 re-expression after restimulation. Our data indicate that IL10 does not become epigenetically marked in human memory Th cells unlike effector cytokine genes such as IFNG. The exclusion of IL-10, but not effector cytokines, from the functional memory of human CD4(+) T lymphocytes ex vivo may reflect the need for appropriate regulation of IL-10 secretion, due to its potent immunoregulatory potential.

  15. A general functional response of cytotoxic T lymphocyte-mediated killing of target cells.

    Science.gov (United States)

    Gadhamsetty, Saikrishna; Marée, Athanasius F M; Beltman, Joost B; de Boer, Rob J

    2014-04-15

    Cytotoxic T lymphocytes (CTLs) kill virus-infected cells and tumor cells, and play a critical role in immune protection. Our knowledge of how the CTL killing efficiency varies with CTL and target cell numbers is limited. Here, we simulate a region of lymphoid tissue using a cellular Potts model to characterize the functional response of CTL killing of target cells, and find that the total killing rate saturates both with the CTL and the target cell densities. The relative saturation in CTL and target cell densities is determined by whether a CTL can kill multiple target cells at the same time, and whether a target cell can be killed by many CTLs together. We find that all the studied regimes can be well described by a double-saturation (DS) function with two different saturation constants. We show that this DS model can be mechanistically derived for the cases where target cells are killed by a single CTL. For the other cases, a biological interpretation of the parameters is still possible. Our results imply that this DS function can be used as a tool to predict the cellular interactions in cytotoxicity data.

  16. Acute exposure to 930 MHz CW electromagnetic radiation in vitro affects reactive oxygen species level in rat lymphocytes treated by iron ions.

    Science.gov (United States)

    Zmyślony, Marek; Politanski, Piotr; Rajkowska, Elzbieta; Szymczak, Wieslaw; Jajte, Jolanta

    2004-07-01

    The aim of this study was to test the hypothesis that the 930 MHz continuous wave (CW) electromagnetic field, which is the carrier of signals emitted by cellular phones, affects the reactive oxygen species (ROS) level in living cells. Rat lymphocytes were used in the experiments. A portion of the lymphocytes was treated with iron ions to induce oxidative processes. Exposures to electromagnetic radiation (power density 5 W/m2, theoretical calculated SAR = 1.5 W/kg) were performed within a GTEM cell. Intracellular ROS were measured by the fluorescent probe dichlorofluorescin diacetate (DCF-DA). The results show that acute (5 and 15 min) exposure does not affect the number of produced ROS. If, however, FeCl2 with final concentration 10 microg/ml was added to the lymphocyte suspensions to stimulate ROS production, after both durations of exposure, the magnitude of fluorescence (ROS level during the experiment) was significantly greater in the exposed lymphocytes. The character of the changes in the number of free radicals observed in our experiments was qualitatively compatible with the theoretical prediction from the model of electromagnetic radiation effect on radical pairs.

  17. Effects of thyroxine on cardiac function and lymphocyte β-adrenoceptors in patients with chronic congestive heart failure

    Institute of Scientific and Technical Information of China (English)

    卢新政; 黄峻; 张晓文; 李新华; 王赤京; 张佩生; 陈永生

    2003-01-01

    Objective To explore the effects of thyroid hormone (TH) on cardiac function and peripheral lymphocyte β-adrenoceptors (β-Ars) of patients with chronic congestive heart failure (CHF). Methods Twenty-eight patients with class Ⅲ or Ⅳ advanced CHF due to dilated cardiomyopathy (DCM) or ischemic cardiomyopathy (ICM) were randomly divided into groups A and B. L-thyroxine (L-T50) was administered to group B. Exercise tolerance, chest X-rays, and echocardiographic parameters were obtained before and after one month of treatment, Ficoll-hypaque solution was used to separate peripheral lymphocytes, and 125I-pindolol radioligand binding was used to measure β-AR levels in peripheral lymphocytes. Results L-T50 therapy improved cardiac output [CO, (2.98±0.31)L/min vs (3.24±0.28) L/min, P<0.01], left ventricular ejection fraction (LVEF, 26.21%±3.21% vs 37.93%±9.01%, P<0.01), and decreased isovolumetric relaxation time (IVRT, 0.12±0.04 vs 0.10±0.02, P<0.01). Serum TH levels and the maximal number of β-AR binding sites (βmax ) in peripheral lymphocytes were lower in patients with CHF than in normal healthy people, but L-T50 administration induced a β-AR up-regulation on peripheral lymphocyte surfaces. L-T50 was well tolerated without episodes of ischemia or arrhythmia. There was no significant change in heart rate or metabolic rate.Conclusion TH administration improves cardiac function and β-AR expression in peripheral lymphocytes of patients with CHF.

  18. Functional Differences between IgM and IgD Signaling in Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Ten Hacken, Elisa; Sivina, Mariela; Kim, Ekaterina; O'Brien, Susan; Wierda, William G; Ferrajoli, Alessandra; Estrov, Zeev; Keating, Michael J; Oellerich, Thomas; Scielzo, Cristina; Ghia, Paolo; Caligaris-Cappio, Federico; Burger, Jan A

    2016-09-15

    BCR signaling is a central pathogenetic pathway in chronic lymphocytic leukemia (CLL). Most CLL cells express BCRs of IgM and IgD isotypes, but the contribution of these isotypes to functional responses remains incompletely defined. We therefore investigated differences between IgM and IgD signaling in freshly isolated peripheral blood CLL cells and in CLL cells cultured with nurselike cells, a model that mimics the lymph node microenvironment. IgM signaling induced prolonged activation of ERK kinases and promoted CLL cell survival, CCL3 and CCL4 chemokine secretion, and downregulation of BCL6, the transcriptional repressor of CCL3 In contrast, IgD signaling induced activation of the cytoskeletal protein HS1, along with F-actin polymerization, which resulted in rapid receptor internalization and failure to support downstream responses, including CLL cell survival and chemokine secretion. IgM and IgD receptor downmodulation, HS1 and ERK activation, chemokine secretion, and BCL6 downregulation were also observed when CLL cells were cocultured with nurselike cells. The Bruton's tyrosine kinase inhibitor ibrutinib effectively inhibited both IgM and IgD isotype signaling. In conclusion, through a variety of functional readouts, we demonstrate very distinct outcomes of IgM and IgD isotype activation in CLL cells, providing novel insight into the regulation of BCR signaling in CLL.

  19. Modulation of B lymphocyte function by an aqueous fraction of the ethanol extract of Cissampelos sympodialis Eichl (Menispermaceae

    Directory of Open Access Journals (Sweden)

    M.S. Alexandre-Moreira

    2003-11-01

    Full Text Available Cissampelos sympodialis Eichl species are used in folk medicine for the treatment of asthma, arthritis and rheumatism. In the present study, we investigated the immunomodulatory effect of an aqueous fraction of a 70% (v/v ethanol extract of C. sympodialis leaves on B lymphocyte function. The hydroalcoholic extract inhibited the in vitro proliferative response of resting B cells induced by LPS (IC50 = 17.2 µg/ml, anti-delta-dextran (IC50 = 13.9 µg/ml and anti-IgM (IC50 = 24.3 µg/ml but did not affect the anti-MHC class II antibody-stimulated proliferative response of B cell blasts obtained by stimulation with IL-4 and anti-IgM. Incubation with the hydroalcoholic extract used at 50 µg/ml induced a 700% increase in intracellular cAMP levels. IgM secretion by resting B cells (obtained from normal mice and polyclonally activated B cells (obtained from Trypanosoma cruzi-infected animals was inhibited by the hydroalcoholic extract. The latter were more sensitive to the hydroalcoholic extract since 6.5 µg/ml induced a 20% inhibition in the response of cells from normal mice while it inhibited the response of B cells from infected animals by 75%. The present data indicate that the alcoholic extract of C. sympodialis inhibited B cell function through an increase in intracellular cAMP levels. The finding that the hydroalcoholic extract inhibited immunoglobulin secretion suggests a therapeutic use for the extract from C. sympodialis in conditions associated with unregulated B cell function and enhanced immunoglobulin secretion. Finally, the inhibitory effect of the hydroalcoholic extract on B cells may indicate an anti-inflammatory effect of this extract.

  20. Isolation of murine hepatic lymphocytes using mechanical dissection for phenotypic and functional analysis of NK1.1 + cells

    Institute of Scientific and Technical Information of China (English)

    Zhong-Jun Dong; Hai-Ming Wei; Rui Sun; Bin Gao; Zhi-Gang Tian

    2004-01-01

    AIM: To choose an appropriate methods for the isolation of hepatic lymphocytes between the mechanical dissection and the enzymatic digestion and investigate the effects of two methods on phenotype and function of hepatic lymphocytes.METHODS: Hepatic lymphocytes were isolated from untreated, poly (I:C)-stimulated or ConA-stimulated mice using the two methods, respectively. The cell yield per liver was evaluated by direct counting under microscope.Effects of digestive. enzymes on the surface markers involved in hepatic lymphocytes were represented by relative change rate [(percentage of post-digestion -percentage of pre-digestion)/percentage of pre-digestion].Phenotypic analyses of the subpopulations of hepatic lymphocytes and intracellular cytokines were detected by flow cytometry. The cytotoxicity of NK cells from wild C57BL/6 or poly (I:C)-stimulated C57BL/6 mice was analyzed with a 4-h 51Cr release assay.RESULTS: NK1.1+ cell markers, NK1.1 and DX5, were significantly down-expressed after enzymatic digestion and their relative change rates were about 28% and 32%,respectively. Compared with the enzymatic digestion, the cell yield isolated from unstimulated, poly (I:C)-treated or ConA-treated mice by mechanical dissection was not significantly decreased. Hepatic lymphocytes isolated by the mechanical dissection comprised more innate immune cells like NK, NKT and γδ cells in normal C57BL/6 mice.After poly (I:C) stimulation, hepatic NK cells rose to about 35%, while NKT cells simultaneously decreased. Following ConA injection, the number of hepatic NKT cells was remarkably reduced to 3.67%. Higher ratio of intracellular IFN-γ+(68%) or TNF-α+(15%) NK1.1+ cells from poly (I:C)-treated mice was obtained using mechanical dissection method than control mice. There was no difference in viability between the mechanical dissection and the enzymatic digestion, and hepatic lymphocytes obtained with the two methods had similar cytotoxicity against YAC-1cells

  1. Differential expression and function of CD27 in chronic lymphocytic leukemia cells expressing ZAP-70.

    Science.gov (United States)

    Lafarge, Sandrine T; Hou, Sen; Pauls, Samantha D; Johnston, James B; Gibson, Spencer B; Marshall, Aaron J

    2015-07-01

    Chronic lymphocytic leukemia is a malignancy driven by abberant B cell signaling and survival. Leukemic B cells accumulate in the peripheral blood and the lymphoid organs where contact with stromal cells and T cells provide critical survival signals. Clinical severity of CLL is associated with several prognostic markers including expression of the kinase ZAP-70. ZAP-70 expression enhances signaling via the B cell antigen receptor and is associated with increased cell adhesion and migration capacity. Here we report that ZAP-70-positive CLL patients display significantly higher expression of the TNF superfamily receptor and memory marker CD27 than do ZAP-70 negative patients. CD27 expression by CLL was acutely elevated upon BCR cross-linking, or upon ectopic expression of ZAP-70. CD27 expression correlated with functional capacity to adhere to stromal cells and antibody blockade of CD27 impaired CLL binding to stroma. These results provide the first evidence for differential expression of CD27 among CLL prognostic groups, suggest a role for ZAP-70 dependent signaling in CD27 induction and implicate CD27 in cell-cell interactions with the lymphoid tissue microenvironment.

  2. Phenotypical and Functional Analysis of Intraepithelial Lymphocytes from Small Intestine of Mice in Oral Tolerance

    Directory of Open Access Journals (Sweden)

    Maristela Ruberti

    2012-01-01

    Full Text Available In this work, we evaluated the effects of administration of OVA on phenotype and function of intraepithelial lymphocytes (IELs from small intestine of transgenic (TGN DO11.10 and wild-type BALB/c mice. While the small intestines from BALB/c presented a well preserved structure, those from TGN showed an inflamed aspect. The ingestion of OVA induced a reduction in the number of IELs in small intestines of TGN, but it did not change the frequencies of CD8+ and CD4+ T-cell subsets. Administration of OVA via oral + ip increased the frequency of CD103+ cells in CD4+ T-cell subset in IELs of both BALB/c and TGN mice and elevated its expression in CD8β+ T-cell subset in IELs of TGN. The frequency of Foxp3+ cells increased in all subsets in IELs of BALB/c treated with OVA; in IELs of TGN, it increased only in CD25+ subset. IELs from BALB/c tolerant mice had lower expression of all cytokines studied, whereas those from TGN showed high expression of inflammatory cytokines, especially of IFN-γ, TGF-β, and TNF-α. Overall, our results suggest that the inability of TGN to become tolerant may be related to disorganization and altered proportions of inflammatory/regulatory T cells in its intestinal mucosa.

  3. 1α,25(OH2 Vitamin D3 Modulates Avian T Lymphocyte Functions without Inducing CTL Unresponsiveness.

    Directory of Open Access Journals (Sweden)

    Nitish Boodhoo

    Full Text Available 1,25-Dihydroxyvitamin D3 (Vitamin D is a naturally synthesized fat soluble vitamin shown to have immunomodulatory, anti-inflammatory and cancer prevention properties in human and murine models. Here, we studied the effects of Vitamin D on the functional abilities of avian T lymphocytes using chicken Interferon (IFN-γ ELISPOT assay, BrdU proliferation assay, Annexin V apoptosis assay and PhosFlow for detecting phosphorylated signalling molecules. The results demonstrate that Vitamin D significantly inhibited the abilities of T lymphocytes to produce IFN-γ and proliferate in vitro (P≤0.05, but retained their ability to undergo degranulation, which is a maker for cytotoxicity of these cells. Similarly, Vitamin D did not inhibit Extracellular signal-Regulated Kinase (ERK 1/2 phosphorylation, a key mediator in T cell signalling, in the stimulated T lymphocytes population, while reduced ERK1/2 phosphorylation levels in the unstimulated cells. Our data provide evidence that Vitamin D has immuno-modulatory properties on chicken T lymphocytes without inducing unresponsiveness and by limiting immuno-pathology can promote protective immunity against infectious diseases of poultry.

  4. Correlation of fine needle aspiration cytology findings with thyroid function test in cases of lymphocytic thyroiditis.

    Science.gov (United States)

    Sood, Neelam; Nigam, Jitendra Singh

    2014-01-01

    Background. Chronic lymphocytic thyroiditis is the second most common thyroid lesion diagnosed on FNAC after goiter. FNAC is reliable tool in the diagnosis of thyroid lesion. Objective. To correlate FNAC cytologic findings with TFT in the lymphocytic thyroiditis. Methods. 175 patients with thyroid swellings were referred for FNAC as well as TFT during 2011-2013. Fine needle aspiration cytology was performed using non-aspiration or aspiration techniques and TFT performed on Beckman culter access 2. Results. Lymphoid infiltrate was seen in 55 cases. The commonest age group of lymphocytic thyroiditis was 21-30 years with male : female ratio being 1 : 10. Anti-TPO and TSH were elevated in 96.16% (25/26) of cases with grade 3 lymphoid infiltrate, 94.12% (16/17) of cases with grade 2, and 91.67% (11/12) of cases with 1 grade. Increased anti-TPO with raised TSH without any lymphoid infiltrate was seen in 5 cases and 5 cases showed only raised TSH without raised anti-TPO and without any lymphoid infiltrate. We observed that grade 3 lymphocytic infiltration has correlation with anti-TPO and TSH together or TSH alone but not with anti-TPO alone. We also observed that anti-TPO and TSH together are significant even if no lymphocytic infiltration is present. Conclusion. Grade 3 lymphocytic infiltration has statistical correlation with anti-TPO and TSH together or TSH alone but not with anti-TPO alone. Anti TPO was adjunct to TSH in grade 3. The presence of Hurthle cell change, giant cells, and granulomas has no statistical correlation with lymphocytic thyroiditis.

  5. Correlation of Fine Needle Aspiration Cytology Findings with Thyroid Function Test in Cases of Lymphocytic Thyroiditis

    Directory of Open Access Journals (Sweden)

    Neelam Sood

    2014-01-01

    Full Text Available Background. Chronic lymphocytic thyroiditis is the second most common thyroid lesion diagnosed on FNAC after goiter. FNAC is reliable tool in the diagnosis of thyroid lesion. Objective. To correlate FNAC cytologic findings with TFT in the lymphocytic thyroiditis. Methods. 175 patients with thyroid swellings were referred for FNAC as well as TFT during 2011–2013. Fine needle aspiration cytology was performed using non-aspiration or aspiration techniques and TFT performed on Beckman culter access 2. Results. Lymphoid infiltrate was seen in 55 cases. The commonest age group of lymphocytic thyroiditis was 21–30 years with male : female ratio being 1 : 10. Anti-TPO and TSH were elevated in 96.16% (25/26 of cases with grade 3 lymphoid infiltrate, 94.12% (16/17 of cases with grade 2, and 91.67% (11/12 of cases with 1 grade. Increased anti-TPO with raised TSH without any lymphoid infiltrate was seen in 5 cases and 5 cases showed only raised TSH without raised anti-TPO and without any lymphoid infiltrate. We observed that grade 3 lymphocytic infiltration has correlation with anti-TPO and TSH together or TSH alone but not with anti-TPO alone. We also observed that anti-TPO and TSH together are significant even if no lymphocytic infiltration is present. Conclusion. Grade 3 lymphocytic infiltration has statistical correlation with anti-TPO and TSH together or TSH alone but not with anti-TPO alone. Anti TPO was adjunct to TSH in grade 3. The presence of Hurthle cell change, giant cells, and granulomas has no statistical correlation with lymphocytic thyroiditis.

  6. Immunological studies in acquired immunodeficiency syndrome. Functional studies of lymphocyte subpopulations

    DEFF Research Database (Denmark)

    Hofmann, B; Ødum, Niels; Platz, P

    1985-01-01

    The lymphocyte transformation response in vitro to mitogens (phytohaemagglutinin, concanavalin A, and pokeweed mitogen) and antigens (purified protein derivative and tetanus) was studied in three patients with acquired immunodeficiency syndrome (AIDS), three patients with pre-AIDS, and six healthy...... controls before and after depletion of T4- or T8-positive cells. In controls, T8-depleted lymphocytes responded as well as peripheral blood mononuclear cells (PBMC) when monocytes were added, whereas T4-depleted cells gave about 50% of this response to mitogens and no response at all to antigens...

  7. Does Acquired Hypothyroidism Affect the Hearing Functions?

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    Ayşe Arduç

    2015-12-01

    Full Text Available Purpose: It is well known that congenital hypothyroidism can cause hearing loss. However, conflicting results were found in studies investigating hearing functions in acquired hypothyroidism. Therefore, we evaluated the audiometric findings in patients with acquired hypothyroidism. Material and Method: The study included 58 patients with hypothyroidism and age- and gender-matched 34 healthy controls. Twenty eight (48.27% patients had subclinical hypothyroidism, and 30 (51.73% had obvious hypothyroidism. All subjects had a normal otoscopic examination and tympanometry. Pure tone audiometry at 250, 500, 1000, 2000, 4000, 6000, and 8000 Hertz (Hz was performed in both groups. Blood pressure measurements and the levels of plasma electrolytes, lipids and vitamin B12 were available in all subjects. Results: Hypothyroidism group and control group were similar with respect to systolic and diastolic blood pressures and plasma glucose, lipid, vitamin B12, calcium, sodium, potassium, and chloride levels. Significantly higher audiometric thresholds (dB at 250 (10 (0-45 vs. 5 (0-15, p<0.001 and 500 Hz (10 (0-40 vs. 10 (-5-15, p=0.003 were recorded in hypothyroid patients compared to that in healthy controls. Hearing thresholds at 250 and 500 Hz correlated positively with thyroid-stimulating hormone (TSH, and negatively with free triiodothyronine and free thyroxine. Subclinical hypothyroid patients had a higher hearing threshold at 250 Hz than healthy controls (p=0.001. Discussion: Our study demonstrated that hearing ability decreases in hypothyroidism, even in subclinical hypothyroidism. The changes in TSH and thyroid hormone levels seem to be directly related to the hearing loss in this population of patients.

  8. The function of T-lymphocyte subtypes of blood in patients with hyper-IgE syndrome

    Institute of Scientific and Technical Information of China (English)

    LEI Xiao-bing; TAN Sheng-shun; ZENG Wei-hui; WANG Jun-min; ZHANG Pan-jian; YUAN Yuan

    2005-01-01

    Objective: To study the function in cellular immunity of patients with hyper-IgE syndrome (HIE). Methods: T-lymphocyte subtypes of the peripheral blood and cutaneous delayed-type hypersensitivity (DTH) to two recall antigens, tetanus toxoid (TT) and purified protein derivative(PPD), were measured in 5 patients with HIE and 15 healthy controls, respectively. Results: The CD4+ cell counts in HIE group were significantly lower than those in the control group (P<0.01). In contrast, CD8+ cells were significantly higher in HIE group than those in the controls. The induration sizes of DTH to two recall antigens were smaller in HIE group than those in controls (P<0.01). Conclusion: There is an immunologic dysfunction of T lymphocytes in the patients with HIE and T cells play an important role in the pathogenesis.

  9. The CC chemokine thymus-derived chemotactic agent 4 (TCA-4, secondary lymphoid tissue chemokine, 6Ckine, exodus-2) triggers lymphocyte function-associated antigen 1-mediated arrest of rolling T lymphocytes in peripheral lymph node high endothelial venules.

    Science.gov (United States)

    Stein, J V; Rot, A; Luo, Y; Narasimhaswamy, M; Nakano, H; Gunn, M D; Matsuzawa, A; Quackenbush, E J; Dorf, M E; von Andrian, U H

    2000-01-03

    T cell homing to peripheral lymph nodes (PLNs) is defined by a multistep sequence of interactions between lymphocytes and endothelial cells in high endothelial venules (HEVs). After initial tethering and rolling via L-selectin, firm adhesion of T cells requires rapid upregulation of lymphocyte function-associated antigen 1 (LFA-1) adhesiveness by a previously unknown pathway that activates a Galpha(i)-linked receptor. Here, we used intravital microscopy of murine PLNs to study the role of thymus-derived chemotactic agent (TCA)-4 (secondary lymphoid tissue chemokine, 6Ckine, Exodus-2) in homing of adoptively transferred T cells from T-GFP mice, a transgenic strain that expresses green fluorescent protein (GFP) selectively in naive T lymphocytes (T(GFP) cells). TCA-4 was constitutively presented on the luminal surface of HEVs, where it was required for LFA-1 activation on rolling T(GFP) cells. Desensitization of the TCA-4 receptor, CC chemokine receptor 7 (CCR7), blocked T(GFP) cell adherence in wild-type HEVs, whereas desensitization to stromal cell-derived factor (SDF)-1alpha (the ligand for CXC chemokine receptor 4 [CXCR4]) did not affect T(GFP) cell behavior. TCA-4 protein was not detected on the luminal surface of PLN HEVs in plt/plt mice, which have a congenital defect in T cell homing to PLNs. Accordingly, T(GFP) cells rolled but did not arrest in plt/plt HEVs. When TCA-4 was injected intracutaneously into plt/plt mice, the chemokine entered afferent lymph vessels and accumulated in draining PLNs. 2 h after intracutaneous injection, luminal presentation of TCA-4 was detectable in a subset of HEVs, and LFA-1-mediated T(GFP) cell adhesion was restored in these vessels. We conclude that TCA-4 is both required and sufficient for LFA-1 activation on rolling T cells in PLN HEVs. This study also highlights a hitherto undocumented role for chemokines contained in afferent lymph, which may modulate leukocyte recruitment in draining PLNs.

  10. Expression of CD45RB functionally distinguishes intestinal T lymphocytes in inflammatory bowel disease.

    NARCIS (Netherlands)

    Hove, T. ten; The Olle, F.; Berkhout, M.; Bruggeman, J.P.; Vyth-Dreese, F.A.; Slors, J.F.M.; Deventer, S.J.H. van; Velde, A.A. te

    2004-01-01

    The importance of CD45RB expression on T cells was already shown in mice where CD45RB(high) expression determines pathogenic potential. In this study, we analyzed the expression of CD45RA, CD45RB, and CD45RO on CD4(+) T lymphocytes in the intestinal mucosa and in the circulation of patients with inf

  11. In vitro effects of plant and mushroom extracts on immunological function of chicken lymphocytes and macrophages

    Science.gov (United States)

    The present study was conducted to examine the effects of milk thistle (Silybum marianum), turmeric (Curcuma longa), reishi mushroom (Ganoderma lucidum), and shiitake mushroom (Lentinus edodes) on innate immunity and tumor cell viability. In vitro culture of chicken spleen lymphocytes with extracts ...

  12. Mesenchymal stromal cells improve salivary function and reduce lymphocytic infiltrates in mice with Sjogren's-like disease.

    Directory of Open Access Journals (Sweden)

    Saeed Khalili

    Full Text Available BACKGROUND: Non-obese diabetic (NOD mice develop Sjögren's-like disease (SS-like with loss of saliva flow and increased lymphocytic infiltrates in salivary glands (SGs. There are recent reports using multipotent mesenchymal stromal cells (MSCs as a therapeutic strategy for autoimmune diseases due to their anti-inflammatory and immunomodulatory capabilities. This paper proposed a combined immuno- and cell-based therapy consisting of: A an injection of complete Freund's adjuvant (CFA to eradicate autoreactive T lymphocytes, and B transplantations of MSCs to reselect lymphocytes. The objective of this was to test the effectiveness of CD45(-/TER119(- cells (MSCs in re-establishing salivary function and in reducing the number of lymphocytic infiltrates (foci in SGs. The second objective was to study if the mechanisms underlying a decrease in inflammation (focus score was due to CFA, MSCs, or CFA+MSCs combined. METHODOLOGY/PRINCIPAL FINDINGS: Donor MSCs were isolated from bones of male transgenic eGFP mice. Eight week-old female NOD mice received one of the following treatments: insulin, CFA, MSC, or CFA+MSC (combined therapy. Mice were followed for 14 weeks post-therapy. CD45(-/TER119(- cells demonstrated characteristics of MSCs as they were positive for Sca-1, CD106, CD105, CD73, CD29, CD44, negative for CD45, TER119, CD11b, had high number of CFU-F, and differentiated into osteocytes, chondrocytes and adipocytes. Both MSC and MSC+CFA groups prevented loss of saliva flow and reduced lymphocytic infiltrations in SGs. Moreover, the influx of T and B cells decreased in all foci in MSC and MSC+CFA groups, while the frequency of Foxp3(+ (T(reg cell was increased. MSC-therapy alone reduced inflammation (TNF-α, TGF-β, but the combination of MSC+CFA reduced inflammation and increased the regenerative potential of SGs (FGF-2, EGF. CONCLUSIONS/SIGNIFICANCE: The combined use of MSC+CFA was effective in both preventing saliva secretion loss and reducing

  13. SIFT: predicting amino acid changes that affect protein function

    OpenAIRE

    Ng, Pauline C.; Henikoff, Steven

    2003-01-01

    Single nucleotide polymorphism (SNP) studies and random mutagenesis projects identify amino acid substitutions in protein-coding regions. Each substitution has the potential to affect protein function. SIFT (Sorting Intolerant From Tolerant) is a program that predicts whether an amino acid substitution affects protein function so that users can prioritize substitutions for further study. We have shown that SIFT can distinguish between functionally neutral and deleterious amino acid changes in...

  14. Transfer of cholesterol from macrophages to lymphocytes in culture.

    Science.gov (United States)

    de Bittencourt Júnior, P I; Curi, R

    1998-02-01

    A major feature of macrophage metabolism is its capacity to produce and export cholesterol. Several reports have shown that the manipulation of lymphocyte cholesterol content elicits important changes in lymphocyte proliferation. These findings lead to an inquiry as to whether macrophage-derived cholesterol released into the lymphocyte surroundings may be transferred to the latter thus affecting lymphocyte function. In this study, cholesterol transfer from macrophages to lymphocytes was examined in vitro using rat cells in culture. The findings indicate that there may be a significant transfer of cholesterol from [4-14C]cholesterol labeled resident peritoneal macrophages to mesenteric lymph node resting lymphocytes (up to 173.9 +/- 2.7 pmol/10(7) lymphocytes/10(7) macrophages when co-cultivated for 48 h), in a lipoprotein-dependent manner. This represents the mass transfer of ca. 17 nmoles of cholesterol molecules per 10(7) lymphocytes from 10(7) macrophages (calculated on the basis of specific radioactivity incorporated into macrophages after the pre-labelling period), which suggests that macrophages are capable of replacing the whole lymphocyte cholesterol pool every 21 h. Moreover, an 111%-increase in the total cholesterol content of lymphocytes was found after co-cultivation with macrophages for 48 h. When compared to peritoneal cells, monocytes/macrophages obtained from circulating blood leukocytes presented a much higher cholesterol transfer capacity to lymphocytes (3.06 +/- 0.10 nmol/10(7) lymphocytes/10(7) macrophages co-cultivated for 24 h). Interestingly, inflammatory macrophages dramatically reduced their cholesterol transfer ability (by up to 91%, as compared to resident macrophages). Cholesterol transfer may involve a humoral influence, since it is not only observed when cells are co-cultivated in a single-well chamber system (cells in direct contact), but also in a two-compartment system (where cells can communicate but not by direct contact). Co

  15. Changes in lymphocyte function and subsets in dogs with naturally occurring chronic renal failure

    OpenAIRE

    Kralova, Simona; Leva, Lenka; Toman, Miroslav

    2010-01-01

    Chronic renal failure (CRF) causes immunosuppresion in humans and is thought to be one of the causes of noninfectious secondary immunosuppression in dogs. Hematological, biochemical, and immunological examinations were performed on blood samples obtained from dogs in various stages of CRF. The number of dogs with lymphopenia increased with the progression of clinical signs. All main subsets of lymphocytes were decreased, but more considerable reduction was detected in B-cells, Tc-cells, and N...

  16. Regulation of Mitochondria Function by TRAF3 in B Lymphocytes and B Cell Malignancies

    Science.gov (United States)

    2014-08-01

    Aim 2. To identify novel TRAF3- interacting proteins in mitochondria of B lymphocytes 1 PI: Ping Xie, PhD Considering that TRAF3 does not...mitochondrial proteins. To test this, we propose to identify novel mitochondrial TRAF3- interacting proteins using biochemical affinity purification...mitochondrial TRAF3- interacting proteins : 100% completed. 2c. Mass spectrometry-based sequencing of purified proteins: 100% completed. 2d. Proteomic

  17. Natural polymorphisms in human APOBEC3H and HIV-1 Vif combine in primary T lymphocytes to affect viral G-to-A mutation levels and infectivity.

    Science.gov (United States)

    Refsland, Eric W; Hultquist, Judd F; Luengas, Elizabeth M; Ikeda, Terumasa; Shaban, Nadine M; Law, Emily K; Brown, William L; Reilly, Cavan; Emerman, Michael; Harris, Reuben S

    2014-11-01

    The Vif protein of HIV-1 allows virus replication by degrading several members of the host-encoded APOBEC3 family of DNA cytosine deaminases. Polymorphisms in both host APOBEC3 genes and the viral vif gene have the potential to impact the extent of virus replication among individuals. The most genetically diverse of the seven human APOBEC3 genes is APOBEC3H with seven known haplotypes. Overexpression studies have shown that a subset of these variants express stable and active proteins, whereas the others encode proteins with a short half-life and little, if any, antiviral activity. We demonstrate that these stable/unstable phenotypes are an intrinsic property of endogenous APOBEC3H proteins in primary CD4+ T lymphocytes and confer differential resistance to HIV-1 infection in a manner that depends on natural variation in the Vif protein of the infecting virus. HIV-1 with a Vif protein hypo-functional for APOBEC3H degradation, yet fully able to counteract APOBEC3D, APOBEC3F, and APOBEC3G, was susceptible to restriction and hypermutation in stable APOBEC3H expressing lymphocytes, but not in unstable APOBEC3H expressing lymphocytes. In contrast, HIV-1 with hyper-functional Vif counteracted stable APOBEC3H proteins as well as all other endogenous APOBEC3s and replicated to high levels. We also found that APOBEC3H protein levels are induced over 10-fold by infection. Finally, we found that the global distribution of stable/unstable APOBEC3H haplotypes correlates with the distribution a critical hyper/hypo-functional Vif amino acid residue. These data combine to strongly suggest that stable APOBEC3H haplotypes present as in vivo barriers to HIV-1 replication, that Vif is capable of adapting to these restrictive pressures, and that an evolutionary equilibrium has yet to be reached.

  18. Natural polymorphisms in human APOBEC3H and HIV-1 Vif combine in primary T lymphocytes to affect viral G-to-A mutation levels and infectivity.

    Directory of Open Access Journals (Sweden)

    Eric W Refsland

    2014-11-01

    Full Text Available The Vif protein of HIV-1 allows virus replication by degrading several members of the host-encoded APOBEC3 family of DNA cytosine deaminases. Polymorphisms in both host APOBEC3 genes and the viral vif gene have the potential to impact the extent of virus replication among individuals. The most genetically diverse of the seven human APOBEC3 genes is APOBEC3H with seven known haplotypes. Overexpression studies have shown that a subset of these variants express stable and active proteins, whereas the others encode proteins with a short half-life and little, if any, antiviral activity. We demonstrate that these stable/unstable phenotypes are an intrinsic property of endogenous APOBEC3H proteins in primary CD4+ T lymphocytes and confer differential resistance to HIV-1 infection in a manner that depends on natural variation in the Vif protein of the infecting virus. HIV-1 with a Vif protein hypo-functional for APOBEC3H degradation, yet fully able to counteract APOBEC3D, APOBEC3F, and APOBEC3G, was susceptible to restriction and hypermutation in stable APOBEC3H expressing lymphocytes, but not in unstable APOBEC3H expressing lymphocytes. In contrast, HIV-1 with hyper-functional Vif counteracted stable APOBEC3H proteins as well as all other endogenous APOBEC3s and replicated to high levels. We also found that APOBEC3H protein levels are induced over 10-fold by infection. Finally, we found that the global distribution of stable/unstable APOBEC3H haplotypes correlates with the distribution a critical hyper/hypo-functional Vif amino acid residue. These data combine to strongly suggest that stable APOBEC3H haplotypes present as in vivo barriers to HIV-1 replication, that Vif is capable of adapting to these restrictive pressures, and that an evolutionary equilibrium has yet to be reached.

  19. Studies on platelet function in bronchial asthma Part 2. Production of 12-hydroxyeicosatetraenoic acid from platelets and the platelet-lymphocyte interaction in bronchial asthmatics

    OpenAIRE

    角南, 宏二

    1992-01-01

    To clarify the role of platelets in the pathogenesis of bronchial asthma, the production of 12-hydroxyeicosatetraenoic acid(12HETE) from platelets of asthmatics was examined by high performance liquid chromatography(HPLC). The effect of platelets on lymphocyte function was also studied by lymphocyte blastogenesis. The results were as follows : 1) The production of 12HETE from platelets of asthmatics were significantly higher than that of normal subjects(p

  20. [Dexamethasone affect on the expression of bcl-2 and mTOR genes in T-lymphocytes from healthy donors].

    Science.gov (United States)

    Fatkhullina, A R; Abramov, S N; Skibo, Iu V; Abramova, Z I

    2014-01-01

    Synthetic glucocorticoids are able to activate apoptosis in the cells by regulating the transcription of the respective genes. Effect of dexamethasone on apoptosis is an established fact. However, its influence on another program of cell death autophagy, is currently unproven. Therefore, in this paper we have analyzed the influence of dexamethasone on the expression of bcl-2 and mTOR genes in T-lymphocytes from healthy donors. The results showed that dexamethasone reduced the expression of bcl-2 and mTOR genes. However, the nature of the effect of dexamethasone on mTOR and bcl-2 expression was different: the expression of bcl-2 gene in the long-term cultivation was maintained at the same reduced level, while the expression of mTOR was first reduced and then increased.

  1. Affect integration and reflective function: clarification of central conceptual issues.

    Science.gov (United States)

    Solbakken, Ole André; Hansen, Roger Sandvik; Monsen, Jon Trygve

    2011-07-01

    The importance of affect regulation, modulation or integration for higher-order reflection and adequate functioning is increasingly emphasized across different therapeutic approaches and theories of change. These processes are probably central to any psychotherapeutic endeavor, whether explicitly conceptualized or not, and in recent years a number of therapeutic approaches have been developed that explicitly target them as a primary area of change. However, there still is important lack of clarity in the field regarding the understanding and operationalization of affect integration, particularly when it comes to specifying underlying mechanisms, the significance of different affect states, and the establishment of operational criteria for measurement. The conceptual relationship between affect integration and reflective function thus remains ambiguous. The present article addresses these topics, indicating ways in which a more complex and exhaustive understanding of integration of affect, cognition and behavior can be attained.

  2. SIFT: Predicting amino acid changes that affect protein function.

    Science.gov (United States)

    Ng, Pauline C; Henikoff, Steven

    2003-07-01

    Single nucleotide polymorphism (SNP) studies and random mutagenesis projects identify amino acid substitutions in protein-coding regions. Each substitution has the potential to affect protein function. SIFT (Sorting Intolerant From Tolerant) is a program that predicts whether an amino acid substitution affects protein function so that users can prioritize substitutions for further study. We have shown that SIFT can distinguish between functionally neutral and deleterious amino acid changes in mutagenesis studies and on human polymorphisms. SIFT is available at http://blocks.fhcrc.org/sift/SIFT.html.

  3. Rapid exacerbation of lymphocytic infundibuloneurohypophysitis

    Science.gov (United States)

    Shibue, Kimitaka; Fujii, Toshihito; Goto, Hisanori; Yamashita, Yui; Sugimura, Yoshihisa; Tanji, Masahiro; Yasoda, Akihiro; Inagaki, Nobuya

    2017-01-01

    Abstract Rationale: Lymphocytic hypophysitis is a relatively rare autoimmune disease defined by lymphocytic infiltration to the pituitary. Its rarity and wide spectrum of clinical manifestations make clarification of the pathology difficult. Here, we describe a case we examined from the primary diagnosis to final discharge, showing the serial progression of lymphocytic infundibuloneurohypophysitis (LINH) to panhypopituitarism with extrapituitary inflammatory invasion in a short period, and responding favorably to high-dose glucocorticoid treatment. Patient concerns: Polyuria, General fatigue and Nausea/Vomiting. Diagnoses: Central diabetes insipidus (CDI), Lymphocytic infundibuloneurohypophysitis (LINH). Interventions: Desmopressin acetate, High-dose glucocorticoid (GC) treatment. Outcomes: He was prescribed desmopressin acetate and subsequently discharged. A month later, he revisited our hospital with general fatigue and nausea/vomiting. A screening test disclosed hypopituitarism with adrenal insufficiency. MRI revealed expanded contrast enhancement to the peripheral extrapituitary lesion. He received high-dose GC treatment and the affected lesion exhibited marked improvement on MRI, along with the recovery of the anterior pituitary function. Lessons: This case demonstrates the potential for classical LINH to develop into panhypopituitarsim. We consider this is the first documentation of approaching the cause of atypical LINH with progressive clinical course from the pathological viewpoint. PMID:28248860

  4. A novel regulatory mechanism of naringenin through inhibition of T lymphocyte function in contact hypersensitivity suppression

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Feng; Tang, Yijun; Gao, Zhe [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093 (China)

    2010-06-25

    Naringenin, a flavonoid in grapefruits and citrus fruits, has been reported to exhibit anti-inflammatory and anti-oxidative activities. Contact hypersensitivity (CHS) is a T cell-mediated immune reaction, and the factors released from macrophages also contribute to this response. Previous studies showed that naringenin suppressed CHS by inhibiting activation and migration of macrophages. However, little is known about naringenin's effects on T lymphocytes. Our study indicated that naringenin potently suppressed picryl chloride (PCl)-induced contact hypersensitivity by inhibiting the proliferation and activation of T lymphocytes. In vitro, both of the activated hapten-specific T cells and the T cells stimulated with anti-CD3/anti-CD28 showed growth arrest after naringenin treatment. Furthermore, naringenin reduced CD69 (the protein level) and cytokines such as IL-2, TNF-{alpha}, and IFN-{gamma} (the mRNA level) expressions which highly expressed by activated T cells. Meanwhile, naringenin also induced T cell apoptosis by upregulation of Bax, Bad, PARP, cleaved-caspase 3 and downregulation of phosphorylated Akt, Bcl-2. These findings suggest that, besides its anti-inflammatory activities in macrophages, naringenin also showed inhibitory effects on the activation and proliferation of T cells to alleviate symptoms of contact hypersensitivity.

  5. Bleomycin-Treated Chimeric Thy1-Deficient Mice with Thy1-Deficient Myofibroblasts and Thy-Positive Lymphocytes Resolve Inflammation without Affecting the Fibrotic Response

    Directory of Open Access Journals (Sweden)

    Pazit Y. Cohen

    2015-01-01

    Full Text Available Lung fibrosis is characterized by abnormal accumulation of fibroblasts in the interstitium of the alveolar space. Two populations of myofibroblasts, distinguished by Thy1 expression, are detected in human and murine lungs. Accumulation of Thy1-negative (Thy1− myofibroblasts was shown in the lungs of humans with idiopathic pulmonary fibrosis (IPF and of bleomycin-treated mice. We aimed to identify genetic changes in lung myofibroblasts following Thy1 crosslinking and assess the impact of specific lung myofibroblast Thy1-deficiency, in vivo, in bleomycin-injured mouse lungs. Thy1 increased in mouse lung lymphocytes following bleomycin injury but decreased in myofibroblasts when fibrosis was at the highest point (14 days, as assessed by immunohistochemistry. Using gene chip analysis, we detected that myofibroblast Thy1 crosslinking mediates downregulation of genes promoting cell proliferation, survival, and differentiation, and reduces production of extracellular matrix (ECM components, while concurrently mediating the upregulation of genes known to foster inflammation and immunological functions. Chimeric Thy1-deficient mice with Thy1+ lymphocytes and Thy1− myofibroblasts showed fibrosis similar to wild-type mice and an increased number of CD4/CD25 regulatory T cells, with a concomitant decrease in inflammation. Lung myofibroblasts downregulate Thy1 expression to increase their proliferation but to diminish the in vivo inflammatory milieu. Inflammation is not essential for evolution of fibrosis as was previously stated.

  6. Lymphocyte Redox Imbalance and Reduced Proliferation after a Single Session of High Intensity Interval Exercise.

    Science.gov (United States)

    Tossige-Gomes, Rosalina; Costa, Karine Beatriz; Ottone, Vinícius de Oliveira; Magalhães, Flávio de Castro; Amorim, Fabiano Trigueiro; Rocha-Vieira, Etel

    2016-01-01

    This study investigated whether an acute session of high-intensity interval training (HIIT) is sufficient to alter lymphocyte function and redox status. Sixteen young healthy men underwent a HIIT session on a cycloergometer, consisting of eight bouts of 1 min at 90-100% of peak power, with 75 seconds of active recovery at 30 W between bouts. Venous blood was collected before, immediately after, and 30 minutes after the HIIT session. In response to Staphylococcus aureus superantigen B (SEB) stimulation, lymphocyte proliferation decreased and the IL-2 concentration increased after the HIIT session. However, the HIIT session had no effect on lymphocyte proliferation or IL-2 response to phytohemagglutinin stimulation. The HIIT session also induced lymphocyte redox imbalance, characterized by an increase in the concentration of thiobarbituric acid reactive substances and a decrease in the activity of the antioxidant enzyme catalase. Lymphocyte viability was not affected by the HIIT session. The frequencies of CD25+ and CD69+ T helper and B lymphocytes in response to superantigen stimulation were lower after exercise, suggesting that superantigen-induced lymphocyte activation was reduced by HIIT. However, HIIT also led to a reduction in the frequency of CD4+ and CD19+ cells, so the frequencies of CD25+ and CD69+ cells within the CD4 and CD19 cell populations were not affected by HIIT. These data indicate that the reduced lymphocyte proliferation observed after HIIT is not due to reduced early lymphocyte activation by superantigen. Our findings show that an acute HIIT session promotes lymphocyte redox imbalance and reduces lymphocyte proliferation in response to superantigenic, but not to mitogenic stimulation. This observation cannot be explained by alteration of the early lymphocyte activation response to superantigen. The manner in which lymphocyte function modulation by an acute HIIT session can affect individual immunity and susceptibility to infection is important

  7. Function if Cooperative Learning in Developing Positive Affect

    Institute of Scientific and Technical Information of China (English)

    佟玉平

    2008-01-01

    This paper focus on the function of cooperative learning in developing positive affect, Including reducing anxiety, increasing motivation, facilitating the development of positive attitudes toward learning and language learning, promoting serf- esteem, as well as supporting different learning styles and encouraging perseverance in the difficult and confusing process of learning a foreign language.

  8. The meaning and relevance of B-cell receptor structure and function in chronic lymphocytic leukemia.

    Science.gov (United States)

    Stevenson, Freda K; Forconi, Francesco; Packham, Graham

    2014-07-01

    The B-cell receptor (BCR) is of critical importance for normal B cells and for the majority of B-cell malignancies, especially chronic lymphocytic leukemia (CLL). The two major subsets of CLL are biologically distinct, being derived from B cells at different stages of differentiation and carrying unmutated (U-CLL) or mutated (M-CLL) IGHV genes. U-CLL, which has a poorer prognosis, often has relatively conserved (stereotypic) IGHV-HD-HJ sequences, indicative of interaction with large (super)antigens and similar to those in normal naive innate B cells. Conserved sequences are less evident in M-CLL, in keeping with its postfollicular origin. However, both subsets exhibit features of chronic antigen exposure in tissue sites, with local proliferative events, but also downregulation of surface immunoglobulin M but not surface immunoglobulin D, a characteristic of normal anergic B cells. BCR-mediated anergy can spread to other receptors such as CXCR4. Circulating CLL cells retain a shadow of tissue-based events that can reverse over time, but the overall extent of anergy is greater in M-CLL. Despite this stereotypic variety and more genomic complexity, BCR-mediated responses in vitro appear relatively homogeneous in U-CLL, but M-CLL is more heterogeneous. The differential balance between antigen-induced proliferation or anergy is the likely determinant of clinical behavior and possibly of response to kinase inhibitors.

  9. A Functional Polymorphism in B and T Lymphocyte Attenuator Is Associated with Susceptibility to Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Mie Oki

    2011-01-01

    Full Text Available Inhibitory coreceptors are thought to play important roles in maintaining immunological homeostasis, and a defect in the negative signals from inhibitory coreceptors may lead to the development of autoimmune diseases. We have recently identified B and T lymphocyte attenuator (BTLA, a new inhibitory coreceptor expressed on immune cells, and we suggest that BTLA may be involved in the development of autoimmune diseases using BTLA-deficient mice. However, the role of BTLA in the pathogenesis of autoimmune diseases in humans remains unknown. We, therefore, examined the possible association between BTLA and rheumatoid arthritis (RA, systemic lupus erythematosus (SLE, and Sjögren's syndrome (SS by conducting a case-control genetic association study. We found that 590C single-nucleotide polymorphism (SNP of BTLA gene was significantly associated with susceptibility to RA, but not to SLE or SS. Furthermore, RA patients bearing this 590C SNP developed the disease significantly earlier than the patients without this allele. We also found that BTLA with 590C allele lacked the inhibitory activity on concanavalin A- and anti-CD3 Ab-induced IL-2 production in Jurkat T cells. These results suggest that BTLA is an RA-susceptibility gene and is involved in the protection from autoimmunity in humans.

  10. Increased production of interleukin-6 by T lymphocytes from patients with multiple myeloma.

    Science.gov (United States)

    Lapeña, P; Prieto, A; Garcia-Suarez, J; Reyes, E; San Miguel, J; Jorda, J; Alvarez-Mon, M

    1996-01-01

    Alterations in T lymphocyte functions may affect other cellular components of the immune system. Several lymphokines produced by T cells are involved in the proliferation and differentiation of human B lymphocytes. Alterations in the secretion of these molecules may be implicated in the development of B cell lymphoproliferative diseases. We have investigated the production of interleukin-2 (IL-2) and interleukin-6 (IL-6) by T lymphocytes from 14 patients with multiple myeloma (MM) and 16 healthy controls. The phenotypical and functional characteristics of these T lymphocytes were also studied. The proliferative response to vegetal lectin phytohemagglutinin (PHA) stimulation was decreased in T lymphocytes from MM patients (p 0.05) but not by exogenous IL-6 (p lectin stimulation, the production of IL-2 by T lymphocytes from those patients was normal, while IL-6 secretion was increased.

  11. Ionic interaction of the HIV-1 V3 domain with CCR5 and deregulation of T lymphocyte function.

    Science.gov (United States)

    Baritaki, Stavroula; Zafiropoulos, Alexis; Sioumpara, Maria; Politis, Manolis; Spandidos, Demetrios A; Krambovitis, Elias

    2002-11-08

    We have reported that the principal neutralizing domain of V3 of the HIV-1 gp120 induces an antigen-specific activation apoptosis of responding effector CD4+ T lymphocytes, a phenomenon inhibited by RANTES, an agonist of CCR5. Here, addressing the question of how a hypervariable region could induce such a selective reaction, we demonstrated that the magnitude of the activation phase was dependent on the number of basic amino acids present in the V3 peptide, an observation confirmed by using V3 peptides with appropriate basic amino acid substitutions. The relative position of the amino acids in the V3 peptide did not affect the biological phenomenon. Using surface plasmon resonance biosensor analysis, we also provided direct evidence of the influence of basic amino acids in the interaction between V3 and the amino terminal domain of CCR5. Sulphation of tyrosines in the CCR5 peptide was essential. Our results confirm gp120 modelling predictions and demonstrate simple molecular ionic interactions as capable of affecting key cell events, the wider biological implications of which need to be further explored.

  12. Childhood trauma and cognitive function in first-episode affective and non-affective psychosis.

    LENUS (Irish Health Repository)

    Aas, Monica

    2011-06-01

    A history of childhood trauma is reportedly more prevalent in people suffering from psychosis than in the general population. Childhood trauma has also been linked to cognitive abnormalities in adulthood, and cognitive abnormalities, in turn, are one of the key clinical features of psychosis. Therefore, this study investigated whether there was a relationship between childhood trauma and cognitive function in patients with first-episode psychosis. The potential impact of diagnosis (schizophrenia or affective psychosis) and gender on this association was also examined.

  13. Cognitive function in the affective disorders: a prospective study.

    Science.gov (United States)

    Bulbena, A; Berrios, G E

    1993-01-01

    A prospective, controlled study of 50 subjects confirmed claims that major depression or mania may cause temporary disorders of attention, memory, visuo-spatial function, and choice reaction time, and cause-independently of medication-the appearance of glabellar tap, positive hand-face test, nuchocephalic reflex, and graphesthesia. On follow-up, all these phenomena either disappeared or markedly improved. Age and age of onset, but not pre-morbid intelligence or history of ECT, seemed to modulate the severity of the cognitive impairment. Presence of delusions predicted poor (but reversible) visuo-spatial function. Cognitive impairment accompanied by reversible soft neurological signs was more marked but patients thus affected surprisingly showed lower depressive scores; this was interpreted as representing a secondary, 'organic' form of affective disorder (i.e. a behavioural phenocopy of depression) characterised by a reduced capacity to experience depressive symptoms and by little improvement at follow-up.

  14. Impact of the Functional CD5 Polymorphism A471V on the Response of Chronic Lymphocytic Leukaemia to Conventional Chemotherapy Regimens

    Science.gov (United States)

    Delgado, Julio; Bielig, Torsten; Bonet, Lizette; Carnero-Montoro, Elena; Puente, Xose S.; Colomer, Dolors; Bosch, Elena; Campo, Elias; Lozano, Francisco

    2016-01-01

    Summary The CD5 lymphocyte receptor -a bona fide immunohistochemical marker of chronic lymphocytic leukaemia (CLL) cells- is a negative regulator of activation signals from the antigen-specific B-cell receptor (BCR). Given that signalling components of the BCR are important contributors to the variable clinical behaviour of CLL, the relevance of functional variants of CD5 on CLL prognosis was explored. The results show that germline-encoded CD5 variants influence the survival to conventional chemotherapies from CLL patients with unmutated IGVH genes. This result supports the notion that CD5 is not only a phenotypic marker but a relevant player in CLL cell biology. PMID:26991857

  15. Lymphocyte Trafficking to Mucosal Tissues

    DEFF Research Database (Denmark)

    Mikhak, Zamaneh; Agace, William Winston; Luster, Andrew D.

    2015-01-01

    Lymphocytes are the key cells of the adaptive immune system that provide antigen-specific responses tailored to the context of antigen exposure. Through cytokine release and antibody production, lymphocytes orchestrate and amplify the recruitment and function of other immune cells and contribute...... to host defense against invading pathogens and the pathogenesis of many inflammatory diseases. Lymphocyte function is critically dependent on their ability to traffic into the correct anatomic locations at the appropriate times. This process is highly regulated and requires that lymphocytes interact...

  16. Lymphocyte Subset Alterations Related to Executive Function Deficits and Repetitive Stereotyped Behavior in Autism

    Science.gov (United States)

    Han, Yvonne M. Y.; Leung, Winnie Wing-man; Wong, Chun Kwok; Lam, Joseph M. K.; Cheung, Mei-Chun; Chan, Agnes S.

    2011-01-01

    Increasing evidence suggests that immunological factors are involved in the pathogenesis of autism spectrum disorders (ASD). The present study examined whether immunological abnormalities are associated with cognitive deficits in children with ASD. Eighteen high-functioning (HFA) and 19 low-functioning (LFA) children with ASD, aged 8-17 years,…

  17. Factors potentially affecting the function of kidney grafts

    Institute of Scientific and Technical Information of China (English)

    LIN Jun; ZHENG Xin; XIE Ze-lin; SUN Wen; ZHANG Lei; TIAN Ye; GUO Yu-wen

    2013-01-01

    Background Donor and recipient risk factors on graft function have been well characterized.The contribution of demographic factors,such as age,gender,and other potential factors of donor and recipient at the time of transplantation on the function of a graft is much less well understood.In this study,we analyzed the effects of factors such as age,gender,etc.,on the short-term and long-term graft function in kidney transplant recipients from living donor.Methods A total of 335 living donors and their recipients,who had kidney transplantation in our center from May 2004 to December 2009,were included.Serum creatinine level was used as the assessment criterion (serum creatinine level lower than 115 mmol/L is normal).Factors related to graft function such as age,gender,blood relation by consanguinity,human leukocyte antigen (HLA) mismatch,ABO type,etc.,were analyzed separately.Results Donor age is the key factor affecting both the short-term and long-term function of a grafted kidney from a living donor.The group with donors younger than 48 years showed the best kidney function post transplantation.Match of gender and age is another important factor that influences the function of grafted kidney from a living donor.The older donor to younger recipient group had the worst outcome after kidney transplantation.After 36 months post transplantation,female donor to male recipient group had worse kidney function compared to other groups.We also found that calcinerin inhibitor used in the maintenance period may influence the function of a grafted kidney.No significant statistical differences were found in consanguinity,blood type,and mismatch of HLA.Conclusions Donor age is an important factor affecting the function of a grafted kidney from a living donor.We also recommend taking nephron,immunology factor,infection,and demographic information all into consideration when assessing the outcome of kidney transplantation.

  18. Functional analysis of the murine T lymphocyte immune response to a protozoan parasite, Leishmania tropica

    Directory of Open Access Journals (Sweden)

    H. D. Engers

    1983-03-01

    Full Text Available The results presented in this review summarize a seirs of experiments designed to characterize the murine T cell imune response to the protozoan parasite Leishmania tropica. Enriched T cell populations and T cell clones specific for L. tropica antigens were derived from lymph nodes of primed mice and maintained in continous culture in vitro. These T lymphocytes were shown (A to express the Lyt 1+ 3- cell surface phenotype, (B to proliferate specifically in vitro in response to parasite antigens, together with a source of irradiated syngeneic macrophages, (C to transfer antigen-specific delayed-type hypersensitivity (DTH responses to normal syngeneic mice, (D to induce specific activation of parasitized macrophages in vitro resulting in the destruction of intracellular parasites, (E to provide specific helper activity for antibody responses in vitro in a hapten-carrier system. Protection studies using these defiened T cell populations should allow the characterization of parasite antigen(s implicated in the induction of cellular immune responses beneficial for the host.Os resultados apresentados nesta revisão, sumariam uma série de experimentos planejados no sentido de caracterizar a resposta imune de linfócitos T de camundongos, para o protozoário parasita Leishmania tropica. Populações enriquecidas de linfócitos T e clones de linfócitos T específicos para antígenos de L. tropica foram derivados de gânglios linfáticos de camundongos primados e a seguir mantidos em cultura contínua in vivo. Ficou demonstrado que estes linfócitos T eram capazes de: A Expressar o fenótipo de superfície celular Lyt 1+ 2-, B Proliferar en vitro especificamente em resposta aos antígenos parasitários quando em presença de macrófagos singênicos irradiados, C Transferir uma resposta tipo hipersensibilidade retardada antiígeno especifico à camundongos normais singênicos, D Induzir ativação específica de macrófagos parasitizados in vitro

  19. Interplay of Polarity Proteins and GTPases in T-Lymphocyte Function

    OpenAIRE

    Ivan Fung; Russell, Sarah M.; Jane Oliaro

    2012-01-01

    Polarity refers to the asymmetric distribution of different cellular components within a cell and is central to many cell functions. In T-cells, polarity regulates the activation, migration, and effector function of cytotoxic T-cells (CTLs) during an immune response. The regulation of asymmetric cell division by polarity proteins may also dictate CTL effector and memory differentiation following antigen presentation. Small GTPases, along with their associated polarity and adaptor proteins, ar...

  20. Interplay of Polarity Proteins and GTPases in T-Lymphocyte Function

    Directory of Open Access Journals (Sweden)

    Ivan Fung

    2012-01-01

    Full Text Available Polarity refers to the asymmetric distribution of different cellular components within a cell and is central to many cell functions. In T-cells, polarity regulates the activation, migration, and effector function of cytotoxic T-cells (CTLs during an immune response. The regulation of asymmetric cell division by polarity proteins may also dictate CTL effector and memory differentiation following antigen presentation. Small GTPases, along with their associated polarity and adaptor proteins, are critical for mediating the polarity changes necessary for T-cell activation and function, and in turn, are regulated by guanine exchange factors (GEFS and GTPase activating proteins (GAPS. For example, a novel GEF, dedicator of cytokinesis 8 (DOCK8 was recently identified as a regulator of immune cell function and mutations in DOCK8 have been detected in patients with severe combined immunodeficiency. Both B and T-cells from DOCK8 mutant mice form defective immunological synapses and have abnormal functions, in addition to impaired immune memory development. This paper will discuss the interplay between polarity proteins and GTPases, and their role in T-cell function.

  1. Bone marrow mesenchymal stromal cells affect the cell cycle arrest effect of genotoxic agents on acute lymphocytic leukemia cells via p21 down-regulation.

    Science.gov (United States)

    Zhang, Yiran; Hu, Kaimin; Hu, Yongxian; Liu, Lizhen; Wang, Binsheng; Huang, He

    2014-09-01

    The effect of bone marrow microenvironment on the cell cycle of acute lymphocytic leukemia (ALL) and the underlying mechanism has not been elucidated. In this study, we found that in normal condition, bone marrow mesenchymal stromal cells (BM-MSCs) had no significant effect on the cell cycle and apoptosis of ALL; in the condition when the cell cycle of ALL was blocked by genotoxic agents, BM-MSCs could increase the S-phase cell ratio and decrease the G2/M phase ratio of ALL. Besides, BM-MSCs could protect ALL cells from drug-induced apoptosis. Then, we proved that BM-MSCs affect the cell cycle arrest effect of genotoxic agents on ALL cells via p21 down-regulation. Moreover, our results indicated that activation of Wnt/β-catenin and Erk pathways might be involved in the BM-MSC-induced down-regulation of p21 in ALL cells. Targeting microenvironment-related signaling pathway may therefore be a potential novel approach for ALL therapy.

  2. Carbon nanotubes enhance cytotoxicity mediated by human lymphocytes in vitro.

    Directory of Open Access Journals (Sweden)

    Zhao Sun

    Full Text Available With the expansion of the potential applications of carbon nanotubes (CNT in biomedical fields, the toxicity and biocompatibility of CNT have become issues of growing concern. Since the immune system often mediates tissue damage during pathogenesis, it is important to explore whether CNT can trigger cytotoxicity through affecting the immune functions. In the current study, we evaluated the influence of CNT on the cytotoxicity mediated by human lymphocytes in vitro. The results showed that while CNT at low concentrations (0.001 to 0.1 µg/ml did not cause obvious cell death or apoptosis directly, it enhanced lymphocyte-mediated cytotoxicity against multiple human cell lines. In addition, CNT increased the secretion of IFN-γ and TNF-α by the lymphocytes. CNT also upregulated the NF-κB expression in lymphocytes, and the blockage of the NF-κB pathway reduced the lymphocyte-mediated cytotoxicity triggered by CNT. These results suggest that CNT at lower concentrations may prospectively initiate an indirect cytotoxicity through affecting the function of lymphocytes.

  3. Cognitive function in unaffected twins discordant for affective disorder

    DEFF Research Database (Denmark)

    Christensen, Maj Vinberg; Kyvik, Kirsten Ohm; Kessing, Lars Vedel

    2006-01-01

    is associated with cognitive impairment. METHOD: In a cross-sectional high-risk case-control study, healthy monozygotic (MZ) and dizygotic (DZ) twins with (High-Risk twins) and without (the control group/Low-Risk twins) a co-twin history of affective disorder were identified through nationwide registers....... Cognitive performance of 203 High-Risk and Low-Risk twins was compared. RESULTS: Healthy twins discordant for unipolar disorder showed lower performance on almost all measures of cognitive function: selective and sustained attention, executive function, language processing and working and declarative memory......, and also after adjustment for demographic variables, subclinical symptoms and minor psychopathology. Healthy twins discordant for bipolar disorder showed lower performance on tests measuring episodic and working memory, also after adjustment for the above-mentioned covariables. The discrete cognitive...

  4. GABA, a natural immunomodulator of T lymphocytes

    DEFF Research Database (Denmark)

    Bjurstöm, Helen; Wang, Junyang; Ericsson, Ida

    2008-01-01

    gamma-aminobutyric acid (GABA) is the main neuroinhibitory transmitter in the brain. Here we show that GABA in the extracellular space may affect the fate of pathogenic T lymphocytes entering the brain. We examined in encephalitogenic T cells if they expressed functional GABA channels that could......M and higher GABA concentrations decreased T cell proliferation. The results are consistent with GABA being immunomodulatory....

  5. High Neutrophil-to-lymphocyte Ratio as Prognostic Factor in Patients Affected by Upper Tract Urothelial Cancer: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Marchioni, Michele; Cindolo, Luca; Autorino, Riccardo; Primiceri, Giulia; Arcaniolo, Davide; De Sio, Marco; Schips, Luigi

    2016-12-29

    Given the increasing interest in the possible role of the neutrophil-to-lymphocyte ratio (NLR) as an easily available oncologic marker for upper tract urothelial cancer (UTUC), we sought to quantify the prognostic effect of this biomarker and assess its consistency in UTUC. A systematic review of the published data was performed up to May 2016 using multiple search engines (PubMed, Ovid, and Scopus) to identify eligible comparative studies. A formal meta-analysis was performed for studies comparing patients with a high and those with a low NLR before surgical treatment of UTUC to determine whether the NLR is an independent predictor of survival. Pooled estimates were calculated using a fixed-effects model if no significant heterogeneity was identified. Alternatively, a random-effects model was used when significant heterogeneity was detected. For continuous outcomes, the weighted mean difference was used as a summary measure. For binary variables, the odds ratio or risk ratio was calculated with the 95% confidence intervals (CIs). Statistical analyses were performed using RevMan, version 5. Six studies with 1710 patients were included. A high NLR was associated with poorer oncologic outcomes in patients affected by UTUC, in particular in terms of overall survival (hazard ratio [HR], 1.97; 95% CI, 1.27-3.04; P = .002) and recurrence-free survival (HR, 1.53; 95% CI, 1.19-1.96; P = .0009) but not cancer-specific survival (HR, 1.25; 95% CI, 0.29-5.41; P = .77). Current evidence suggests that the NLR might have an independent role as a prognostic factor in patients affected by UTUC undergoing surgical treatment. The NLR potentially represents an easily available measurement of prognosis; however, it requires validation in larger prospective studies.

  6. Dehydration affects brain structure and function in healthy adolescents.

    Science.gov (United States)

    Kempton, Matthew J; Ettinger, Ulrich; Foster, Russell; Williams, Steven C R; Calvert, Gemma A; Hampshire, Adam; Zelaya, Fernando O; O'Gorman, Ruth L; McMorris, Terry; Owen, Adrian M; Smith, Marcus S

    2011-01-01

    It was recently observed that dehydration causes shrinkage of brain tissue and an associated increase in ventricular volume. Negative effects of dehydration on cognitive performance have been shown in some but not all studies, and it has also been reported that an increased perceived effort may be required following dehydration. However, the effects of dehydration on brain function are unknown. We investigated this question using functional magnetic resonance imaging (fMRI) in 10 healthy adolescents (mean age = 16.8, five females). Each subject completed a thermal exercise protocol and nonthermal exercise control condition in a cross-over repeated measures design. Subjects lost more weight via perspiration in the thermal exercise versus the control condition (P Dehydration following the thermal exercise protocol led to a significantly stronger increase in fronto-parietal blood-oxygen-level-dependent (BOLD) response during an executive function task (Tower of London) than the control condition, whereas cerebral perfusion during rest was not affected. The increase in BOLD response after dehydration was not paralleled by a change in cognitive performance, suggesting an inefficient use of brain metabolic activity following dehydration. This pattern indicates that participants exerted a higher level of neuronal activity in order to achieve the same performance level. Given the limited availability of brain metabolic resources, these findings suggest that prolonged states of reduced water intake may adversely impact executive functions such as planning and visuo-spatial processing.

  7. Can the hydrophilicity of functional monomers affect chemical interaction?

    Science.gov (United States)

    Feitosa, V P; Ogliari, F A; Van Meerbeek, B; Watson, T F; Yoshihara, K; Ogliari, A O; Sinhoreti, M A; Correr, A B; Cama, G; Sauro, S

    2014-02-01

    The number of carbon atoms and/or ester/polyether groups in spacer chains may influence the interaction of functional monomers with calcium and dentin. The present study assessed the chemical interaction and bond strength of 5 standard-synthesized phosphoric-acid ester functional monomers with different spacer chain characteristics, by atomic absorption spectroscopy (AAS), ATR-FTIR, thin-film x-ray diffraction (TF-XRD), scanning electron microscopy (SEM), and microtensile bond strength (μTBS). The tested functional monomers were 2-MEP (two-carbon spacer chain), 10-MDP (10-carbon), 12-MDDP (12-carbon), MTEP (more hydrophilic polyether spacer chain), and CAP-P (intermediate hydrophilicity ester spacer). The intensity of monomer-calcium salt formation measured by AAS differed in the order of 12-MDDP=10-MDP>CAP-P>MTEP>2-MEP. FTIR and SEM analyses of monomer-treated dentin surfaces showed resistance to rinsing for all monomer-dentin bonds, except with 2-MEP. TF-XRD confirmed the weaker interaction of 2-MEP. Highest µTBS was observed for 12-MDDP and 10-MDP. A shorter spacer chain (2-MEP) of phosphate functional monomers induced formation of unstable monomer-calcium salts, and lower chemical interaction and dentin bond strength. The presence of ester or ether groups within longer spacer carbon chains (CAP-P and MTEP) may affect the hydrophilicity, μTBS, and also the formation of monomer-calcium salts.

  8. How does temperature affect the function of tissue macrophages?

    Science.gov (United States)

    Lee, Chen-Ting; Repasky, Elizabeth A.

    2011-03-01

    Macrophages create a major danger signal following injury or infection and upon activation release pro-inflammatory cytokines, which in turn help to generate febrile conditions. Thus, like other cells of the body, tissue macrophages are often exposed to naturally occurring elevations in tissue temperature during inflammation and fever. However, whether macrophages sense and respond to temperature changes in a specific manner which modulates their function is still not clear. In this brief review, we highlight recent studies which have analyzed the effects of temperatures on macrophage function, and summarize the possible underlying molecular mechanisms which have been identified. Mild, physiological range hyperthermia has been shown to have both pro- and anti-inflammatory roles in regulating macrophage inflammatory cytokine production and at the meeting presentation, we will show new data demonstrating that hyperthermia can indeed exert both positive and negative signals to macrophages. While some thermal effects are correlated with the induction of heat shock factors/heat shock proteins, overall it is not clear how mild hyperthermia can exert both pro- and anti-inflammatory functions. We also summarize data which shows that hyperthermia can affect other macrophage effector functions, including the anti-tumor cytotoxicity. Overall, these studies may help us to better understand the immunological role of tissue temperature and may provide important information needed to maximize the application of heat in the treatment of various diseases including cancer.

  9. Immunomodulatory effects of Alliums and Ipomoea batata extracts on lymphocytes and macrophages functions in White Leghorn chickens: in vitro study.

    Science.gov (United States)

    Hanieh, Hamza; Narabara, Kiyoaki; Tanaka, Yuji; Gu, Zhigang; Abe, Asaki; Kondo, Yasuhiro

    2012-01-01

    We previously described that supplementary garlic, onion and purple sweet potato (PSP) enhance humoral immune response in White Leghorn chickens. In the present in vitro study, we investigated the effects of garlic (GE), onion (OE) and PSP (PSPE) extracts on proliferation, interleukin (IL)-2 and interferon (INF)-γ gene expression of stimulated lymphocytes. The effects on microbicidal activity, reactive oxygen species (ROS) and nitric oxide (NO) productions of stimulated peritoneal macrophages were studied as well. The results showed that GE augmented Concanavalin A (ConA)-induced splenocytes (4, 8 and 16µg/mL) and thymocytes (2, 4 and 8µg/mL) proliferations, and gene expression of IL-2 (8 and 16µg/mL) and INF-γ (16µg/mL). None of the examined extracts had mitogenic effect nor stimulated bursacytes response to phorbol 12-myristate 13-acetate (PMA). Macrophages exhibited superior microbicidal activity and ROS production with GE at 4 and 8µg/mL and with OE at 25.6µg/mL. None of the extracts showed stimulatory effects on NO production. The extracts showed concentration-dependent inhibitory effects on all measured parameters at higher concentrations. Taken together, it is likely that garlic has direct stimulatory effects on immune cell functions, whereas the in vitro inhibitory effects of onion and PSP were likely attributed to high flavonoid contents.

  10. [Preparation of polyclonal antibody against sAPRIL and analysis of function in suppressing sAPRIL-mediated lymphocyte proliferation].

    Science.gov (United States)

    Du, Ben-Jun; Gao, Quan-Sheng; Lan, Zhi; Fan, Jun-Wen; Ding, Lu-Jing; Li, Min; Qi, Yuan-Yuan; Kong, Wei

    2011-08-01

    This study was aimed to prepare the polyclonal antibody against the soluble proliferation-inducing ligand (sAPRIL) antigen and to investigate its effects in suppressing sAPRIL mediated lymphocyte proliferation. Mutated recombinant sAPRIL protein, which lacks biological activity but maintains immunogenicity, was used as antigen to immunize humanized SCID mice. Sera were obtained at 6 weeks after immunization. Indirect ELISA and Western blot were used to detect the antibody titer and specificity. The inhibition of polyclonal antibodies on Raji and Jurkat cell proliferation stimulated by sAPRIL was assessed by the MTT assay. The results showed that the mutant of sAPRIL could induce the production of polyclonal antibodies against human sAPRIL. Western blot and indirect ELISA analyses indicated that the anti-serum had higher specificity with a titer of 1:640. Functional analysis revealed that these polyclonal antibodies significantly inhibited the proliferation of Raji and Jurkat cell stimulated by sAPRIL (p polyclonal antibody against human sAPRIL is successfully prepared, which can inhibit the proliferation of Raji and Jurkat cells stimulated by sAPRIL in vitro.

  11. Dual functions of interferon regulatory factors 7C in Epstein-Barr virus-mediated transformation of human B lymphocytes.

    Directory of Open Access Journals (Sweden)

    Yong Zhao

    Full Text Available Epstein-Barr virus (EBV infection is associated with several human malignancies. Interferon (IFN regulatory factor 7 (IRF-7 has several splicing variants, and at least the major splicing variant (IRF-7A has oncogenic potential and is associated with EBV transformation processes. IRF-7C is an alternative splicing variant with only the DNA-binding domain of IRF-7. Whether IRF-7C is present under physiological conditions and its functions in viral transformation are unknown. In this report, we prove the existence of IRF-7C protein and RNA in certain cells under physiological conditions, and find that high levels of IRF-7C are associated with EBV transformation of human primary B cells in vitro as well as EBV type III latency. EBV latent membrane protein 1 (LMP-1 stimulates IRF-7C expression in B lymphocytes. IRF-7C has oncogenic potential in rodent cells and partially restores the growth properties of EBV-transformed cells under a growth-inhibition condition. A tumor array experiment has identified six primary tumor specimens with high levels of IRF-7C protein--all of them are lymphomas. Furthermore, we show that the expression of IRF-7C is apparently closely associated with other IRF-7 splicing variants. IRF-7C inhibits the function of IRF-7 in transcriptional regulation of IFN genes. These data suggest that EBV may use splicing variants of IRF-7 for its transformation process in two strategies: to use oncogenic properties of various IRF-7 splicing variants, but use one of its splicing variants (IRF-7C to block the IFN-induction function of IRF-7 that is detrimental for viral transformation. The work provides a novel relation of host/virus interactions, and has expanded our knowledge about IRFs in EBV transformation.

  12. Bisphenol A affects androgen receptor function via multiple mechanisms.

    Science.gov (United States)

    Teng, Christina; Goodwin, Bonnie; Shockley, Keith; Xia, Menghang; Huang, Ruili; Norris, John; Merrick, B Alex; Jetten, Anton M; Austin, Christopher P; Tice, Raymond R

    2013-05-25

    Bisphenol A (BPA), is a well-known endocrine disruptor compound (EDC) that affects the normal development and function of the female and male reproductive system, however the mechanisms of action remain unclear. To investigate the molecular mechanisms of how BPA may affect ten different nuclear receptors, stable cell lines containing individual nuclear receptor ligand binding domain (LBD)-linked to the β-Gal reporter were examined by a quantitative high throughput screening (qHTS) format in the Tox21 Screening Program of the NIH. The results showed that two receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), are affected by BPA in opposite direction. To confirm the observed effects of BPA on ERα and AR, we performed transient transfection experiments with full-length receptors and their corresponding response elements linked to luciferase reporters. We also included in this study two BPA analogs, bisphenol AF (BPAF) and bisphenol S (BPS). As seen in African green monkey kidney CV1 cells, the present study confirmed that BPA and BPAF act as ERα agonists (half maximal effective concentration EC50 of 10-100 nM) and as AR antagonists (half maximal inhibitory concentration IC50 of 1-2 μM). Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881. BPS with lower estrogenic activity (EC50 of 2.2 μM), did not compete with R1881 for AR binding, when tested at 30 μM. Finally, the effects of BPA were also evaluated in a nuclear translocation assays using EGPF-tagged receptors. Similar to 17β-estradiol (E2) which was used as control, BPA was able to enhance ERα nuclear foci formation but at a 100-fold higher concentration. Although BPA was able to bind AR, the nuclear translocation was reduced. Furthermore, BPA was unable to induce functional foci in the nuclei and is consistent with the transient transfection study that BPA is unable to activate AR.

  13. Functional roles affect diversity-succession relationships for boreal beetles.

    Directory of Open Access Journals (Sweden)

    Heloise Gibb

    Full Text Available Species diversity commonly increases with succession and this relationship is an important justification for conserving large areas of old-growth habitats. However, species with different ecological roles respond differently to succession. We examined the relationship between a range of diversity measures and time since disturbance for boreal forest beetles collected over a 285 year forest chronosequence. We compared responses of "functional" groups related to threat status, dependence on dead wood habitats, diet and the type of trap in which they were collected (indicative of the breadth of ecologies of species. We examined fits of commonly used rank-abundance models for each age class and traditional and derived diversity indices. Rank abundance distributions were closest to the Zipf-Mandelbrot distribution, suggesting little role for competition in structuring most assemblages. Diversity measures for most functional groups increased with succession, but differences in slopes were common. Evenness declined with succession; more so for red-listed species than common species. Saproxylic species increased in diversity with succession while non-saproxylic species did not. Slopes for fungivores were steeper than other diet groups, while detritivores were not strongly affected by succession. Species trapped using emergence traps (log specialists responded more weakly to succession than those trapped using flight intercept traps (representing a broader set of ecologies. Species associated with microhabitats that accumulate with succession (fungi and dead wood thus showed the strongest diversity responses to succession. These clear differences between functional group responses to forest succession should be considered in planning landscapes for optimum conservation value, particularly functional resilience.

  14. Human severe combined immunodeficiency disease: phenotypic and functional characteristics of peripheral B lymphocytes.

    Science.gov (United States)

    Gougeon, M L; Drean, G; Le Deist, F; Dousseau, M; Fevrier, M; Diu, A; Theze, J; Griscelli, C; Fischer, A

    1990-11-01

    Human severe combined immunodeficiency disease (SCID) includes an X-chromosome-linked type characterized by a complete absence of mature T cells, hypogammaglobulinemia but normal or elevated number of B cells, suggesting that the disease results from a block in early T cell differentiation. It has been shown that B cells from obligate carrier women of this disorder exhibit the preferential use of the nonmutant X chromosome as the active X (as shown for T cells), suggesting that the SCID gene product has a direct effect on B cells as well as on T cells. To examine this question, we analyzed the phenotypic and functional characteristics of peripheral B cells from nine infants with SCID. We found a constant absence of spontaneously expressed activation Ag on B cell membrane from all SCID patients tested which contrasts with the phenotypic pattern exhibited by age-matched infants whom all cells bearing surface Ig express the 4F2 Ag and to a lesser extent the transferrin receptor. Concurrently, B cells from SCID patients have a profound impairment in their responses to stimuli that induce in vitro B cell proliferation and differentiation. Although rIL-2 and low-Mr B cell growth factor are potent inducers of proliferation on age-matched infants' B cells, they are poorly efficient in inducing proliferation of anti-mu-activated SCID B cells. This impairment is not related to the resting B cell phenotype of SCID B cells as shown by comparison with normal resting B cells. Furthermore, we observed an apparent block in B cell differentiation inasmuch as neither rIL-2 nor rIL-6 could support SAC-activated SCID B cell differentiation, both lymphokines being very efficient in inducing SAC-activated age-matched infants' B cell or purified resting B cell differentiation. These results suggest that the SCID gene defect has a direct effect on B cells and is required during B cell maturation.

  15. Leukoreduction system chambers are an efficient, valid, and economic source of functional monocyte-derived dendritic cells and lymphocytes.

    Science.gov (United States)

    Pfeiffer, Isabell A; Zinser, Elisabeth; Strasser, Erwin; Stein, Marcello F; Dörrie, Jan; Schaft, Niels; Steinkasserer, Alexander; Knippertz, Ilka

    2013-11-01

    The demand for human monocyte-derived dendritic cells (moDCs), as well as for primary human B and T lymphocytes for immunological research purposes has been increased in recent years. Classically, these monocytes are isolated from blood, leukapheresis products or buffy coats of healthy donors by plastic adherence of peripheral blood mononuclear cells (PBMCs), followed by stimulation with granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4, while lymphocytes are usually isolated from the non-adherent fraction (NAF) by magnetic cell sorting. However, donor-blood is a limited resource and not every blood bank offers leukapheresis products or buffy coats for laboratory use. Additionally, a leukapheresis is very expensive and also the generation/isolation of cells is time- and cost-intensive. To overcome some of these obstacles, we evaluated if low-cost leukoreduction system chambers (LRSCs), which arise after routine donor plateletpheresis procedures, and are usually discarded, would be an alternative and appropriate source of PBMCs to generate moDCs and to isolate lymphocytes. By analyzing the number and phenotype of immature and mature dendritic cells (DCs), as well as of B and T lymphocytes derived from LRSCs, we found all cells to be of high quantity and quality. Further investigations on DCs comprising transwell migration assays, allogeneic mixed lymphocyte reactions (MLR), cytokine secretion assays, and cytotoxic T cell induction assays revealed high migratory, as well as stimulatory capacity of these cells. In addition, DCs and T cells were efficiently electroporated with mRNA and showed characteristic cytokine production after co-culture, demonstrating LRSCs as an efficient, valid, and economic source for generation of moDCs and lymphocytes for research purposes.

  16. Chemokines, lymphocytes, and HIV

    Directory of Open Access Journals (Sweden)

    Farber J.M.

    1998-01-01

    Full Text Available Chemokines are members of a family of more than 30 human cytokines whose best-described activities are as chemotactic factors for leukocytes and that are presumed to be important in leukocyte recruitment and trafficking. While many chemokines can act on lymphocytes, the roles of chemokines and their receptors in lymphocyte biology are poorly understood. The recent discoveries that chemokines can suppress infection by HIV-1 and that chemokine receptors serve, along with CD4, as obligate co-receptors for HIV-1 entry have lent urgency to studies on the relationships between chemokines and lymphocytes. My laboratory has characterized Mig and Crg-2/IP-10, chemokines that are induced by IFN-g and that specifically target lymphocytes, particularly activated T cells. We have demonstrated that the genes for these chemokines are widely expressed during experimental infections in mice with protozoan and viral pathogens, but that the patterns of mig and crg-2 expression differed, suggesting non-redundant roles in vivo. Our related studies to identify new chemokine receptors from activated lymphocytes resulted in the cloning of STRL22 and STRL33. We and others have shown that STRL22 is a receptor for the CC chemokine MIP-3a, and STRL22 has been re-named CCR6. Although STRL33 remains an orphan receptor, we have shown that it can function as a co-receptor for HIV-1 envelope glycoproteins, and that it is active with a broader range of HIV-1 envelope glycoproteins than the major co-receptors described to date. The ability of STRL33 to function with a wide variety of envelope glycoproteins may become particularly important if therapies are instituted to block other specific co-receptors. We presume that investigations into the roles of chemokines and their receptors in lymphocyte biology will provide information important for understanding the pathogenesis of AIDS and for manipulating immune and inflammatory responses for clinical benefit

  17. Studies on rabbit lymphocytes in vitro

    Science.gov (United States)

    Sell, S.; Gell, P. G. H.

    1969-01-01

    Anti-allotypic sera that have no known allotypic determinants other than those also present in the genotype of the lymphocyte donor are as able to induce lymphocyte `blast' transformation in vitro as are anti-allotypic sera that do have allotypic determinants that are not present in the lymphocyte donor. Therefore, anti-allotypic sera do not appear to function in the stimulation of blast transformation by providing access for any of the known allotypic determinants into lymphocytes. PMID:5769980

  18. Phenotypic and Functional Characterization of Peripheral Blood Lymphocytes from Various Age- and Sex-Specific Groups of Owl Monkeys (Aotus nancymaae).

    Science.gov (United States)

    Nehete, Pramod N; Nehete, Bharti P; Chitta, Sriram; Williams, Lawrence E; Abee, Christian R

    2017-02-01

    Owl monkeys (Aotus nancymaae) are New World NHP that serve an important role in vaccine development and as a model for human disease conditions such as malaria. Despite the past contributions of this animal model, limited information is available about the phenotype and functional properties of peripheral blood lymphocytes in reference to sex and age. Using a panel of human antibodies and a set of standardized human immune assays, we identified and characterized various peripheral blood lymphocyte subsets, evaluated the immune functions of T cells, and analyzed cytokines relative to sex and age in healthy owl monkeys. We noted age- and sex-dependent changes in CD28+ (an essential T cell costimulatory molecule) and CD95+ (an apoptotic surface marker) T cells and various levels of cytokines in the plasma. In immune assays of freshly isolated peripheral blood mononuclear cells, IFNγ and perforin responses were significantly higher in female than in male monkeys and in young adults than in juvenile and geriatric groups, despite similar lymphocyte (particularly T cell) populations in these groups. Our current findings may be useful in exploring Aotus monkeys as a model system for the study of aging, susceptibility to infectious diseases, and age-associated differences in vaccine efficacy, and other challenges particular to pediatric and geriatric patients.

  19. Involvement of lymphocyte function-associated antigen-1 (LFA-1) in HIV infection: inhibition by monoclonal antibody

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C; Mathiesen, Lars Reinhardt

    1991-01-01

    Monoclonal antibodies (MAbs) against the alpha- and beta-chain of lymphocyte-associated antigen-1 (LFA-1) were examined for inhibition of HIV-1 infection in vitro. Infection of the T cell line MT4 and the monocytic cell line U937 by isolates HTLVIIIB and SSI-002, respectively was inhibited...

  20. Functional and phenotypic changes in human lymphocytes after coincubation with Leishmania donovani in vitro

    DEFF Research Database (Denmark)

    Hviid, L; Sørensen, A L; Kharazmi, A

    1990-01-01

    that the inhibition of the proliferative response to PHA by live L. donovani in vitro is associated with early processes in lymphocyte activation. Further studies on the inhibitory phenomena described may be of potential significance in the investigation of the suppressive mechanisms in human visceral leishmaniasis....

  1. Enteroantigen (eAg)-binding B lymphocytes in the mouse - phenotype, distribution, function and eAg-specific antibody secretion

    DEFF Research Database (Denmark)

    Venning, Freja Albjerg; Trempenau, Mette Louise; Schmidt, Esben

    2013-01-01

    Studies reporting beneficial effects of B lymphocytes in autoimmune diseases have been accumulating and a regulatory role for certain B cell subsets is hence getting more and more recognition. Recently, B cells were shown to exhibit a regulatory effect in a T cell transfer model of colitis. Here,...

  2. Subpopulations of bovine T lymphocytes collected during foot-and-mouth disease virus infection are affected by freezing, but are subsequently stable in frozen samples

    Science.gov (United States)

    Immunophenotyping of peripheral-blood lymphocytes by flow cytometry is an important tool for infectious disease research. In many live-animal experiments and other longitudinal studies, the processing, prompt staining, and analysis of fresh samples is a logistical challenge and daily variation can c...

  3. Cytokines and T-lymphocyte subsets in healthy post-menopausal women: estrogen retards bone loss without affecting the release of IL-1 or IL-1ra

    DEFF Research Database (Denmark)

    Abrahamsen, Bo; Bendtzen, Klaus; Beck-Nielsen, H

    1997-01-01

    Interleukin (IL)-1 is a potent inducer of bone resorption, and an increased secretion of the IL-1 agonists IL-1 alpha and IL-1 beta relative to the IL-1 receptor antagonist (IL-1ra) has been proposed as a mechanism leading to post-menopausal osteoporosis. T-lymphocytes are capable of secreting bone...... resorptive cytokines and have also been linked with bone metabolism and the development of osteoporosis. Cytokine secretion from whole blood cell cultures was compared between two randomized groups of healthy early post-menopausal women (mean age 52.5 yrs, N = 91) and lymphocyte subsets were quantitated...... by flow cytometry. One group received cyclic estrogen-gestagen replacement therapy (ERT) while the other group was untreated. In spite of a significant bone maintaining effect of ERT, the basal and LPS-stimulated secretion of IL-1 alpha, IL-1 beta, and IL-1ra was identical in the two groups...

  4. Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration.

    Science.gov (United States)

    Morin, Nicole A; Oakes, Patrick W; Hyun, Young-Min; Lee, Dooyoung; Chin, Y Eugene; Chin, Eugene Y; King, Michael R; Springer, Timothy A; Shimaoka, Motomu; Tang, Jay X; Reichner, Jonathan S; Kim, Minsoo

    2008-01-21

    Precise spatial and temporal regulation of cell adhesion and de-adhesion is critical for dynamic lymphocyte migration. Although a great deal of information has been learned about integrin lymphocyte function-associated antigen (LFA)-1 adhesion, the mechanism that regulates efficient LFA-1 de-adhesion from intercellular adhesion molecule (ICAM)-1 during T lymphocyte migration is unknown. Here, we show that nonmuscle myosin heavy chain IIA (MyH9) is recruited to LFA-1 at the uropod of migrating T lymphocytes, and inhibition of the association of MyH9 with LFA-1 results in extreme uropod elongation, defective tail detachment, and decreased lymphocyte migration on ICAM-1, without affecting LFA-1 activation by chemokine CXCL-12. This defect was reversed by a small molecule antagonist that inhibits both LFA-1 affinity and avidity regulation, but not by an antagonist that inhibits only affinity regulation. Total internal reflection fluorescence microscopy of the contact zone between migrating T lymphocytes and ICAM-1 substrate revealed that inactive LFA-1 is selectively localized to the posterior of polarized T lymphocytes, whereas active LFA-1 is localized to their anterior. Thus, during T lymphocyte migration, uropodal adhesion depends on LFA-1 avidity, where MyH9 serves as a key mechanical link between LFA-1 and the cytoskeleton that is critical for LFA-1 de-adhesion.

  5. Exercise Training Alleviates Hypoxia-induced Mitochondrial Dysfunction in the Lymphocytes of Sedentary Males

    Science.gov (United States)

    Tsai, Hsing-Hua; Chang, Shao-Chiang; Chou, Cheng-Hsien; Weng, Tzu-Pin; Hsu, Chih-Chin; Wang, Jong-Shyan

    2016-01-01

    This study elucidates how interval and continuous exercise regimens affect the mitochondrial functionality of lymphocytes under hypoxic stress. Sixty healthy sedentary males were randomly assigned to engage in either high-intensity interval training (HIIT, 3 min intervals at 80% and 40% VO2max, n = 20) or moderate-intensity continuous training (MICT, sustained 60% VO2max, n = 20) for 30 min/day, 5 days/week for 6 weeks or were assigned to a control group that did not receive exercise intervention (n = 20). Lymphocyte phenotypes/mitochondrial functionality under hypoxic exercise (HE, 100 W under 12% O2) were determined before and after the various interventions. Before the intervention, HE (i) increased the mobilization of senescent (CD57+/CD28−) lymphocytes into the blood, (ii) decreased the ATP-linked O2 consumption rate (OCR), the reserve capacity of OCR, and the citrate synthase activity in the mitochondria, and (iii) lowered the mitochondrial membrane potential (MP) and elevated the matrix oxidant burden (MOB) of lymphocytes. However, both HIIT and MICT significantly (i) decreased blood senescent lymphocyte counts, (ii) enhanced the mitochondrial OCR with increased citrate synthase and succinate dehydrogenase activities, (iii) increased mitochondrial MP and decreased MOB and (iv) increased the ratio of mitofusin to DRP-1 in lymphocytes after HE. Thus, we concluded that either HIIT or MICT effectively improves lymphocyte mitochondrial functionality by enhancing oxidative phosphorylation and suppressing oxidative damage under hypoxic conditions. PMID:27731374

  6. Continuous theta burst transcranial magnetic stimulation affects brain functional connectivity.

    Science.gov (United States)

    Dan Cao; Yingjie Li; Ling Wei; Yingying Tang

    2016-08-01

    Prefrontal cortex (PFC) plays an important role in the emotional processing as well as in the functional brain network. Hyperactivity in the right dorsolateral prefrontal cortex (DLPFC) would be found in anxious participants. However, it is still unclear what the role of PFC played in a resting functional network. Continuous theta burst transcranial magnetic stimulation (cTBS) is an effective tool to create virtual lesions on brain regions. In this paper, we applied cTBS over right prefrontal area, and investigated the effects of cTBS on the brain activity for functional connectivity by the method of graph theory. We recorded 64-channels EEG on thirteen healthy participants in the resting condition and emotional tasks before and after 40 s of cTBS. This work focused on the effect of cTBS on cortical activities in the resting condition by calculating the coherence between EEG channels and building functional networks before and after cTBS in the delta, theta, alpha and beta bands. Results revealed that 1) The functional connectivity after cTBS was significantly increased compared with that before cTBS in delta, theta, alpha and beta bands in the resting condition; 2) The efficiency-cost reached the maximum before and after cTBS both with the cost about 0.3 in the bands above, which meant that the information transmission of functional brain network with this cost was highly efficient; 3) the clustering coefficient and path length after cTBS was significantly increased in delta, theta and beta bands. In conclusion, cTBS over PFC indeed enhanced the functional connectivity in the resting condition. In addition, the information transmission in the resting brain network was highly efficient with the cost about 0.3.

  7. Factors affecting functional prognosis of patients with hip fracture

    DEFF Research Database (Denmark)

    Kristensen, M T

    2011-01-01

    Having a hip fracture is considered one of the most fatal fractures for elderly people, resulting in impaired function, and increased morbidity and mortality. This challenges clinicians in identifying patients at risk of worse outcome, in order to optimise and intensify treatment in these patient...

  8. Indoor Particles Affect Vascular Function in the Aged

    DEFF Research Database (Denmark)

    Bräuner, Elvira Vaclavik; Forchhammer, Lykke; Møller, Peter;

    2008-01-01

    -4058 and 7718-12988 particles per cm3, respectively) in their homes. Measurements and results. Microvascular function was assessed non-invasively by measuring digital peripheral artery tone following arm ischemia. Secondary endpoints included hemoglobin, red blood cells, platelet count, coagulation factors, P...

  9. Seed treatments affect functional and antinutritional properties of amaranth flours

    NARCIS (Netherlands)

    Gamel, T.H.; Linssen, J.P.H.; Mesallam, A.S.; Damir, A.A.; Shekib, L.A.

    2006-01-01

    The effects of seed treatments, including cooking, popping germination and flour air classification, on the functional properties and antinutritional factors of Amaranthus caudatus and Amaranthus cruentus seeds were studied. Thermal treatments increased the water absorption with a maximum value of 5

  10. Ectomycorrhizal symbiosis affects functional diversity of rhizosphere fluorescent pseudomonads

    NARCIS (Netherlands)

    Frey-Klett, P.; Chavatte, M.; Clausse, M.L.; Courrier, S.; Roux, Le C.; Raaijmakers, J.M.; Giovanna Martinotti, M.; Pierrat, J.C.; Garbaye, J.

    2005-01-01

    Here we characterized the effect of the ectomycorrhizal symbiosis on the genotypic and functional diversity of soil Pseudomonas fluorescens populations and analysed its possible consequences in terms of plant nutrition, development and health. ¿ Sixty strains of P. fluorescens were isolated from the

  11. Does vitamin C deficiency affect cognitive development and function?

    DEFF Research Database (Denmark)

    Hansen, Stine Normann; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2014-01-01

    Vitamin C is a pivotal antioxidant in the brain and has been reported to have numerous functions, including reactive oxygen species scavenging, neuromodulation, and involvement in angiogenesis. Absence of vitamin C in the brain has been shown to be detrimental to survival in newborn SVCT2(-/-) mi...

  12. Lipid Bilayer Composition Affects Transmembrane Protein Orientation and Function

    Directory of Open Access Journals (Sweden)

    Katie D. Hickey

    2011-01-01

    Full Text Available Sperm membranes change in structure and composition upon ejaculation to undergo capacitation, a molecular transformation which enables spermatozoa to undergo the acrosome reaction and be capable of fertilization. Changes to the membrane environment including lipid composition, specifically lipid microdomains, may be responsible for enabling capacitation. To study the effect of lipid environment on proteins, liposomes were created using lipids extracted from bull sperm membranes, with or without a protein (Na+ K+-ATPase or -amylase. Protein incorporation, function, and orientation were determined. Fluorescence resonance energy transfer (FRET confirmed protein inclusion in the lipid bilayer, and protein function was confirmed using a colourometric assay of phosphate production from ATP cleavage. In the native lipid liposomes, ATPase was oriented with the subunit facing the outer leaflet, while changing the lipid composition to 50% native lipids and 50% exogenous lipids significantly altered this orientation of Na+ K+-ATPase within the membranes.

  13. Experimental conditions affecting functional comparison of highly active glutathione transferases.

    Science.gov (United States)

    Fedulova, Natalia; Mannervik, Bengt

    2011-06-01

    Glutathione transferases (GSTs, EC 2.5.1.18) possess multiple functions and have potential applications in biotechnology. Direct evidence of underestimation of activity of human GST A3-3 and porcine GST A2-2 measured at submicromolar enzyme concentrations is reported here for the first time. The combination of time-dependent and enzyme concentration-dependent loss of activity and the choice of the organic solvent for substrates were found to cause irreproducibility of activity measurements of GSTs. These effects contribute to high variability of activity values of porcine GST A2-2 and human Alpha-class GSTs reported in the literature. Adsorption of GSTs to surfaces was found to be the main explanation of the observed phenomena. Several approaches to improved functional comparison of highly active GSTs are proposed.

  14. Alginate overproduction affects Pseudomonas aeruginosa biofilm structure and function

    DEFF Research Database (Denmark)

    Hentzer, Morten; Teitzel, G.M.; Balzer, G.J.;

    2001-01-01

    During the course of chronic cystic fibrosis (CF) infections, Pseudomonas aeruginosa undergoes a conversion to a mucoid phenotype, which is characterized by overproduction of the exopolysaccharide alginate. Chronic P. aeruginosa infections involve surface-attached, highly antibiotic-resistant com......During the course of chronic cystic fibrosis (CF) infections, Pseudomonas aeruginosa undergoes a conversion to a mucoid phenotype, which is characterized by overproduction of the exopolysaccharide alginate. Chronic P. aeruginosa infections involve surface-attached, highly antibiotic......-resistant communities of microorganisms organized in biofilms. Although biofilm formation and the conversion to mucoidy are both important aspects of CF pathogenesis, the relationship between them is at the present unclear. In this study, we report that the overproduction of alginate affects biofilm development...

  15. Genes affecting β-cell function in type 1 diabetes

    DEFF Research Database (Denmark)

    Fløyel, Tina; Kaur, Simranjeet; Pociot, Flemming

    2015-01-01

    Type 1 diabetes (T1D) is a multifactorial disease resulting from an immune-mediated destruction of the insulin-producing pancreatic β cells. Several environmental and genetic risk factors predispose to the disease. Genome-wide association studies (GWAS) have identified around 50 genetic regions...... that affect the risk of developing T1D, but the disease-causing variants and genes are still largely unknown. In this review, we discuss the current status of T1D susceptibility loci and candidate genes with focus on the β cell. At least 40 % of the genes in the T1D susceptibility loci are expressed in human...... islets and β cells, where they according to recent studies modulate the β-cell response to the immune system. As most of the risk variants map to noncoding regions of the genome, i.e., promoters, enhancers, intergenic regions, and noncoding genes, their possible involvement in T1D pathogenesis as gene...

  16. Risk factors affecting somatosensory function after sagittal split osteotomy

    DEFF Research Database (Denmark)

    Thygesen, Torben Henrik; Jensen, Allan Bardow; Helleberg, M;

    2008-01-01

    Purpose The aim of this study was to evaluate potential individual and intraoperative risk factors associated with bilateral sagittal split osteotomy (BSSO) and to correlate the findings with postoperative changes in somatosensory function. Patients and Methods A total of 18 men and 29 women (mean...... and free dissection of the inferior alveolar nerve during BSSO increased self-reported changes in lower lip sensation and lower lip tactile threshold after BSSO (P discrimination (P

  17. Does caregiving stress affect cognitive function in older women?

    Science.gov (United States)

    Lee, Sunmin; Kawachi, Ichiro; Grodstein, Francine

    2004-01-01

    Increasing numbers of women provide care to their ill spouses; however, no studies have examined possible effects of caregiving stress on cognitive function. We administered 6 tests of cognitive function to 13740 Nurses' Health Study participants aged 70-79 years. We collected information on caregiving and numerous potential confounding variables via biennial mailed questionnaires. After adjustment for potential confounders (age, education, mental health index, vitality index, use of antidepressants, and history of high blood pressure, diabetes, and heart disease), we found modest but significantly increased risks of low cognitive function on three of the cognitive tests among women who provided care to a disabled or ill spouse compared with women who did not provide any care. For example, on the TICS, a test of general cognition, the risk of a low score was 31% higher in women who provided care compared with women who did not (RR = 1.31, 95% CI 1.10, 1.56). We found a moderately increased risk of poor performance on several cognitive tests among women who provided care to their disabled or ill husbands.

  18. Prenatal drug exposure affects neonatal brain functional connectivity.

    Science.gov (United States)

    Salzwedel, Andrew P; Grewen, Karen M; Vachet, Clement; Gerig, Guido; Lin, Weili; Gao, Wei

    2015-04-01

    Prenatal drug exposure, particularly prenatal cocaine exposure (PCE), incurs great public and scientific interest because of its associated neurodevelopmental consequences. However, the neural underpinnings of PCE remain essentially uncharted, and existing studies in school-aged children and adolescents are confounded greatly by postnatal environmental factors. In this study, leveraging a large neonate sample (N = 152) and non-invasive resting-state functional magnetic resonance imaging, we compared human infants with PCE comorbid with other drugs (such as nicotine, alcohol, marijuana, and antidepressant) with infants with similar non-cocaine poly drug exposure and drug-free controls. We aimed to characterize the neural correlates of PCE based on functional connectivity measurements of the amygdala and insula at the earliest stage of development. Our results revealed common drug exposure-related connectivity disruptions within the amygdala-frontal, insula-frontal, and insula-sensorimotor circuits. Moreover, a cocaine-specific effect was detected within a subregion of the amygdala-frontal network. This pathway is thought to play an important role in arousal regulation, which has been shown to be irregular in PCE infants and adolescents. These novel results provide the earliest human-based functional delineations of the neural-developmental consequences of prenatal drug exposure and thus open a new window for the advancement of effective strategies aimed at early risk identification and intervention.

  19. Alterations in lymphocyte subset patterns and co-stimulatory molecules in patients with Alzheimer disease

    Institute of Scientific and Technical Information of China (English)

    XUE Shou-ru; XU Dong-hua; YANG Xin-xin; DONG Wan-li

    2009-01-01

    @@ Alzheimer disease (AD) is characterized by the presence of β-amyloid (Aβ) plaques in the brain.1 More evidence of inflammatory parameters, such as, complement factors, proinflammatory cytokines and lymphocytes has been found to be co-localized with Aβ plaques,1,2 The research in the past decades has demonstrated abnormalities of both the humoral and cellular immune responses, suggesting an association of immunological aberration and AD. The total percentage of lymphocytes was not found to be altered, whereas the alterations of T-cell function, differentiation and subset distribution have still been unresolved.3,4 A significantly decreased function of suppressor as well as helper T-cells and natural killer (NK) cells in AD patients has been observed. Studies on lymphocyte subpopulations showed conflicting results, while other studies could not find alterations in lymphocyte subset distribution. In the present study, we assume the immune system dysregulation depending on a defective immune response which also affects lymphocyte differentiation and subset distribution. We investigated T lymphocyte subset pattems and co-stimulatory molecules, as well as B lymphocytes and NK cells in peripheral blood of AD patients and age matched healthy controls.

  20. TRPML cation channels regulate the specialized lysosomal compartment of vertebrate B-lymphocytes.

    Science.gov (United States)

    Song, Yumei; Dayalu, Rashmi; Matthews, Sharon A; Scharenberg, Andrew M

    2006-12-01

    B-lymphocytes possess a specialized lysosomal compartment, the regulated transformation of which has been implicated in B-cell antigen presentation. Members of the mucolipin (TRPML) family of cation channels have been implicated in regulated vesicular transport in several tissues, but a role for TRPML function in lymphocyte vesicular transport physiology has not been previously described. To address the role of TRPML proteins in lymphocyte vesicular transport, we analyzed the lysosomal compartment in cultured B-lymphocytes engineered to lack TRPML1 or after expression of N- or C-terminal GFP fusion proteins of TRPML1 or TRPML2. Consistent with previous analyses of lymphocytes derived from human patients with mutations in TRPML1, we were not able to detect abnormalities in the lysosomes of TRPML1-deficient DT40 B-lymphocytes. However, while N-terminal GFP fusions of TRPML2 localized to normal appearing lysosomes, C-terminal GFP fusions of either TRPML1 or TRPML2 acted to antagonize endogenous TRPML function, localizing to large vesicular structures, the histological properties of which were indistinguishable from the enlarged lysosomes observed in affected tissues of TRPML1-deficient humans. Endocytosed B-cell receptors were delivered to these enlarged lysosomes, demonstrating that a TRPML-dependent process is required for normal regulation of the specialized lysosome compartment of vertebrate B-lymphocytes.

  1. Involvement of lymphocyte function-associated antigen-1 (LFA-1) in HIV infection: inhibition by monoclonal antibody

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C; Mathiesen, Lars Reinhardt;

    1991-01-01

    Monoclonal antibodies (MAbs) against the alpha- and beta-chain of lymphocyte-associated antigen-1 (LFA-1) were examined for inhibition of HIV-1 infection in vitro. Infection of the T cell line MT4 and the monocytic cell line U937 by isolates HTLVIIIB and SSI-002, respectively was inhibited...... in a concentration dependent manner by MAb against the beta-chain but not against the alpha-chain. No cross-reactivity was found between MAb against LFA-1 and against the CD4 receptor (MAb Leu3a). MAbs against the beta-chain and the CD4 receptor were found to act synergistically in inhibiting HIV infection....... These data indicate that the beta-chain of LFA-1 in addition to the CD4 receptor may be involved in HIV infection in vitro....

  2. Visual function affects prosocial behaviors in older adults.

    Science.gov (United States)

    Teoli, Dac A; Smith, Merideth D; Leys, Monique J; Jain, Priyanka; Odom, J Vernon

    2016-02-01

    Eye-related pathological conditions such as glaucoma, diabetic retinopathy, and age-related macular degeneration commonly lead to decreased peripheral/central field, decreased visual acuity, and increased functional disability. We sought to answer if relationships exist between measures of visual function and reported prosocial behaviors in an older adult population with eye-related diagnoses. The sample consisted of adults, aged ≥ 60 years old, at an academic hospital's eye institute. Vision ranged from normal to severe impairment. Medical charts determined the visual acuities, ocular disease, duration of disease (DD), and visual fields (VF). Measures of giving help were via validated questionnaires on giving formal support (GFS) and giving informal support; measures of help received were perceived support (PS) and informal support received (ISR). ISR had subscales: tangible support (ISR-T), emotional support (ISR-E), and composite (ISR-C). Visual acuities of the better and worse seeing eyes were converted to LogMAR values. VF information converted to a 4-point rating scale of binocular field loss severity. DD was in years. Among 96 participants (mean age 73.28; range 60-94), stepwise regression indicated a relationship of visual variables to GFS (p < 0.05; Multiple R (2) = 0.1679 with acuity-better eye, VF rating, and DD), PS (p < 0.05; Multiple R (2) = 0.2254 with acuity-better eye), ISR-C (p < 0.05; Multiple R (2) = 0.041 with acuity-better eye), and ISR-T (p < 0.05; Multiple R (2) = 0.1421 with acuity-better eye). The findings suggest eye-related conditions can impact levels and perceptions of support exchanges. Our data reinforces the importance of visual function as an influence on prosocial behavior in older adults.

  3. Persistent expression and function of P-glycoprotein on peripheral blood lymphocytes identifies corticosteroid resistance in patients with systemic lupus erythematosus.

    Science.gov (United States)

    Kansal, Amit; Tripathi, Deepak; Rai, Mohit K; Agarwal, Vikas

    2016-02-01

    Corticosteroids (CS) are the mainstay of treatment in systemic lupus erythematosus (SLE) patients. However, some patients have poor response to CS treatment. Among the multiple mechanisms of CS resistance, overexpression of P-glycoprotein (P-gp) on peripheral blood lymphocytes (PBL) may be one of them as this result in efflux of CS from lymphocytes. Thus, we evaluated the role of P-gp protein on PBLs in patients with SLE in its response to CS therapy. SLE patients (n = 42) (fulfilling ACR revised criteria) who were naïve to CS and immunosuppressive drugs were enrolled. Disease activity was assessed using SLE disease activity index (SLEDAI) and expression, and function of P-gp was evaluated by flow cytometry at baseline and after 3 months of therapy with CS. At 3 months, patients with SLEDAI >4 and SLEDAI ≤4 were grouped as nonresponders and responders, respectively. P-gp expression was significantly increased on PBLs of SLE patients as compared to healthy controls (p < 0.001). P-gp expression and function correlated with SLEDAI (r = 0.49, p = 0.005; and r = 0.49, p = 0.001, respectively). P-gp expression and function were not different in responders and nonresponders at baseline. However, at 3 months of CS therapy, P-gp expression and function decreased in responders (p < 0.001 and p < 0.005, respectively), whereas in nonresponders, it remained unchanged. Persistent overexpression and activity of P-gp are associated with poor response to CS in CS naïve patients of SLE.

  4. 热性惊厥导致T细胞功能改变的观察%Immune-Functional Changes of T-lymphocytes in Children with Febrile Convulsions

    Institute of Scientific and Technical Information of China (English)

    陈遂 陈遂; 邹峥; 梅魁敏; 陈志军; 徐淑娟

    2000-01-01

    探讨热性惊厥患儿外周血T淋巴细胞免疫功能的变化。方法:应用APSAP法检测82例热性惊厥患儿、40例上呼吸道感染患儿及40例正常小儿T淋巴细胞亚群、CD25抗原在自然状态和PHA激活后的活化状态的百分率。结果:热性惊厥患儿外周血中,CD3、CD4、CD4/CD8比值,均显著低于两对照组;热性惊厥患儿在自然状态下的CD25抗原表达率明显低于两对照组,经PHA刺激后,CD25抗原表达在各组均显著增多,但热性惊厥组仍低于两对照组。结论:热性惊厥患儿存在着细胞免疫损害,这可能是热性惊厥发生和复发的一个重要因素。预防热性惊厥复发,必须从提高细胞免疫功能着手。%To ineestigate the immune-functional changes of T-lymphocytes of peripheral blood in chil dren with febrile convulsions. Methods: Eighty-two children with febrile convulsions, forty with acute upper respiratory tract infection and forty normals were studied. The distribution of T-lymphocytes subsets, the expression of active marker CD25+ before and after PHA stimulation were investigated by APAAP assay. Results:Compared with the other control groups, the percentages of CD3, CD4 and CD4/CD8 ratio of T-lymphocytes were all significantly depressed in the peripheral blood in children with febrile convulsions. The expression rate of CD25 antigen before PHA stimulation was significantly lower than those in two control groups. After PHA stimulation, the expression rates of CD25 antigen were all higher than before, but the rate of the febrile convulsion group was still lower than those of the control groups. Conclusion: Impairment of T-lymphocyte s-mediated immune function was associated with febrile convulsion and it might be a important cause of occurrence of febrile convulsion in children. For prevention and reduction of recurrence and subsequent brain damage, it is important to improve the T-lymphocyte s-mediated immune function of the

  5. Affected functional networks associated with sentence production in classic galactosemia.

    Science.gov (United States)

    Timmers, Inge; van den Hurk, Job; Hofman, Paul Am; Zimmermann, Luc Ji; Uludağ, Kâmil; Jansma, Bernadette M; Rubio-Gozalbo, M Estela

    2015-08-07

    Patients with the inherited metabolic disorder classic galactosemia have language production impairments in several planning stages. Here, we assessed potential deviations in recruitment and connectivity across brain areas responsible for language production that may explain these deficits. We used functional magnetic resonance imaging (fMRI) to study neural activity and connectivity while participants carried out a language production task. This study included 13 adolescent patients and 13 age- and gender-matched healthy controls. Participants passively watched or actively described an animated visual scene using two conditions, varying in syntactic complexity (single words versus a sentence). Results showed that patients recruited additional and more extensive brain regions during sentence production. Both groups showed modulations with syntactic complexity in left inferior frontal gyrus (IFG), a region associated with syntactic planning, and in right insula. In addition, patients showed a modulation with syntax in left superior temporal gyrus (STG), whereas the controls did not. Further, patients showed increased activity in right STG and right supplementary motor area (SMA). The functional connectivity data showed similar patterns, with more extensive connectivity with frontal and motor regions, and restricted and weaker connectivity with superior temporal regions. Patients also showed higher baseline cerebral blood flow (CBF) in right IFG and trends towards higher CBF in bilateral STG, SMA and the insula. Taken together, the data demonstrate that language abnormalities in classic galactosemia are associated with specific changes within the language network. These changes point towards impairments related to both syntactic planning and speech motor planning in these patients.

  6. Modeled Microgravity Affects Fibroblast Functions Related to Wound Healing

    Science.gov (United States)

    Cialdai, Francesca; Vignali, Leonardo; Morbidelli, Lucia; Colciago, Alessandra; Celotti, Fabio; Santi, Alice; Caselli, Anna; Cirri, Paolo; Monici, Monica

    2017-02-01

    Wound healing is crucial for the survival of an organism. Therefore, in the perspective of space exploration missions, it is important to understand if and how microgravity conditions affect the behavior of the cell populations involved in wound healing and the evolution of the process. Since fibroblasts are the major players in tissue repair, this study was focused on the behavior of fibroblasts in microgravity conditions, modeled by a RCCS. Cell cytoskeleton was studied by immunofluorescence microscopy, the ability to migrate was assessed by microchemotaxis and scratch assay, and the expression of markers of fibroblast activation, angiogenesis, and inflammation was assessed by western blot. Results revealed that after cell exposure to modeled microgravity conditions, a thorough rearrangement of microtubules occurred and α-SMA bundles were replaced by a tight network of faulty and disorganized filaments. Exposure to modeled microgravity induced a decrease in α-SMA and E-CAD expressions. Also, the expression of the pro-angiogenic protein VEGF decreased, while that of the inflammatory signal COX-2 increased. Fibroblast ability to adhere, migrate, and respond to chemoattractants (PRP), closely related to cytoskeleton integrity and membrane junctions, was significantly impaired. Nevertheless, PRP was able to partially restore fibroblast migration.

  7. Modeled Microgravity Affects Fibroblast Functions Related to Wound Healing

    Science.gov (United States)

    Cialdai, Francesca; Vignali, Leonardo; Morbidelli, Lucia; Colciago, Alessandra; Celotti, Fabio; Santi, Alice; Caselli, Anna; Cirri, Paolo; Monici, Monica

    2017-01-01

    Wound healing is crucial for the survival of an organism. Therefore, in the perspective of space exploration missions, it is important to understand if and how microgravity conditions affect the behavior of the cell populations involved in wound healing and the evolution of the process. Since fibroblasts are the major players in tissue repair, this study was focused on the behavior of fibroblasts in microgravity conditions, modeled by a RCCS. Cell cytoskeleton was studied by immunofluorescence microscopy, the ability to migrate was assessed by microchemotaxis and scratch assay, and the expression of markers of fibroblast activation, angiogenesis, and inflammation was assessed by western blot. Results revealed that after cell exposure to modeled microgravity conditions, a thorough rearrangement of microtubules occurred and α-SMA bundles were replaced by a tight network of faulty and disorganized filaments. Exposure to modeled microgravity induced a decrease in α-SMA and E-CAD expressions. Also, the expression of the pro-angiogenic protein VEGF decreased, while that of the inflammatory signal COX-2 increased. Fibroblast ability to adhere, migrate, and respond to chemoattractants (PRP), closely related to cytoskeleton integrity and membrane junctions, was significantly impaired. Nevertheless, PRP was able to partially restore fibroblast migration.

  8. Normal lymphocyte immunophenotype in an elderly population

    Directory of Open Access Journals (Sweden)

    Sâmia Macedo Queiroz Mota Castellão Tavares

    2014-06-01

    Full Text Available OBJECTIVE: The aim of this work was to evaluate the lymphocyte immunophenotype in an elderly population.METHODS: This study enrolled 35 over 60-year-old volunteers and a control group composed of 35 young adults. The study included elderly without diseases that might affect the functioning of the immune system. These individuals were consulted by doctors and after a physical examination, laboratory tests were performed using a Beckman Coulter (r flow cytometer. The GraphPad Prism computer program was employed for statistical analysis with the level of significance being set for p-values <0.05.RESULTS: There is a statistically significant reduction in the number of lymphocytes (CD8 +, CD2 + and CD3 + cells in the elderly compared to young adults. These low rates are explained by changes attributed to aging and may be partly responsible for the reduction in the cellular immune response, lower proliferative activity and the low cytotoxicity of lymphocytes.CONCLUSION: These parameters showed greater impairment of adaptive immunity in the elderly population and can therefore explain the greater fragility of the aged body to developing diseases.

  9. Low level methylmercury exposure affects neuropsychological function in adults

    Directory of Open Access Journals (Sweden)

    Platt Illeane

    2003-06-01

    , consistent with a dose-dependent effect. Conclusions This study suggests that adults exposed to MeHg may be at risk for deficits in neurocognitive function. The functions disrupted in adults, namely attention, fine-motor function and verbal memory, are similar to some of those previously reported in children with prenatal exposures.

  10. Osmotic stress affects functional properties of human melanoma cell lines

    CERN Document Server

    La Porta, Caterina A M; Pasini, Maria; Laurson, Lasse; Alava, Mikko J; Zapperi, Stefano; Amar, Martine Ben

    2015-01-01

    Understanding the role of microenvironment in cancer growth and metastasis is a key issue for cancer research. Here, we study the effect of osmotic pressure on the functional properties of primary and metastatic melanoma cell lines. In particular, we experimentally quantify individual cell motility and transmigration capability. We then perform a circular scratch assay to study how a cancer cell front invades an empty space. Our results show that primary melanoma cells are sensitive to a low osmotic pressure, while metastatic cells are less. To better understand the experimental results, we introduce and study a continuous model for the dynamics of a cell layer and a stochastic discrete model for cell proliferation and diffusion. The two models capture essential features of the experimental results and allow to make predictions for a wide range of experimentally measurable parameters.

  11. Endocannabinoids affect the reproductive functions in teleosts and amphibians.

    Science.gov (United States)

    Cottone, E; Guastalla, A; Mackie, K; Franzoni, M F

    2008-04-16

    Following the discovery in the brain of the bonyfish Fugu rubripes of two genes encoding for type 1 cannabinoid receptors (CB1A and CB1B), investigations on the phylogeny of these receptors have indicated that the cannabinergic system is highly conserved. Among the multiple functions modulated by cannabinoids/endocannabinoids through the CB1 receptors one of the more investigated is the mammalian reproduction. Therefore, since studies performed in animal models other than mammals might provide further insight into the biology of these signalling molecules, the major aim of the present paper was to review the comparative data pointing toward the endocannabinoid involvement in the reproductive control of non-mammalian vertebrates, namely bonyfish and amphibians. The expression and distribution of CB1 receptors were investigated in the CNS and gonads of two teleosts, Pelvicachromis pulcher and Carassius auratus as well as in the anuran amphibians Xenopus laevis and Rana esculenta. In general the large diffusion of neurons targeted by cannabinoids in both fish and amphibian forebrain indicate endocannabinoids as pivotal local messengers in several neural circuits involved in either sensory integrative activities, like the olfactory processes (in amphibians) and food response (in bonyfish), or neuroendocrine machinery (in both). By using immunohistochemistry for CB1 and GnRH-I, the codistribution of the two signalling molecules was found in the fish basal telencephalon and preoptic area, which are key centers for gonadotropic regulation in all vertebrates. A similar topographical codistribution was observed also in the septum of the telencephalon in Rana esculenta and Xenopus laevis. Interestingly, the double standard immunofluorescence on the same brain section, aided with a laser confocal microscope, showed that in anurans a subset of GnRH-I neurons exhibited also the CB1 immunostaining. The fact that CB1-LI-IR was found indeed in the FSH gonadotrophs of the Xenopus

  12. Neurology of Affective Prosody and Its Functional-Anatomic Organization in Right Hemisphere

    Science.gov (United States)

    Ross, Elliott D.; Monnot, Marilee

    2008-01-01

    Unlike the aphasic syndromes, the organization of affective prosody in brain has remained controversial because affective-prosodic deficits may occur after left or right brain damage. However, different patterns of deficits are observed following left and right brain damage that suggest affective prosody is a dominant and lateralized function of…

  13. 67. Do prenatal intracardiac echogenic foci affect postnatal cardiac function?

    Directory of Open Access Journals (Sweden)

    R. Bader

    2016-07-01

    Full Text Available Echogenic foci in the prenatal hear is not an uncommon finding. To determine whether prenatally diagnosed intracardiac echogenic foci are associated with neonatal cardiac dysfunction and persistence. Fetuses in which intracardiac echogenic foci were shown on prenatal sonography at 1 perinatal center from (September 2009 to December 2013 underwent postnatal echocardiography at ages 1 month to1 year. A single pediatric cardiologist assessed cardiac function by measuring the left ventricular shortening fraction and myocardial performance index. The presence of tricuspid valve regurgitation was also sought. Prenatally 60 fetuses had intracardiac echogenic foci mean age ± SD at diagnosis (23 ± 3.1. 53 (88.3% had left ventricular intracardiac echogenic foci, and 7 (11.6% had right ventricular intracardiac echogenic foci. 12 preganant ladies were lost for follow up (2 fetuses of 7 (28.5% with right ventricular intracardiac echogenic foci., and 10 fetuses of 53 (18.8% with LV intracardiac echogenic foci %. Post natally, those infants, 32 (66.6% males and 16 (33.3% females were examined. At a mean age ± SD of 7.4 ± 3.1 months. Prenatally, all infants had a normal left ventricular shortening fraction. The overall mean left ventricular myocardial performance index (reference value, 0.36 ± 0.06, was normal for both infants with left ventricular intracardiac echogenic foci (0.32 ± 0.01 and those with right ventricular intracardiac echogenic foci (0.33 ± 0.05. Trace tricuspid valve regurgitation were noted in 15 (31% of the infants. Left ventricular intracardiac echogenic foci persisted in 15 infants (34.8%, whereas right ventricular intracardiac echogenic foci persisted in 1 infant (20%. Prenatally diagnosed intracardiac echogenic foci can be persistent but is not associated with myocardial dysfunction in the first year of life.

  14. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation.

    Science.gov (United States)

    Read, S; Malmström, V; Powrie, F

    2000-07-17

    It is now clear that functionally specialized regulatory T (Treg) cells exist as part of the normal immune repertoire, preventing the development of pathogenic responses to both self- and intestinal antigens. Here, we report that the Treg cells that control intestinal inflammation express the same phenotype (CD25(+)CD45RB(low)CD4(+)) as those that control autoimmunity. Previous studies have failed to identify how CD25(+) Treg cells function in vivo. Our studies reveal that the immune-suppressive function of these cells in vivo is dependent on signaling via the negative regulator of T cell activation cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), as well as secretion of the immune-suppressive cytokine transforming growth factor beta. Strikingly, constitutive expression of CTLA-4 among CD4(+) cells was restricted primarily to Treg cells, suggesting that CTLA-4 expression by these cells is involved in their immune-suppressive function. These findings raise the possibility that Treg cell function contributes to the immune suppression characteristic of CTLA-4 signaling. Identification of costimulatory molecules involved in the function of Treg cells may facilitate further characterization of these cells and development of new therapeutic strategies for the treatment of inflammatory diseases.

  15. Molecular defects in the ABCA1 pathway affect platelet function.

    Science.gov (United States)

    Schmitz, Gerd; Schambeck, Christian M

    2006-01-01

    Platelet function is sensitive to alterations in cholesterol metabolism, and hypercholesterolemia is associated with enhanced platelet reagibility. Atherogenic low-density lipoproteins (LDL), in particular oxidized LDL, activate src-kinase-family-dependent signalling. In contrast, antiatherogenic high-density lipoproteins(HDL) inhibit platelet aggregation and target the phosphatidylinositol phospholipase C (PI-PLC) pathway. Sphingosine 1-phosphate is a major HDL component and may be crucial for downstream reactions of collagen-induced glycoprotein VI signalling and phosphoinositide 3-kinase. The ATP-binding cassette transporter A1 (ABCA1) regulates cell membrane phospholipid and cholesterol homeostasis and their release to lipid-poor apolipoprotein AI to generate prebeta-HDL precursor particles. ABCA1 also interacts with modulators of vesicular trafficking and number and impaired release of dense bodies from platelets. The ABCA1-NH2-terminus-associated Syntaxin-13, a SNARE complex protein, interacts with syntaxin 13-interacting protein (pallidin) whose deficiency leads to impaired platelet granule release from the dense granule Adapter Protein-3 (AP-3)-related pathway. Interestingly, the cholesterol transporter ABCG1 in addition to ABCA1 is another constituent of the AP-3 pathway, and disorders of lysosome-related organelles such as the Hermansky-Pudlack syndrome complex, Chediak-Higashi syndrome and the ceroid lipofuscinoses provide new opportunities to understand AP-3 pathway-related disorders and the irrelation to membrane phospholipid processing. ABCA1 mutations are involved in dysregulated vesicular trafficking from the trans golgi compartment to the plasma membrane, and ABCA1 R1925Q was shown to contribute to Scott syndrome, a phospholipid-processing disorder of missing surface exposure of phosphatidlyserine. The P2Y12 receptor triggers dense granule secretion by downstream effectors including the G-protein-coupled inward rectifier K+ channel-4 (GIRK-4), and

  16. Familial clustering of executive functioning in affected sibling pair families with ADHD.

    NARCIS (Netherlands)

    Slaats-Willemse, D.I.; Swaab-Barneveld, H.J.; Sonneville, L.

    2005-01-01

    OBJECTIVE: To investigate familial clustering of executive functioning (i.e., response inhibition, fine visuomotor functioning, and attentional control) in attention-deficit/hyperactivity disorder (ADHD)-affected sibling pairs. METHOD: Fifty-two affected sibling pairs aged 6 to 18 years and diagnose

  17. [EFFECT OF 4-METHYLPYRAZOLE ON IMMUNE RESPONSE, FUNCTION OF Th1 AND Th2 LYMPHOCYTES, AND CYTOKINE CONCENTRATION IN RAT BLOOD AFTER ACUTE METHANOL POISONING].

    Science.gov (United States)

    Zabrodskii, P F; Maslyakov, V V; Gromov, M S

    2016-01-01

    It was established in experiments on noninbred albino rats that the acute intoxication with methanol (1.0 LD50) decreased cellular and humoral immune responses, Th2-lymphocyte activity (to a greater extent as compared to the function of Th1 cells), reduced the blood concentration of immunoregulatory (IFN-g, IL-2, IL-4) and proinflammatory (TNF, IL-1b, IL-6) cytokines on the average by 36.5% (p Methanol antidote 4-methylpyrazole (non-competitive inhibitor of alcohol dehydrogenase) administered upon acute intoxication with methanol at a dose of 1.0 DL50 partially reduces the intoxication-induced suppression of humoral and cellular immune response, activity of T-helper cells, and production of IL-4 and restores blood levels of TNF, IL-1b, IFN-γ, IL-4, IL-2, IL-6 to the control values.

  18. Multipronged functional proteomics approaches for global identification of altered cell signalling pathways in B-cell chronic lymphocytic leukaemia.

    Science.gov (United States)

    Díez, Paula; Lorenzo, Seila; Dégano, Rosa M; Ibarrola, Nieves; González-González, María; Nieto, Wendy; Almeida, Julia; González, Marcos; Orfao, Alberto; Fuentes, Manuel

    2016-04-01

    Chronic lymphocytic leukaemia (CLL) is a malignant B cell disorder characterized by its high heterogeneity. Although genomic alterations have been broadly reported, protein studies are still in their early stages. Herein, a 224-antibody microarray has been employed to study the intracellular signalling pathways in a cohort of 14 newly diagnosed B-CLL patients as a preliminary study for further investigations. Several protein profiles were differentially identified across the cytogenetic and molecular alterations presented in the samples (deletion 13q14 and 17p13.1, trisomy 12, and NOTCH1 mutations) by a combination of affinity and MS/MS proteomics approaches. Among others altered cell signalling pathways, PKC family members were identified as down-regulated in nearly 75% of the samples tested with the antibody arrays. This might explain the rapid progression of the disease when showing p53, Rb1, or NOTCH1 mutations due to PKC-proteins family plays a critical role favouring the slowly progressive indolent behaviour of CLL. Additionally, the antibody microarray results were validated by a LC-MS/MS quantification strategy and compared to a transcriptomic CLL database. In summary, this research displays the usefulness of proteomic strategies to globally evaluate the protein alterations in CLL cells and select the possible biomarkers to be further studied with larger sample sizes.

  19. ATM function and its relationship with ATM gene mutations in chronic lymphocytic leukemia with the recurrent deletion (11q22.3-23.2).

    Science.gov (United States)

    Jiang, Y; Chen, H-C; Su, X; Thompson, P A; Liu, X; Do, K-A; Wierda, W; Keating, M J; Plunkett, W

    2016-09-02

    Approximately 10-20% of chronic lymphocytic leukemia (CLL) patients exhibit del(11q22-23) before treatment, this cohort increases to over 40% upon progression following chemoimmunotherapy. The coding sequence of the DNA damage response gene, ataxia-telangiectasia-mutated (ATM), is contained in this deletion. The residual ATM allele is frequently mutated, suggesting a relationship between gene function and clinical response. To investigate this possibility, we sought to develop and validate an assay for the function of ATM protein in these patients. SMC1 (structural maintenance of chromosomes 1) and KAP1 (KRAB-associated protein 1) were found to be unique substrates of ATM kinase by immunoblot detection following ionizing radiation. Using a pool of eight fluorescence in situ hybridization-negative CLL samples as a standard, the phosphorylation of SMC1 and KAP1 from 46 del (11q22-23) samples was analyzed using normal mixture model-based clustering. This identified 13 samples (28%) that were deficient in ATM function. Targeted sequencing of the ATM gene of these samples, with reference to genomic DNA, revealed 12 somatic mutations and 15 germline mutations in these samples. No strong correlation was observed between ATM mutation and function. Therefore, mutation status may not be taken as an indicator of ATM function. Rather, a direct assay of the kinase activity should be used in the development of therapies.

  20. Serum cytokines, T lymphocyte subsets and STAT3 function in patients with herpes zoster as well as the intervention effect of mouse nerve growth factor

    Institute of Scientific and Technical Information of China (English)

    Yun Xu; Ling-Ling Tan; Kai Wang; Juan-Juan Zhang; Li-Jing Zhang

    2016-01-01

    Objective:To assess the levels of serum cytokines, T lymphocyte subsets and STAT3 in patients with herpes zoster as well as the intervention effect of mouse nerve growth factor. Methods:A total of 102 patients with herpes zoster were selected as observation group and received mouse nerve growth factor intervention, and 100 cases of normal people who received physical examination in our hospital during the same period as the healthy control group. The levels of serum Th1/Th2 cytokines, IgG subclass and complements and T lymphocyte subsets as well as STAT3 function of observation group before and after treatment and healthy control group were detected.Results: Serum IL-2 andγ-IFN levels of observation group after treatment were higher than those before treatment while IL-4, IL-5, IL-10 and TNF-α levels were lower than those before treatment (P<0.05); serum IgG1, IgG3, IgG4, C3 and C4 values of observation group after treatment were higher than those before treatment while IgG2 value was lower than that before treatment (P<0.05); CD3, CD4 and CD4/CD8 levels of observation group after treatment were higher than those before treatment while CD8 level was lower than that before treatment (P<0.05); STAT3, p-STAT3 and JAK2 expression levels of observation group after treatment were lower than those before treatment (P<0.05).Conclusions:There are abnormal immune system and STAT3 signaling pathway function in patients with herpes zoster, and mouse nerve growth factor intervention can restore multisystem balance and accelerate disease rehabilitation, and has positive clinical significance.

  1. Consumption of purple sweet potato leaves modulates human immune response: T-lymphocyte functions, lytic activity of natural killer cell and antibody production

    Institute of Scientific and Technical Information of China (English)

    Chiao-Ming Chen; Sing-Chung Li; Ya-Ling Lin; Ching-Yun Hsu; Ming-Jer Shieh; Jen-Fang Liu

    2005-01-01

    AIM: To study the immunological effects of physiological doses of purple sweet potato leaves (PSPL).METHODS: The randomized crossover study (two periods,each lasting for 2 wk) involved 16 healthy non-smoking adults of normal weight. The 6-wk study consisted of a run-in (wk 1) PSPL diet (daily consumption of 200 g PSPL) or a control diet (low polyphenols, with the amount of carotenoids adjusted to the same level as that of PSPL) (wk 2-3), washout diet (wk 4), and switched diet (wk 5-6). Fasting blood was collected weekly in the morning. T-lymphocyte function was assessed via the proliferation and secretion of immunoreactive cytokines.Salivary IgA secretion and the specific cytotoxic activities of cytotoxic T lymphocytes and natural killer (NK) cells were determined.RESULTS: The plasma β-carotene level increased with time in both groups, while the plasma polyphenol level decreased in the control group, and no significant difference was detected between the two groups.Although plasma polyphenol levels did not significantly increase in the PSPL group at the end of the study, they were significantly elevated in urine. PSPL consumption produced a significant increase in proliferation responsiveness of peripheral blood mononuclear cells (PBMC) and their secretion of immunoreactive IL-2 and IL-4. As well, lytic activity in NK cells was elevated in a time-dependent fashion. Salivary TgA secretion significantly decreased in control group after 2 wk, and returned to baseline following dietary switch to PSPL.CONCLUSION: Consumption of PSPL modulates various immune functions including increased proliferation responsiveness of PBMC, secretion of cytokines IL-2 and IL-4, and the lytic activity of NK cells. The responsible determinants of PSPL remain to be elucidated, as does the biological significance of the present observations.

  2. Walterinnesia aegyptia venom combined with silica nanoparticles enhances the functioning of normal lymphocytes through PI3K/AKT, NFκB and ERK signaling

    Directory of Open Access Journals (Sweden)

    Badr Gamal

    2012-02-01

    Full Text Available Abstract Background The toxicity of snake venom varies over time in some species. The venom of newborn and small juvenile snakes appears to be more potent than adults of the same species, and a bite from a snake that has not fed recently, such as one that has just emerged from hibernation, is more dangerous than one that has recently fed due to the larger volume of venom injected. Therefore, the potency of a snake's venom is typically determined using the LD50 or IC50 tests. In the present study, we evaluated the anti-tumor potential of snake venom from Walterinnesia aegyptia (WEV on the human breast carcinoma cell line MDA-MB-231, as well as its effect on the normal mice peripheral blood mononuclear cells (PBMCs. Results This venom was used alone (WEV or in combination with silica nanoparticles (WEV+NP. The IC50 values of WEV alone and WEV+NP in the MDA-MB-231 cells were determined to be 50 ng/ml and 20 ng/ml, respectively. Interestingly, at these concentrations, the venom did not affect the viability of normal human PBMCs. To investigate the in vivo effects of this venom further, three groups of mice were used (15 mice in each group: Group I was the control, Group II was subcutaneously injected with WEV, and Group III was injected with WEV+NP. Using flow cytometry and western blot analysis, we found that the blood lymphocytes of WEV-injected mice exhibited a significant increase in actin polymerization and cytoskeletal rearrangement in response to CXCL12 through the activation of AKT, NF-κB and ERK. These lymphocytes also showed a significant increase in their proliferative capacity in response to mitogen stimulation compared with those isolated from the control mice (P Conclusion Our data reveal the unique biological effects of WEV, and we demonstrated that its combination with nanoparticles strongly enhanced these biological effects.

  3. Signaling in Human and Murine Lymphocytes in Microgravity: Parallels and Contrasts

    Science.gov (United States)

    Neal, Pellis; Alamelu, Sundaresan; Kulkarni, A. D.; Yamauchi, K.

    2006-01-01

    Immune function in space undergoes dramatic changes, some of which are detrimental to lymphocyte function. These changes may lead to significant immune suppression. Studies with human lymphocytes both in space flight and with ground-based models (NASA in vitro ground-based microgravity analog) indicate that T cell activation is inhibited in microgravity. Other lymphocyte functions, such as locomotion, are also inhibited. There is about an 80 percent homology in the immune response of mice to that of humans. A murine model was investigated because of its ability to parallel some microgravity using hind limb suspension. In in vivo antiorthostatically (AOS)-suspended mice, T cell activation is greatly suppressed, with the majority of activation related cytokines being inhibited. PHA activation in lymphocytes derived from AOS mice (in vivo ground-based microgravity analog) is also suppressed. Calcium ionophore studies in human lymphocytes exposed to modeled microgravity indicate that the calcium pathways are probably unaffected in microgravity. IP3 (inositol triphosphate) receptor expression in both human and mouse lymphocytes cultured in modeled microgravity indicate no suppression of calcium signaling. In the human system, microgravity seems to inhibit signaling cascades either at the level of, or up-stream of, Protein Kinase C (PKC). In particular, a membrane event, such as phospholipase C gamma 1 activity in human lymphocytes is affected, with its direct upstream effector, LAT, being deficiently expressed. In the mouse pathway, LAT is undiminished while another critical intermediate, SLP-76, is diminished significantly. This study identifies critical stages in the human and mouse immune systems and in lymphocytes as a function of microgravity.

  4. Modulation of phenotype and function of human CD4+CD25+ T regulatory lymphocytes mediated by cAMP elevating agents

    Directory of Open Access Journals (Sweden)

    Antonella Riccomi

    2016-09-01

    Full Text Available We have shown that Cholera Toxin (CT and other cyclic AMP (cAMP elevating agents induce up-regulation of the inhibitory molecule CTLA-4 in human resting CD4+ T lymphocytes, which following the treatment acquired suppressive functions. In this study, we evaluated the effect of cAMP elevating agents on human CD4+CD25+ T cells, which include the T regulatory (Treg cells that play a pivotal role in the maintenance of immunological tolerance. We found that cAMP elevating agents induce up-regulation of CTLA-4 in CD4+CD25- and further enhance its expression in CD4+CD25+ T cells. We observed an increase of two isoforms of mRNA coding for the membrane and the soluble CTLA-4 molecules, suggesting that the regulation of CTLA-4 expression by cAMP is at the transcriptional level. In addition, we found that the increase of cAMP in CD4+CD25+ T cells converts the CD4+CD25+Foxp3- T cells in CD4+CD25+Foxp3+ T cells, whereas the increase of cAMP in CD4+CD25- T cells did not up-regulate Foxp3 in the absence of activation stimuli. To investigate the function of these cells, we performed an in vitro suppression assay by culturing CD4+CD25+ T cells untreated or pre-treated with CT with anti-CD3 mAbs-stimulated autologous PBMC. We found that CT enhances the inhibitory function of CD4+CD25+ T cells, CD4+ and CD8+ T cell proliferation and IFNγ production are strongly inhibited by CD4+CD25+ T cells pre-treated with cAMP elevating agents. Furthermore, we found that CD4+CD25+ T lymphocytes pre-treated with cAMP elevating agents induce the up-regulation of CD80 and CD86 co-stimulatory molecules on immature dendritic cells (DCs in the absence of antigenic stimulation, however without leading to full DC maturation. These data show that the increase of intracellular cAMP modulates the phenotype and function of human CD4+CD25+ T cells.

  5. In vitro effects of mesenchymal stem cells on secreting function of T lymphocytes and CD4~+CD25~+T cells from patients with immune thrombo-cytopenia

    Institute of Scientific and Technical Information of China (English)

    赵霞

    2014-01-01

    Objective To analyze in vitro the effect of mesenchymal stem cells(MSCs)on secreting cytokines by T lymphocytes and ratio of CD4+CD25+T cells from patients with immune thrombocytopenia(ITP).Methods Human bone marrow-derived MSCs were isolated by Ficoll Hypaque and cultured for proliferating to passage cells.Allogeneic T lymphocytes

  6. Peripheral blood lymphocyte cell subsets in subjects with chronic obstructive pulmonary disease: association with smoking, IgE and lung function

    NARCIS (Netherlands)

    J.W. de Jong (Jan Willem); B. van der Belt-Gritter; G.H. Koëter (Gerard); D.S. Postma (Dirkje)

    1997-01-01

    textabstractIn contrast to the numerous studies which show that lymphocytes play an important role in the pathogenesis of asthma, few studies have investigated the role of lymphocytes in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of the present study

  7. Effects of environmental stressors on lymphocyte proliferation in Florida manatees, Trichechus manatus latirostris.

    Science.gov (United States)

    Walsh, Cathy J; Luer, Carl A; Noyes, David R

    2005-02-10

    The health of many Florida manatees (Trichechus manatus latirostris) is adversely affected each year by exposure to cold weather or harmful algal blooms (red tide; Karenia brevis). Exposures can be sublethal, resulting in stressed animals that are rescued and taken to authorized facilities for rehabilitation, or lethal if exposures are prolonged or unusually severe. To investigate whether sublethal environmental exposures can impair immune function in manatees, rendering animals vulnerable to disease or death, mitogen-induced proliferation was assessed in lymphocytes from manatees exposed to cold temperatures (N=20) or red tide (N=19) in the wild, and compared to lymphocyte responses from healthy free-ranging manatees (N=32). All animals sampled for this study were adults. Lymphocytes were stimulated in vitro with either concanavalin A (ConA) or phytohemagglutinin (PHA) and proliferation was assessed after 96 h using incorporation of the thymidine analog, bromodeoxyuridine (BrdU), into newly synthesized DNA. Proliferation of lymphocytes from manatees rescued from exposure to red tide or cold-stress was approximately one-third that of lymphocytes from healthy free-ranging manatees. To examine the direct effects of red tide toxins on lymphocyte function, mitogen-induced proliferation was assessed following co-culture of lymphocytes with K. brevis toxin extracts. Stimulation indices decreased with increasing toxin concentration, with a significant decrease in proliferation occurring in the presence of 400 ng red tide toxins/ml. When lymphocytes from cold-stressed manatees were co-cultured with red tide toxin extracts, proliferative responses were reduced even further, suggesting multiple stressors may have synergistic effects on immune function in manatees.

  8. Deviations in upper limb function of the less-affected side in congenital hemiparesis

    NARCIS (Netherlands)

    Steenbergen, B.; Meulenbroek, R.G.J.

    2006-01-01

    In the present study we examined upper-limb function of the less-affected side in young adolescents with congenital hemiparesis (cerebral palsy: CP). Five participants with hemiparetic CP and five control participants performed a cyclical reach-and-grasp task with the less-affected hand towards targ

  9. Development of Affective Theory of Mind Across Adolescence: Disentangling the Role of Executive Functions

    NARCIS (Netherlands)

    Vetter, N.C.; Altgassen, A.M.; Phillips, L.H.; Mahy, C.E.V.; Kliegel, M.

    2013-01-01

    Theory of mind, the ability to understand mental states, involves inferences about others' cognitive (cognitive theory of mind) and emotional (affective theory of mind) mental states. The current study explored the role of executive functions in developing affective theory of mind across adolescence

  10. The immunodeficiency of bone marrow-transplanted patients. II. CD8-related suppression by patient lymphocytes of the response of donor lymphocytes to mitogens, antigens, and allogeneic cells

    DEFF Research Database (Denmark)

    Ødum, Niels; Hofmann, B; Jacobsen, N;

    1987-01-01

    Lymphocytes from 21 patients sampled 1-6 months after bone marrow transplantation (BMT) were tested for functional suppressor activity against marrow-donor lymphocytes in the lymphocyte transformation test. Suppression of donor responses to allogeneic (i.e. mixed lymphocyte reaction, MLR...

  11. Neisserial outer membrane vesicles bind the coinhibitory receptor carcinoembryonic antigen-related cellular adhesion molecule 1 and suppress CD4+ T lymphocyte function.

    Science.gov (United States)

    Lee, Hannah S W; Boulton, Ian C; Reddin, Karen; Wong, Henry; Halliwell, Denise; Mandelboim, Ofer; Gorringe, Andrew R; Gray-Owen, Scott D

    2007-09-01

    Pathogenic Neisseria bacteria naturally liberate outer membrane "blebs," which are presumed to contribute to pathology, and the detergent-extracted outer membrane vesicles (OMVs) from Neisseria meningitidis are currently employed as meningococcal vaccines in humans. While the composition of these vesicles reflects the bacteria from which they are derived, the functions of many of their constituent proteins remain unexplored. The neisserial colony opacity-associated Opa proteins function as adhesins, the majority of which mediate bacterial attachment to human carcinoembryonic antigen-related cellular adhesion molecules (CEACAMs). Herein, we demonstrate that the Opa proteins within OMV preparations retain the capacity to bind the immunoreceptor tyrosine-based inhibitory motif-containing coinhibitory receptor CEACAM1. When CD4(+) T lymphocytes were exposed to OMVs from Opa-expressing bacteria, their activation and proliferation in response to a variety of stimuli were effectively halted. This potent immunosuppressive effect suggests that localized infection will generate a "zone of inhibition" resulting from the diffusion of membrane blebs into the surrounding tissues. Moreover, it demonstrates that OMV-based vaccines must be developed from strains that lack CEACAM1-binding Opa variants.

  12. Polysaccharides PS-G and protein LZ-8 from Reishi (Ganoderma lucidum) exhibit diverse functions in regulating murine macrophages and T lymphocytes.

    Science.gov (United States)

    Yeh, Chen-Hao; Chen, Hsiao-Chin; Yang, Jeng-Je; Chuang, Wen-I; Sheu, Fuu

    2010-08-11

    Bioactive components in Ganoderma lucidum mainly include polysaccharides (PS-G) and immunomodulatory protein Ling Zhi-8 (LZ-8). These components may have diverse regulatory functions in the immune system. However, the PS-G preparations from different procedures still contained partial LZ-8 residue, indicating that the specific target and regulating function of PS-G and LZ-8 were not fully understood. In the present study, PS-G was subjected to 15% TCA for removing proteins and the LZ-8 detection using anti-LZ-8 monoclonal antibodies showed a remarkable 89.7% protein reduction of the deproteinized PS-G (dpPS-G). The Saccharomyces cerevisiae which expressed recombinant LZ-8 protein (rLZ-8) without glycosylation was generated and then compared with dpPS-G in the induction toward murine primary macrophage and T lymphocytic cells. The peritoneal macrophages from TLR4-deficient and wild type mice revealed that TLR4 was a putative receptor of dpPS-G, mediating the TNF-alpha, IL-1beta and IL-12p70 cytokine production and CD86, MHC II expression on macrophages, while rLZ-8 enhanced the production of IL-1beta, IL-12p70, CD86, and MHC II expression by another obscure route. rLZ-8-treated macrophages enhanced the release of IFN-gamma and IL-2 by murine CD4(+) and CD8(+) T cells, whereas dpPS-G treatment did not enhance the release of IFN-gamma and IL-2. Furthermore, although the direct rLZ-8-treatment conduced dramatic CD154, CD44 expression on CD3(+) T cells and increased IL-2, IFN-gamma secretion on CD4(+) and CD8(+) T cells, the dpPS-G was incapable of priming CD3(+), CD4(+) or CD8(+) T cells unitarily. Taken together, these results demonstrated that LZ-8 could activate murine macrophages and T lymphocytes but PS-G was merely the activator for macrophages, suggesting their diverse roles in activating the innate and adaptive immunity.

  13. Perception of affective prosody in major depression: a link to executive functions?

    Science.gov (United States)

    Uekermann, Jennifer; Abdel-Hamid, Mona; Lehmkämper, Caroline; Vollmoeller, Wolfgang; Daum, Irene

    2008-07-01

    Major depression is associated with impairments of executive functions and affect perception deficits, both being linked to dysfunction of fronto-subcortical networks. So far, little is known about the relationship between cognitive and affective deficits in major depression. In the present investigation, affect perception and executive functions were assessed in 29 patients with a diagnosis of major depression (Dep) and 29 healthy controls (HC). Both groups were comparable on IQ, age, and gender distribution. Depressed patients showed deficits of perception of affective prosody, which were significantly related to inhibition, set shifting, and working memory. Our findings suggest a significant association between cognitive deficits and affect perception impairments in major depression, which may be of considerable clinical relevance and might be addressed in treatment approaches. Future studies are desirable to investigate the nature of the association in more detail.

  14. Negative affect predicts social functioning across schizophrenia and bipolar disorder: Findings from an integrated data analysis.

    Science.gov (United States)

    Grove, Tyler B; Tso, Ivy F; Chun, Jinsoo; Mueller, Savanna A; Taylor, Stephan F; Ellingrod, Vicki L; McInnis, Melvin G; Deldin, Patricia J

    2016-09-30

    Most people with a serious mental illness experience significant functional impairment despite ongoing pharmacological treatment. Thus, in order to improve outcomes, a better understanding of functional predictors is needed. This study examined negative affect, a construct comprised of negative emotional experience, as a predictor of social functioning across serious mental illnesses. One hundred twenty-seven participants with schizophrenia, 113 with schizoaffective disorder, 22 with psychosis not otherwise specified, 58 with bipolar disorder, and 84 healthy controls (N=404) completed self-report negative affect measures. Elevated levels of negative affect were observed in clinical participants compared with healthy controls. For both clinical and healthy control participants, negative affect measures were significantly correlated with social functioning, and consistently explained significant amounts of variance in functioning. For clinical participants, this relationship persisted even after accounting for cognition and positive/negative symptoms. The findings suggest that negative affect is a strong predictor of outcome across these populations and treatment of serious mental illnesses should target elevated negative affect in addition to cognition and positive/negative symptoms.

  15. Earthworm functional traits and interspecific interactions affect plant nitrogen acquisition and primary production

    NARCIS (Netherlands)

    Andriuzzi, Walter; Schmidt, Olaf; Brussaard, L.; Faber, J.H.; Bolger, T.

    2016-01-01

    We performed a greenhouse experiment to test how the functional diversity of earthworms, the dominant group of soil macro-invertebrates in many terrestrial ecosystems, affects nitrogen cycling and plant growth. Three species were chosen to represent a range of functional traits: Lumbricus terrestris

  16. The role of affect in attentional functioning for younger and older adults

    Directory of Open Access Journals (Sweden)

    Soo Rim eNoh

    2012-08-01

    Full Text Available Although previous research has shown that positive affect (PA and negative affect (NA modulate attentional functioning in distinct ways, few studies have considered whether the links between affect and attentional functioning may vary as a function of age. Using the Attention Network Test (Fan, McCandliss, Sommer, Raz, & Posner, 2002, we tested whether participants’ current state of PA and NA influenced distinct attentional functions (i.e., alerting, orienting, and executive attention and how the relationships between affective states and attentional functioning differ in younger (18-25 yrs and older (60-85 yrs age groups. The results revealed that higher PA was associated with lower alerting efficiency; however, this pattern did not vary by age group. While there were age differences in alerting efficiency, these age differences were mediated by PA, indicating that the higher state PA found in older adults may contribute to age differences in alerting. Furthermore, age group moderated the relationship between PA and orienting as well as NA and orienting. That is, higher levels of PA and lower levels of NA were associated with enhanced orienting efficiency in older adults. Neither PA nor NA had any influence on executive attention. The current results suggest that positive and negative affect may influence attentional functioning in distinct ways, but that these patterns may depend on age groups.

  17. Assessment of p53 and ATM functionality in chronic lymphocytic leukemia by multiplex ligation-dependent probe amplification.

    Science.gov (United States)

    te Raa, G D; Moerland, P D; Leeksma, A C; Derks, I A; Yigittop, H; Laddach, N; Loden-van Straaten, M; Navrkalova, V; Trbusek, M; Luijks, D M; Zenz, T; Skowronska, A; Hoogendoorn, M; Stankovic, T; van Oers, M H; Eldering, E; Kater, A P

    2015-08-06

    The ATM-p53 DNA-damage response (DDR) pathway has a crucial role in chemoresistance in CLL, as indicated by the adverse prognostic impact of genetic aberrations of TP53 and ATM. Identifying and distinguishing TP53 and ATM functional defects has become relevant as epigenetic and posttranscriptional dysregulation of the ATM/p53 axis is increasingly being recognized as the underlying cause of chemoresistance. Also, specific treatments sensitizing TP53- or ATM-deficient CLL cells are emerging. We therefore developed a new ATM-p53 functional assay with the aim to (i) identify and (ii) distinguish abnormalities of TP53 versus ATM and (iii) enable the identification of additional defects in the ATM-p53 pathway. Reversed transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) was used to measure ATM and/or p53-dependent genes at the RNA level following DNA damage using irradiation. Here, we showed that this assay is able to identify and distinguish three subgroups of CLL tumors (i.e., TP53-defective, ATM-defective and WT) and is also able to detect additional samples with a defective DDR, without molecular aberrations in TP53 and/or ATM. These findings make the ATM-p53 RT-MLPA functional assay a promising prognostic tool for predicting treatment responses in CLL.

  18. CD226 (DNAM-1) is involved in lymphocyte function-associated antigen 1 costimulatory signal for naive T cell differentiation and proliferation.

    Science.gov (United States)

    Shibuya, Kazuko; Shirakawa, Jun; Kameyama, Tomie; Honda, Shin-Ichiro; Tahara-Hanaoka, Satoko; Miyamoto, Akitomo; Onodera, Masafumi; Sumida, Takayuki; Nakauchi, Hiromitsu; Miyoshi, Hiroyuki; Shibuya, Akira

    2003-12-15

    Upon antigen recognition by the T cell receptor, lymphocyte function-associated antigen 1 (LFA-1) physically associates with the leukocyte adhesion molecule CD226 (DNAM-1) and the protein tyrosine kinase Fyn. We show that lentiviral vector-mediated mutant (Y-F322) CD226 transferred into naive CD4+ helper T cells (Ths) inhibited interleukin (IL)-12-independent Th1 development initiated by CD3 and LFA-1 ligations. Moreover, proliferation induced by LFA-1 costimulatory signal was suppressed in mutant (Y-F322) CD226-transduced naive CD4+ and CD8+ T cells in the absence of IL-2. These results suggest that CD226 is involved in LFA-1-mediated costimulatory signals for triggering naive T cell differentiation and proliferation. We also demonstrate that although LFA-1, CD226, and Fyn are polarized at the immunological synapse upon stimulation with anti-CD3 in CD4+ and CD8+ T cells, lipid rafts are polarized in CD4+, but not CD8+, T cells. Moreover, proliferation initiated by LFA-1 costimulatory signal is suppressed by lipid raft disruption in CD4+, but not CD8+, T cells, suggesting that the LFA-1 costimulatory signal is independent of lipid rafts in CD8+ T cells.

  19. The CD11a partner in Sus scrofa lymphocyte function-associated antigen-1 (LFA-1: mRNA cloning, structure analysis and comparison with mammalian homologues

    Directory of Open Access Journals (Sweden)

    Thomas Anne VT

    2005-10-01

    Full Text Available Abstract Background Lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18, alphaLbeta2, the most abundant and widely expressed beta2-integrin, is required for many cellular adhesive interactions during the immune response. Many studies have shown that LFA-1 is centrally involved in the pathogenesis of several diseases caused by Repeats-in-toxin (RTX -producing bacteria. Results The porcine-LFA-1 CD11a (alpha subunit coding sequence was cloned, sequenced and compared with the available mammalian homologues in this study. Despite some focal differences, it shares all the main characteristics of these latter. Interestingly, as in sheep and humans, an allelic variant with a triplet insertion resulting in an additional Gln-744 was consistently identified, which suggests an allelic polymorphism that might be biologically relevant. Conclusion Together with the pig CD18-encoding cDNA, which has been available for a long time, the sequence data provided here will allow the successful expression of porcine CD11a, thus giving the first opportunity to express the Sus scrofa beta2-integrin LFA-1 in vitro as a tool to examine the specificities of inflammation in the porcine species.

  20. Neuroendocrine function in survivors of childhood acute lymphocytic leukemia and non-Hodgkins lymphoma: a study of pulsatile growth hormone and gonadotropin secretions

    Energy Technology Data Exchange (ETDEWEB)

    Mauras, N.; Sabio, H.; Rogol, A.D.

    To assess the neuroendocrine function of long-term survivors of childhood hematologic malignancies, 10 patients who had acute lymphocytic leukemia and two who had non-Hodgkins lymphoma (NHL) (mean age 13.5 +/- 1 year) were studied, who were treated with similar chemotherapeutic regimens with or without 2400 rads of prophylactic cranial irradiation. Pharmacologic growth hormone (GH) stimulation tests and three graded doses of the GH-releasing hormone (1-40-OH-GRH, 0.1, 0.3, and 1 microgram/kg) were administered. Venous sampling for GH and gonadotropin determinations was done at 20-min intervals for 24 h, and a new computerized pulse detection algorithm was used to analyze pulses. All the patients who had neuroendocrine abnormalities were in the cranially irradiated group. Two of the 12 patients were GH deficient, and had abnormal 24-h secretory profiles, blunted GH responses to pharmacologic stimuli, and minimal responses to the three doses of GRH. The pulsatile properties of luteinizing hormone (LH) were normal in 10 of the 12 nongonadally irradiated patients, irrespective of previous cranial irradiation and pubertal stage, when compared with available normative data.

  1. Exosomes derived from dendritic cells improve cardiac function via activation of CD4(+) T lymphocytes after myocardial infarction.

    Science.gov (United States)

    Liu, Haibo; Gao, Wei; Yuan, Jie; Wu, Chaoneng; Yao, Kang; Zhang, Li; Ma, Leilei; Zhu, Jianbing; Zou, Yunzeng; Ge, Junbo

    2016-02-01

    CD4(+) T cell activation plays a key role in facilitating wound healing after myocardial infarction (MI). Exosomes (EXs) secreted from dendritic cells (DCs) can activate T cells in tumor models; however, whether DEXs (DC-EXs) can mediate CD4(+) T cell activation and improve wound healing post-MI remains unknown. This study sought to determine whether DEXs mediate CD4(+) T cell activation and improve cardiac function post-MI in mice. We used supernatants of hypoxic primary or necrotic HL-1 cardiomyocytes to simulate the post-MI cardiomyocyte microenvironment in vitro. Cultured bone marrow-derived DCs (BMDCs) from mice were stimulated with the supernatants of normal (Control group), hypoxic primary or necrotic HL-1 cardiomyocytes (MI group); a subset of BMDCs remained unstimulated (Negative group). DEXs were then isolated from the BMDC supernatants and either incubated with CD4(+) T cells or injected into mice via the tail vein. In this study, we found that the supernatants of both hypoxic primary and necrotic HL-1 cardiomyocytes upregulate DC maturation markers. After the injection of DEXs, a greater number of MI-DEXs are recruited by the mouse spleen and with greater rapidity than control- or negative-DEXs. Confocal imaging and flow cytometry revealed that MI-DEXs exhibited higher uptake by splenic CD4(+) T cells than the control- and negative-DEXs, and this increase was correlated with significantly greater increases in the expression of chemokines and the inflammatory cytokines IFN-γ and TNF by the CD4(+) T cells in vitro and in vivo. In addition, the injection of MI-DEXs improved cardiac function in mice post-MI. These results suggest that DEXs could mediate the activation of CD4(+) T cells through an endocrine mechanism and improve cardiac function post-MI. Our findings provide the basis for a novel strategy for the treatment of MI through the systemic delivery of DEXs.

  2. Impairment of executive function and attention predicts onset of affective disorder in healthy high-risk twins

    DEFF Research Database (Denmark)

    Vinberg, Maj; Miskowiak, Kamilla W; Kessing, Lars Vedel

    2013-01-01

    To investigate whether measures of cognitive function can predict onset of affective disorder in individuals at heritable risk.......To investigate whether measures of cognitive function can predict onset of affective disorder in individuals at heritable risk....

  3. Hypothesis: Leukocyte Endogenous Mediator/Endogenous Pyrogen/Lymphocyte-Activating Factor Modulates the Development of Nonspecific and Specific Immunity and Affects Nutritional Status

    Science.gov (United States)

    1982-04-01

    become kocyte function and maintain cell-mediated "’toxic." Thus the ammonia moiety that is immunological processes. Glucagon. in phar- released when... spleen cells (49). LEM/EP/LAF in- of nutrition and infection. Geneva: WHO. 1968. duces macrophages to make colony-stimulat- 12. Wilmore DW. Kinney JM...mouse spleen Accession lou’ NTIS ORA&I DTJCI ___ "LLCTI; , Just if ivetiou.... .w Di~tribution/ Availatbility Codes A t O -- Avail and/or D t SpecCIll 90to 2ed 4I

  4. Affect and the brain's functional organization: a resting-state connectivity approach.

    Directory of Open Access Journals (Sweden)

    Christiane S Rohr

    Full Text Available The question of how affective processing is organized in the brain is still a matter of controversial discussions. Based on previous initial evidence, several suggestions have been put forward regarding the involved brain areas: (a right-lateralized dominance in emotional processing, (b hemispheric dominance according to positive or negative valence, (c one network for all emotional processing and (d region-specific discrete emotion matching. We examined these hypotheses by investigating intrinsic functional connectivity patterns that covary with results of the Positive and Negative Affective Schedule (PANAS from 65 participants. This approach has the advantage of being able to test connectivity rather than activation, and not requiring a potentially confounding task. Voxelwise functional connectivity from 200 regions-of-interest covering the whole brain was assessed. Positive and negative affect covaried with functional connectivity involving a shared set of regions, including the medial prefrontal cortex, the anterior cingulate, the visual cortex and the cerebellum. In addition, each affective domain had unique connectivity patterns, and the lateralization index showed a right hemispheric dominance for negative affect. Therefore, our results suggest a predominantly right-hemispheric network with affect-specific elements as the underlying organization of emotional processes.

  5. Plant species and functional group combinations affect green roof ecosystem functions.

    Directory of Open Access Journals (Sweden)

    Jeremy Lundholm

    Full Text Available BACKGROUND: Green roofs perform ecosystem services such as summer roof temperature reduction and stormwater capture that directly contribute to lower building energy use and potential economic savings. These services are in turn related to ecosystem functions performed by the vegetation layer such as radiation reflection and transpiration, but little work has examined the role of plant species composition and diversity in improving these functions. METHODOLOGY/PRINCIPAL FINDINGS: We used a replicated modular extensive (shallow growing- medium green roof system planted with monocultures or mixtures containing one, three or five life-forms, to quantify two ecosystem services: summer roof cooling and water capture. We also measured the related ecosystem properties/processes of albedo, evapotranspiration, and the mean and temporal variability of aboveground biomass over four months. Mixtures containing three or five life-form groups, simultaneously optimized several green roof ecosystem functions, outperforming monocultures and single life-form groups, but there was much variation in performance depending on which life-forms were present in the three life-form mixtures. Some mixtures outperformed the best monocultures for water capture, evapotranspiration, and an index combining both water capture and temperature reductions. Combinations of tall forbs, grasses and succulents simultaneously optimized a range of ecosystem performance measures, thus the main benefit of including all three groups was not to maximize any single process but to perform a variety of functions well. CONCLUSIONS/SIGNIFICANCE: Ecosystem services from green roofs can be improved by planting certain life-form groups in combination, directly contributing to climate change mitigation and adaptation strategies. The strong performance by certain mixtures of life-forms, especially tall forbs, grasses and succulents, warrants further investigation into niche complementarity or

  6. Funcionalidad de la glicoproteína P linfocitaria en la colitis ulcerosa P-glycoprotein functional activity in peripheral blood lymphocytes in ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Catalina M. Cortada

    2009-10-01

    Full Text Available La glicoproteína gp-P, codificada por el MDR1 es una bomba de eflujo transmembrana capaz de movilizar una gran cantidad de fármacos de uso frecuente. Se expresa en la cara luminal del epitelio intestinal, en linfocitos y otros tejidos con función de barrera. MDR1 ha sido postulado como gen candidato en la colitis ulcerosa. El objetivo del presente trabajo fue evaluar la función de la gp-P en linfocitos aislados de sangre periférica de pacientes con colitis en actividad (n = 27 clasificados clínicamente como refractarios (n=16 o respondedores (n = 11 al tratamiento. Se estudió el eflujo de rodamina 123, sustrato de la glicoproteína P, en ausencia y presencia del inhibidor verapamilo (100 μM determinando la fluorescencia intracelular por citometría de flujo. Los resultados se expresaron evaluando el comportamiento de dos marcadores que corresponden al % de células que contienen máxima (M1/mínima (M2 concentración del colorante, reflejando inactividad/actividad de la bomba. Utilizando el test de Kruskal-Wallis y post test de Dunn, se observaron diferencias significativas entre refractarios versus respondedores (p P-glycoprotein (P-gp, encoded by MDR-1, is a transmembrane efflux pump that has been involved in relevant clinical drug transport. It is expressed in lymphocytes, luminal epithelium of colon and other tissues with barrier function. MDR1 was proposed as a candidate gene for ulcerative colitis. The aim of the present work was to investigate the role of P-gp in therapeutic response of ulcerative colitis by studying its functionality in lymphocytes isolated from peripheral blood. Samples were taken from 27 patients with active colitis classified clinically in refractory (n = 16 and responders (n = 11 to treatment. Rhodamine 123 (a fluorescent P-glycoprotein substrate efflux was studied by flow cytometry as absence and presence of an inhibitor (verapamil, 100 μM. Data were expressed evaluating the behaviour of two markers defined

  7. Bendamustine Plus Alemtuzumab for Refractory Chronic Lymphocytic Leukemia (CLL)

    Science.gov (United States)

    2013-08-20

    Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  8. Metal ion levels and lymphocyte counts

    DEFF Research Database (Denmark)

    Penny, Jeannette Ø; Varmarken, Jens-Erik; Ovesen, Ole

    2013-01-01

    BACKGROUND AND PURPOSE: Wear particles from metal-on-metal arthroplasties are under suspicion for adverse effects both locally and systemically, and the DePuy ASR Hip Resurfacing System (RHA) has above-average failure rates. We compared lymphocyte counts in RHA and total hip arthroplasty (THA......) and investigated whether cobalt and chromium ions affected the lymphocyte counts. METHOD: In a randomized controlled trial, we followed 19 RHA patients and 19 THA patients. Lymphocyte subsets and chromium and cobalt ion concentrations were measured at baseline, at 8 weeks, at 6 months, and at 1 and 2 years....... RESULTS: The T-lymphocyte counts for both implant types declined over the 2-year period. This decline was statistically significant for CD3(+)CD8(+) in the THA group, with a regression coefficient of -0.04 × 10(9)cells/year (95% CI: -0.08 to -0.01). Regression analysis indicated a depressive effect...

  9. DISC1 gene and affective psychopathology: a combined structural and functional MRI study.

    Science.gov (United States)

    Opmeer, Esther M; van Tol, Marie-José; Kortekaas, Rudie; van der Wee, Nic J A; Woudstra, Saskia; van Buchem, Mark A; Penninx, Brenda W; Veltman, Dick J; Aleman, André

    2015-02-01

    The gene Disrupted-In-Schizophrenia-1 (DISC1) has been indicated as a determinant of psychopathology, including affective disorders, and shown to influence prefrontal cortex (PFC) and hippocampus functioning, regions of major interest for affective disorders. We aimed to investigate whether DISC1 differentially modulates brain function during executive and memory processing, and morphology in regions relevant for depression and anxiety disorders (affective disorders). 128 participants, with (n = 103) and without (controls; n = 25) affective disorders underwent genotyping for Ser704Cys (with Cys-allele considered as risk-allele) and structural and functional (f) Magnetic Resonance Imaging (MRI) during visuospatial planning and emotional episodic memory tasks. For both voxel-based morphometry and fMRI analyses, we investigated the effect of genotype in controls and explored genotypeXdiagnosis interactions. Results are reported at p < 0.05 FWE small volume corrected. In controls, Cys-carriers showed smaller bilateral (para)hippocampal volumes compared with Ser-homozygotes, and lower activation in the anterior cingulate cortex (ACC) and dorsolateral PFC during visuospatial planning. In anxiety patients, Cys-carriers showed larger (para)hippocampal volumes and more ACC activation during visuospatial planning. In depressive patients, no effect of genotype was observed and overall, no effect of genotype on episodic memory processing was detected. We demonstrated that Ser704Cys-genotype influences (para)hippocampal structure and functioning the dorsal PFC during executive planning, most prominently in unaffected controls. Results suggest that presence of psychopathology moderates Ser704Cys effects.

  10. Inflammatory conditions affect gene expression and function of human adipose tissue-derived mesenchymal stem cells

    NARCIS (Netherlands)

    M.J. Crop (Meindert); C.C. Baan (Carla); S.S. Korevaar (Sander); J.N.M. IJzermans (Jan); M. Pescatori (Mario); A. Stubbs (Andrew); W.F.J. van IJcken (Wilfred); M.H. Dahlke (Marc); E. Eggenhofer (Elke); W. Weimar (Willem); M.J. Hoogduijn (Martin)

    2010-01-01

    textabstractThere is emerging interest in the application of mesenchymal stem cells (MSC) for the prevention and treatment of autoimmune diseases, graft-versus-host disease and allograft rejection. It is, however, unknown how inflammatory conditions affect phenotype and function of MSC. Adipose tiss

  11. Automatic Processing of Emotional Faces in High-Functioning Pervasive Developmental Disorders: An Affective Priming Study

    Science.gov (United States)

    Kamio, Yoko; Wolf, Julie; Fein, Deborah

    2006-01-01

    This study examined automatic processing of emotional faces in individuals with high-functioning Pervasive Developmental Disorders (HFPDD) using an affective priming paradigm. Sixteen participants (HFPDD and matched controls) were presented with happy faces, fearful faces or objects in both subliminal and supraliminal exposure conditions, followed…

  12. What Is Chronic Lymphocytic Leukemia?

    Science.gov (United States)

    ... Chronic Lymphocytic Leukemia (CLL) About Chronic Lymphocytic Leukemia What Is Chronic Lymphocytic Leukemia? Cancer starts when cells ... body, including the lymph nodes, liver, and spleen. What is leukemia? Leukemia is a cancer that starts ...

  13. Major Histocompatibility Complex-Dependent Cytotoxic T Lymphocyte Repertoire and Functional Avidity Contribute to Strain-Specific Disease Susceptibility after Murine Respiratory Syncytial Virus Infection ▿

    Science.gov (United States)

    Jessen, Birthe; Faller, Simone; Krempl, Christine D.; Ehl, Stephan

    2011-01-01

    Susceptibility to respiratory syncytial virus (RSV) infection in mice is genetically determined. While RSV causes little pathology in C57BL/6 mice, pulmonary inflammation and weight loss occur in BALB/c mice. Using major histocompatibility complex (MHC)-congenic mice, we observed that the H-2d allele can partially transfer disease susceptibility to C57BL/6 mice. This was not explained by altered viral elimination or differences in the magnitude of the overall virus-specific cytotoxic T lymphocyte (CTL) response. However, H-2d mice showed a more focused response, with 70% of virus-specific CTL representing Vβ8.2+ CTL directed against the immunodominant epitope M2-1 82, while in H-2b mice only 20% of antiviral CTL were Vβ9+ CTL specific for the immunodominant epitope M187. The immunodominant H-2d-restricted CTL lysed target cells less efficiently than the immunodominant H-2b CTL, probably contributing to prolonged CTL stimulation and cytokine-mediated immunopathology. Accordingly, reduction of dominance of the M2-1 82-specific CTL population by introduction of an M187 response in the F1 generation of a C57BL/6N × C57BL/6-H-2d mating (C57BL/6-H-2dxb mice) attenuated disease. Moreover, disease in H-2d mice was less pronounced after infection with an RSV mutant failing to activate M2-1 82-specific CTL or after depletion of Vβ8.2+ cells. These data illustrate how the MHC-determined diversity and functional avidity of CTL responses contribute to disease susceptibility after viral infection. PMID:21795345

  14. The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases

    Directory of Open Access Journals (Sweden)

    Maulilio John Kipanyula

    2016-01-01

    Full Text Available The ongoing epidemics of metabolic diseases and increase in the older population have increased the incidences of neurodegenerative diseases. Evidence from murine and cell line models has implicated calcineurin-nuclear factor of activated T-lymphocytes (NFAT signaling pathway, a Ca2+/calmodulin-dependent major proinflammatory pathway, in the pathogenesis of these diseases. Neurotoxins such as amyloid-β, tau protein, and α-synuclein trigger abnormal calcineurin/NFAT signaling activities. Additionally increased activities of endogenous regulators of calcineurin like plasma membrane Ca2+-ATPase (PMCA and regulator of calcineurin 1 (RCAN1 also cause neuronal and glial loss and related functional alterations, in neurodegenerative diseases, psychotic disorders, epilepsy, and traumatic brain and spinal cord injuries. Treatment with calcineurin/NFAT inhibitors induces some degree of neuroprotection and decreased reactive gliosis in the central and peripheral nervous system. In this paper, we summarize and discuss the current understanding of the roles of calcineurin/NFAT signaling in physiology and pathologies of the adult and developing nervous system, with an emphasis on recent reports and cutting-edge findings. Calcineurin/NFAT signaling is known for its critical roles in the developing and adult nervous system. Its role in physiological and pathological processes is still controversial. However, available data suggest that its beneficial and detrimental effects are context-dependent. In view of recent reports calcineurin/NFAT signaling is likely to serve as a potential therapeutic target for neurodegenerative diseases and conditions. This review further highlights the need to characterize better all factors determining the outcome of calcineurin/NFAT signaling in diseases and the downstream targets mediating the beneficial and detrimental effects.

  15. The effect of affective bibliotherapy on clients' functioning in group therapy.

    Science.gov (United States)

    Shechtman, Zipora; Nir-Shfrir, Rivka

    2008-01-01

    Abstract The effect of affective group bibliotherapy (GB) was compared to affective group therapy (GT) on patients' functioning in therapy and their session impression. Three small groups totaling twenty-five in-patients in a hospital in Israel participated in the study. Clients concurrently participated in both group types, undergoing three sessions in each condition. In-therapy behaviors were assessed through the Client Behavior System (CBS; Hill & O'Brien, 1999). Results indicated that in the GB condition compared to the GT condition, clients showed less resistance, used simple responses less frequently, and expressed greater affective exploration. The Session Evaluation Questionnaire (SEQ; Stiles et al., 1994) was used to measure clients' impressions of the sessions. Results indicated that patients evaluated the two treatment conditions equally. Overall, the results support earlier findings, suggesting that affective bibliotherapy can be an effective method of treatment.

  16. Longer term improvement in neurocognitive functioning and affective distress among methamphetamine users who achieve stable abstinence.

    Science.gov (United States)

    Iudicello, Jennifer E; Woods, Steven P; Vigil, Ofilio; Scott, J Cobb; Cherner, Mariana; Heaton, Robert K; Atkinson, J Hampton; Grant, Igor

    2010-08-01

    Chronic use of methamphetamine (MA) is associated with neuropsychological dysfunction and affective distress. Some normalization of function has been reported after abstinence, but little in the way of data is available on the possible added benefits of long-term sobriety. To address this, we performed detailed neuropsychological and affective evaluations in 83 MA-dependent individuals at a baseline visit and following an average one-year interval period. Among the 83 MA-dependent participants, 25 remained abstinent, and 58 used MA at least once during the interval period. A total of 38 non-MA-addicted, demographically matched healthy comparison (i.e., HC) participants were also examined. At baseline, both MA-dependent participants who were able to maintain abstinence and those who were not performed significantly worse than the healthy comparison subjects on global neuropsychological functioning and were significantly more distressed. At the one-year follow-up, both the long-term abstainers and healthy comparison groups showed comparable global neuropsychological performance and affective distress levels, whereas the MA-dependent group who continued to use MA were worse than the comparison participants in terms of global neuropsychological functioning and affective distress. An interaction was observed between neuropsychological impairment at baseline, MA abstinence, and cognitive improvement, with abstinent MA-dependent participants who were neuropsychologically impaired at baseline demonstrating significantly and disproportionately greater improvement in processing speed and slightly greater improvement in motor abilities than the other participants. These results suggest partial recovery of neuropsychological functioning and improvement in affective distress upon sustained abstinence from MA that may extend beyond a year or more.

  17. An investigation on pharmacy functions and services affecting satisfaction of patients with prescriptions in community pharmacies.

    Science.gov (United States)

    Sakurai, Hidehiko; Nakajima, Fumio; Tada, Yuichirou; Yoshikawa, Emi; Iwahashi, Yoshiki; Fujita, Kenji; Hayase, Yukitoshi

    2009-05-01

    Various functions expected by patient expects are needed with progress in the system for separation of dispensing and prescribing functions. In this investigation, the relationship between patient satisfaction and pharmacy function were analyzed quantitatively. A questionnaire survey was conducted in 178 community pharmacies. Questions on pharmacy functions and services totaled 87 items concerning information service, amenities, safety, personnel training, etc. The questionnaires for patients had five-grade scales and composed 11 items (observed variables). Based on the results, "the percentage of satisfied patients" was determined. Multivariate analysis was performed to investigate the relationship between patient satisfaction and pharmacy functions or services provided, to confirm patient's evaluation of the pharmacy, and how factors affected comprehensive satisfaction. In correlation analysis, "the number of pharmacists" and "comprehensive satisfaction" had a negative correlation. Other interesting results were obtained. As a results of factor analysis, three latent factors were obtained: the "human factor," "patients' convenience," and "environmental factor," Multiple regression analysis showed that the "human factor" affected "comprehensive satisfaction" the most. Various pharmacy functions and services influence patient satisfaction, and improvement in their quality increases patient satisfaction. This will result in the practice of patient-centered medicine.

  18. Study on the lymphocyte immunity function in intravenous drug users with HIV infection in certain area%某省HIV阳性的静脉吸毒人群淋巴细胞免疫功能研究

    Institute of Scientific and Technical Information of China (English)

    朱红艳; 欧阳红梅; 宋建新; 甸自金; 张芹; 蒋雅先

    2011-01-01

    目的 探讨人类免疫缺陷病毒(HIV)阳性的静脉吸毒者细胞免疫功能的变化.方法 对静脉吸毒人员组成的HIV阳性组和HIV阴性组与健康对照组检测丙型肝炎病毒(HCV)感染率及淋巴细胞绝对值.结果 HIV阳性组和HIV阴性组HCV感染率分别是94.59%和82.93%;HIV阳性组T淋巴细胞亚群及自然杀伤(NK)细胞群均有不同程度的变化.结论 HIV阳性的静脉吸毒人群淋巴细胞免疫功能发生了不同程度的变化.%Objective To explore the lymphocyte immunity function in intravenous drug users with HIV infection. Methods HCV infection and absolute counts of T lymphocyte subsets were analyzed for intravenous drug users with or without HIV infec tion and healthy controls. Results The infection rates of HCV were 82.9% and 94.59% in HIV negative and HIV positive drug users respectively. There were changes of T lymphocyte subsets and natural killer cells for different degree in HIV positive drug us ers. Conclusion There could be certain alternations of lymphocyte immunity function in HIV positive intravenous drug users.

  19. Seasonal changes in haematology, lymphocyte transferrin receptors and intracellular iron in Ironman triathletes and untrained men.

    Science.gov (United States)

    Broadbent, Suzanne

    2011-01-01

    We investigated whether 12 months of chronic endurance training would affect haematology, CD4(+) lymphocyte transferrin receptor (CD71) expression, CD4(+) intracellular iron and the incidence of upper respiratory tract illnesses (URTI) in Ironman triathletes compared with untrained men. Resting venous blood samples were taken from 15 Ironman triathletes (TR 30 ± 5 year) and 12 untrained men (UT 30 ± 6 year) every 4 weeks for 12 months. Erythrocyte, leukocyte and platelet concentration, haematocrit, haemoglobin (Hb) and mean corpuscular haemoglobin (MCHC) were measured with a full blood count. CD4(+) lymphocytes were analysed for changes in transferrin receptor (CD71) expression (CD4(+)CD71(+)), and intracellular iron (Fe(3+)), by flow cytometry. The TR group had significantly lower Hb, MCHC, and platelets for 10, 9 and 11 months, respectively; lower CD4(+)CD71(+) (3 months) and Fe(3+) (1 month), respectively; higher CD4(+)CD71(+) (1 month); a higher lymphocyte count for 4 months. There were no between-group differences in other variables. In both groups haematology and lymphocytes increased during spring, early summer and winter and decreased during late summer/late winter, with an inverse relationship between CD4(+)CD71(+) and Fe(3+). The TR group reported significantly fewer URTI than the UT. Low Hb and MCHC suggest an iron deficiency which may affect triathlete performance. Monthly changes in lymphocytes, CD4(+)CD71(+) and Fe(3+) suggested that spring, summer and late autumn are associated with CD4(+) proliferation. There may be seasonal relationships between haematology and lymphocyte function, independent of endurance training, possibly affecting performance but not the incidence of URTI.

  20. Effect of endogenous catecholamines on apoptosis of Con A-activated lymphocytes of rats.

    Science.gov (United States)

    Jiang, Jian-Lan; Peng, Yu-Ping; Qiu, Yi-Hua; Wang, Jian-Jun

    2007-12-01

    Our previous studies show that lymphocytes express tyrosine hydroxylase (TH) and synthesize catecholamines (CAs) including dopamine, epinephrine and norepinephrine, and that the lymphocytes-derived endogenous CAs affect function of lymphocytes via autocrine/paracrine pathways. Over recent years, induction of apoptosis has been suggested to be a possible mechanism underlying the endogenous CAs-mediated lymphocyte proliferation, differentiation and activation. However, direct effect of the lymphocytes-synthesized CAs on lymphocyte apoptosis is less known. In the present study, TH inhibitor alpha-methyl-p-tyrosine (alpha-MT) and monoamine oxydase inhibitor pargyline were employed to block the synthesis and degradation of CAs in lymphocytes activated by concanavalin A (Con A). Apoptotic cells and apoptosis-related genes and proteins, Bax, Bcl-2, Fas, Fas-Ligand (FasL) and caspase-3, were examined in the lymphocytes treated with alpha-MT or pargyline by means of Annexin V/propidium iodide (PI) staining, real-time PCR and Western blot analyses, respectively. The treatment with alpha-MT of 10(-6) M and 10(-5) M (not 10(-7) M) notably reduced intracellular and supernatant DA, E and NE of the Con A-activated lymphocytes in a dose-dependent manner, and correspondingly, the treatment induced a remarkable decrease of apoptotic lymphocytes but not necrotic cells. The expression of Bax, Fas, FasL and caspase-3 mRNAs and proteins was significantly inhibited in the Con A-activated lymphocytes after the cells were treated with alpha-MT of 10(-6) M and 10(-5) M; but the expression of Bcl-2 mRNA and protein was dramatically increased by the alpha-MT treatment. Contrarily, the treatment with pargyline of 10(-6) M and 10(-5) M (not 10(-7) M) evidently increased the intracellular and supernatant DA, E and NE contents of the Con A-activated lymphocytes in a dose-dependent manner, and meanwhile, it caused a striking increase of apoptotic lymphocytes but not necrotic cells. The expression

  1. Prenatal ontogeny of lymphocyte subpopulations in pigs.

    Science.gov (United States)

    Sinkora, M; Sinkora, J; Reháková, Z; Splíchal, I; Yang, H; Parkhouse, R M; Trebichavsk, I

    1998-12-01

    Although porcine lymphocytes have been classified into numerous subpopulations in postnatal animals, little is known about the ontogeny of these complex cell subsets. Using double- and triple-colour flow cytometry (FCM), we investigated the surface phenotype of fetal lymphoid cells in the thymus, cord blood, spleen and mesenteric lymph nodes at different stages of gestation. It was found that the major lymphocyte subpopulations started to appear at the beginning of the second third of the gestation period, with B cells being the earliest lymphocyte subpopulation to appear in the periphery. The T-cell receptor (TCR) gamma delta+ cells were the earliest detectable T-cell subset, developing first in the thymus and subsequently arriving in the periphery. Later in ontogeny, however, the number of TCRalpha beta+ lymphocytes rapidly increased, becoming the predominant T cells both in the thymus and in the periphery. Cells with the phenotype of adult natural killer cells were also identified in pig fetuses, though their nature and functional roles remain to be investigated. In addition, CD2 was expressed on most B cells whilst very few CD4+ TCRalpha beta+ cells or CD2+ TCRgamma delta+ cells expressed CD8, suggesting that the expression of CD2 and CD8 may reflect the functional status of the cells in postnatal animals. Taken together, this study has provided a systematic analysis of fetal porcine lymphocyte subpopulations and may provide the base for studies to establish the physiological roles of these lymphocyte subsets.

  2. Detection of TP53 dysfunction in chronic lymphocytic leukemia by an in vitro functional assay based on TP53 activation by the non-genotoxic drug Nutlin-3: a proposal for clinical application

    OpenAIRE

    Pozzo, Federico; Dal Bo, Michele; Peragine, Nadia; Bomben, Riccardo; Zucchetto, Antonella; Rossi, Francesca Maria; Degan, Massimo; Rossi, Davide; Chiarenza, Annalisa; Grossi, Alberto; Di Raimondo, Francesco; Zaja, Francesco; Pozzato, Gabriele; Secchiero, Paola; Gaidano, Gianluca

    2013-01-01

    Background TP53 defects, i.e. 17p13 deletion and/or nucleotide mutations, associate with short survival and chemorefractoriness in chronic lymphocytic leukemia (CLL). In this context, since direct sequencing of the TP53 gene does not evaluate TP53 functionality, a functional assessment of TP53 pathway may be of interest to identify high risk CLL. By taking advantage of a training cohort of 100 CLL and a validation cohort of 40 CLL with different patterns of TP53 mutation/deletion by FISH and ...

  3. Fish oil affects immune function in 9 to 12 month old infants

    DEFF Research Database (Denmark)

    Damsgaard, Camilla Trab; Lauritzen, Lotte; Kjær, Tanja;

    Background - n-3 Polyunsaturated fatty acids (PUFA) are thought to affect immune function and may affect immune maturation in early life. Objective - To examine if fish oil supplementation in late infancy could modify immune function. Design - A 2×2 intervention with fish oil (3.4 ± 1.1 ml....../day) or no fish oil and cow’s milk or infant formula from 9 to 12 month of age in 64 healthy Danish infants. Before and after the intervention we measured the fatty acid composition of erythrocyte (RBC) membranes, plasma IgE levels, C-reactive protein and soluble IL-2 receptors (sIL-2R) as well as cytokine...... production in whole-blood cultures stimulated with lipopolysaccharide (LPS)/phytohaemaglutinin (PHA) or Lactobacillus paracasei for 22 h. IgA was measured in feces at 10 months of age. Results - Fish oil supplementation effectively raised RBC n-3 PUFA (p...

  4. The relationship between sleep-wake cycle and cognitive functioning in young people with affective disorders.

    Directory of Open Access Journals (Sweden)

    Joanne S Carpenter

    Full Text Available Although early-stage affective disorders are associated with both cognitive dysfunction and sleep-wake disruptions, relationships between these factors have not been specifically examined in young adults. Sleep and circadian rhythm disturbances in those with affective disorders are considerably heterogeneous, and may not relate to cognitive dysfunction in a simple linear fashion. This study aimed to characterise profiles of sleep and circadian disturbance in young people with affective disorders and examine associations between these profiles and cognitive performance. Actigraphy monitoring was completed in 152 young people (16-30 years; 66% female with primary diagnoses of affective disorders, and 69 healthy controls (18-30 years; 57% female. Patients also underwent detailed neuropsychological assessment. Actigraphy data were processed to estimate both sleep and circadian parameters. Overall neuropsychological performance in patients was poor on tasks relating to mental flexibility and visual memory. Two hierarchical cluster analyses identified three distinct patient groups based on sleep variables and three based on circadian variables. Sleep clusters included a 'long sleep' cluster, a 'disrupted sleep' cluster, and a 'delayed and disrupted sleep' cluster. Circadian clusters included a 'strong circadian' cluster, a 'weak circadian' cluster, and a 'delayed circadian' cluster. Medication use differed between clusters. The 'long sleep' cluster displayed significantly worse visual memory performance compared to the 'disrupted sleep' cluster. No other cognitive functions differed between clusters. These results highlight the heterogeneity of sleep and circadian profiles in young people with affective disorders, and provide preliminary evidence in support of a relationship between sleep and visual memory, which may be mediated by use of antipsychotic medication. These findings have implications for the personalisation of treatments and improvement

  5. The relationship between sleep-wake cycle and cognitive functioning in young people with affective disorders.

    Science.gov (United States)

    Carpenter, Joanne S; Robillard, Rébecca; Lee, Rico S C; Hermens, Daniel F; Naismith, Sharon L; White, Django; Whitwell, Bradley; Scott, Elizabeth M; Hickie, Ian B

    2015-01-01

    Although early-stage affective disorders are associated with both cognitive dysfunction and sleep-wake disruptions, relationships between these factors have not been specifically examined in young adults. Sleep and circadian rhythm disturbances in those with affective disorders are considerably heterogeneous, and may not relate to cognitive dysfunction in a simple linear fashion. This study aimed to characterise profiles of sleep and circadian disturbance in young people with affective disorders and examine associations between these profiles and cognitive performance. Actigraphy monitoring was completed in 152 young people (16-30 years; 66% female) with primary diagnoses of affective disorders, and 69 healthy controls (18-30 years; 57% female). Patients also underwent detailed neuropsychological assessment. Actigraphy data were processed to estimate both sleep and circadian parameters. Overall neuropsychological performance in patients was poor on tasks relating to mental flexibility and visual memory. Two hierarchical cluster analyses identified three distinct patient groups based on sleep variables and three based on circadian variables. Sleep clusters included a 'long sleep' cluster, a 'disrupted sleep' cluster, and a 'delayed and disrupted sleep' cluster. Circadian clusters included a 'strong circadian' cluster, a 'weak circadian' cluster, and a 'delayed circadian' cluster. Medication use differed between clusters. The 'long sleep' cluster displayed significantly worse visual memory performance compared to the 'disrupted sleep' cluster. No other cognitive functions differed between clusters. These results highlight the heterogeneity of sleep and circadian profiles in young people with affective disorders, and provide preliminary evidence in support of a relationship between sleep and visual memory, which may be mediated by use of antipsychotic medication. These findings have implications for the personalisation of treatments and improvement of functioning in

  6. The Relationship between Sleep-Wake Cycle and Cognitive Functioning in Young People with Affective Disorders

    Science.gov (United States)

    Carpenter, Joanne S.; Robillard, Rébecca; Lee, Rico S. C.; Hermens, Daniel F.; Naismith, Sharon L.; White, Django; Whitwell, Bradley; Scott, Elizabeth M.; Hickie, Ian B.

    2015-01-01

    Although early-stage affective disorders are associated with both cognitive dysfunction and sleep-wake disruptions, relationships between these factors have not been specifically examined in young adults. Sleep and circadian rhythm disturbances in those with affective disorders are considerably heterogeneous, and may not relate to cognitive dysfunction in a simple linear fashion. This study aimed to characterise profiles of sleep and circadian disturbance in young people with affective disorders and examine associations between these profiles and cognitive performance. Actigraphy monitoring was completed in 152 young people (16–30 years; 66% female) with primary diagnoses of affective disorders, and 69 healthy controls (18–30 years; 57% female). Patients also underwent detailed neuropsychological assessment. Actigraphy data were processed to estimate both sleep and circadian parameters. Overall neuropsychological performance in patients was poor on tasks relating to mental flexibility and visual memory. Two hierarchical cluster analyses identified three distinct patient groups based on sleep variables and three based on circadian variables. Sleep clusters included a ‘long sleep’ cluster, a ‘disrupted sleep’ cluster, and a ‘delayed and disrupted sleep’ cluster. Circadian clusters included a ‘strong circadian’ cluster, a ‘weak circadian’ cluster, and a ‘delayed circadian’ cluster. Medication use differed between clusters. The ‘long sleep’ cluster displayed significantly worse visual memory performance compared to the ‘disrupted sleep’ cluster. No other cognitive functions differed between clusters. These results highlight the heterogeneity of sleep and circadian profiles in young people with affective disorders, and provide preliminary evidence in support of a relationship between sleep and visual memory, which may be mediated by use of antipsychotic medication. These findings have implications for the personalisation of treatments

  7. Adaptation gap hypothesis: How differences between users’ expected and perceived agent functions affect their subjective impression

    Directory of Open Access Journals (Sweden)

    Takanori Komatsu

    2011-02-01

    Full Text Available We describe an “adaptation gap” that indicates the differences between the functions of artificial agents that users expect before starting their interactions and the functions they perceive after their interactions. We investigated the effect of this adaptation gap on users’ impressions of artificial agents because any variations in impression before and after the start of an interaction determines whether the user feels that this agent is worth interacting with. The results showed that positive or negative signs of the adaptation gap and subjective impression scores of agents before the experiment significantly affected the users’ final impressions of the agents.

  8. Testing two mechanisms by which rational and irrational beliefs may affect the functionality of inferences.

    Science.gov (United States)

    Bond, F W; Dryden, W; Briscoe, R

    1999-12-01

    This article describes a role playing experiment that examined the sufficiency hypothesis of Rational Emotive Behaviour Therapy (REBT). This proposition states that it is sufficient for rational and irrational beliefs to refer to preferences and musts, respectively, if those beliefs are to affect the functionality of inferences (FI). Consistent with the REBT literature (e.g. Dryden, 1994; Dryden & Ellis, 1988; Palmer, Dryden, Ellis & Yapp, 1995) results from this experiment showed that rational and irrational beliefs, as defined by REBT, do affect FI. Specifically, results showed that people who hold a rational belief form inferences that are significantly more functional than those that are formed by people who hold an irrational belief. Contrary to REBT theory, the sufficiency hypothesis was not supported. Thus, results indicated that it is not sufficient for rational and irrational beliefs to refer to preferences and musts, respectively, if those beliefs are to affect the FI. It appears, then, that preferences and musts are not sufficient mechanisms by which rational and irrational beliefs, respectively, affect the FI. Psychotherapeutic implications of these findings are considered.

  9. Amygdala perfusion is predicted by its functional connectivity with the ventromedial prefrontal cortex and negative affect.

    Directory of Open Access Journals (Sweden)

    Garth Coombs

    Full Text Available BACKGROUND: Previous studies have shown that the activity of the amygdala is elevated in people experiencing clinical and subclinical levels of anxiety and depression (negative affect. It has been proposed that a reduction in inhibitory input to the amygdala from the prefrontal cortex and resultant over-activity of the amygdala underlies this association. Prior studies have found relationships between negative affect and 1 amygdala over-activity and 2 reduced amygdala-prefrontal connectivity. However, it is not known whether elevated amygdala activity is associated with decreased amygdala-prefrontal connectivity during negative affect states. METHODS: Here we used resting-state arterial spin labeling (ASL and blood oxygenation level dependent (BOLD functional magnetic resonance imaging (fMRI in combination to test this model, measuring the activity (regional cerebral blood flow, rCBF and functional connectivity (correlated fluctuations in the BOLD signal of one subregion of the amygdala with strong connections with the prefrontal cortex, the basolateral nucleus (BLA, and subsyndromal anxiety levels in 38 healthy subjects. RESULTS: BLA rCBF was strongly correlated with anxiety levels. Moreover, both BLA rCBF and anxiety were inversely correlated with the strength of the functional coupling of the BLA with the caudal ventromedial prefrontal cortex. Lastly, BLA perfusion was found to be a mediator of the relationship between BLA-prefrontal connectivity and anxiety. CONCLUSIONS: These results show that both perfusion of the BLA and a measure of its functional coupling with the prefrontal cortex directly index anxiety levels in healthy subjects, and that low BLA-prefrontal connectivity may lead to increased BLA activity and resulting anxiety. Thus, these data provide key evidence for an often-cited circuitry model of negative affect, using a novel, multi-modal imaging approach.

  10. Affective response to a loved one's pain: insula activity as a function of individual differences.

    Directory of Open Access Journals (Sweden)

    Viridiana Mazzola

    Full Text Available Individual variability in emotion processing may be associated with genetic variation as well as with psychological predispositions such as dispositional affect styles. Our previous fMRI study demonstrated that amygdala reactivity was independently predicted by affective-cognitive styles (phobic prone or eating disorders prone and genotype of the serotonin transporter in a discrimination task of fearful facial expressions. Since the insula is associated with the subjective evaluation of bodily states and is involved in human feelings, we explored whether its activity could also vary in function of individual differences. In the present fMRI study, the association between dispositional affects and insula reactivity has been examined in two groups of healthy participants categorized according to affective-cognitive styles (phobic prone or eating disorders prone. Images of the faces of partners and strangers, in both painful and neutral situations, were used as visual stimuli. Interaction analyses indicate significantly different activations in the two groups in reaction to a loved one's pain: the phobic prone group exhibited greater activation in the left posterior insula. These results demonstrate that affective-cognitive style is associated with insula activity in pain empathy processing, suggesting a greater involvement of the insula in feelings for a certain cohort of people. In the mapping of individual differences, these results shed new light on variability in neural networks of emotion.

  11. Verbal marking of affect by children with Asperger Syndrome and high functioning autism during spontaneous interactions with family members.

    Science.gov (United States)

    Müller, Eve; Schuler, Adriana

    2006-11-01

    Verbal marking of affect by older children with Asperger Syndrome (AS) and high functioning autism (HFA) during spontaneous interactions is described. Discourse analysis of AS and HFA and typically developing children included frequency of affective utterances, affective initiations, affective labels and affective explanations, attribution of affective responses to self and others, and positive and negative markers of affect. Findings indicate that children with AS and HFA engaged in a higher proportion of affect marking and provided a higher proportion of affective explanations than typically developing children, yet were less likely to initiate affect marking sequences or talk about the affective responses of others. No significant differences were found between groups in terms of the marking of positive and negative affect.

  12. Acute Lymphocytic Leukemia

    Science.gov (United States)

    ... for information in your local library and on the Internet. Good sources include the National Cancer Institute, the ... mayoclinic.org/diseases-conditions/acute-lymphocytic-leukemia/basics/definition/CON-20042915 . Mayo Clinic Footer Legal Conditions and ...

  13. Psychosocial Functioning in Depressive Patients: A Comparative Study between Major Depressive Disorder and Bipolar Affective Disorder

    Directory of Open Access Journals (Sweden)

    Shubham Mehta

    2014-01-01

    Full Text Available Introduction. Major depressive disorder (MDD and bipolar affective disorder (BAD are among the leading causes of disability. These are often associated with widespread impairments in all domains of functioning including relational, occupational, and social. The main aim of the study was to examine and compare nature and extent of psychosocial impairment of patients with MDD and BAD during depressive phase. Methodology. 96 patients (48 in MDD group and 48 in BAD group were included in the study. Patients were recruited in depressive phase (moderate to severe depression. Patients having age outside 18–45 years, psychotic symptoms, mental retardation, and current comorbid medical or axis-1 psychiatric disorder were excluded. Psychosocial functioning was assessed using Range of Impaired Functioning Tool (LIFE-RIFT. Results. Domains of work, interpersonal relationship, life satisfaction, and recreation were all affected in both groups, but the groups showed significant difference in global psychosocial functioning score only (P=0.031 with BAD group showing more severe impairment. Conclusion. Bipolar depression causes higher global psychosocial impairment than unipolar depression.

  14. The protective function of personal growth initiative among a genocide-affected population in Rwanda.

    Science.gov (United States)

    Blackie, Laura E R; Jayawickreme, Eranda; Forgeard, Marie J C; Jayawickreme, Nuwan

    2015-07-01

    The aim of the current study was to investigate the extent to which individual differences in personal growth initiative (PGI) were associated with lower reports of functional impairment of daily activities among a genocide-affected population in Rwanda. PGI measures an individual's motivation to develop as a person and the extent to which he or she is active in setting goals that work toward achieving self-improvement. We found that PGI was negatively associated with functional impairment when controlling for depression, posttraumatic stress disorder, and other demographic factors. Our results suggest that PGI may constitute an important mindset for facilitating adaptive functioning in the aftermath of adversity and in the midst of psychological distress, and as such they might have practical applications for the development of intervention programs.

  15. SHARPIN Regulates Uropod Detachment in Migrating Lymphocytes

    Directory of Open Access Journals (Sweden)

    Jeroen Pouwels

    2013-11-01

    Full Text Available SHARPIN-deficient mice display a multiorgan chronic inflammatory phenotype suggestive of altered leukocyte migration. We therefore studied the role of SHARPIN in lymphocyte adhesion, polarization, and migration. We found that SHARPIN localizes to the trailing edges (uropods of both mouse and human chemokine-activated lymphocytes migrating on intercellular adhesion molecule-1 (ICAM-1, which is one of the major endothelial ligands for migrating leukocytes. SHARPIN-deficient cells adhere better to ICAM-1 and show highly elongated tails when migrating. The increased tail lifetime in SHARPIN-deficient lymphocytes decreases the migration velocity. The adhesion, migration, and uropod defects in SHARPIN-deficient lymphocytes were rescued by reintroducing SHARPIN into the cells. Mechanistically, we show that SHARPIN interacts directly with lymphocyte-function-associated antigen-1 (LFA-1, a leukocyte counterreceptor for ICAM-1, and inhibits the expression of intermediate and high-affinity forms of LFA-1. Thus, SHARPIN controls lymphocyte migration by endogenously maintaining LFA-1 inactive to allow adjustable detachment of the uropods in polarized cells.

  16. Loss of signal transduction and inhibition of lymphocyte locomotion in a ground-based model of microgravity

    Science.gov (United States)

    Sundaresan, Alamelu; Risin, Diana; Pellis, Neal R.; McIntire, L. V. (Principal Investigator)

    2002-01-01

    Inflammatory adherence to, and locomotion through the interstitium is an important component of the immune response. Conditions such as microgravity and modeled microgravity (MMG) severely inhibit lymphocyte locomotion in vitro through gelled type I collagen. We used the NASA rotating wall vessel bioreactor or slow-turning lateral vessel as a prototype for MMG in ground-based experiments. Previous experiments from our laboratory revealed that when lymphocytes (human peripheral blood mononuclear cells [PBMCs]) were first activated with phytohemaglutinin followed by exposure to MMG, locomotory capacity was not affected. In the present study, MMG inhibits lymphocyte locomotion in a manner similar to that observed in microgravity. Phorbol myristate acetate (PMA) treatment of PBMCs restored lost locomotory capacity by a maximum of 87%. Augmentation of cellular calcium flux with ionomycin had no restorative effect. Treatment of lymphocytes with mitomycin C prior to exposure to MMG, followed by PMA, restored locomotion to the same extent as when nonmitomycin C-treated lymphocytes were exposed to MMG (80-87%), suggesting that deoxyribonucleic acid replication is not essential for the restoration of locomotion. Thus, direct activation of protein kinase C (PKC) with PMA was effective in restoring locomotion in MMG comparable to the normal levels seen in Ig cultures. Therefore, in MMG, lymphocyte calcium signaling pathways were functional, with defects occurring at either the level of PKC or upstream of PKC.

  17. Plant diversity and functional groups affect Si and Ca pools in aboveground biomass of grassland systems.

    Science.gov (United States)

    Schaller, Jörg; Roscher, Christiane; Hillebrand, Helmut; Weigelt, Alexandra; Oelmann, Yvonne; Wilcke, Wolfgang; Ebeling, Anne; Weisser, Wolfgang W

    2016-09-01

    Plant diversity is an important driver of nitrogen and phosphorus stocks in aboveground plant biomass of grassland ecosystems, but plant diversity effects on other elements also important for plant growth are less understood. We tested whether plant species richness, functional group richness or the presence/absence of particular plant functional groups influences the Si and Ca concentrations (mmol g(-1)) and stocks (mmol m(-2)) in aboveground plant biomass in a large grassland biodiversity experiment (Jena Experiment). In the experiment including 60 temperate grassland species, plant diversity was manipulated as sown species richness (1, 2, 4, 8, 16) and richness and identity of plant functional groups (1-4; grasses, small herbs, tall herbs, legumes). We found positive species richness effects on Si as well as Ca stocks that were attributable to increased biomass production. The presence of particular functional groups was the most important factor explaining variation in aboveground Si and Ca stocks (mmol m(-2)). Grass presence increased the Si stocks by 140 % and legume presence increased the Ca stock by 230 %. Both the presence of specific plant functional groups and species diversity altered Si and Ca stocks, whereas Si and Ca concentration were affected mostly by the presence of specific plant functional groups. However, we found a negative effect of species diversity on Si and Ca accumulation, by calculating the deviation between mixtures and mixture biomass proportions, but in monoculture concentrations. These changes may in turn affect ecosystem processes such as plant litter decomposition and nutrient cycling in grasslands.

  18. Progression in the study on the phagocytosis function of B lymphocyte%B淋巴细胞吞噬功能研究进展

    Institute of Scientific and Technical Information of China (English)

    高杨; 高继鑫; 刘玉峰

    2009-01-01

    以往的观点认为只有巨噬细胞、单核细胞、粒细胞和树突状细胞是专职的吞噬细胞,而B细胞作为免疫系统的抗体产生细胞,虽然能够产生特异的免疫球蛋白与抗原结合,却不具备吞噬能力.但最近的研究指出硬骨鱼类(彩虹鳟鱼)和两栖类(爪蟾)的B细胞可以吞噬颗粒抗原,首次揭示了进化上较为原始的B细胞同样具有吞噬能力.众多研究提示哺乳动物B-1 B细胞很可能具有吞噬能力.%It was accepted in the past that only these cells such as macrophage, histoleucocyte, granular cell and dendritic cell are phagocytes, while B lymphocyte has no ability to phagocytize, although it can generate specific immune globulin for antigen binding. However recent studies indicate that B lymphocyte of osteichthyes (trout) and amphibia (xenopus laevis) can phagocytize particulate antigen, these studies for the first time re-vealed that relatively archaic B lymphocyte has ability to phagocytize too. Numerous studies reveal that B-1 cell in mammalian probably has ability to phagocytize.

  19. Arrival order among native plant functional groups does not affect invasibility of constructed dune communities.

    Science.gov (United States)

    Mason, T J; French, K; Jolley, D

    2013-10-01

    Different arrival order scenarios of native functional groups to a site may influence both resource use during development and final community structure. Arrival order may then indirectly influence community resistance to invasion. We present a mesocosm experiment of constructed coastal dune communities that monitored biotic and abiotic responses to different arrival orders of native functional groups. Constructed communities were compared with unplanted mesocosms. We then simulated a single invasion event by bitou (Chrysanthemoides monilifera ssp. rotundata), a dominant exotic shrub of coastal communities. We evaluated the hypothesis that plantings with simultaneous representation of grass, herb and shrub functional groups at the beginning of the experiment would more completely sequester resources and limit invasion than staggered plantings. Staggered plantings in turn would offer greater resource use and invasion resistance than unplanted mesocosms. Contrary to our expectations, there were few effects of arrival order on abiotic variables for the duration of the experiment and arrival order was unimportant in final community invasibility. All planted mesocosms supported significantly more invader germinants and significantly less invader abundance than unplanted mesocosms. Native functional group plantings may have a nurse effect during the invader germination and establishment phase and a competitive function during the invader juvenile and adult phase. Arrival order per se did not affect resource use and community invasibility in our mesocosm experiment. While grass, herb and shrub functional group plantings will not prevent invasion success in restored communities, they may limit final invader biomass.

  20. Effect of chloroquine on human lymphocyte proliferation

    DEFF Research Database (Denmark)

    Bygbjerg, Ib Christian; Flachs, H

    1986-01-01

    the response to pokeweed mitogen. The response to concanavalin A and to various antigens was suppressed, especially the response to large particulate antigens. Oral intake of 300 mg of chloroquine base/week did not affect the lymphocyte proliferative responses. 600 mg of base/week decreased the response...

  1. Functional connectivity of pain-mediated affect regulation in Borderline Personality Disorder.

    Directory of Open Access Journals (Sweden)

    Inga Niedtfeld

    Full Text Available Affective instability and self-injurious behavior are important features of Borderline Personality Disorder. Whereas affective instability may be caused by a pattern of limbic hyperreactivity paired with dysfunctional prefrontal regulation mechanisms, painful stimulation was found to reduce affective arousal at the neural level, possibly underlying the soothing effect of pain in BPD.We used psychophysiological interactions to analyze functional connectivity of (para- limbic brain structures (i.e. amygdala, insula, anterior cingulate cortex in Borderline Personality Disorder in response to painful stimulation. Therefore, we re-analyzed a dataset from 20 patients with Borderline Personality Disorder and 23 healthy controls who took part in an fMRI-task inducing negative (versus neutral affect and subsequently applying heat pain (versus warmth perception.Results suggest an enhanced negative coupling between limbic as well as paralimbic regions and prefrontal regions, specifically with the medial and dorsolateral prefrontal cortex, when patients experienced pain in addition to emotional arousing pictures. When neutral pictures were combined with painful heat sensation, we found positive connectivity in Borderline Personality Disorder between (para-limbic brain areas and parts of the basal ganglia (lentiform nucleus, putamen, as well areas involved in self-referential processing (precuneus and posterior cingulate.We found further evidence for alterations in the emotion regulation process in Borderline Personality Disorder, in the way that pain improves the inhibition of limbic activity by prefrontal areas. This study provides new insights in pain processing in BPD, including enhanced coupling of limbic structures and basal ganglia.

  2. Modulation of α power and functional connectivity during facial affect recognition.

    Science.gov (United States)

    Popov, Tzvetan; Miller, Gregory A; Rockstroh, Brigitte; Weisz, Nathan

    2013-04-03

    Research has linked oscillatory activity in the α frequency range, particularly in sensorimotor cortex, to processing of social actions. Results further suggest involvement of sensorimotor α in the processing of facial expressions, including affect. The sensorimotor face area may be critical for perception of emotional face expression, but the role it plays is unclear. The present study sought to clarify how oscillatory brain activity contributes to or reflects processing of facial affect during changes in facial expression. Neuromagnetic oscillatory brain activity was monitored while 30 volunteers viewed videos of human faces that changed their expression from neutral to fearful, neutral, or happy expressions. Induced changes in α power during the different morphs, source analysis, and graph-theoretic metrics served to identify the role of α power modulation and cross-regional coupling by means of phase synchrony during facial affect recognition. Changes from neutral to emotional faces were associated with a 10-15 Hz power increase localized in bilateral sensorimotor areas, together with occipital power decrease, preceding reported emotional expression recognition. Graph-theoretic analysis revealed that, in the course of a trial, the balance between sensorimotor power increase and decrease was associated with decreased and increased transregional connectedness as measured by node degree. Results suggest that modulations in α power facilitate early registration, with sensorimotor cortex including the sensorimotor face area largely functionally decoupled and thereby protected from additional, disruptive input and that subsequent α power decrease together with increased connectedness of sensorimotor areas facilitates successful facial affect recognition.

  3. Analgesic nephropathy selectively affecting a unilateral non-functioning hypoplastic kidney.

    Science.gov (United States)

    Granese, J; Brightbill, K; Osborne, P; Cox, C E; Gaber, L W

    2007-08-01

    Analgesic nephropathy results from chronic abuse of non-narcotic analgesics, most frequently with the use of phenacetin and mixed analgesic preparations. Renal papillary necrosis and chronic interstitial nephritis with progressive scarring are characteristic of the histopathology of analgesic nephropathy. Typically, papillary necrosis in these patients is bilateral and affects almost all renal papillae. This report describes a case of severe analgesic nephropathy that discriminantly affected a unilateral non-functioning kidney and spared the contralateral normally developed kidney. The patient herein consumed therapeutic doses of acetaminophen and naproxen daily and for several years. We estimated the cumulative doses of acetaminophen and naproxen used by the patient during that period to be approximately 1.0 and 0.4 kg, respectively. The cumulative dose of acetaminophen is at the threshold of doses that were traditionally associated with an increased risk for end-stage kidney failure. Simultaneous intake of both analgesics could have had a synergetic adverse effect on renal function. This case also demonstrates that preexisting renal insufficiency is prerequisite to the development of analgesic nephropathy. Conversely, kidneys with normal function are resistant to the chronic nephrotoxicity associated with habitual analgesic use.

  4. Social-adaptive and psychological functioning of patients affected by Fabry disease.

    Science.gov (United States)

    Laney, Dawn Alyssia; Gruskin, Daniel J; Fernhoff, Paul M; Cubells, Joseph F; Ousley, Opal Y; Hipp, Heather; Mehta, Ami J

    2010-12-01

    Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficiency of alpha-galactosidase A. In addition to the debilitating physical symptoms of FD, there are also under-recognized and poorly characterized psychiatric features. As a first step toward characterizing psychiatric features of FD, we administered the Achenbach adult self report questionnaire to 30 FD patients and the Achenbach adult behavior checklist questionnaire to 28 partners/parents/friends of FD patients. Data from at least one of the questionnaires were available on 33 subjects. Analysis focused on social-adaptive functioning in various aspects of daily life and on criteria related to the Diagnostic and statistical manual of mental disorders IV (DSM-IV). Adaptive functioning scale values, which primarily measure social and relationship functioning and occupational success, showed that eight FD patients (six female and two male) had mean adaptive functioning deficits as compared to population norms. Greater rates of depression (P personality (P Individuals affected by Fabry disease exhibited social-adaptive functioning deficits that were significantly correlated with anxiety, depression, antisocial behavior, and AD/H problems in a sampling of our male and female patients aged between 18 years and 59 years.

  5. Cure Kinetics of Epoxy Nanocomposites Affected by MWCNTs Functionalization: A Review

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Saeb

    2013-01-01

    Full Text Available The current paper provides an overview to emphasize the role of functionalization of multiwalled carbon nanotubes (MWCNTs in manipulating cure kinetics of epoxy nanocomposites, which itself determines ultimate properties of the resulting compound. In this regard, the most commonly used functionalization schemes, that is, carboxylation and amidation, are thoroughly surveyed to highlight the role of functionalized nanotubes in controlling the rate of autocatalytic and vitrification kinetics. The current literature elucidates that the mechanism of curing in epoxy/MWCNTs nanocomposites remains almost unaffected by the functionalization of carbon nanotubes. On the other hand, early stage facilitation of autocatalytic reactions in the presence of MWCNTs bearing amine groups has been addressed by several researchers. When carboxylated nanotubes were used to modify MWCNTs, the rate of such reactions diminished as a consequence of heterogeneous dispersion within the epoxy matrix. At later stages of curing, however, the prolonged vitrification was seen to be dominant. Thus, the type of functional groups covalently located on the surface of MWCNTs directly affects the degree of polymer-nanotube interaction followed by enhancement of curing reaction. Our survey demonstrated that most widespread efforts ever made to represent multifarious surface-treated MWCNTs have not been directed towards preparation of epoxy nanocomposites, but they could result in property synergism.

  6. Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function.

    Science.gov (United States)

    Baruch, Kuti; Deczkowska, Aleksandra; David, Eyal; Castellano, Joseph M; Miller, Omer; Kertser, Alexander; Berkutzki, Tamara; Barnett-Itzhaki, Zohar; Bezalel, Dana; Wyss-Coray, Tony; Amit, Ido; Schwartz, Michal

    2014-10-03

    Aging-associated cognitive decline is affected by factors produced inside and outside the brain. By using multiorgan genome-wide analysis of aged mice, we found that the choroid plexus, an interface between the brain and the circulation, shows a type I interferon (IFN-I)-dependent gene expression profile that was also found in aged human brains. In aged mice, this response was induced by brain-derived signals, present in the cerebrospinal fluid. Blocking IFN-I signaling within the aged brain partially restored cognitive function and hippocampal neurogenesis and reestablished IFN-II-dependent choroid plexus activity, which is lost in aging. Our data identify a chronic aging-induced IFN-I signature, often associated with antiviral response, at the brain's choroid plexus and demonstrate its negative influence on brain function, thereby suggesting a target for ameliorating cognitive decline in aging.

  7. Developing fragility functions for the areas affected by the 2009 Samoa earthquake and tsunami

    Directory of Open Access Journals (Sweden)

    H. Gokon

    2014-01-01

    Full Text Available Fragility functions in terms of flow depth, flow velocity and hydrodynamic force are developed to evaluate structural vulnerability in the areas affected by the 2009 Samoa earthquake and tsunami. First, numerical simulations of tsunami propagation and inundation are conducted to reproduce the features of tsunami inundation. To validate the results, flow depths measured in field surveys and waveforms measured by Deep-ocean Assessment and Reporting of Tsunamis (DART gauges are utilized. Next, building damage is investigated by manually detecting changes between pre- and post-tsunami high-resolution satellite images. Finally, the data related to tsunami features and building damage are integrated using GIS, and tsunami fragility functions are developed based on the statistical analyses.

  8. Thyroid, brain and mood modulation in affective disorder: insights from molecular research and functional brain imaging.

    Science.gov (United States)

    Bauer, M; London, E D; Silverman, D H; Rasgon, N; Kirchheiner, J; Whybrow, P C

    2003-11-01

    The efficacy resulting from adjunctive use of supraphysiological doses of levothyroxine has emerged as a promising approach to therapy and prophylaxis for refractory mood disorders. Most patients with mood disorders who receive treatment with supraphysiological doses of levothyroxine have normal peripheral thyroid hormone levels, and also respond differently to the hormone and tolerate it better than healthy individuals and patients with primary thyroid diseases. Progress in molecular and functional brain imaging techniques has provided a new understanding of these phenomena, illuminating the relationship between thyroid function, mood modulation and behavior. Thyroid hormones are widely distributed in the brain and have a multitude of effects on the central nervous system. Notably many of the limbic system structures where thyroid hormone receptors are prevalent have been implicated in the pathogenesis of mood disorders. The influence of the thyroid system on neurotransmitters (particularly serotonin and norepinephrine), which putatively play a major role in the regulation of mood and behavior, may contribute to the mechanisms of mood modulation. Recent functional brain imaging studies using positron emission tomography (PET) with [ (18)F]-fluorodeoxyglucose demonstrated that thyroid hormone treatment with levothyroxine affects regional brain metabolism in patients with hypothyroidism and bipolar disorder. Theses studies confirm that thyroid hormones are active in modulating metabolic function in the mature adult brain, and provide intriging neuroanatomic clues that may guide future research.

  9. No adverse affect after harvesting of free fibula osteoseptocutaneous flaps on gait function.

    Science.gov (United States)

    Maurer-Ertl, Werner; Glehr, Mathias; Friesenbichler, Joerg; Sadoghi, Patrick; Wiedner, Maria; Haas, Franz; Leithner, Andreas; Windhager, Reinhard; Zwick, Ernst B

    2012-07-01

    The aim of this study was to analyze gait function and muscular strength on donor site after harvesting of a vascularized fibula osteoseptocutaneous flap. Nine patients with a mean follow-up of 33 months (range, 7-59) and a mean resection length of the middle portion of the fibula of 18.0 cm (range, 14.0-23.0) underwent an instrumented three-dimensional gait analysis to evaluate gait function. Furthermore, CYBEX II extremity system was used for muscular strength measurements. Subjective muscle strength measurements were performed according to Kendall et al. and were classified according to the British Medical Research Council. Intraindividual comparison between the operated and the nonoperated leg revealed no significant differences for gait function parameters (cadence, velocity, and stride length, P > 1.00) and for muscular strength measurements for flexion (knee: P = 0.93, ankle: P = 0.54) and extension (knee: P = 0.97, ankle: P= 0.21), respectively. In conclusion, intraindividual comparison of the operated and nonoperated sides after harvesting of the middle portion of the fibula for gaining a free fibula osteoseptocutaneous flap has no adverse affect on gait function or muscular flexion and extension strength on donor site at a mean follow-up of 33 months.

  10. Arabidopsis AtADF1 is Functionally Affected by Mutations on Actin Binding Sites

    Institute of Scientific and Technical Information of China (English)

    Chun-Hai Dong; Wei-Ping Tang; Jia-Yao Liu

    2013-01-01

    The plant actin depolymerizing factor (ADF) binds to both monomeric and filamentous actin,and is directly involved in the depolymerization of actin filaments.To better understand the actin binding sites of the Arabidopsis thaliana L.AtADF1,we generated mutants of AtADF1 and investigated their functions in vitro and in vivo.Analysis of mutants harboring amino acid substitutions revealed that charged residues (Arg98 and Lys100) located at the α-helix 3 and forming an actin binding site together with the N-terminus are essential for both G-and F-actin binding.The basic residues on the β-strand 5 (K82/A) and the α-helix 4 (R135/A,R137/A) form another actin binding site that is important for F-actin binding.Using transient expression of CFP-tagged AtADF1 mutant proteins in onion (Allium cepa) peel epidermal cells and transgenic Arabidopsis thaliana L.plants overexpressing these mutants,we analyzed how these mutant proteins regulate actin organization and affect seedling growth.Our results show that the ADF mutants with a lower affinity for actin filament binding can still be functional,unless the affinity foractin monomers is also affected.The G-actin binding activity of the ADF plays an essential role in actin binding,depolymerization of actin polymers,and therefore in the control of actin organization.

  11. Attachment style predicts affect, cognitive appraisals, and social functioning in daily life.

    Science.gov (United States)

    Sheinbaum, Tamara; Kwapil, Thomas R; Ballespí, Sergi; Mitjavila, Mercè; Chun, Charlotte A; Silvia, Paul J; Barrantes-Vidal, Neus

    2015-01-01

    The way in which attachment styles are expressed in the moment as individuals navigate their real-life settings has remained an area largely untapped by attachment research. The present study examined how adult attachment styles are expressed in daily life using experience sampling methodology (ESM) in a sample of 206 Spanish young adults. Participants were administered the Attachment Style Interview (ASI) and received personal digital assistants that signaled them randomly eight times per day for 1 week to complete questionnaires about their current experiences and social context. As hypothesized, participants' momentary affective states, cognitive appraisals, and social functioning varied in meaningful ways as a function of their attachment style. Individuals with an anxious attachment, as compared with securely attached individuals, endorsed experiences that were congruent with hyperactivating tendencies, such as higher negative affect, stress, and perceived social rejection. By contrast, individuals with an avoidant attachment, relative to individuals with a secure attachment, endorsed experiences that were consistent with deactivating tendencies, such as decreased positive states and a decreased desire to be with others when alone. Furthermore, the expression of attachment styles in social contexts was shown to be dependent upon the subjective appraisal of the closeness of social contacts, and not merely upon the presence of social interactions. The findings support the ecological validity of the ASI and the person-by-situation character of attachment theory. Moreover, they highlight the utility of ESM for investigating how the predictions derived from attachment theory play out in the natural flow of real life.

  12. Chemical and Conformational Diversity of Modified Nucleosides Affects tRNA Structure and Function

    Directory of Open Access Journals (Sweden)

    Ville Y. P. Väre

    2017-03-01

    Full Text Available RNAs are central to all gene expression through the control of protein synthesis. Four major nucleosides, adenosine, guanosine, cytidine and uridine, compose RNAs and provide sequence variation, but are limited in contributions to structural variation as well as distinct chemical properties. The ability of RNAs to play multiple roles in cellular metabolism is made possible by extensive variation in length, conformational dynamics, and the over 100 post-transcriptional modifications. There are several reviews of the biochemical pathways leading to RNA modification, but the physicochemical nature of modified nucleosides and how they facilitate RNA function is of keen interest, particularly with regard to the contributions of modified nucleosides. Transfer RNAs (tRNAs are the most extensively modified RNAs. The diversity of modifications provide versatility to the chemical and structural environments. The added chemistry, conformation and dynamics of modified nucleosides occurring at the termini of stems in tRNA’s cloverleaf secondary structure affect the global three-dimensional conformation, produce unique recognition determinants for macromolecules to recognize tRNAs, and affect the accurate and efficient decoding ability of tRNAs. This review will discuss the impact of specific chemical moieties on the structure, stability, electrochemical properties, and function of tRNAs.

  13. 镉致脾淋巴细胞功能抑制与细胞凋亡的关系%The relationship between cadmium-induced inhibition of splenic lymphocyte function and cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    冯丰; 薛彬; 张铣

    2001-01-01

    目的采用体外作用的方式观察氯化镉引起的脾淋巴细胞功能抑制与镉诱导的细胞凋亡之间的关系。方法在实验中选择了3.10、6.25、12.50、25.00、50.00 μmol/L共5个浓度的氯化镉,在体外与小鼠淋巴细胞共育不同时间后,采用MTT颜色反应法观察淋巴细胞转化,用DNA凝胶电泳法及流式细胞仪法检测细胞凋亡。结果 25.00和50.00 μmol/L氯化镉对小鼠脾淋巴细胞的转化功能产生明显抑制作用,并有剂量-反应关系,这两个浓度的氯化镉对淋巴细胞转化功能的抑制率:刀豆蛋白A刺激组分别为50%和78%,脂多糖刺激组分别为39%和55%;同时12.50~50.00 μmol/L氯化镉可诱导脾淋巴细胞发生凋亡,流式细胞仪检测结果为30%~60%。在较高浓度下氯化镉还可以引起细胞存活率下降,并且氯化镉诱导细胞凋亡的作用与其抑制脾淋巴细胞功能的作用相比,作用时间短、作用浓度低。结论氯化镉在体外可能以诱导细胞发生凋亡作为其抑制脾淋巴细胞功能的一种机制。%Objective To explore the relationship between cadmium-induced inhibition of splenic lymphocyte function and cell apoptosis in vitro.Methods The splenic lymphocytes of mice were exposed to 3.10, 6.25, 12.50, 25.00, 50.00 μmol/L of cadmiun chloride (CdCl2) for various time period, to measure the lymphocyte transformation by MTT colorimetric assay and to detect the apoptosis in splenocytes by DNA agarose electrophoresis and flow cytometry (FACS).Results CdCl2 could significantly inhibit the function of lymphocyte transformation in a dose-response pattern at concentrations of 25.00 and 50.00 μmol/L, with inhibition rates of 50% and 78% in ConA-stimulating group and 39% and 55% in LPS-stimulating group, respectively.CdCl2 could also induce apoptosis of splenic cells at concentrations of 12.50 to 50.00 μmol/L.Results of FACS analysis showed 30%-60% of cell apoptosis

  14. STN1 OB Fold Mutation Alters DNA Binding and Affects Selective Aspects of CST Function

    Science.gov (United States)

    Bhattacharjee, Anukana; Stewart, Jason; Chaiken, Mary; Price, Carolyn M.

    2016-01-01

    Mammalian CST (CTC1-STN1-TEN1) participates in multiple aspects of telomere replication and genome-wide recovery from replication stress. CST resembles Replication Protein A (RPA) in that it binds ssDNA and STN1 and TEN1 are structurally similar to RPA2 and RPA3. Conservation between CTC1 and RPA1 is less apparent. Currently the mechanism underlying CST action is largely unknown. Here we address CST mechanism by using a DNA-binding mutant, (STN1 OB-fold mutant, STN1-OBM) to examine the relationship between DNA binding and CST function. In vivo, STN1-OBM affects resolution of endogenous replication stress and telomere duplex replication but telomeric C-strand fill-in and new origin firing after exogenous replication stress are unaffected. These selective effects indicate mechanistic differences in CST action during resolution of different replication problems. In vitro binding studies show that STN1 directly engages both short and long ssDNA oligonucleotides, however STN1-OBM preferentially destabilizes binding to short substrates. The finding that STN1-OBM affects binding to only certain substrates starts to explain the in vivo separation of function observed in STN1-OBM expressing cells. CST is expected to engage DNA substrates of varied length and structure as it acts to resolve different replication problems. Since STN1-OBM will alter CST binding to only some of these substrates, the mutant should affect resolution of only a subset of replication problems, as was observed in the STN1-OBM cells. The in vitro studies also provide insight into CST binding mechanism. Like RPA, CST likely contacts DNA via multiple OB folds. However, the importance of STN1 for binding short substrates indicates differences in the architecture of CST and RPA DNA-protein complexes. Based on our results, we propose a dynamic DNA binding model that provides a general mechanism for CST action at diverse forms of replication stress. PMID:27690379

  15. Relationship of mercury to cognitive, affective and perceptual motor functioning in a normal sample in Hawaii

    Energy Technology Data Exchange (ETDEWEB)

    Sine, L.F.

    1983-01-01

    Although the effects of toxic levels of mercury have been well documented, the effects of subclinical levels of mercury on normal populations have generally not been studied. The purpose of this investigation was to assess the impact of mercury risk factors on cognition, affect, psychopathology, and known mercury-related symptoms in a normal sample in Hawaii exposed to subclinical although elevated levels of elemental mercury through inhalation associated with volcanic activity and of methylmercury mostly through ingestion of large ocean species fish. The following summarizes the findings and conclusions of the study: 1) a four week test-retest reliability using 41 of the subjects showed that the 41 measures used in the study exhibited an average correlation of .78. Using all 413 subjects, the average internal consistency measured by Cronbach's ..cap alpha.. was .82 for the 17 affect, psychopathology, and symptom measures; 2) nine mercury source variables were used to predict the amount of total mercury in hair. Interestingly, none of the source variables predicted hair total mercury; 3) the source variables in addition to hair total mercury and statistical control variables were used to predict the twenty-two functioning variables in the four domains cited above with a relative absence of relationships noted. This finding indicates that the normal population in Hawaii appears not to be at risk; and 4) one historical mercury source variable, reported fish intake when young, related to six functioning variables - the psychopathology measures of Somatization, Obsessive-Compulsive and Anxiety as well as the Sensory, Affect and Mental symptoms - with Beta weights in the .15 to .20 range. The implications of the findings were discussed and suggestions offered for future research especially with respect to specific high risk subgroups.

  16. Sydnone SYD-1 affects the metabolic functions of isolated rat hepatocytes.

    Science.gov (United States)

    Brandt, Anna Paula; Pires, Amanda do Rocio Andrade; Rocha, Maria Eliane Merlin; Noleto, Guilhermina Rodrigues; Acco, Alexandra; de Souza, Carlos Eduardo Alves; Echevarria, Aurea; Canuto, André Vinícius dos Santos; Cadena, Sílvia Maria Suter Correia

    2014-07-25

    Previously, we demonstrated that sydnone SYD-1 (3-[4-chloro-3-nitrophenyl]-1,2,3-oxadiazolium-5-olate) impairs the mitochondrial functions linked to energy provision and suggested that this effect could be associated with its antitumor activity. Herein, we evaluated the effects of SYD-1 (25 and 50 μM) on rat hepatocytes to determine its cytotoxicity on non-tumor cells. SYD-1 (25 and 50 μM) did not affect the viability of hepatocytes in suspension after 1-40 min of incubation. However, the viability of the cultured hepatocytes was decreased by ∼66% as a consequence of treatment with SYD-1 (50 μM) for 18 h. Under the same conditions, SYD-1 promoted an increase in the release of LDH by ∼19%. The morphological changes in the cultured cells treated with SYD-1 (50 μM) were suggestive of cell distress, which was demonstrated by the presence of rounded hepatocytes, cell fragments and monolayer impairment. Furthermore, fluorescence microscopy showed an increase in the annexin label after treatment with SYD-1 (50 μM), suggesting that apoptosis had been induced in these cells. SYD-1 did not affect the states of respiration in the suspended hepatocytes, but the pyruvate levels were decreased by ∼36%, whereas the lactate levels were increased by ∼22% (for the 50 μM treatment). The basal and uncoupled states of respiration of the cultured hepatocytes were inhibited by ∼79% and ∼51%, respectively, by SYD-1 (50 μM). In these cells, SYD-1 (50 μM) increased the pyruvate and lactate levels by ∼84% and ∼16%, respectively. These results show that SYD-1 affects important metabolic functions related to energy provision in hepatocytes and that this effect was more pronounced on cells in culture than those in suspension.

  17. Breakfast staple types affect brain gray matter volume and cognitive function in healthy children.

    Science.gov (United States)

    Taki, Yasuyuki; Hashizume, Hiroshi; Sassa, Yuko; Takeuchi, Hikaru; Asano, Michiko; Asano, Kohei; Kawashima, Ryuta

    2010-12-08

    Childhood diet is important for brain development. Furthermore, the quality of breakfast is thought to affect the cognitive functioning of well-nourished children. To analyze the relationship among breakfast staple type, gray matter volume, and intelligence quotient (IQ) in 290 healthy children, we used magnetic resonance images and applied voxel-based morphometry. We divided subjects into rice, bread, and both groups according to their breakfast staple. We showed that the rice group had a significantly larger gray matter ratio (gray matter volume percentage divided by intracranial volume) and significantly larger regional gray matter volumes of several regions, including the left superior temporal gyrus. The bread group had significantly larger regional gray and white matter volumes of several regions, including the right frontoparietal region. The perceptual organization index (POI; IQ subcomponent) of the rice group was significantly higher than that of the bread group. All analyses were adjusted for age, gender, intracranial volume, socioeconomic status, average weekly frequency of having breakfast, and number of side dishes eaten for breakfast. Although several factors may have affected the results, one possible mechanism underlying the difference between the bread and the rice groups may be the difference in the glycemic index (GI) of these two substances; foods with a low GI are associated with less blood-glucose fluctuation than are those with a high GI. Our study suggests that breakfast staple type affects brain gray and white matter volumes and cognitive function in healthy children; therefore, a diet of optimal nutrition is important for brain maturation during childhood and adolescence.

  18. Breakfast staple types affect brain gray matter volume and cognitive function in healthy children.

    Directory of Open Access Journals (Sweden)

    Yasuyuki Taki

    Full Text Available Childhood diet is important for brain development. Furthermore, the quality of breakfast is thought to affect the cognitive functioning of well-nourished children. To analyze the relationship among breakfast staple type, gray matter volume, and intelligence quotient (IQ in 290 healthy children, we used magnetic resonance images and applied voxel-based morphometry. We divided subjects into rice, bread, and both groups according to their breakfast staple. We showed that the rice group had a significantly larger gray matter ratio (gray matter volume percentage divided by intracranial volume and significantly larger regional gray matter volumes of several regions, including the left superior temporal gyrus. The bread group had significantly larger regional gray and white matter volumes of several regions, including the right frontoparietal region. The perceptual organization index (POI; IQ subcomponent of the rice group was significantly higher than that of the bread group. All analyses were adjusted for age, gender, intracranial volume, socioeconomic status, average weekly frequency of having breakfast, and number of side dishes eaten for breakfast. Although several factors may have affected the results, one possible mechanism underlying the difference between the bread and the rice groups may be the difference in the glycemic index (GI of these two substances; foods with a low GI are associated with less blood-glucose fluctuation than are those with a high GI. Our study suggests that breakfast staple type affects brain gray and white matter volumes and cognitive function in healthy children; therefore, a diet of optimal nutrition is important for brain maturation during childhood and adolescence.

  19. Realistic changes in seaweed biodiversity affect multiple ecosystem functions on a rocky shore.

    Science.gov (United States)

    Bracken, Matthew E S; Williams, Susan L

    2013-09-01

    Given current threats to biodiversity, understanding the effects of diversity changes on the functions and services associated with intact ecosystems is of paramount importance. However, limited realism in most biodiversity studies makes it difficult to link the large and growing body of evidence for important functional consequences of biodiversity change to real-world losses of biodiversity. Here, we explored two methods of incorporating realism into biodiversity research: (1) the use of two-, five-, and eight-species assemblages that mimicked those that we observed in surveys of seaweed biodiversity patterns on a northern California (USA) rocky shore and the explicit comparison of those assemblages to random assemblages compiled from the same local species pool; and (2) the measurement of two fundamental ecosystem functions, nitrate uptake and photosynthesis, both of which contribute to growth of primary producers. Specifically, we measured nitrate uptake rates of seaweed assemblages as a function of initial nitrate concentrations and photosynthetic rates as a function of irradiance levels for both realistic and random assemblages of seaweeds. We only observed changes in ecosystem functioning along a richness gradient for realistic assemblages, and both maximum nitrate uptake rates (V(max)) and photosynthetic light use efficiency values (alpha(p) = P(max)/I(K)) were higher in realistic assemblages than in random assemblages. Furthermore, the parameter affected by changes in richness depended on the function being measured. Both V(max) and alpha(p) declined with increasing richness in nonrandom assemblages due to a combination of species identity effects (for V(max) and overyielding effects (for both V(max) and alpha(p)). In contrast, neither nitrate uptake efficiency values (alpha(N) = V(max)/K(s)), nor maximum photosynthetic rates (Pmax) changed along the gradient in seaweed species richness. Furthermore, overyielding was only evident in realistic assemblages

  20. Earthworm-Mycorrhiza Interactions Can Affect the Diversity, Structure and Functioning of Establishing Model Grassland Communities

    Science.gov (United States)

    Zaller, Johann G.; Heigl, Florian; Grabmaier, Andrea; Lichtenegger, Claudia; Piller, Katja; Allabashi, Roza; Frank, Thomas; Drapela, Thomas

    2011-01-01

    Both earthworms and arbuscular mycorrhizal fungi (AMF) are important ecosystem engineers co-occurring in temperate grasslands. However, their combined impacts during grassland establishment are poorly understood and have never been studied. We used large mesocosms to study the effects of different functional groups of earthworms (i.e., vertically burrowing anecics vs. horizontally burrowing endogeics) and a mix of four AMF taxa on the establishment, diversity and productivity of plant communities after a simulated seed rain of 18 grassland species comprising grasses, non-leguminous forbs and legumes. Moreover, effects of earthworms and/or AMF on water infiltration and leaching of ammonium, nitrate and phosphate were determined after a simulated extreme rainfall event (40 l m−2). AMF colonisation of all three plant functional groups was altered by earthworms. Seedling emergence and diversity was reduced by anecic earthworms, however only when AMF were present. Plant density was decreased in AMF-free mesocosms when both anecic and endogeic earthworms were active; with AMF also anecics reduced plant density. Plant shoot and root biomass was only affected by earthworms in AMF-free mesocosms: shoot biomass increased due to the activity of either anecics or endogeics; root biomass increased only when anecics were active. Water infiltration increased when earthworms were present in the mesocosms but remained unaffected by AMF. Ammonium leaching was increased only when anecics or a mixed earthworm community was active but was unaffected by AMF; nitrate and phosphate leaching was neither affected by earthworms nor AMF. Ammonium leaching decreased with increasing plant density, nitrate leaching decreased with increasing plant diversity and density. In order to understand the underlying processes of these interactions further investigations possibly under field conditions using more diverse belowground communities are required. Nevertheless, this study demonstrates that

  1. Earthworm-mycorrhiza interactions can affect the diversity, structure and functioning of establishing model grassland communities.

    Directory of Open Access Journals (Sweden)

    Johann G Zaller

    Full Text Available Both earthworms and arbuscular mycorrhizal fungi (AMF are important ecosystem engineers co-occurring in temperate grasslands. However, their combined impacts during grassland establishment are poorly understood and have never been studied. We used large mesocosms to study the effects of different functional groups of earthworms (i.e., vertically burrowing anecics vs. horizontally burrowing endogeics and a mix of four AMF taxa on the establishment, diversity and productivity of plant communities after a simulated seed rain of 18 grassland species comprising grasses, non-leguminous forbs and legumes. Moreover, effects of earthworms and/or AMF on water infiltration and leaching of ammonium, nitrate and phosphate were determined after a simulated extreme rainfall event (40 l m(-2. AMF colonisation of all three plant functional groups was altered by earthworms. Seedling emergence and diversity was reduced by anecic earthworms, however only when AMF were present. Plant density was decreased in AMF-free mesocosms when both anecic and endogeic earthworms were active; with AMF also anecics reduced plant density. Plant shoot and root biomass was only affected by earthworms in AMF-free mesocosms: shoot biomass increased due to the activity of either anecics or endogeics; root biomass increased only when anecics were active. Water infiltration increased when earthworms were present in the mesocosms but remained unaffected by AMF. Ammonium leaching was increased only when anecics or a mixed earthworm community was active but was unaffected by AMF; nitrate and phosphate leaching was neither affected by earthworms nor AMF. Ammonium leaching decreased with increasing plant density, nitrate leaching decreased with increasing plant diversity and density. In order to understand the underlying processes of these interactions further investigations possibly under field conditions using more diverse belowground communities are required. Nevertheless, this study

  2. Analysis of common and specific mechanisms of liver function affected by nitrotoluene compounds.

    Directory of Open Access Journals (Sweden)

    Youping Deng

    Full Text Available BACKGROUND: Nitrotoluenes are widely used chemical manufacturing and munitions applications. This group of chemicals has been shown to cause a range of effects from anemia and hypercholesterolemia to testicular atrophy. We have examined the molecular and functional effects of five different, but structurally related, nitrotoluenes on using an integrative systems biology approach to gain insight into common and disparate mechanisms underlying effects caused by these chemicals. METHODOLOGY/PRINCIPAL FINDINGS: Sprague-Dawley female rats were exposed via gavage to one of five concentrations of one of five nitrotoluenes [2,4,6-trinitrotoluene (TNT, 2-amino-4,6-dinitrotoluene (2ADNT 4-amino-2,6-dinitrotoulene (4ADNT, 2,4-dinitrotoluene (2,4DNT and 2,6-dinitrotoluene (2,6DNT] with necropsy and tissue collection at 24 or 48 h. Gene expression profile results correlated well with clinical data and liver histopathology that lead to the concept that hematotoxicity was followed by hepatotoxicity. Overall, 2,4DNT, 2,6DNT and TNT had stronger effects than 2ADNT and 4ADNT. Common functional terms, gene expression patterns, pathways and networks were regulated across all nitrotoluenes. These pathways included NRF2-mediated oxidative stress response, aryl hydrocarbon receptor signaling, LPS/IL-1 mediated inhibition of RXR function, xenobiotic metabolism signaling and metabolism of xenobiotics by cytochrome P450. One biological process common to all compounds, lipid metabolism, was found to be impacted both at the transcriptional and lipid production level. CONCLUSIONS/SIGNIFICANCE: A systems biology strategy was used to identify biochemical pathways affected by five nitroaromatic compounds and to integrate data that tie biochemical alterations to pathological changes. An integrative graphical network model was constructed by combining genomic, gene pathway, lipidomic, and physiological endpoint results to better understand mechanisms of liver toxicity and

  3. Plant species richness and functional traits affect community stability after a flood event.

    Science.gov (United States)

    Fischer, Felícia M; Wright, Alexandra J; Eisenhauer, Nico; Ebeling, Anne; Roscher, Christiane; Wagg, Cameron; Weigelt, Alexandra; Weisser, Wolfgang W; Pillar, Valério D

    2016-05-19

    Climate change is expected to increase the frequency and magnitude of extreme weather events. It is therefore of major importance to identify the community attributes that confer stability in ecological communities during such events. In June 2013, a flood event affected a plant diversity experiment in Central Europe (Jena, Germany). We assessed the effects of plant species richness, functional diversity, flooding intensity and community means of functional traits on different measures of stability (resistance, resilience and raw biomass changes from pre-flood conditions). Surprisingly, plant species richness reduced community resistance in response to the flood. This was mostly because more diverse communities grew more immediately following the flood. Raw biomass increased over the previous year; this resulted in decreased absolute value measures of resistance. There was no clear response pattern for resilience. We found that functional traits drove these changes in raw biomass: communities with a high proportion of late-season, short-statured plants with dense, shallow roots and small leaves grew more following the flood. Late-growing species probably avoided the flood, whereas greater root length density might have allowed species to better access soil resources brought from the flood, thus growing more in the aftermath. We conclude that resource inputs following mild floods may favour the importance of traits related to resource acquisition and be less associated with flooding tolerance.

  4. Aesthetic and Functional Rehabilitation of the Primary Dentition Affected by Amelogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Maria Carolina Salomé Marquezin

    2015-01-01

    Full Text Available The objective of this case report was to describe the oral rehabilitation of a five-year-old boy patient diagnosed with amelogenesis imperfecta (AI in the primary dentition. AI is a group of hereditary disorders that affects the enamel structure. The patient was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of AI. The treatment was oral rehabilitation of the primary molars with stainless steel crowns and resin-filled celluloid forms. The main objectives of the selected treatment were to enhance the esthetics, restore masticatory function, and eliminate the teeth sensitivity. The child was monitored in the pediatric dentistry clinic at four-month intervals until the mixed dentition stage. Treatment not only restored function and esthetic, but also showed a positive psychological impact and thereby improved perceived quality of life. The preventive, psychological, and curative measures of a young child with AI were successful. This result can encourage the clinicians to seek a cost-effective technique such as stainless steel crowns, and resin-filled celluloid forms to reestablish the oral functions and improve the child’s psychosocial development.

  5. Cognitive and cognitive-motor interventions affecting physical functioning: A systematic review

    Directory of Open Access Journals (Sweden)

    Murer Kurt

    2011-06-01

    Full Text Available Abstract Background Several types of cognitive or combined cognitive-motor intervention types that might influence physical functions have been proposed in the past: training of dual-tasking abilities, and improving cognitive function through behavioral interventions or the use of computer games. The objective of this systematic review was to examine the literature regarding the use of cognitive and cognitive-motor interventions to improve physical functioning in older adults or people with neurological impairments that are similar to cognitive impairments seen in aging. The aim was to identify potentially promising methods that might be used in future intervention type studies for older adults. Methods A systematic search was conducted for the Medline/Premedline, PsycINFO, CINAHL and EMBASE databases. The search was focused on older adults over the age of 65. To increase the number of articles for review, we also included those discussing adult patients with neurological impairments due to trauma, as these cognitive impairments are similar to those seen in the aging population. The search was restricted to English, German and French language literature without any limitation of publication date or restriction by study design. Cognitive or cognitive-motor interventions were defined as dual-tasking, virtual reality exercise, cognitive exercise, or a combination of these. Results 28 articles met our inclusion criteria. Three articles used an isolated cognitive rehabilitation intervention, seven articles used a dual-task intervention and 19 applied a computerized intervention. There is evidence to suggest that cognitive or motor-cognitive methods positively affects physical functioning, such as postural control, walking abilities and general functions of the upper and lower extremities, respectively. The majority of the included studies resulted in improvements of the assessed functional outcome measures. Conclusions The current evidence on the

  6. Metacognitive Awareness of Facial Affect in Higher-Functioning Children and Adolescents with Autism Spectrum Disorder.

    Science.gov (United States)

    McMahon, Camilla M; Henderson, Heather A; Newell, Lisa; Jaime, Mark; Mundy, Peter

    2016-03-01

    Higher-functioning participants with and without autism spectrum disorder (ASD) viewed a series of face stimuli, made decisions regarding the affect of each face, and indicated their confidence in each decision. Confidence significantly predicted accuracy across all participants, but this relation was stronger for participants with typical development than participants with ASD. In the hierarchical linear modeling analysis, there were no differences in face processing accuracy between participants with and without ASD, but participants with ASD were more confident in their decisions. These results suggest that individuals with ASD have metacognitive impairments and are overconfident in face processing. Additionally, greater metacognitive awareness was predictive of better face processing accuracy, suggesting that metacognition may be a pivotal skill to teach in interventions.

  7. Hypoxia transiently affects skeletal muscle hypertrophy in a functional overload model.

    Science.gov (United States)

    Chaillou, Thomas; Koulmann, Nathalie; Simler, Nadine; Meunier, Adélie; Serrurier, Bernard; Chapot, Rachel; Peinnequin, Andre; Beaudry, Michèle; Bigard, Xavier

    2012-03-01

    Hypoxia induces a loss of skeletal muscle mass, but the signaling pathways and molecular mechanisms involved remain poorly understood. We hypothesized that hypoxia could impair skeletal muscle hypertrophy induced by functional overload (Ov). To test this hypothesis, plantaris muscles were overloaded during 5, 12, and 56 days in female rats exposed to hypobaric hypoxia (5,500 m), and then, we examined the responses of specific signaling pathways involved in protein synthesis (Akt/mTOR) and breakdown (atrogenes). Hypoxia minimized the Ov-induced hypertrophy at days 5 and 12 but did not affect the hypertrophic response measured at day 56. Hypoxia early reduced the phosphorylation levels of mTOR and its downstream targets P70(S6K) and rpS6, but it did not affect the phosphorylation levels of Akt and 4E-BP1, in Ov muscles. The role played by specific inhibitors of mTOR, such as AMPK and hypoxia-induced factors (i.e., REDD1 and BNIP-3) was studied. REDD1 protein levels were reduced by overload and were not affected by hypoxia in Ov muscles, whereas AMPK was not activated by hypoxia. Although hypoxia significantly increased BNIP-3 mRNA levels at day 5, protein levels remained unaffected. The mRNA levels of the two atrogenes MURF1 and MAFbx were early increased by hypoxia in Ov muscles. In conclusion, hypoxia induced a transient alteration of muscle growth in this hypertrophic model, at least partly due to a specific impairment of the mTOR/P70(S6K) pathway, independently of Akt, by an undefined mechanism, and increased transcript levels for MURF1 and MAFbx that could contribute to stimulate the proteasomal proteolysis.

  8. Identification and Functional Characterization of GAA Mutations in Colombian Patients Affected by Pompe Disease.

    Science.gov (United States)

    Niño, Mónica Yasmín; Mateus, Heidi Eliana; Fonseca, Dora Janeth; Kroos, Marian A; Ospina, Sandra Yaneth; Mejía, Juan Fernando; Uribe, Jesús Alfredo; Reuser, Arnold J J; Laissue, Paul

    2013-01-01

    Pompe disease (PD) is a recessive metabolic disorder characterized by acid α-glucosidase (GAA) deficiency, which results in lysosomal accumulation of glycogen in all tissues, especially in skeletal muscles. PD clinical course is mainly determined by the nature of the GAA mutations. Although ~400 distinct GAA sequence variations have been described, the genotype-phenotype correlation is not always evident.In this study, we describe the first clinical and genetic analysis of Colombian PD patients performed in 11 affected individuals. GAA open reading frame sequencing revealed eight distinct mutations related to PD etiology including two novel missense mutations, c.1106 T > C (p.Leu369Pro) and c.2236 T > C (p.Trp746Arg). In vitro functional studies showed that the structural changes conferred by both mutations did not inhibit the synthesis of the 110 kD GAA precursor form but affected the processing and intracellular transport of GAA. In addition, analysis of previously described variants located at this position (p.Trp746Gly, p.Trp746Cys, p.Trp746Ser, p.Trp746X) revealed new insights in the molecular basis of PD. Notably, we found that p.Trp746Cys mutation, which was previously described as a polymorphism as well as a causal mutation, displayed a mild deleterious effect. Interestingly and by chance, our study argues in favor of a remarkable Afro-American and European ancestry of the Colombian population. Taken together, our report provides valuable information on the PD genotype-phenotype correlation, which is expected to facilitate and improve genetic counseling of affected individuals and their families.

  9. How measurement artifacts affect cerebral autoregulation outcomes: A technical note on transfer function analysis.

    Science.gov (United States)

    Meel-van den Abeelen, Aisha S S; de Jong, Daan L K; Lagro, Joep; Panerai, Ronney B; Claassen, Jurgen A H R

    2016-05-01

    Cerebral autoregulation (CA) is the mechanism that aims to maintain adequate cerebral perfusion during changes in blood pressure (BP). Transfer function analysis (TFA), the most reported method in literature to quantify CA, shows large between-study variability in outcomes. The aim of this study is to investigate the role of measurement artifacts in this variation. Specifically, the role of distortion in the BP and/or CBFV measurementon TFA outcomes was investigated. The influence of three types of artifacts on TFA outcomes was studied: loss of signal, motion artifacts, and baseline drifts. TFA metrics of signals without the simulated artifacts were compared with those of signals with artifacts. TFA outcomes scattered highly when more than 10% of BP signal or over 8% of the CBFV signal was lost, or when measurements contained one or more artifacts resulting from head movement. Furthermore, baseline drift affected interpretation of TFA outcomes when the power in the BP signal was 5 times the power in the LF band. In conclusion, loss of signal in BP and loss in CBFV, affects interpretation of TFA outcomes. Therefore, it is vital to validate signal quality to the defined standards before interpreting TFA outcomes.

  10. Macrofauna assemblage composition and soil moisture interact to affect soil ecosystem functions

    Science.gov (United States)

    Collison, E. J.; Riutta, T.; Slade, E. M.

    2013-02-01

    Changing climatic conditions and habitat fragmentation are predicted to alter the soil moisture conditions of temperate forests. It is not well understood how the soil macrofauna community will respond to changes in soil moisture, and how changes to species diversity and community composition may affect ecosystem functions, such as litter decomposition and soil fluxes. Moreover, few studies have considered the interactions between the abiotic and biotic factors that regulate soil processes. Here we attempt to disentangle the interactive effects of two of the main factors that regulate soil processes at small scales - moisture and macrofauna assemblage composition. The response of assemblages of three common temperate soil invertebrates (Glomeris marginata Villers, Porcellio scaber Latreille and Philoscia muscorum Scopoli) to two contrasting soil moisture levels was examined in a series of laboratory mesocosm experiments. The contribution of the invertebrates to the leaf litter mass loss of two common temperate tree species of contrasting litter quality (easily decomposing Fraxinus excelsior L. and recalcitrant Quercus robur L.) and to soil CO2 fluxes were measured. Both moisture conditions and litter type influenced the functioning of the invertebrate assemblages, which was greater in high moisture conditions compared with low moisture conditions and on good quality vs. recalcitrant litter. In high moisture conditions, all macrofauna assemblages functioned at equal rates, whereas in low moisture conditions there were pronounced differences in litter mass loss among the assemblages. This indicates that species identity and assemblage composition are more important when moisture is limited. We suggest that complementarity between macrofauna species may mitigate the reduced functioning of some species, highlighting the importance of maintaining macrofauna species richness.

  11. Attachment Style Predicts Affect, Cognitive Appraisals, and Social Functioning in Daily Life

    Directory of Open Access Journals (Sweden)

    Tamara eSheinbaum

    2015-03-01

    Full Text Available The way in which attachment styles are expressed in the moment as individuals navigate their real-life settings has remained an area largely untapped by attachment research. The present study examined how adult attachment styles are expressed in daily life using Experience Sampling Methodology (ESM in a sample of 206 Spanish young adults. Participants were administered the Attachment Style Interview and received personal digital assistants that signaled them randomly eight times per day for one week to complete questionnaires about their current experiences and social context. As hypothesized, participants’ momentary affective states, cognitive appraisals, and social functioning varied in meaningful ways as a function of their attachment style. Individuals with an anxious attachment, as compared with securely attached individuals, endorsed experiences that were congruent with hyperactivating tendencies, such as higher negative affect, stress, and perceived social rejection. By contrast, individuals with an avoidant attachment, relative to individuals with a secure attachment, endorsed experiences that were consistent with deactivating tendencies, such as decreased positive states and a decreased desire to be with others when alone. Furthermore, the expression of attachment styles in social contexts was shown to be dependent upon the subjective appraisal of the closeness of social contacts, and not merely upon the presence of social interactions. The findings support the ecological validity of the Attachment Style Interview and the person-by-situation character of attachment theory. Moreover, they highlight the utility of ESM for investigating how the predictions derived from attachment theory play out in the natural flow of real life.

  12. Behavioral Functions of the Mesolimbic Dopaminergic System: an Affective Neuroethological Perspective

    Science.gov (United States)

    Alcaro, Antonio; Huber, Robert; Panksepp, Jaak

    2008-01-01

    The mesolimbic dopaminergic (ML-DA) system has been recognized for its central role in motivated behaviors, various types of reward, and, more recently, in cognitive processes. Functional theories have emphasized DA's involvement in the orchestration of goal-directed behaviors, and in the promotion and reinforcement of learning. The affective neuroethological perspective presented here, views the ML-DA system in terms of its ability to activate an instinctual emotional appetitive state (SEEKING) evolved to induce organisms to search for all varieties of life-supporting stimuli and to avoid harms. A description of the anatomical framework in which the ML system is embedded is followed by the argument that the SEEKING disposition emerges through functional integration of ventral basal ganglia (BG) into thalamocortical activities. Filtering cortical and limbic input that spread into BG, DA transmission promotes the “release” of neural activity patterns that induce active SEEKING behaviors when expressed at the motor level. Reverberation of these patterns constitutes a neurodynamic process for the inclusion of cognitive and perceptual representations within the extended networks of the SEEKING urge. In this way, the SEEKING disposition influences attention, incentive salience, associative learning, and anticipatory predictions. In our view, the rewarding properties of drugs of abuse are, in part, caused by the activation of the SEEKING disposition, ranging from appetitive drive to persistent craving depending on the intensity of the affect. The implications of such a view for understanding addiction are considered, with particular emphasis on factors predisposing individuals to develop compulsive drug seeking behaviors. PMID:17905440

  13. LYMPHOCYTE APOPTOSIS IN PSORIASIS

    Directory of Open Access Journals (Sweden)

    О. M. Kapuler

    2006-01-01

    Full Text Available Abstract. Forty-two patients with progressive vulgar psoriasis (PASI = 19.7 ± 1.5 and 40 healthy volunteers were under investigation. Psoriatic patients were characterized by increased number of CD4+ CD95+ peripheral blood T lymphocytes, which correlates with clinical psoriatic score, and by increased levels of soluble Fas (sFas in serum, as compared to controls (resp., 1868.1 ± 186.8 pg/ml vs. 1281.4 ± 142.5 pg/ml, PLSD = 0.019. The levels of spontaneous lymphocyte apoptosis and anti-Fas (Mab-induced apoptosis in psoriatic patients did not differ from the controls. However, apoptosis induced by “oxidative stress” (50 M Н202, 4 hrs was depressed in the patients. Moreover, a simultaneous assessment of cell cycle structure (metachromatic staining with Acridine Orange, apoptosis and Fas receptor expression (AnnV-FITC/antiFas mAbs-PE staining following a short-term mitogenic stimulation (PHA-P, 5 µg/ml, 24 hrs were performed. We found no marked differences in mitogenic reactivity, activation-induced apoptosis, and activation-induced Fas receptor expression when studying lymphocytes from healthy donors and psoriatic patients. However, PHA-activated lymphocytes from psoriatic patients displayed a significantly decreased ratio of AnnV+CD95+ to the total AnnV+ subpopulation, thus suggesting a decreased role of Fas-dependent mechanisms of apoptosis during the cell activation. The data obtained confirm a view, that an abnormal lymphocyte “apoptotic reactivity”, which plays a crucial role in the mechanisms of autoimmunity, may also of importance in the pathogenesis of psoriasis.

  14. Standardisation and quality assurance of lymphocyte proliferation assays for use in the assessment of immune function. European Concerted Action on Immunological and Virological Markers of HIV Disease Progression.

    Science.gov (United States)

    Froebel, K S; Pakker, N G; Aiuti, F; Bofill, M; Choremi-Papadopoulou, H; Economidou, J; Rabian, C; Roos, M T; Ryder, L P; Miedema, F; Raab, G M

    1999-07-30

    Lymphocyte proliferation is a widely used technique to assess immune competence. However, the technique is subject to a large degree of variation, some biological and some technical. In this study, the components of variation in whole blood proliferation assays were analysed over time, using both antibody and mitogenic stimulants. The levels of variation within individual samples, between individuals and between groups of individuals over time were examined. A method of transforming the data is proposed which reduces the coefficients of variation to an acceptable level, and which expresses individual results as a standardised count. This method overcomes the problem of different levels of absolute counts, it corrects for time sensitive errors and allows data from multiple laboratories to be pooled.

  15. 5'-Ectonucleotidase/CD73 expression on lymph-circulating lymphocytes and lymphatic endothelial cells offers new paths to explore barrier function.

    Science.gov (United States)

    Sidibé, Adama; Imhof, Beat A

    2015-02-01

    5'-Nucleotidase/CD73 is a key enzyme in the regulation of purinergic signaling, hydrolyzing extracellular AMP to produce adenosine, which is critical in the blood vascular system and in immunosuppression. CD73 is expressed by both blood endothelial cells and lymphatic endothelial cells. Although the role of CD73 on blood endothelial cells in controlling vascular permeability and leukocyte trafficking has been studied, the role of lymphatic CD73 has thus far remained unknown. In this issue of European Journal of Immunology, Yegutkin et al. [Eur. J. Immunol. 2015. 45: 562-573] compare CD73 activity in the endothelia of lymphatics and blood vessels and investigate the CD73(+) lymphocyte subpopulations possibly involved in immunoregulation. This Commentary will discuss how the authors' work sheds light on the differential use of CD73 by these two cell populations to control endothelial permeability and sprouting.

  16. Sensory integration dysfunction affects efficacy of speech therapy on children with functional articulation disorders

    Directory of Open Access Journals (Sweden)

    Tung LC

    2013-01-01

    = 70.393; P > 0.001 and interaction between the pre/post speech therapy treatment and groups (F = 11.119; P = 0.002.Conclusions: Speech therapy can improve the articulation performance of children who have functional articulation disorders whether or not they have SID, but it results in significantly greater improvement in children without SID. SID may affect the treatment efficiency of speech therapy in young children with articulation disorders.Keywords: children, functional articulation disorders, sensory integration dysfunction, speech therapy, efficacy

  17. Mitochondrial apoptosis of lymphocyte is induced in type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    Xu Hui; Chen Yanbo; Li Yanxiang; Xia Fangzhen; Han Bing; Zhang Huixin; Zhai Hualing

    2014-01-01

    Background Lymphocyte function and homeostasis is associated with immune defence to infection.Apoptosis of lymphocytes might be a considerably important component which has an impact on immunity to infections in people with hyperglycemia.The aim of this study was to explore the mitochondrial apoptosis pathway of lymphocyte in diabetic patients.Methods Sixty patients with type 2 diabetes mellitus and fifty healthy volunteers were included in this study.Annexin V and propidiumiodide (Pl) were joined in the isolated lymphocytes and the rate of lymphocyte apoptosis was calculated with flow cytometry.Observation of the lymphocytes was done using transmission electron microscopy; mitochondria had been extracted and then mitochondrial membrane potential (MMP) was detected to assess mitochondrial function; the mRNA level of Bcl-2,cytochrome c (Cyt-C),caspase-9 and caspase-3 were analyzed by real-time reverse transcriptionpolymerase chain reaction (RT-PCR).Results Apoptosis rate of lymphocyte was significantly higher in diabetic group than that in normal control group (P <0.05).Transmission electron microscopy showed lymphocyte shrinkage and breakage,chromatin condensation and less mitochondria; a fall in MMP levels was also evident; Bcl-2 concentration was reduced and the expressions of caspase-9,caspase-3 and Cyt-C were elevated (P <0.05) in diabetic patients.Conclusions The rate of lymphocyte apoptosis was significantly higher in type 2 diabetic patients than that in normal population.Mitochondrial apoptosis pathway may play a very important role in decreasing function of lymphocyte in diabetes.

  18. B lymphocytes not required for progression from insulitis to diabetes in non-obese diabetic mice.

    Science.gov (United States)

    Charlton, B; Zhang, M D; Slattery, R M

    2001-12-01

    Previous studies have implicated B lymphocytes in the pathogenesis of diabetes in the non-obese diabetic (NOD) mouse. While it is clear that B lymphocytes are necessary, it has not been clear at which stage of disease they play a role; early, late or both. To clarify when B lymphocytes are needed, T lymphocytes were transferred from 5-week-old NOD female mice to age-matched NOD/severe combined immunodeficiency (SCID) recipient mice. NOD/SCID mice, which lack functionally mature T and B lymphocytes, do not normally develop insulitis or insulin-dependent diabetes melitus (IDDM). The NOD/SCID mice that received purified T lymphocytes from 5-week-old NOD mice subsequently developed insulitis and diabetes even though they did not have detectable B lymphocytes. This suggests that while B lymphocytes may be essential for an initial priming event they are not requisite for disease progression in the NOD mouse.

  19. Functional assessment of human coding mutations affecting skin pigmentation using zebrafish.

    Directory of Open Access Journals (Sweden)

    Zurab R Tsetskhladze

    Full Text Available A major challenge in personalized medicine is the lack of a standard way to define the functional significance of the numerous nonsynonymous, single nucleotide coding variants that are present in each human individual. To begin to address this problem, we have used pigmentation as a model polygenic trait, three common human polymorphisms thought to influence pigmentation, and the zebrafish as a model system. The approach is based on the rescue of embryonic zebrafish mutant phenotypes by "humanized" zebrafish orthologous mRNA. Two hypomorphic polymorphisms, L374F in SLC45A2, and A111T in SLC24A5, have been linked to lighter skin color in Europeans. The phenotypic effect of a second coding polymorphism in SLC45A2, E272K, is unclear. None of these polymorphisms had been tested in the context of a model organism. We have confirmed that zebrafish albino fish are mutant in slc45a2; wild-type slc45a2 mRNA rescued the albino mutant phenotype. Introduction of the L374F polymorphism into albino or the A111T polymorphism into slc24a5 (golden abolished mRNA rescue of the respective mutant phenotypes, consistent with their known contributions to European skin color. In contrast, the E272K polymorphism had no effect on phenotypic rescue. The experimental conclusion that E272K is unlikely to affect pigmentation is consistent with a lack of correlation between this polymorphism and quantitatively measured skin color in 59 East Asian humans. A survey of mutations causing human oculocutaneous albinism yielded 257 missense mutations, 82% of which are theoretically testable in zebrafish. The developed approach may be extended to other model systems and may potentially contribute to our understanding the functional relationships between DNA sequence variation, human biology, and disease.

  20. Role of Affective Self-Regulatory Efficacy in Diverse Spheres of Psychosocial Functioning.

    Science.gov (United States)

    Bandura, Albert; Caprara, Gian Vittorio; Barbaranelli, Claudio; Gerbino, Maria; Pastorelli, Concetta

    2003-01-01

    Examined influence of perceived self-efficacy for affect regulation with older adolescents. Found that self-efficacy to regulate affect related to high efficacy to manage academic development, resist social pressures for antisocial activities, and engage with empathy in others' emotional experiences. Perceived self-efficacy for affect regulation…

  1. Developing a function impairment measure for children affected by political violence: a mixed methods approach in Indonesia

    NARCIS (Netherlands)

    Tol, W.A.; Komproe, I.H.; Jordans, M.J.D.; Susanty, D.; de Jong, J.T.V.M.

    2011-01-01

    Objective: Practitioners in political violence-affected settings would benefit from rating scales that assess child function impairment in a reliable and valid manner when designing and evaluating interventions. We developed a procedure to construct child function impairment rating scales using reso

  2. Prospective associations between forms and functions of aggression and social and affective processes during early childhood.

    Science.gov (United States)

    Ostrov, Jamie M; Murray-Close, Dianna; Godleski, Stephanie A; Hart, Emily J

    2013-09-01

    The central goal of this study was to examine the prospective associations between forms (i.e., physical and relational) and functions (i.e., proactive and reactive) of aggressive behavior with social (i.e., peer rejection) and affective (i.e., anger, emotion regulation skills) processes during early childhood (N = 96, mean age = 42.80 months, SD = 7.57). A cross-lagged path analysis revealed that proactive relational aggression was uniquely associated with decreases in peer rejection, whereas reactive relational aggression was associated with increases in peer rejection over time. Proactive relational aggression predicted decreases in anger, whereas reactive relational aggression tended to be associated with increases in anger. Proactive relational aggression uniquely predicted increases in emotion regulation skills, whereas reactive relational aggression tended to be associated with decreases in emotion regulation skills over time. Finally, anger was significantly associated with increases in several subtypes of aggressive behavior. In sum, the findings provide further support for the distinction between subtypes of aggressive behavior in young children.

  3. Novel function of perforin in negatively regulating CD4+T cell activation by affecting calcium signaling

    Institute of Scientific and Technical Information of China (English)

    Enguang Bi; Kairui Mao; Jia Zou; Yuhan Zheng; Bing Sun; Chunjian Huang; Yu Hu; Xiaodong Wu; Weiwen Deng; Guomei Lin; Zhiduo Liu; Lin Tian; Shuhui Sun

    2009-01-01

    Perforin is a pore-forming protein engaged mainly in mediating target T cell death and is employed by cytotoxic Tlymphocytes (CTLs) and natural killer cells. However, whether it also plays a role in conventional CD4+ T cell func-tion remains unclear. Here we report that in perforin-deficient (PKO) mice, CD4+ T cells are hyperproliferative in response to T cell receptor (TCR) stimulation. This feature of hyperproliferation is accompanied by the enhancement both in cell division and in IL-2 secretion. It seems that the perforin deficiency does not influence T cell development in thymus spleen and lymph node. In vivo, perforin deficiency results in increased antigen-specific T cell prolifera-tion and antibody production. Furthermore, PKO mice are more susceptible to experimental autoimmune uveitis. To address the molecular mechanism, we found that after TCR stimulation, CD44 T cells from PKO mice display an increased intracellular calcium flux and subsequently enhance activation of transcription factor NFATI. Our results indicate that perforin plays a negative role in regulating CD4+ T cell activation and immune response by affecting TCR-dependent Ca2+ signaling.

  4. Identification of archaeal proteins that affect the exosome function in vitro

    Directory of Open Access Journals (Sweden)

    Palhano Fernando L

    2010-05-01

    Full Text Available Abstract Background The archaeal exosome is formed by a hexameric RNase PH ring and three RNA binding subunits and has been shown to bind and degrade RNA in vitro. Despite extensive studies on the eukaryotic exosome and on the proteins interacting with this complex, little information is yet available on the identification and function of archaeal exosome regulatory factors. Results Here, we show that the proteins PaSBDS and PaNip7, which bind preferentially to poly-A and AU-rich RNAs, respectively, affect the Pyrococcus abyssi exosome activity in vitro. PaSBDS inhibits slightly degradation of a poly-rA substrate, while PaNip7 strongly inhibits the degradation of poly-A and poly-AU by the exosome. The exosome inhibition by PaNip7 appears to depend at least partially on its interaction with RNA, since mutants of PaNip7 that no longer bind RNA, inhibit the exosome less strongly. We also show that FITC-labeled PaNip7 associates with the exosome in the absence of substrate RNA. Conclusions Given the high structural homology between the archaeal and eukaryotic proteins, the effect of archaeal Nip7 and SBDS on the exosome provides a model for an evolutionarily conserved exosome control mechanism.

  5. Personality, clinical features, and test instructions can affect executive functions in Eating Disorders.

    Science.gov (United States)

    Pignatti, Riccardo; Bernasconi, Valentina

    2013-04-01

    Cognitive deficits in Eating Disorders have been related to the executive function domain. Yet, to date, only few works investigated the relationship between neuropsychological and clinical issues, and these studies were separately conducted either on Anorexia Nervosa (AN) or Bulimia Nervosa (BN). In this study, three groups of AN, BN and matched controls were administered the Trail Making Test, the Wisconsin Card Sorting Test, and the Hayling Sentence Completion Test, in addition to personality and clinical assessments (Temperament and Character Inventory, SCL-90-R, EDI-2). Results from AN indicated a relationship between cognitive rigidity and fixed psychological traits. Conversely, BN showed broader correlations among slowness, inhibition, and psychopathology-state indexes, confirming the clear relation published in the literature. We also hypothesize that task peculiar characteristics can affect high-order attentional activities in Eating Disorders. In fact, these patients do not differ from controls when the examiner provides overt instruction and run-in examples, but they can find serious difficulties when the correct rule is to be derived and modified from feedbacks during the test, as in the Wisconsin Card Sorting Test. Perfectionist stable traits support this hypothesis, especially in AN, as excessive cognitive control can either improve or damage set-shifting and decision-making procedures.

  6. Naloxonazine, an Amastigote-Specific Compound, Affects Leishmania Parasites through Modulation of Host-Encoded Functions

    Science.gov (United States)

    Vanhollebeke, Benoit; Caljon, Guy; Wolfe, Alan R.; McKerrow, James; Dujardin, Jean-Claude

    2016-01-01

    Host-directed therapies (HDTs) constitute promising alternatives to traditional therapy that directly targets the pathogen but is often hampered by pathogen resistance. HDT could represent a new treatment strategy for leishmaniasis, a neglected tropical disease caused by the obligate intracellular parasite Leishmania. This protozoan develops exclusively within phagocytic cells, where infection relies on a complex molecular interplay potentially exploitable for drug targets. We previously identified naloxonazine, a compound specifically active against intracellular but not axenic Leishmania donovani. We evaluated here whether this compound could present a host cell-dependent mechanism of action. Microarray profiling of THP-1 macrophages treated with naloxonazine showed upregulation of vATPases, which was further linked to an increased volume of intracellular acidic vacuoles. Treatment of Leishmania-infected macrophages with the vATPase inhibitor concanamycin A abolished naloxonazine effects, functionally demonstrating that naloxonazine affects Leishmania amastigotes indirectly, through host cell vacuolar remodeling. These results validate amastigote-specific screening approaches as a powerful way to identify alternative host-encoded targets. Although the therapeutic value of naloxonazine itself is unproven, our results further demonstrate the importance of intracellular acidic compartments for host defense against Leishmania, highlighting the possibility of targeting this host cell compartment for anti-leishmanial therapy. PMID:28036391

  7. Demethylation of Cancer/Testis Antigens and CpG ODN Stimulation Enhance Dendritic Cell and Cytotoxic T Lymphocyte Function in a Mouse Mammary Model

    Directory of Open Access Journals (Sweden)

    Jun-Zhong Sun

    2013-01-01

    Full Text Available Background. Cancer/testis antigens (CTAs are ideal targets for cancer immunotherapy in virtue of their restricted expression profile in normal tissues. However, CTA-targeted immunotherapy has been rather disappointing clinical setting for CTAs are downregulated by cytosine-phosphate-guanosine (CpG methylation in their promoter regions, so that tumor cells have low immunogenicity. Methods. We reinduced mouse CTA P1A through demethylation process and generated P1A-specific cytotoxic lymphocytes (CTLs by immunizing BALB/c (H-2d mice with dendritic cells pulsed with a P1A-specific peptide and CpG oligodeoxynucleotide (ODN immune adjuvant. Results. We found that demethylation and CpG ODN immune adjuvant stimulation facilitated DC maturation and enhanced the allogenic capacity of P1A-specific CTLs against target cells both in vitro and in vivo. Conclusions. Our results suggested that CTA induction and immune adjuvant stimulation is a feasible strategy in cancer immunotherapy.

  8. Stereological quantification of lymphocytes in skin biopsies from atopic dermatitis patients

    DEFF Research Database (Denmark)

    Ellingsen, A R; Sørensen, F B; Larsen, Jytte Overgaard;

    2001-01-01

    with controls, the number of lymphocytes in biopsies increased by a factor of 6.8 in active eczema and a factor of 1.8 in clinically normal skin. If 20% of skin is affected by eczema the total number of lymphocytes located in the affected skin can be estimated to 1.27 x 10(10). A patient with clinically...

  9. Propionic acid secreted from propionibacteria induces NKG2D ligand expression on human-activated T lymphocytes and cancer cells

    DEFF Research Database (Denmark)

    Andresen, Lars; Hansen, Karen Aagaard; Jensen, Helle

    2009-01-01

    We found that propionic acid secreted from propionibacteria induces expression of the NKG2D ligands MICA/B on activated T lymphocytes and different cancer cells, without affecting MICA/B expression on resting peripheral blood cells. Growth supernatant from propionibacteria or propionate alone could...... that propionate, produced either by bacteria or during cellular metabolism, has significant immunoregulatory function and may be cancer prophylactic....

  10. A decorin-deficient matrix affects skin chondroitin/dermatan sulfate levels and keratinocyte function

    Science.gov (United States)

    Nikolovska, Katerina; Renke, Jana K.; Jungmann, Oliver; Grobe, Kay; Iozzo, Renato V.; Zamfir, Alina D.; Seidler, Daniela G.

    2016-01-01

    Decorin is a small leucine-rich proteoglycan harboring a single glycosaminoglycan chain, which, in skin, is mainly composed of dermatan sulfate (DS). Mutant mice with targeted disruption of the decorin gene (Dcn−/−) exhibit an abnormal collagen architecture in the dermis and reduced tensile strength, collectively leading to a skin fragility phenotype. Notably, Ehlers-Danlos patients with mutations in enzymes involved in the biosynthesis of DS display a similar phenotype, and recent studies indicate that DS is involved in growth factor binding and signaling. To determine the impact of the loss of DS-decorin in the dermis, we analyzed the glycosaminoglycan content of Dcn−/− and wild-type mouse skin. The total amount of chondroitin/dermatan sulfate (CS/DS) was increased in the Dcn−/− skin, but was overall less sulfated with a significant reduction in bisulfated ΔDiS2,X (X=4 or 6) disaccharide units, due to the reduced expression of uronyl 2-O sulfotransferase (Ust). With increasing age, sulfation declined; however, Dcn−/− CS/DS was constantly undersulfated vis-à-vis wild-type. Functionally, we found altered fibroblast growth factor (Fgf)-7 and -2 binding due to changes in the micro-heterogeneity of skin Dcn−/− CS/DS. To better delineate the role of decorin, we used a 3D Dcn−/− fibroblast cell culture model. We found that the CS/DS extracts of wild-type and Dcn−/− fibroblasts were similar to the skin sugars, and this correlated with the lack of uronyl 2-O sulfotransferase in the Dcn−/− fibroblasts. Moreover, Ffg7 binding to total CS/DS was attenuated in the Dcn−/− samples. Surprisingly, wild-type CS/DS significantly reduced the binding of Fgf7 to keratinocytes in concentration dependent manner unlike the Dcn−/− CS/DS that only affected the binding at higher concentrations. Although binding to cell-surfaces was quite similar at higher concentrations, keratinocyte proliferation was differentially affected. Higher concentration of

  11. Pons to Posterior Cingulate Functional Projections Predict Affective Processing Changes in the Elderly Following Eight Weeks of Meditation Training.

    Science.gov (United States)

    Shao, Robin; Keuper, Kati; Geng, Xiujuan; Lee, Tatia M C

    2016-08-01

    Evidence indicates meditation facilitates affective regulation and reduces negative affect. It also influences resting-state functional connectivity between affective networks and the posterior cingulate (PCC)/precuneus, regions critically implicated in self-referential processing. However, no longitudinal study employing active control group has examined the effect of meditation training on affective processing, PCC/precuneus connectivity, and their association. Here, we report that eight-week meditation, but not relaxation, training 'neutralized' affective processing of positive and negative stimuli in healthy elderly participants. Additionally, meditation versus relaxation training increased the positive connectivity between the PCC/precuneus and the pons, the direction of which was largely directed from the pons to the PCC/precuneus, as revealed by dynamic causal modeling. Further, changes in connectivity between the PCC/precuneus and pons predicted changes in affective processing after meditation training. These findings indicate meditation promotes self-referential affective regulation based on increased regulatory influence of the pons on PCC/precuneus, which new affective-processing strategy is employed across both resting state and when evaluating affective stimuli. Such insights have clinical implications on interventions on elderly individuals with affective disorders.

  12. Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2016-10-04

    Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia

  13. Functional dominance rather than taxonomic diversity and functional diversity mainly affects community aboveground biomass in the Inner Mongolia grassland.

    Science.gov (United States)

    Zhang, Qing; Buyantuev, Alexander; Li, Frank Yonghong; Jiang, Lin; Niu, Jianming; Ding, Yong; Kang, Sarula; Ma, Wenjing

    2017-03-01

    The relationship between biodiversity and productivity has been a hot topic in ecology. However, the relative importance of taxonomic diversity and functional characteristics (including functional dominance and functional diversity) in maintaining community productivity and the underlying mechanisms (including selection and complementarity effects) of the relationship between diversity and community productivity have been widely controversial. In this study, 194 sites were surveyed in five grassland types along a precipitation gradient in the Inner Mongolia grassland of China. The relationships between taxonomic diversity (species richness and the Shannon-Weaver index), functional dominance (the community-weighted mean of four plant traits), functional diversity (Rao's quadratic entropy), and community aboveground biomass were analyzed. The results showed that (1) taxonomic diversity, functional dominance, functional diversity, and community aboveground biomass all increased from low to high precipitation grassland types; (2) there were significant positive linear relationships between taxonomic diversity, functional dominance, functional diversity, and community aboveground biomass; (3) the effect of functional characteristics on community aboveground biomass is greater than that of taxonomic diversity; and (4) community aboveground biomass depends on the community-weighted mean plant height, which explained 57.1% of the variation in the community aboveground biomass. Our results suggested that functional dominance rather than taxonomic diversity and functional diversity mainly determines community productivity and that the selection effect plays a dominant role in maintaining the relationship between biodiversity and community productivity in the Inner Mongolia grassland.

  14. Land-use systems affect Archaeal community structure and functional diversity in western Amazon soils

    Directory of Open Access Journals (Sweden)

    Acácio Aparecido Navarrete

    2011-10-01

    Full Text Available The study of the ecology of soil microbial communities at relevant spatial scales is primordial in the wide Amazon region due to the current land use changes. In this study, the diversity of the Archaea domain (community structure and ammonia-oxidizing Archaea (richness and community composition were investigated using molecular biology-based techniques in different land-use systems in western Amazonia, Brazil. Soil samples were collected in two periods with high precipitation (March 2008 and January 2009 from Inceptisols under primary tropical rainforest, secondary forest (5-20 year old, agricultural systems of indigenous people and cattle pasture. Denaturing gradient gel electrophoresis of polymerase chain reaction-amplified DNA (PCR-DGGE using the 16S rRNA gene as a biomarker showed that archaeal community structures in crops and pasture soils are different from those in primary forest soil, which is more similar to the community structure in secondary forest soil. Sequence analysis of excised DGGE bands indicated the presence of crenarchaeal and euryarchaeal organisms. Based on clone library analysis of the gene coding the subunit of the enzyme ammonia monooxygenase (amoA of Archaea (306 sequences, the Shannon-Wiener function and Simpson's index showed a greater ammonia-oxidizing archaeal diversity in primary forest soils (H' = 2.1486; D = 0.1366, followed by a lower diversity in soils under pasture (H' = 1.9629; D = 0.1715, crops (H' = 1.4613; D = 0.3309 and secondary forest (H' = 0.8633; D = 0.5405. All cloned inserts were similar to the Crenarchaeota amoA gene clones (identity > 95 % previously found in soils and sediments and distributed primarily in three major phylogenetic clusters. The findings indicate that agricultural systems of indigenous people and cattle pasture affect the archaeal community structure and diversity of ammonia-oxidizing Archaea in western Amazon soils.

  15. Probability distribution functions of turbulence in seepage-affected alluvial channel

    Science.gov (United States)

    Sharma, Anurag; Kumar, Bimlesh

    2017-02-01

    The present experimental study is carried out on the probability distribution functions (PDFs) of turbulent flow characteristics within near-bed-surface and away-from-bed surfaces for both no seepage and seepage flow. Laboratory experiments were conducted in the plane sand bed for no seepage (NS), 10% seepage (10%S) and 15% seepage (15%) cases. The experimental calculation of the PDFs of turbulent parameters such as Reynolds shear stress, velocity fluctuations, and bursting events is compared with theoretical expression obtained by Gram-Charlier (GC)-based exponential distribution. Experimental observations follow the computed PDF distributions for both no seepage and seepage cases. Jensen-Shannon divergence (JSD) method is used to measure the similarity between theoretical and experimental PDFs. The value of JSD for PDFs of velocity fluctuation lies between 0.0005 to 0.003 while the JSD value for PDFs of Reynolds shear stress varies between 0.001 to 0.006. Even with the application of seepage, the PDF distribution of bursting events, sweeps and ejections are well characterized by the exponential distribution of the GC series, except that a slight deflection of inward and outward interactions is observed which may be due to weaker events. The value of JSD for outward and inward interactions ranges from 0.0013 to 0.032, while the JSD value for sweep and ejection events varies between 0.0001 to 0.0025. The theoretical expression for the PDF of turbulent intensity is developed in the present study, which agrees well with the experimental observations and JSD lies between 0.007 and 0.015. The work presented is potentially applicable to the probability distribution of mobile-bed sediments in seepage-affected alluvial channels typically characterized by the various turbulent parameters. The purpose of PDF estimation from experimental data is that it provides a complete numerical description in the areas of turbulent flow either at a single or finite number of points.

  16. First-episode medication-naive major depressive disorder is associated with altered resting brain function in the affective network.

    Directory of Open Access Journals (Sweden)

    Xiaocui Zhang

    Full Text Available BACKGROUND: Major depressive disorder (MDD has been associated with abnormal structure and function of the brain's affective network, including the amygdala and orbitofrontal cortex (OFC. However, it is unclear if alterations of resting-state function in this affective network are present at the initial onset of MDD. AIMS: To examine resting-state function of the brain's affective network in first-episode, medication-naive patients with MDD compared to healthy controls (HCs. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI was performed on 32 first-episode, medication-naive young adult patients with MDD and 35 matched HCs. The amplitude of low-frequency fluctuations (ALFF of the blood oxygen level-dependent (BOLD signal and amygdala-seeded functional connectivity (FC were investigated. RESULTS: Compared to HC, MDD patients showed reduced ALFF in the bilateral OFC and increased ALFF in the bilateral temporal lobe extending to the insular and left fusiform cortices. Enhanced anti-correlation of activity between the left amygdala seed and the left OFC was found in MDD patients but not in HCs. CONCLUSIONS: Reduced ALFF in the OFC suggests hypo-functioning of emotion regulation in the affective network. Enhanced anti-correlation of activity between the amygdala and OFC may reflect dysfunction of the amygdala-OFC network and additionally represent a pathological process of MDD.

  17. Lymphocyte 'homing' and chronic inflammation.

    Science.gov (United States)

    Sakai, Yasuhiro; Kobayashi, Motohiro

    2015-07-01

    Chronic inflammation is a response to prolonged exposure to injurious stimuli that harm and destroy tissues and promote lymphocyte infiltration into inflamed sites. Following progressive accumulation of lymphocytes, the histology of inflamed tissue begins to resemble that of peripheral lymphoid organs, which can be referred to as lymphoid neogenesis or formation of tertiary lymphoid tissues. Lymphocyte recruitment to inflamed tissues is also reminiscent of lymphocyte homing to peripheral lymphoid organs. In the latter, under physiological conditions, homing receptors expressed on lymphocytes adhere to vascular addressin expressed on high endothelial venules (HEVs), initiating a lymphocyte migration process composed of sequential adhesive interactions. Intriguingly, in chronic inflammation, HEV-like vessels are induced de novo, despite the fact that the inflamed site is not originally lymphoid tissue, and these vessels contribute to lymphocyte recruitment in a manner similar to physiological lymphocyte homing. In this review, we first describe physiological lymphocyte homing mechanisms focusing on vascular addressins. We then describe HEV-like vessel-mediated pathogenesis seen in various chronic inflammatory disorders such as Helicobacter pylori gastritis, inflammatory bowel disease (IBD), autoimmune pancreatitis and sclerosing sialadenitis, as well as chronic inflammatory cell neoplasm MALT lymphoma, with reference to our work and that of others.

  18. Lymphocytic Interstitial Pneumonia.

    Science.gov (United States)

    Panchabhai, Tanmay S; Farver, Carol; Highland, Kristin B

    2016-09-01

    Lymphocytic interstitial pneumonia (LIP) is a rare lung disease on the spectrum of benign pulmonary lymphoproliferative disorders. LIP is frequently associated with connective tissue diseases or infections. Idiopathic LIP is rare; every attempt must be made to diagnose underlying conditions when LIP is diagnosed. Computed tomography of the chest in patients with LIP may reveal ground-glass opacities, centrilobular and subpleural nodules, and randomly distributed thin-walled cysts. Demonstrating polyclonality with immunohistochemistry is the key to differentiating LIP from lymphoma. The 5-year mortality remains between 33% and 50% and is likely to vary based on the underlying disease process.

  19. Emotional Processing in High-Functioning Autism--Physiological Reactivity and Affective Report

    Science.gov (United States)

    Bolte, Sven; Feineis-Matthews, Sabine; Poustka, Fritz

    2008-01-01

    This study examined physiological response and affective report in 10 adult individuals with autism and 10 typically developing controls. An emotion induction paradigm using stimuli from the International Affective Picture System was applied. Blood pressure, heart and self-ratings of experienced valence (pleasure), arousal and dominance (control)…

  20. Alcohol Use in College Students as a Function of Reinforcement Sensitivity, Life Events, and Affect

    Science.gov (United States)

    Lee, Hyoung Suk

    2010-01-01

    Mood has been commonly viewed as an important determinant of drinking, but studies of positive and negative affect and alcohol use have reported inconsistent results. It has been suggested that the relationship between negative affect and heavy drinking or drinking problems depends on individual vulnerability dimensions such as personality. Gray's…

  1. Predicting the Accuracy of Facial Affect Recognition: The Interaction of Child Maltreatment and Intellectual Functioning

    Science.gov (United States)

    Shenk, Chad E.; Putnam, Frank W.; Noll, Jennie G.

    2013-01-01

    Previous research demonstrates that both child maltreatment and intellectual performance contribute uniquely to the accurate identification of facial affect by children and adolescents. The purpose of this study was to extend this research by examining whether child maltreatment affects the accuracy of facial recognition differently at varying…

  2. Bioluminescent assay for human lymphocyte blast transformation.

    Science.gov (United States)

    Bulanova, E G; Budagyan, V M; Romanova, N A; Brovko LYu; Ugarova, N N

    1995-05-01

    One of the basic tests of in vitro evaluation of immune cell functional activity is a proliferative response of lymphocytes on the action of external stimuli such as mitogenic lectines, antigens, etc. We compared two methods used to assess the lymphocyte functional status. (1) [3H]thymidine incorporation and (2) bioluminescence for determination of intracellular ATP in blast cells. Comparison has been done for healthy donors and patients with proven low immunological status. The proposed bioluminescent method for evaluation of the proliferative response was shown to be sensitive enough for diagnostic purposes. This method allows one to process a large number of samples at the same time and correlates highly with the radionuclide test use hazardous radioactive materials.

  3. Decreased deformability of lymphocytes in chronic lymphocytic leukemia

    Science.gov (United States)

    Zheng, Yi; Wen, Jun; Nguyen, John; Cachia, Mark A.; Wang, Chen; Sun, Yu

    2015-01-01

    This paper reports the first study of stiffness/deformability changes of lymphocytes in chronic lymphocytic leukemia (CLL) patients, demonstrating that at the single cell level, leukemic metastasis progresses are accompanied by biophysical property alterations. A microfluidic device was utilized to electrically measure cell volume and transit time of single lymphocytes from healthy and CLL patients. The results from testing thousands of cells reveal that lymphocytes from CLL patients have higher stiffness (i.e., lower deformability), as compared to lymphocytes in healthy samples, which was also confirmed by AFM indentation tests. This observation is in sharp contrast to the known knowledge on other types of metastatic cells (e.g., breast and lung cancer cells) whose stiffness becomes lower as metastasis progresses.

  4. Chronic lymphocytic leukaemia

    Science.gov (United States)

    Kipps, Thomas J.; Stevenson, Freda K.; Wu, Catherine J.; Croce, Carlo M.; Packham, Graham; Wierda, William G.; O’Brien, Susan; Gribben, John; Rai, Kanti

    2017-01-01

    Chronic lymphocytic leukaemia (CLL) is a malignancy of CD5+ B cells that is characterized by the accumulation of small, mature-appearing lymphocytes in the blood, marrow and lymphoid tissues. Signalling via surface immunoglobulin, which constitutes the major part of the B cell receptor, and several genetic alterations play a part in CLL pathogenesis, in addition to interactions between CLL cells and other cell types, such as stromal cells, T cells and nurse-like cells in the lymph nodes. The clinical progression of CLL is heterogeneous and ranges from patients who require treatment soon after diagnosis to others who do not require therapy for many years, if at all. Several factors, including the immunoglobulin heavy-chain variable region gene (IGHV) mutational status, genomic changes, patient age and the presence of comorbidities, should be considered when defining the optimal management strategies, which include chemotherapy, chemoimmunotherapy and/or drugs targeting B cell receptor signalling or inhibitors of apoptosis, such as BCL-2. Research on the biology of CLL has profoundly enhanced our ability to identify patients who are at higher risk for disease progression and our capacity to treat patients with drugs that selectively target distinctive phenotypic or physiological features of CLL. How these and other advances have shaped our current understanding and treatment of patients with CLL is the subject of this Primer. PMID:28102226

  5. Metabolism pathways in chronic lymphocytic leukemia.

    Science.gov (United States)

    Rozovski, Uri; Hazan-Halevy, Inbal; Barzilai, Merav; Keating, Michael J; Estrov, Zeev

    2016-01-01

    Alterations in chronic lymphocytic leukemia (CLL) cell metabolism have been studied by several investigators. Unlike normal B lymphocytes or other leukemia cells, CLL cells, like adipocytes, store lipids and utilize free fatty acids (FFA) to produce chemical energy. None of the recently identified mutations in CLL directly affects metabolic pathways, suggesting that genetic alterations do not directly contribute to CLL cells' metabolic reprogramming. Conversely, recent data suggest that activation of STAT3 or downregulation of microRNA-125 levels plays a crucial role in the utilization of FFA to meet the CLL cells' metabolic needs. STAT3, known to be constitutively activated in CLL, increases the levels of lipoprotein lipase (LPL) that mediates lipoprotein uptake and shifts the CLL cells' metabolism towards utilization of FFA. Herein, we review the evidence for altered lipid metabolism, increased mitochondrial activity and formation of reactive oxygen species (ROS) in CLL cells, and discuss the possible therapeutic strategies to inhibit lipid metabolism pathways in patient with CLL.

  6. Managing diversity : How leaders' multiculturalism and colorblindness affect work group functioning

    NARCIS (Netherlands)

    Meeussen, Loes; Otten, Sabine; Phalet, Karen

    2014-01-01

    Workforces are becoming increasingly diverse and leaders face the challenge of managing their groups to minimize costs and maximize benefits of diversity. This paper investigates how leaders' multiculturalism and colorblindness affect cultural minority and majority members' experiences of connectedn

  7. Does neurocognitive function affect cognitive bias toward an emotional stimulus? Association between general attentional ability and attentional bias toward threat

    OpenAIRE

    2014-01-01

    Background: Although poorer cognitive performance has been found to be associated with anxiety, it remains unclear whether neurocognitive function affects biased cognitive processing toward emotional information. We investigated whether general cognitive function evaluated with a standard neuropsychological test predicts biased cognition, focusing on attentional bias toward threat. Methods: One hundred and five healthy young adults completed a dot-probe task measuring attentional bias and ...

  8. Obinutuzumab in chronic lymphocytic leukemia.

    Science.gov (United States)

    Dupuis, Jehan

    2015-09-01

    Obinutuzumab is the second next-generation monoclonal anti-CD20 antibody (after ofatumumab) to enter clinical practice in chronic lymphocytic leukemia. Its superiority in association with chlorambucil as compared with chlorambucil alone has led to its approval as a first-line treatment for chronic lymphocytic leukemia, for patients who are not candidates for a more intensive treatment.

  9. BRAF and MEK inhibition variably affect GD2-specific chimeric antigen receptor (CAR) T-cell function in vitro.

    Science.gov (United States)

    Gargett, Tessa; Fraser, Cara K; Dotti, Gianpietro; Yvon, Eric S; Brown, Michael P

    2015-01-01

    Cancer immunotherapy has long been used in the treatment of metastatic melanoma, and an anti-CTLA-4 monoclonal antibody treatment has recently been approved by the US Food and Drug Administration. Targeted therapies such as small molecule kinase inhibitors targeting deregulated mitogen-activated protein kinase (MAPK) signaling have markedly improved melanoma control in up to 50% of metastatic disease patients and have likewise been recently approved. Combination therapies for melanoma have been proposed as a way to exploit the high-level but short-term responses associated with kinase inhibitor therapies and the low-level but longer-term responses associated with immunotherapy. Cancer immunotherapy now includes adoptive transfer of autologous tumor-specific chimeric antigen receptor (CAR) T cells and this mode of therapy is a candidate for combination with small molecule drugs. This paper describes CART cells that target GD2-expressing melanoma cells and investigates the effects of approved MAPK pathway-targeted therapies for melanoma [vemurafenib (Vem), dabrafenib (Dab), and trametinib (Tram)] on the viability, activation, proliferation, and cytotoxic T lymphocyte activity of these CAR T cells, as well as on normal peripheral blood mononuclear cells. We report that, although all these drugs lead to inhibition of stimulated T cells at high concentrations in vitro, only Vem inhibited T cells at concentrations equivalent to reported plasma concentrations in treated patients. Although the combination of Dab and Tram also resulted in inhibition of T-cell effector functions at some therapeutic concentrations, Dab itself had little adverse effect on CAR T-cell function. These findings may have implications for novel therapeutic combinations of adoptive CAR T-cell immunotherapy and MAPK pathway inhibitors.

  10. Does introduction of clover in an agricultural grassland affect the food base and functional diversity of Collembola?

    DEFF Research Database (Denmark)

    D'Annibale, Alessandra; Sechi, Valentina; Larsen, Thomas

    2016-01-01

    Introduction of legumes (i.e. white clover) in agricultural grasslands is a common practice to improve yields, but how this affects soil fauna populations, particularly mesofauna, is still poorly understood. We investigated taxonomical and functional differences of Collembola communities between ...

  11. Detecting Differential Item Functioning in the Japanese Version of the Multiple Affect Adjective Check List--Revised

    Science.gov (United States)

    Yasuda, Tomoyuki; Lei, Pui-Wa; Suen, Hoi K.

    2007-01-01

    This study examines the differential item functioning (DIF) of the English version and the Japanese-translated version of the Multiple Affect Adjective Check List--Revised (MAACL-R) using the logistic regression (LR) procedure. The results of the LR are supplemented by multiple group confirmatory factor analysis (MGCFA). A total of five items are…

  12. Factors Affecting the Functionality of Postgraduate Programs in Natural Sciences and Engineering in a Northwest State in Mexico

    Science.gov (United States)

    Valdés Cuervo, Angel Alberto; Estévez Nenninger, Etty Haydeé; Wendlandt Amezaga, Teodoro Rafael; Vera Noriega, José Ángel

    2015-01-01

    From the researchers' perspective, the study aimed to identify factors affecting the functionality of postgraduate programs in natural sciences and engineering in a north-western Mexican state. Through the typical cases method, 25 researchers who worked in six doctorate programs in the region were selected. From the perception of these…

  13. Synergistic Cytotoxicity of Melatonin and New-generation Anticancer Drugs Against Leukemia Lymphocytes But Not Normal Lymphocytes.

    Science.gov (United States)

    Zhelev, Zhivko; Ivanova, Donika; Bakalova, Rumiana; Aoki, Ichio; Higashi, Tatsuya

    2017-01-01

    The present study demonstrates specific sensitization of leukemia lymphocytes towards anticancer drugs using melatonin and clarifies the role of reactive oxygen species (ROS) for induction of apoptosis. The study covers four conventional and 11 new-generation anticancer drugs. Four parameters were analyzed simultaneously in leukemia and normal lymphocytes treated with drug, melatonin, or their combination: cell viability, induction of apoptosis, level of reactive oxygen species (ROS), and level of protein-carbonyl products. Almost all investigated combinations of melatonin with new-generation anticancer drugs were characterized by synergistic cytotoxicity towards leukemia lymphocytes, while the combinations with conventional drugs exhibited additive or antagonistic effects on cell viability. In leukemia lymphocytes, the additive cytotoxicity of doxorubicin plus melatonin was accompanied by low levels of ROS and protein-carbonyl products, as well as by suppression of apoptosis. In normal lymphocytes, none of the studied parameters changed significantly compared to cells treated with doxorubicin only. The combinations of everolimus plus melatonin and barasertib plus melatonin exhibited impressive synergistic cytotoxic effects on leukemia lymphocytes but did not affect the viability of normal lymphocytes. In leukemia cells, the synergistic cytotoxicity was accompanied by strong induction of apoptosis but a decrease of ROS to a level below that of the control. In normal lymphocytes, these combinations did not affect the level of ROS nor of protein-carbonyl products, and did not induce apoptosis. The data suggest that melatonin is a promising supplementary component in chemotherapy which allows the therapeutic doses of anticancer drugs to be reduced, minimizing their side-effects.

  14. Why do cytotoxic T lymphocytes fail to eliminate hepatitis C virus? Lessons from studies using major histocompatibility complex class I peptide tetramers.

    Science.gov (United States)

    Lechner, F; Sullivan, J; Spiegel, H; Nixon, D F; Ferrari, B; Davis, A; Borkowsky, B; Pollack, H; Barnes, E; Dusheiko, G; Klenerman, P

    2000-08-29

    Hepatitis C virus (HCV) infection is a major public health problem, affecting an estimated 3% of the world's population, and over 10% in some countries. Infection in most cases becomes persistent, and can lead to hepatic inflammation, fibrosis and liver failure. The T lymphocyte reponse, in particular that mediated by cytotoxic T lymphocytes (CTLs), is likely to be involved in determining the outcome of infection, although its overall role is not clear. The use of major histocompatibility complex (MHC) class I peptide tetrameric complexes (tetramers) to study antiviral CTL responses has revolutionized our approach to the study of human infection. We have used a panel of MHC class I tetramers to analyse immune responses in HCV-infected individuals at various stages of disease. We find that the CTL response against HCV is vigorous in its early phases but dwindles over time both in terms of lymphocyte number and function. A number of potential explanations for this 'CTL failure' are discussed.

  15. Genetic variation in serotonin transporter function affects human fear expression indexed by fear-potentiated startle

    NARCIS (Netherlands)

    Klumpers, F.; Heitland, I.; Oosting, R.S.; Kenemans, J.L.; Baas, J.M.

    2012-01-01

    The serotonin transporter (SERT) plays a crucial role in anxiety. Accordingly, variance in SERT functioning appears to constitute an important pathway to individual differences in anxiety. The current study tested the hypothesis that genetic variation in SERT function is associated with variability

  16. How Do Cognitive Function and Knowledge Affect Heart Failure Self-Care?

    Science.gov (United States)

    Dickson, Victoria Vaughan; Lee, Christopher S.; Riegel, Barbara

    2011-01-01

    Despite extensive patient education, few heart failure (HF) patients master self-care. Impaired cognitive function may explain why patient education is ineffective. A concurrent triangulation mixed methods design was used to explore how knowledge and cognitive function influence HF self-care. A total of 41 adults with HF participated in interviews…

  17. PLATELET-FUNCTION ANALYSIS AFTER IN-VITRO TREATMENT WITH HEMOSTASIS-AFFECTING COMPONENTS

    NARCIS (Netherlands)

    TIGCHELAAR, [No Value; MONNINK, SHJ; HAAN, J; TABUCHI, N; VANOEVEREN, W

    1995-01-01

    An overall platelet function test in whole blood, which simulates conditions under arterial pressure, is useful in measuring the effect of polymer materials on blood hemostatic function. We performed biocompatibility tests with materials or plasma substitutes by interaction of blood from healthy vol

  18. Affective dysfunctions in adolescents at risk for psychosis : Emotion awareness and social functioning

    NARCIS (Netherlands)

    van Rijn, Sophie; Schothorst, Patricia; van 't Wout, Mascha; Sprong, Mirjam; Ziermans, Tim; van Engeland, Herman; Aleman, Andre; Swaab, Hanna

    2011-01-01

    Studies of individuals at ultra high risk (UHR) for psychosis have revealed deviations in cognitive and neural development before the onset of psychosis. As affective impairments are among the core dysfunctions in psychotic disorders such as schizophrenia, this study assessed emotion processing and

  19. Functional Richness and Identity Do Not Strongly Affect Invasibility of Constructed Dune Communities.

    Science.gov (United States)

    Mason, Tanya J; French, Kristine; Jolley, Dianne F

    2017-01-01

    Biotic effects are often used to explain community structure and invasion resistance. We evaluated the contribution of functional richness and identity to invasion resistance and abiotic resource availability using a mesocosm experiment. We predicted that higher functional richness would confer greater invasion resistance through greater resource sequestration. We also predicted that niche pre-emption and invasion resistance would be higher in communities which included functional groups similar to the invader than communities where all functional groups were distinct from the invader. We constructed communities of different functional richness and identity but maintained constant species richness and numbers of individuals in the resident community. The constructed communities represented potential fore dune conditions following invader control activities along the Australian east coast. We then simulated an invasion event by bitou (Chrysanthemoides monilifera ssp. rotundata DC. Norl.), a South African shrub invader. We used the same bitou propagule pressure across all treatments and monitored invasion success and resource availability for 13 months. Contrary to our predictions, we found that functional richness did not mediate the number of bitou individuals or bitou cover and functional identity had little effect on invasion success: there was a trend for the grass single functional group treatment to supress bitou individuals, but this trend was obscured when grasses were in multi functional group treatments. We found that all constructed communities facilitated bitou establishment and suppressed bitou cover relative to unplanted mesocosms. Abiotic resource use was either similar among planted communities, or differences did not relate to invasion success (with the exception of light availability). We attribute invasion resistance to bulk plant biomass across planted treatments rather than their functional group arrangement.

  20. Functional Correlates of childhood maltreatment and symptom severity during affective theory of mind tasks in chronic depression.

    Science.gov (United States)

    Hentze, Charlotte; Walter, Henrik; Schramm, Elisabeth; Drost, Sarah; Schoepf, Dieter; Fangmeier, Thomas; Mattern, Margarete; Normann, Claus; Zobel, Ingo; Schnell, Knut

    2016-04-30

    Among multiple etiological factors of depressive disorders, childhood maltreatment (CM) gains increasing attention as it confers susceptibility for depression and predisposes to chronicity. CM assumedly inhibits social-cognitive development, entailing interactional problems as observed in chronic depression (CD), especially in affective theory of mind (ToM). However, the extent of CM among CD patients varies notably as does the severity of depressive symptoms. We tested whether the extent of CM or depressive symptoms correlates with affective ToM functions in CD patients. Regional brain activation measured by functional magnetic resonance imaging during an affective ToM task was tested for correlation with CM, assessed by the Childhood Trauma Questionnaire (CTQ), and symptom severity, assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS), in 25 unmedicated CD patients (mean age 41.52, SD 11.13). Amygdala activation during affective ToM correlated positively with CTQ total scores, while (para)hippocampal response correlated negatively with MADRS scores. Our findings suggest that differential amygdala activation in affective ToM in CD is substantially modulated by previous CM and not by the pathophysiological equivalents of current depressive symptoms. This illustrates the amygdala's role in the mediation of CM effects. The negative correlation of differential (para)hippocampal activation and depressive symptom severity indicates reduced integration of interactional experiences during depressive states.

  1. Ecological Momentary Assessment of social functioning in schizophrenia: impact of performance appraisals and affect on social interactions.

    Science.gov (United States)

    Granholm, Eric; Ben-Zeev, Dror; Fulford, Daniel; Swendsen, Joel

    2013-04-01

    Research concerning the complex interplay between factors that contribute to poor social functioning in schizophrenia has been hampered by limitations of traditional measures, most notably the ecological validity and accuracy of retrospective self-report and interview measures. Computerized Ecological Momentary Assessment (EMAc) permits the real-time assessment of relationships between daily life experiences, thoughts, feelings, and behaviors. In the current study, EMAc was used to record daily social interactions, subjective performance appraisals of these interactions (e.g., "I succeeded/failed"; "I was liked/rejected"), and affect in 145 individuals with schizophrenia or schizoaffective disorder. Participants completed electronic questionnaires on a personal digital assistant (PDA) four times per day for one week. Time-lagged multilevel modeling of the data revealed that more positive interaction appraisals at any point in a day were associated with greater positive affect which, in turn, was a strong predictor of more social interactions over subsequent hours. Social functioning, therefore, was linked to positive performance beliefs about social interactions that were associated with greater positive affect. The findings suggest a useful treatment target for cognitive behavioral therapy and other psychosocial interventions that can be used to challenge defeatist beliefs and increase positive affect to enhance social functioning in schizophrenia.

  2. Cell Death Mechanisms Induced by Cytotoxic Lymphocytes

    Institute of Scientific and Technical Information of China (English)

    Ch(a)vez-Gal(a)n L; Arenas-Del Angel MC; Zenteno E; Ch(a)vez R; Lascurain R

    2009-01-01

    One of the functions of the immune system is to recognize and destroy abnormal or infected cells to maintain homeostasis. This is accomplished by cytotoxic lymphocytes. Cytotoxicity is a highly organized multifactor process. Here, we reviewed the apoptosis pathways induced by the two main cytotoxic lymphocyte subsets, natural killer (NK) cells and CD8+T cells. In base to recent experimental evidence, we reviewed NK receptors involved in recognition of target-cell, as well as lytic molecules such as perforin, granzymes-A and -B, and granulysin. In addition, we reviewed the Fas-FasL intercellular linkage mediated pathway, and briefly the cross-linking of tumor necrosis factor (TNF) and TNF receptor pathway. We discussed three models of possible molecular interaction between lyric molecules from effector cytotoxic cells and target-cell membrane to induction of apoptosis.

  3. Children with cerebral palsy and periventricular white matter injury: does gestational age affect functional outcome?

    Science.gov (United States)

    Harvey, Adrienne R; Randall, Melinda; Reid, Susan M; Lee, Katherine J; Imms, Christine; Rodda, Jillian; Eldridge, Beverley; Orsini, Francesca; Reddihough, Dinah

    2013-09-01

    This study aimed to determine differences in functional profiles and movement disorder patterns in children aged 4-12 years with cerebral palsy (CP) and periventricular white matter injury (PWMI) born >34 weeks gestation compared with those born earlier. Eligible children born between 1999 and 2006 were recruited through the Victorian CP register. Functional profiles were determined using the Gross Motor Function Classification System (GMFCS), Manual Abilities Classification System (MACS), Communication Function Classification System (CFCS), Functional Mobility Scale (FMS) and Bimanual Fine Motor Function (BFMF). Movement disorder and topography were classified using the Surveillance of Cerebral Palsy in Europe (SCPE) classification. 49 children born >34 weeks (65% males, mean age 8 y 9 mo [standard deviation (SD) 2 y 2 mo]) and 60 children born ≤ 34 weeks (62% males, mean age 8 y 2 mo [SD 2 y 2 mo]) were recruited. There was evidence of differences between the groups for the GMFCS (p=0.003), FMS 5, 50 and 500 (p=0.003, 0.002 and 0.012), MACS (p=0.04) and CFCS (p=0.035), with a greater number of children born ≤ 34 weeks more severely impaired compared with children born later. Children with CP and PWMI born >34 weeks gestation had milder limitations in gross motor function, mobility, manual ability and communication compared with those born earlier.

  4. Fate of thymic lymphocytes. [/sup 125/IudR and /sup 3/HTdR tracer studies in mice

    Energy Technology Data Exchange (ETDEWEB)

    Laissue, J A; Chanana, A D; Cronkite, E P; Joel, D D

    1976-01-01

    Data are summarized from a number of studies on the fate of thymic lymphocytes. Results are reported from studies in mice in which /sup 125/IudR and /sup 3/HTdR were used as tracers to study the production, maturation, migration, and life span of thymic lymphocytes. It is pointed out that thymus-derived cells constitute the majority of recirculating lymphocytes and that peripheral, differentiated thymus-derived lymphocytes exhibit a number of immunological functions. 114 references.

  5. Isolation, purification and function of mouse CD4 + CD25+ regulatory T lymphocytes in vitro%小鼠CD4+CD25+T调节细胞的分离、纯化及其功能检测

    Institute of Scientific and Technical Information of China (English)

    王百林; 刘增军; 翟淑萍; 陈义发; 秦欢; 刘秋玲

    2010-01-01

    Objective To establish a method for isolation and purification of CD4+ CD25+ regulatory T lymphocytes (Treg), and to identify partial functions of these cells. Methods Lymphocytes were isolated from the mouse spleens and then CD4+ CD25+ T cells were sorted by magnetic bead cell sorting (MACS) system. The purity of CD4+ CD25+ T cells were analyzed by flow cytometry (FCM). The activity of them was detected by trypan blue staining. Interleukin (IL)-2 and IL-10 levels in culture supernatant were determined by enzyme linked immunosorbent assay (ELISA). Results The purity of CD4+ CD25+ T cells sorted by MACS was 83%-96%. There was significant difference in the levels of IL-2 and IL-10 secreted by lymphocytes among CD4+ CD25+ Treg group [ (10.25±3.31), (40.32±8.05) ng/L], CD4+ CD25- T group [(58.21±13.05),(11.52±3.01)ng/L] and mixed culture group [ (39.54±13.82), (31.25±4.36)ng/L (P<0.05,P<0.01).Conclusion High purity of CD4+ CD25+ Treg with immune regulatory function can be isolated by MACS. The immunosuppression of CD4+ CD25+ Treg to CD4+ CD25- T was related to the regulation of IL-10 through IL-2.%目的 探讨小鼠CD4+CD25+T调节细胞(Treg)的分离培养、纯化及其部分功能检测.方法 采用免疫磁珠分离法(MACS)对分离小鼠的脾淋巴细胞进行分选CD4+CD25+Treg细胞,锥虫蓝细胞染色检测其活性,流式细胞仪检测分选所得活性细胞的纯度,酶联免疫吸附试验(ELISA)检测培养上清液中白细胞介素(IL)-2、IL-10水平的浓度.结果 MACS分离的CD4+CD25+Treg细胞的纯度达83%~96%.体外培养中Treg组、T组和混合组IL-2和IL-10的平均水平分别为:(10.25±2.31)、(40.32±8.05)ng/L;(5 8.21±13.05)、(11.52±3.01)ng/L;(39.54±12.82)、(31.25±4.36)ng/L,数据差异有统计学意义(P<0.05,P<0.01).结论 采用MACS系统两步法,可获得高纯度、具有免疫抑制功能的Treg细胞,该细胞对CD4+CD25-T细胞的免疫抑制作用可能是通过IL-10对IL-2的调节作用实现的.

  6. miR-125b affects mitochondrial biogenesis and impairs brite adipocyte formation and function

    Directory of Open Access Journals (Sweden)

    Maude Giroud

    2016-08-01

    Conclusion: Collectively, our results demonstrate that miR-125b-5p plays an important role in the repression of brite adipocyte function by modulating oxygen consumption and mitochondrial gene expression.

  7. Restoration of hip architecture with bipolar hemiarthroplasty in the elderly : does it affect early functional outcome?

    NARCIS (Netherlands)

    Hartel, Maximilian; Arndt, Marius; Eulenburg, Christine Zu; Petersen, Jan Philipp; Rueger, Johannes M.; Hoffmann, Michael

    2014-01-01

    Reconstruction of the anatomic architecture correlates with functional outcome in patients receiving elective total hip arthroplasty. In theory similar rules should apply for bipolar hemiarthroplasty in femoral neck fractures. The influence of anatomic restoration after bipolar hemiarthroplasty on s

  8. Sevoflurane exposure in 7-day-old rats affects neurogenesis,neurodegeneration and neurocognitive function

    Institute of Scientific and Technical Information of China (English)

    Fang Fang; Zhanggang Xue; Jing Cang

    2012-01-01

    Objective Sevoflurane is widely used in pediatric anesthesia and former studies showed that it causes neurodegeneration in the developing brain.The present study was carried out to investigate the effects of sevoflurane on neurogenesis,neurodegeneration and behavior.Methods We administered 5-bromodeoxyuridine,an S-phase marker,before,during,and after 4 h of sevoflurane given to rats on postnatal day 7 to assess dentate gyrus progenitor proliferation and Fluoro-Jade staining for degeneration.Spatial reference memory was tested 2 and 6 weeks after anesthesia.Results Sevoflurane decreased progenitor proliferation and increased cell death until at least 4 days after anesthesia.Spatial reference memory was not affected at 2 weeks but was affected at 6 weeks after sevoflurane administration.Conclusion Sevoflurane reduces neurogenesis and increases the death of progenitor cells in developing brain.This might mediate the lateonset neurocognitive outcome after sevoflurane application.

  9. Stressed to death: implication of lymphocyte apoptosis for psychoneuroimmunology

    Science.gov (United States)

    Shi, Yufang; Devadas, Satish; Greeneltch, Kristy M.; Yin, Deling; Allan Mufson, R.; Zhou, Jian-nian

    2003-01-01

    Psychological and physical stressors best exemplify the intercommunication of the immune and the nervous systems. It has been shown that stress significantly impacts leukocyte cellularity and immune responses and alters susceptibility to various diseases. While acute stress has been shown to enhance immune responses, chronic stress often leads to immunosuppression. Among many criteria examined upon exposure to chronic stress, the reduction in lymphocyte mitogenic response and lymphocyte cellularity are commonly assessed. We have reported that chronic restraint stress could induce lymphocyte reduction, an effect dependent on endogenous opioids. Interestingly, the effect of endogenous opioids was found to be exerted through increasing the expression of a cell death receptor, Fas, and an increased sensitivity of lymphocytes to apoptosis. Stress-induced lymphocyte reduction was not affected by adrenalectomy. In this review, based on available literature and our recent data, we will discuss the role of the hypothalamic-pituitary-adrenal axis and endogenous opioids and examine the mechanisms by which chronic stress modulates lymphocyte apoptosis.

  10. The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo

    OpenAIRE

    Whyte, Lauren S.; Ryberg, Erik; Sims, Natalie A.; Ridge, Susan A.; Mackie, Ken; Greasley, Peter J.; Ross, Ruth A.; Rogers, Michael J

    2009-01-01

    GPR55 is a G protein-coupled receptor recently shown to be activated by certain cannabinoids and by lysophosphatidylinositol (LPI). However, the physiological role of GPR55 remains unknown. Given the recent finding that the cannabinoid receptors CB1 and CB2 affect bone metabolism, we examined the role of GPR55 in bone biology. GPR55 was expressed in human and mouse osteoclasts and osteoblasts; expression was higher in human osteoclasts than in macrophage progenitors. Although the GPR55 agonis...

  11. Aesthetic And Functional Rehabilitation Of The Primary Dentition Affected By Amelogenesis Imperfecta.

    OpenAIRE

    Maria Carolina Salomé Marquezin; Bruna Raquel Zancopé; Larissa Ferreira Pacheco; Maria Beatriz Duarte Gavião; Fernanda Miori Pascon

    2015-01-01

    The objective of this case report was to describe the oral rehabilitation of a five-year-old boy patient diagnosed with amelogenesis imperfecta (AI) in the primary dentition. AI is a group of hereditary disorders that affects the enamel structure. The patient was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of AI. The treatment was oral rehabilitation of the primary molars wit...

  12. Maternal early-life trauma and affective parenting style: the mediating role of HPA-axis function.

    Science.gov (United States)

    Juul, Sarah H; Hendrix, Cassandra; Robinson, Brittany; Stowe, Zachary N; Newport, D Jeffrey; Brennan, Patricia A; Johnson, Katrina C

    2016-02-01

    A history of childhood trauma is associated with increased risk for psychopathology and interpersonal difficulties in adulthood and, for those who have children, impairments in parenting and increased risk of negative outcomes in offspring. Physiological and behavioral mechanisms are poorly understood. In the current study, maternal history of childhood trauma was hypothesized to predict differences in maternal affect and HPA axis functioning. Mother-infant dyads (N = 255) were assessed at 6 months postpartum. Mothers were videotaped during a 3-min naturalistic interaction, and their behavior was coded for positive, neutral, and negative affect. Maternal salivary cortisol was measured six times across the study visit, which also included an infant stressor paradigm. Results showed that childhood trauma history predicted increased neutral affect and decreased mean cortisol in the mothers and that cortisol mediated the association between trauma history and maternal affect. Maternal depression was not associated with affective measures or cortisol. Results suggest that early childhood trauma may disrupt the development of the HPA axis, which in turn impairs affective expression during mother-infant interactions in postpartum women. Interventions aimed at treating psychiatric illness in postpartum women may benefit from specific components to assess and treat trauma-related symptoms and prevent secondary effects on parenting.

  13. Aging affects epidermal Langerhans cell development and function and alters their miRNA gene expression profile.

    Science.gov (United States)

    Xu, Ying-Ping; Qi, Rui-Qun; Chen, Wenbin; Shi, Yuling; Cui, Zhi-Zhong; Gao, Xing-Hua; Chen, Hong-Duo; Zhou, Li; Mi, Qing-Sheng

    2012-11-01

    Immunosenescence is a result of progressive decline in immune system function with advancing age. Epidermal Langerhans cells (LCs), belonging to the dendritic cell (DC) family, act as sentinels to play key roles in the skin immune responses. However, it has not been fully elucidated how aging affects development and function of LCs. Here, we systemically analyzed LC development and function during the aging process in C57BL/6J mice, and performed global microRNA (miRNA) gene expression profiles in aged and young LCs. We found that the frequency and maturation of epidermal LCs were significantly reduced in aged mice starting at 12 months of age, while the Langerin expression and ability to phagocytose Dextran in aged LCs were increased compared to LCs from aged and young mice. Functionally, aged LCs were impaired in their capacity to induce OVA-specific CD4+ and CD8+ T cell proliferation. Furthermore, the expression of miRNAs in aged epidermal LCs showed a distinct profile compared to young LCs. Most interestingly, aging-regulated miRNAs potentially target TGF-β-dependent and non- TGF-β-dependent signal pathways related to LCs. Overall, our data suggests that aging affects LCs development and function, and that age-regulated miRNAs may contribute to the LC developmental and functional changes in aging.

  14. Laboratorial diagnosis of lymphocytic meningitis

    Directory of Open Access Journals (Sweden)

    Sérgio Monteiro de Almeida

    2007-10-01

    Full Text Available Meningitis is the main infectious central nervous system (CNS syndrome. Viruses or bacteria can cause acute meningitis of infectious etiology. The term "Aseptic Meningitis" denotes a clinical syndrome with a predominance of lymphocytes in the cerebrospinal fluid (CSF, with no common bacterial agents identified in the CSF. Viral meningitis is considered the main cause of lymphocyte meningitis. There are other etiologies of an infectious nature. CSF examination is essential to establish the diagnosis and to identify the etiological agent of lymphocytic meningitis. We examined CSF characteristics and the differential diagnosis of the main types of meningitis.

  15. Effect of bilirubin on the function of T lymphocytes of premature infants and the mechanism%胆红素对早产儿T淋巴细胞功能的影响及相关机制的研究

    Institute of Scientific and Technical Information of China (English)

    马琳; 江莲

    2012-01-01

    目的:探讨不同血清胆红素水平对早产儿T淋巴细胞功能的影响.方法:应用流式细胞仪法测定不同胎龄、不同胆红素水平下CD4+、CD8+、白细胞介素-4(Interleukin-4、IL-4)、肿瘤坏死因子-γ(Tumor necrosis factor-γ、IFN-v)、Fas基因表达.结果:①胎龄≥32周早产儿的CD4+和CD8+表达量>胎龄<32周早产儿,差异有统计学意义(P<0.05).②不同胆红素浓度对早产儿T淋巴细胞功能的影响:胆红素153.9~220.6 μmol/L组和胆红素>220,6 μmol/L组早产儿CD4+的表达水平均明显低于无黄疸组和胆红素<153.9 μmol/L组(P<0.05);胆红素>220.6 μmol/L组早产儿CD8+的表达水平低于无黄疸组、胆红素<153.9 μmol/L组和胆红素153.9-220.6 μmol/L组(P<0.05).IL-4的表达量与4组比较无差异(P>0.05).IFN-γ的表达量于胆红素153.9~220.6 μmol/L组和胆红素>220.6 μmol/L组均<无黄疸组和胆红素<153.9 μmol/L组(P<0.05).Fas基因的表达量于胆红素153.9~220.6 μmol/L组和胆红素>220.6 μmol/L组均高于无黄疸组和胆红素< 153.9 μmoL/L组(P<0.05).结论:①胎龄是影响早产儿T淋巴细胞功能的重要因素之一,胎龄越小免疫功能越低.②黄疸对早产儿T淋巴细胞功能有显著抑制作用,随胆红素浓度的增加抑制作用越显著,同时Fas基因的表达量逐渐增高,提示此种抑制作用与淋巴细胞凋亡增多有关.%Objective: To explore the effects of different levels of serum bilirubin on the function of T lymphocytes of premature infants. Methods: Flow cytometry was used to detect the expression levels of CD4+ , CD8+, interleukin -4, tumor necrosis factor-γ, and Fas gene among the premature infants of different fetal ages and bilirubin levels. Results: The expression levels of CD4 + and CD8 + in premature infants of fetal age ≥32 weeks were significantly higher than those in premature infants of fetal age 220.6 μmol/L group were significantly lower than

  16. Affecting Rhomboid-3 function causes a dilated heart in adult Drosophila.

    Directory of Open Access Journals (Sweden)

    Lin Yu

    2010-05-01

    Full Text Available Drosophila is a well recognized model of several human diseases, and recent investigations have demonstrated that Drosophila can be used as a model of human heart failure. Previously, we described that optical coherence tomography (OCT can be used to rapidly examine the cardiac function in adult, awake flies. This technique provides images that are similar to echocardiography in humans, and therefore we postulated that this approach could be combined with the vast resources that are available in the fly community to identify new mutants that have abnormal heart function, a hallmark of certain cardiovascular diseases. Using OCT to examine the cardiac function in adult Drosophila from a set of molecularly-defined genomic deficiencies from the DrosDel and Exelixis collections, we identified an abnormally enlarged cardiac chamber in a series of deficiency mutants spanning the rhomboid 3 locus. Rhomboid 3 is a member of a highly conserved family of intramembrane serine proteases and processes Spitz, an epidermal growth factor (EGF-like ligand. Using multiple approaches based on the examination of deficiency stocks, a series of mutants in the rhomboid-Spitz-EGF receptor pathway, and cardiac-specific transgenic rescue or dominant-negative repression of EGFR, we demonstrate that rhomboid 3 mediated activation of the EGF receptor pathway is necessary for proper adult cardiac function. The importance of EGF receptor signaling in the adult Drosophila heart underscores the concept that evolutionarily conserved signaling mechanisms are required to maintain normal myocardial function. Interestingly, prior work showing the inhibition of ErbB2, a member of the EGF receptor family, in transgenic knock-out mice or individuals that received herceptin chemotherapy is associated with the development of dilated cardiomyopathy. Our results, in conjunction with the demonstration that altered ErbB2 signaling underlies certain forms of mammalian cardiomyopathy, suggest

  17. Changes in the Expression of Transcription Factors Involved in Modulating the Expression of EPO-R in Activated Human CD4-Positive Lymphocytes.

    Science.gov (United States)

    Lisowska, Katarzyna A; Frackowiak, Joanna E; Mikosik, Anna; Witkowski, Jacek M

    2013-01-01

    We have recently described the presence of the erythropoietin receptor (EPO-R) on CD4(+) lymphocytes and demonstrated that its expression increases during their activation, reaching a level reported to be typical for erythroid progenitors. This observation suggests that EPO-R expression is modulated during lymphocyte activation, which may be important for the cells' function. Here we investigated whether the expression of GATA1, GATA3 and Sp1 transcription factors is correlated with the expression of EPO-R in human CD4(+) lymphocytes stimulated with monoclonal anti-CD3 antibody. The expression of GATA1, GATA3 and Sp1 transcription factors in CD4(+) cells was estimated before and after stimulation with anti-CD3 antibody by Western Blot and flow cytometry. The expression of EPO-R was measured using real-time PCR and flow cytometry. There was no change in the expression of GATA1 and GATA3 in CD4(+) lymphocytes after stimulation with anti-CD3 antibody. However, stimulation resulted in the significantly increased expression of the Sp1 factor. CD4(+) lymphocytes stimulated with anti-CD3 antibody exhibited an increase in both the expression level of EPOR gene and the number of EPO-R molecules on the cells' surface, the latter being significantly correlated with the increased expression of Sp1. Sp1 is noted to be the single transcription factor among the ones studied whose level changes as a result of CD4(+) lymphocyte stimulation. It seems that Sp1 may significantly affect the number of EPO-R molecules present on the surface of activated CD4(+) lymphocytes.

  18. Effect of radiation on cell interactions with respect to the phenomenon of inactivation on non-syngeneic stem cells. A radiation-induced change in B-lymphocyte function

    Energy Technology Data Exchange (ETDEWEB)

    Petrov, R.V.; Dozmorov, I.M.; Lutsenko, G.V.; Nikolaeva, I.S.; Rudneva, T.B. (Institut Biofiziki, Moscow (USSR))

    A study was made of the changes in the mode of interaction between T- and B-lymphocytes of mouse lymph nodes with respect to the phenomenon of inactivation of non-syngeneic haemopoietic stem cells. It was shown that irradiation of B-lymphocytes with doses of 77.4-232.2 mC/kg changes their helper activity into a suppressor activity with regard to T-cell-killers having a low electrophoretic mobility.

  19. Gravitational environment produced by a superconducting magnet affects osteoblast morphology and functions

    Science.gov (United States)

    Qian, Airong; Zhang, Wei; Weng, Yuanyuan; Tian, Zongcheng; Di, Shengmeng; Yang, Pengfei; Yin, Dachuan; Hu, Lifang; Wang, Zhe; Xu, Huiyun; Shang, Peng

    The aims of this study are to investigate the effects of gravitational environment produced by a superconducting magnet on osteoblast morphology, proliferation and adhesion. A superconducting magnet which can produce large gradient high magnetic field (LGHMF) and provide three apparent gravity levels (0g,1gand2g) was employed to simulate space gravity environment. The effects of LGHMF on osteoblast morphology, proliferation, adhesion and the gene expression of fibronectin and collagen I were detected by scanning electron microscopy, immunocytochemistry, adhesion assays and real time PCR, respectively, after exposure of osteoblasts to LGHMF for 24 h. Osteoblast morphology was affected by LGHMF (0g,1gand2g) and the most evident morphology alteration was observed at 0g condition. Proliferative abilities of MC3T3 and MG-63 cell were affected under LGHMF (0g,1gand2g) conditions compared to control condition. The adhesive abilities of MC3T3 and MG-63 cells to extracellular matrix (ECM) proteins (fibronectin, laminin, collagen IV) were also affected by LGHMF (0g,1gand2g), moreover, the effects of LGHMF on osteoblast adhesion to different ECM proteins were different. Fibronectin gene expression in MG63 cells under zero gravity condition was increased significantly compared to other conditions. Collagen I gene expression in MG-63 and MC3T3 cells was altered by both magnetic field and alerted gravity. The study indicates that the superconducting magnet which can produce LGHMF may be a novel ground-based space gravity simulator and can be used for biological experiment at cellular level.

  20. Deficient fear conditioning in psychopathy as a function of interpersonal and affective disturbances

    Directory of Open Access Journals (Sweden)

    Ralf eVeit

    2013-10-01

    Full Text Available The diminished fear reactivity is one of the most valid physiological findings in psychopathy research. In a fear conditioning paradigm, with faces as conditioned stimulus (CS and electric shock as unconditioned stimulus (US, we investigated a sample of 14 high psychopathic violent offenders. Event related potentials, skin conductance responses (SCR as well as subjective ratings of the CSs were collected. This study assessed to which extent the different facets of the psychopathy construct contribute to the fear conditioning deficits observed in psychopaths. Participants with high scores on the affective facet subscale of the Psychopathy Checklist-Revised (PCL-R showed weaker conditioned fear responses and lower N100 amplitudes compared to low scorers. In contrast, high scorers on the affective facet rated the CS+ (paired more negatively than low scorers regarding the CS- (unpaired. Regarding the P300, high scores on the interpersonal facet were associated with increased amplitudes to the CS+ compared to the CS-, while the opposed pattern was found with the antisocial facet. Both, the initial and terminal contingent negative variation indicated a divergent pattern: participants with pronounced interpersonal deficits, showed increased cortical negativity to the CS+ compared to the CS-, whereas a reversed CS+/CS- differentiation was found in offenders scoring high on the antisocial facet. The present study revealed that deficient fear conditioning in psychopathy was most pronounced in offenders with high scores on the affective facet. Event related potentials suggest that participants with distinct interpersonal deficits showed increased information processing, whereas the antisocial facet was linked to decreased attention and interest to the CS+. These data indicate that an approach to the facets of psychopathy can help to resolve ambiguous findings in psychopathy research and enables a more precise and useful description of this disorder.

  1. Life and death of lymphocytes: a role in immunesenescence

    Directory of Open Access Journals (Sweden)

    Agrawal Sudhanshu

    2005-08-01

    Full Text Available Abstract Human aging is associated with progressive decline in immune functions, increased frequency of infections. Among immune functions, a decline in T cell functions during aging predominates. In this review, we will discuss the molecular signaling in two major pathways of apoptosis, namely death receptor pathway and mitochondrial pathway, and their alterations in both T and B lymphocytes in human aging with a special emphasis on naïve and different memory subsets of CD8+ T cells. We will also discuss a possible role of lymphocyte apoptosis in immune senescence.

  2. X-ray irradiation affects Gadd45 mRNA expression in human peripheral blood lymphocytes%X 射线对人周围血淋巴细胞 Gadd45 mRNA 表达影响

    Institute of Scientific and Technical Information of China (English)

    王恰; 李明芳; 杨爱初; 杨宇华; 梁晓阳; 严茂胜

    2015-01-01

    Objective To analyze the relative expression level of Growth arrest and DNA damage gene (Gadd)45 mRNA of human peripheral blood lymphocytes after X-ray irradiation with different doses and time,and to explore the possibility of Gadd45 gene as a biological dosimeter.Methods i)Dose-effect experiment.The healthy human peripheral blood were irradiated by 0.00,0.10,0.25,0.50,1.00,2.00,3.00 and 5.00 Gy X-ray and the lymphocytes were separated for measurement.ii)Time-effect experiment.The healthy human peripheral blood were irradiated by 2.00 Gy X-ray and the lymphocytes were separated and then cultivate for measurement after cultivation time of 0,3,6,12,24 and 48 hours.The real-time fluorescent quantitative polymerase chain reaction method was used to detect Gadd45 mRNA expression level. Results i)The relative expression level of Gadd45 mRNA increased with the increasing dose from 0.00 to 0.50 Gy.The linear regression equation was ^y =1.056 9 +7.132 2 x (determination coefficient was 0.992,P <0.01 ).The relative expression level of Gadd45 mRNA achieved the peak value when the irradiation dose was 0.50 Gy,which was 4.53 times of that with 0.00 Gy dose irradiation.The relative expression level of Gadd45 mRNA gradually decreased in 0.50-5.00 Gy.ii)In the period of 3-12 hours after 2.00 Gy of X-ray irradiation,the relative expression level of Gadd45 mRNA increased with the increasing exposure time.The linear regression equation was ^y =-6.366 0 +4.965 0 x (determination coefficient was 0.932,P <0.05).It achieved the peak value at the time of 12 hours,which was 57.68 times of that with 0-hour time group.During the time of 24-48 hours after irradiation,the relative expression level of Gadd45 mRNA decreased sharply,the 48-hour group was 2.08 times of 0-hour time group.Conclusion X-ray irradiation up-regulated the expression level of Gadd45 mRNA.There was a good dose-effect and time-effect relation in specific dose and time range.Further study is needed to explore if Gadd45

  3. T-cell receptor Vβ repertoire of CD8+ T-lymphocyte subpopulations in cutaneous leishmaniasis patients from the state of Rio de Janeiro, Brazil

    Science.gov (United States)

    Ferraz, Raquel; Cunha, Clarissa Ferreira; Pimentel, Maria Inês; Lyra, Marcelo Rosandiski; Schubach, Armando Oliveira; de Mendonça, Sérgio Coutinho Furtado; Da-Cruz, Alda Maria; Bertho, Alvaro Luiz

    2015-01-01

    In human cutaneous leishmaniasis (CL), the immune response is mainly mediated by T-cells. The role of CD8+ T-lymphocytes, which are related to healing or deleterious functions, in affecting clinical outcome is controversial. The aim of this study was to evaluate T-cell receptor diversity in late-differentiated effector (LDE) and memory CD8+ T-cell subsets in order to create a profile of specific clones engaged in deleterious or protective CL immune responses. Healthy subjects, patients with active disease (PAD) and clinically cured patients were enrolled in the study. Total CD8+ T-lymphocytes showed a disturbance in the expression of the Vβ2, Vβ9, Vβ13.2, Vβ18 and Vβ23 families. The analyses of CD8+T-lymphocyte subsets showed high frequencies of LDE CD8+T-lymphocytes expressing Vβ12 and Vβ22 in PAD, as well as effector-memory CD8+ T-cells expressing Vβ22. We also observed low frequencies of effector and central-memory CD8+ T-cells expressing Vβ2 in PAD, which correlated with a greater lesion size. Particular Vβ expansions point to CD8+ T-cell clones that are selected during CL immune responses, suggesting that CD8+ T-lymphocytes expressing Vβ12 or Vβ22 are involved in a LDE response and that Vβ2 contractions in memory CD8+T-cells are associated with larger lesions. PMID:26107186

  4. Migration of Th1 lymphocytes is regulated by CD152 (CTLA-4-mediated signaling via PI3 kinase-dependent Akt activation.

    Directory of Open Access Journals (Sweden)

    Karin Knieke

    Full Text Available Efficient adaptive immune responses require the localization of T lymphocytes in secondary lymphoid organs and inflamed tissues. To achieve correct localization of T lymphocytes, the migration of these cells is initiated and directed by adhesion molecules and chemokines. It has recently been shown that the inhibitory surface molecule CD152 (CTLA-4 initiates Th cell migration, but the molecular mechanism underlying this effect remains to be elucidated. Using CD4 T lymphocytes derived from OVA-specific TCR transgenic CD152-deficient and CD152-competent mice, we demonstrate that chemokine-triggered signal transduction is differentially regulated by CD152 via phosphoinositide 3-kinase (PI3K-dependent activation of protein kinase B (PKB/Akt. In the presence of CD152 signaling, the chemoattractant CCL4 selectively induces the full activation of Akt via phosphorylation at threonine 308 and serine 473 in pro-inflammatory Th lymphocytes expressing the cognate chemokine receptor CCR5. Akt signals lead to cytoskeleton rearrangements, which are indispensable for migration. Therefore, this novel Akt-modulating function of CD152 signals affecting T cell migration demonstrates that boosting CD152 or its down-stream signal transduction could aid therapies aimed at sensitizing T lymphocytes for optimal migration, thus contributing to a precise and effective immune response.

  5. The regulation of SIRT2 function by cyclin-dependent kinases affects cell motility.

    NARCIS (Netherlands)

    Pandithage, R.; Lilischkis, R.; Harting, K.; Wolf, A.; Jedamzik, B.; Luscher-Firzlaff, J.; Vervoorts, J.; Lasonder, E.; Kremmer, E.; Knoll, B.; Luscher, B.

    2008-01-01

    Cyclin-dependent kinases (Cdks) fulfill key functions in many cellular processes, including cell cycle progression and cytoskeletal dynamics. A limited number of Cdk substrates have been identified with few demonstrated to be regulated by Cdk-dependent phosphorylation. We identify on protein express

  6. Elucidating How Surface Functionalization of Multiwalled Carbon Nanotube Affects Nanostructured MWCNT/Titania Hybrid Materials

    Directory of Open Access Journals (Sweden)

    Cheng-Fu Yang

    2015-01-01

    Full Text Available The new class of multiwalled carbon nanotube (MWCNT/titania nanocomposites was prepared using a sol-gel technique. The addition of titania to MWCNTs has the potential to provide new capability for the development of electrical devices by taking advantage of the favorable electric characteristics of MWCNTs. MWCNTs were first functionalized with carboxyl, acyl chloride, amine, and hydroxyl groups and were then dispersed in a tetraisopropyl titanate (TIPT solution via ultrasonic processing. After gelation, well-dispersed titania in the MWCNT/titania nanocomposites was obtained. Functionalized MWCNTs with varied functional groups were proved by Fourier transform infrared spectroscopy (FT-IR. For the nanocomposites, the degree of the sol-gel process were proved by Raman spectroscopy and wide-angle X-ray diffraction (WAXD. Furthermore, the morphology of the MWCNT/titania nanocomposites was observed using transmission electron microscopy (TEM. In the sol-gel process, the functionalized MWCNTs with carboxyl, acyl chloride, amine, and hydroxyl groups have resulted in the carbon nanotube-graft-titania nanocomposites with a network structure of titania between the carbon nanotubes.

  7. Does Gender-Specific Differential Item Functioning Affect the Structure in Vocational Interest Inventories?

    Science.gov (United States)

    Beinicke, Andrea; Pässler, Katja; Hell, Benedikt

    2014-01-01

    The study investigates consequences of eliminating items showing gender-specific differential item functioning (DIF) on the psychometric structure of a standard RIASEC interest inventory. Holland's hexagonal model was tested for structural invariance using a confirmatory methodological approach (confirmatory factor analysis and randomization…

  8. Age and environment affect constitutive immune function in Red Knots (Calidris canutus)

    NARCIS (Netherlands)

    Buehler, Deborah M.; Tieleman, B. Irene; Piersma, Theunis; Guglielmo, C.G.

    2009-01-01

    We studied subspecies, age and environmental effects on constitutive immune function (natural antibody and complement titres, haptoglobin activity and leukocyte concentrations) in Red Knots (Calidris canutus). We compared C. c. islandica and C. c. canutus in the Wadden Sea and found no difference in

  9. Can focused US with a diagnostic US contrast agent favorably affect renal function?

    Science.gov (United States)

    Sica, Domenic A

    2009-12-01

    Focused ultrasonography (US) with simultaneous administration of a US microbubble contrast agent was used to transiently increase the glomerular filtration rate while altering the sieving properties of glomeruli in normal rabbits. In its current form, this process has very limited application potential to states of abnormal renal function.

  10. Preterm Birth Affects Dorsal-Stream Functioning Even after Age 6

    Science.gov (United States)

    Santos, A.; Duret, M.; Mancini, J.; Gire, C.; Deruelle, C.

    2009-01-01

    With increasing numbers of preterm infants surviving, the impact of preterm birth on later cognitive development presents a major interest. This study investigates the impact of preterm birth on later dorsal- and ventral-stream functioning. An atypical pattern of performance was found for preterm children relative to full-term controls, but in the…

  11. The parasitic copepod Lernaeocera branchialis negatively affects cardiorespiratory function in Gadus morhua

    DEFF Research Database (Denmark)

    Behrens, Jane W.; Seth, H.; Axelsson, M.

    2014-01-01

    The parasitic copepod Lernaeocera branchialis had a negative effect on cardiorespiratory function in Atlantic cod Gadus morhua such that it caused pronounced cardiac dysfunction with irregular rhythm and reduced stroke amplitude compared with uninfected fish. In addition, parasite infection...... depressed the postprandial cardiac output and oxygen consumption...

  12. Functional Measurement Analysis of Brand Equity: Does Brand Name Affect Perceptions of Quality?

    Science.gov (United States)

    Hilgenkamp, Heather; Shanteau, James

    2010-01-01

    This research project used Functional Measurement to examine how the brand name of consumer products impacts intended purchasing decisions. Thirty undergraduate students tested actual products from three different product categories (crayons, tissues, and tortilla chips). Each product category consisted of three different brands; one with high…

  13. Loss of methylation at the IFNG promoter and CNS-1 is associated with the development of functional IFN-γ memory in human CD4(+) T lymphocytes.

    Science.gov (United States)

    Dong, Jun; Chang, Hyun-Dong; Ivascu, Claudia; Qian, Yu; Rezai, Soheila; Okhrimenko, Anna; Cosmi, Lorenzo; Maggi, Laura; Eckhardt, Florian; Wu, Peihua; Sieper, Joachim; Alexander, Tobias; Annunziato, Francesco; Gossen, Manfred; Li, Jun; Radbruch, Andreas; Thiel, Andreas

    2013-03-01

    Cytokine memory for IFN-γ production by effector/memory Th1 cells plays a key role in both protective and pathological immune responses. To understand the epigenetic mechanism determining the ontogeny of effector/memory Th1 cells characterized by stable effector functions, we identified a T-cell-specific methylation pattern at the IFNG promoter and CNS-1 in ex vivo effector/memory Th1 cells, and investigated methylation dynamics of these regions during the development of effector/memory Th1 cells. During Th1 differentiation, demethylation occurred at both the promoter and CNS-1 regions of IFNG as early as 16 h, and this process was independent of cell proliferation and DNA synthesis. Using an IFN-γ capture assay, we found early IFN-γ-producing cells from 2-day differentiating cultures acquired "permissive" levels of demethylation and developed into effector/memory Th1 cells undergoing progressive demethylation at the IFNG promoter and CNS-1 when induced by IL-12. Methylation levels of these regions in effector/memory Th1 cells of peripheral blood from rheumatoid arthritis patients correlated inversely with reduced frequencies of IFN-γ-producers, coincident with recruitment of effector/memory Th1 cells to the site of inflammation. Thus, after termination of TCR stimulation, IL-12 signaling potentiates the stable functional IFN-γ memory in effector/memory Th1 cells characterized by hypomethylation at the IFNG promoter and CNS-1.

  14. Lymphocytic hypophysitis masquerading as pituitary adenoma

    Directory of Open Access Journals (Sweden)

    Rajneesh Mittal

    2012-01-01

    Full Text Available Introduction: Pituitary hypophysitis (PH is characterized by pituitary infiltration of lymphocytes, macrophages, and plasma cells that could lead to loss of pituitary function. Hypophysitis may be autoimmune or secondary to systemic diseases or infections. Based on the histopathological findings PH is classified into lymphocytic, granulomatous, xanthomatous, mixed forms (lymphogranulomatous, xanthogranulomatous, necrotizing and Immunoglobulin- G4 (IgG4 plasmacytic types. Objective: To report a case of lymphocytic hypophysitis (LH. Case Report: A 15-year-old girl presented with history of headache, amenorrhea, and history of polyuria for past 4 months. Initial evaluation had suppressed follicular stimulating hormone (<0.01 mIU/ml, high prolactin levels (110.85 ng/ml and diabetes insipidus (DI. Magnetic resonance imaging of sella was suggestive of pituitary macroadenoma with partial compression over optic chiasma. Patient underwent surgical decompression. Yellowish firm tissue was evacuated and xanthochromic fluid was aspirated. Histopathology was suggestive of LH. She resumed her cycles postoperatively after 4 months, prolactin levels normalized, however, she continues to have DI and is on desmopressin spray. This case has been presented here for its rare presentation in an adolescent girl because it is mostly seen in young females and postpartum period and its unique presentation as an expanding pituitary mass with optic chiasma compression. Conclusion: Definitive diagnosis of LH is based on histopathological evaluation. Therapeutic approach should be based on the grade of suspicion and clinical manifestations of LH.

  15. Representations of modality-specific affective processing for visual and auditory stimuli derived from functional magnetic resonance imaging data.

    Science.gov (United States)

    Shinkareva, Svetlana V; Wang, Jing; Kim, Jongwan; Facciani, Matthew J; Baucom, Laura B; Wedell, Douglas H

    2014-07-01

    There is converging evidence that people rapidly and automatically encode affective dimensions of objects, events, and environments that they encounter in the normal course of their daily routines. An important research question is whether affective representations differ with sensory modality. This research examined the nature of the dependency of affect and sensory modality at a whole-brain level of analysis in an incidental affective processing paradigm. Participants were presented with picture and sound stimuli that differed in positive or negative valence in an event-related functional magnetic resonance imaging experiment. Global statistical tests, applied at a level of the individual, demonstrated significant sensitivity to valence within modality, but not valence across modalities. Modality-general and modality-specific valence hypotheses predict distinctly different multidimensional patterns of the stimulus conditions. Examination of lower dimensional representation of the data demonstrated separable dimensions for valence processing within each modality. These results provide support for modality-specific valence processing in an incidental affective processing paradigm at a whole-brain level of analysis. Future research should further investigate how stimulus-specific emotional decoding may be mediated by the physical properties of the stimuli.

  16. THE ROLE OF THE DIFFERENT SUBPOPULATIONS OF CD4+Т LYMPHOCYTES DURING PREGNANCY

    Directory of Open Access Journals (Sweden)

    D. I. Sokolov

    2016-01-01

    Full Text Available An important role in the formation of immunological tolerance during pregnancy play T lymphocytes. In the present review discusses the characteristics of T lymphocytes, decidua and placenta, especially their migration and functional activity during pregnancy. The review discusses the role of the subpopulations of Th1, Th17, Th2 and Treg lymphocytes in the formation of the placenta and the immune regulation of pregnancy, as well as their interaction with the cells of the decidua and trophoblast.

  17. A major population of mucosal memory CD4+ T cells, coexpressing IL-18Rα and DR3, display innate lymphocyte functionality

    DEFF Research Database (Denmark)

    Holmkvist, P.; Roepstorff, K.; Uronen-Hansson, H.

    2015-01-01

    , IL-5, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-22 in the presence of IL-12/ IL-18. TL1a synergized with IL-15 to enhance this response, while suppressing IL-15-induced IL-10 production. TL1a- and IL-15-mediated cytokine induction required the presence of IL-18, whereas...... induction of IL-5, IL-13, GM-CSF, and IL-22 was IL-12 independent. IL-18Rα+DR3+CD4+ T cells with similar functionality were present in human skin, nasal polyps, and, in particular, the intestine, where in chronic inflammation they localized with IL-18-producing cells in lymphoid aggregates. Collectively...

  18. Genes that affect brain structure and function identified by rare variant analyses of Mendelian neurologic disease

    Science.gov (United States)

    Karaca, Ender; Harel, Tamar; Pehlivan, Davut; Jhangiani, Shalini N.; Gambin, Tomasz; Akdemir, Zeynep Coban; Gonzaga-Jauregui, Claudia; Erdin, Serkan; Bayram, Yavuz; Campbell, Ian M.; Hunter, Jill V.; Atik, Mehmed M.; Van Esch, Hilde; Yuan, Bo; Wiszniewski, Wojciech; Isikay, Sedat; Yesil, Gozde; Yuregir, Ozge O.; Bozdogan, Sevcan Tug; Aslan, Huseyin; Aydin, Hatip; Tos, Tulay; Aksoy, Ayse; De Vivo, Darryl C.; Jain, Preti; Geckinli, B. Bilge; Sezer, Ozlem; Gul, Davut; Durmaz, Burak; Cogulu, Ozgur; Ozkinay, Ferda; Topcu, Vehap; Candan, Sukru; Cebi, Alper Han; Ikbal, Mevlit; Gulec, Elif Yilmaz; Gezdirici, Alper; Koparir, Erkan; Ekici, Fatma; Coskun, Salih; Cicek, Salih; Karaer, Kadri; Koparir, Asuman; Duz, Mehmet Bugrahan; Kirat, Emre; Fenercioglu, Elif; Ulucan, Hakan; Seven, Mehmet; Guran, Tulay; Elcioglu, Nursel; Yildirim, Mahmut Selman; Aktas, Dilek; Alikaşifoğlu, Mehmet; Ture, Mehmet; Yakut, Tahsin; Overton, John D.; Yuksel, Adnan; Ozen, Mustafa; Muzny, Donna M.; Adams, David R.; Boerwinkle, Eric; Chung, Wendy K.; Gibbs, Richard A.; Lupski, James R

    2015-01-01

    Development of the human nervous system involves complex interactions between fundamental cellular processes and requires a multitude of genes, many of which remain to be associated with human disease. We applied whole exome sequencing to 128 mostly consanguineous families with neurogenetic disorders that often included brain malformations. Rare variant analyses for both single nucleotide variant (SNV) and copy number variant (CNV) alleles allowed for identification of 45 novel variants in 43 known disease genes, 41 candidate genes, and CNVs in 10 families, with an overall potential molecular cause identified in >85% of families studied. Among the candidate genes identified, we found PRUNE, VARS, and DHX37 in multiple families, and homozygous loss of function variants in AGBL2, SLC18A2, SMARCA1, UBQLN1, and CPLX1. Neuroimaging and in silico analysis of functional and expression proximity between candidate and known disease genes allowed for further understanding of genetic networks underlying specific types of brain malformations. PMID:26539891

  19. The new PR of states: How nation branding practices affect the security function of public diplomacy

    DEFF Research Database (Denmark)

    Rasmussen, Rasmus Kjærgaard; Merkelsen, Henrik

    2012-01-01

    terrorism to national security initially served as a catalyst for new public diplomacy initiatives. But as the initiatives were implemented within a framework of nation branding the focus on risk reduction became subjected to a marketing logic and a new focus on economic objectives took over. The paper......This paper investigates how the role of public relations practice in public diplomacy is undergoing a transformation as a consequence of the influence from nation branding. A case study of the Danish government's response to the so-called Cartoon Crisis illustrates how the threat from international...... points to a possible future status of public diplomacy under the influence of nation branding: Public diplomacy may maintain a function pertinent to national security but as this function is incapable of managing real risks it will only serve as auto-communication that legitimizes security policy towards...

  20. Telomerase RNA stem terminus element affects template boundary element function, telomere sequence, and shelterin binding.

    Science.gov (United States)

    Webb, Christopher J; Zakian, Virginia A

    2015-09-08

    The stem terminus element (STE), which was discovered 13 y ago in human telomerase RNA, is required for telomerase activity, yet its mode of action is unknown. We report that the Schizosaccharomyces pombe telomerase RNA, TER1 (telomerase RNA 1), also contains a STE, which is essential for telomere maintenance. Cells expressing a partial loss-of-function TER1 STE allele maintained short stable telomeres by a recombination-independent mechanism. Remarkably, the mutant telomere sequence was different from that of wild-type cells. Generation of the altered sequence is explained by reverse transcription into the template boundary element, demonstrating that the STE helps maintain template boundary element function. The altered telomeres bound less Pot1 (protection of telomeres 1) and Taz1 (telomere-associated in Schizosaccharomyces pombe 1) in vivo. Thus, the S. pombe STE, although distant from the template, ensures proper telomere sequence, which in turn promotes proper assembly of the shelterin complex.

  1. The direct and indirect effects of the negative affectivity trait on self reported physical function among patients with upper extremity conditions.

    Science.gov (United States)

    Talaei-Khoei, Mojtaba; Mohamadi, Amin; Mellema, Jos J; Tourjee, Stephen M; Ring, David; Vranceanu, Ana-Maria

    2016-12-30

    Negative affectivity is a personality trait that predisposes people to psychological distress and low life satisfaction. Negative affectivity may also affect pain intensity and physical function in patients with musculoskeletal conditions. We explored the association of negative affectivity to pain intensity and self-reported physical function, and tested whether pain intensity mediates the effect of negative affectivity on physical function. In a cross-sectional study, 102 patients with upper extremity musculoskeletal conditions presenting to an orthopedic surgeon completed self-report measures of negative affectivity, pain intensity, and physical function in addition to demographic and injury information. We used the Preacher and Hayes' bootstrapping approach to quantify the indirect effect of negative affectivity on physical function through pain intensity. Negative affectivity correlated with greater pain intensity and lower self-reported physical function significantly. Also, pain intensity mediated the association of negative affectivity with physical function. The indirect effect accounted for one-third of the total effect. To conclude, negative affectivity is associated with decreased engagement in daily life activities both directly, but also indirectly through increased pain intensity. Treatments targeting negative affectivity may be more economical and efficient for alleviation of pain and limitations associated with musculoskeletal illness than those addressing coping strategies or psychological distress.

  2. Can common functional gene variants affect visual discrimination in metacontrast masking?

    Directory of Open Access Journals (Sweden)

    Margus Maksimov

    Full Text Available Mechanisms of visual perception should be robustly fast and provide veridical information about environmental objects in order to facilitate survival and successful coping. Because species-specific brain mechanisms for fast vision must have evolved under heavy pressure for efficiency, it has been held that different human individuals see the physical world in the same way and produce psychophysical functions of visual discrimination that are qualitatively the same. For many years, this assumption has been implicitly accepted in vision research studying extremely fast, basic visual processes, including studies of visual masking. However, in recent studies of metacontrast masking surprisingly robust individual differences in the qualitative aspects of subjects' performance have been found. As the basic species-specific visual functions very likely are based on universal brain mechanisms of vision, these differences probably are the outcome of variability in ontogenetic development (i.e., formation of idiosyncrasic skills of perception. Such developmental differences can be brought about by variants of genes that are differentially expressed in the course of CNS development. The objective of this study was to assess whether visual discrimination in metacontrast masking is related to three widely studied genetic polymorphisms implicated in brain function and used here as independent variables. The findings suggest no main effects of BDNF Val66Met, NRG1/rs6994992, or 5-HTTLPR polymorphisms on metacontrast performance, but several notable interactions of genetic variables with gender, stage of the sequence of experimental trials, perceptual strategies, and target/mask shape congruence were found. Thus, basic behavioral functions of fast vision may be influenced by common genetic variability. Also, when left uncontrolled, genetic factors may seriously confound variables in vision research using masking, obscure clear theoretical interpretation, lead to

  3. Elementary Neurocognitive Function, Facial Affect Recognition and Social-skills in Schizophrenia

    OpenAIRE

    Meyer, Melissa B.; Kurtz, Matthew M.

    2009-01-01

    Social-skill deficits are pervasive in schizophrenia and negatively impact many key aspects of functioning. Prior studies have found that measures of elementary neurocognition and social cognition are related to social-skills. In the present study we selected a range of neurocognitive measures and examined their relationship with identification of happy and sad faces and performance-based social-skills. Fifty-three patients with schizophrenia or schizoaffective disorder participated. Results ...

  4. A loss-of-function mutation in Calmodulin2 gene affects pollen germination in Arabidopsis thaliana.

    Science.gov (United States)

    Landoni, Michela; De Francesco, Alessandra; Galbiati, Massimo; Tonelli, Chiara

    2010-10-01

    Calmodulin (CAM) is an ubiquitous calcium binding protein whose function is to translate the signals, perceived as calcium concentration variations, into the appropriate cellular responses. In Arabidopsis thaliana there are 4 CAM isoforms which are highly similar, encoded by 7 genes, and one possible explanation proposed for the evolutionary conservation of the CAM gene family is that the different genes have acquired different functions so that they play possibly overlapping but non-identical roles. Here we report the characterization of the Arabidopsis mutant cam2-2, identified among the lines of the gene-trapping collection EXOTIC because of a distorted segregation of kanamycin resistance. Phenotypic analysis showed that in normal growth conditions cam2-2 plants were indistinguishable from the wild type while genetic analysis showed a reduced transmission of the cam2-2 allele through the male gametophyte and in vitro pollen germination revealed a reduced level of germination in comparison with the wild type. These results provide genetic evidence of the involvement of a CAM gene in pollen germination and support the theory of functional diversification of the CAM gene family.

  5. Viewing nature scenes positively affects recovery of autonomic function following acute-mental stress.

    Science.gov (United States)

    Brown, Daniel K; Barton, Jo L; Gladwell, Valerie F

    2013-06-04

    A randomized crossover study explored whether viewing different scenes prior to a stressor altered autonomic function during the recovery from the stressor. The two scenes were (a) nature (composed of trees, grass, fields) or (b) built (composed of man-made, urban scenes lacking natural characteristics) environments. Autonomic function was assessed using noninvasive techniques of heart rate variability; in particular, time domain analyses evaluated parasympathetic activity, using root-mean-square of successive differences (RMSSD). During stress, secondary cardiovascular markers (heart rate, systolic and diastolic blood pressure) showed significant increases from baseline which did not differ between the two viewing conditions. Parasympathetic activity, however, was significantly higher in recovery following the stressor in the viewing scenes of nature condition compared to viewing scenes depicting built environments (RMSSD; 50.0 ± 31.3 vs 34.8 ± 14.8 ms). Thus, viewing nature scenes prior to a stressor alters autonomic activity in the recovery period. The secondary aim was to examine autonomic function during viewing of the two scenes. Standard deviation of R-R intervals (SDRR), as change from baseline, during the first 5 min of viewing nature scenes was greater than during built scenes. Overall, this suggests that nature can elicit improvements in the recovery process following a stressor.

  6. Titanium dioxide nanoparticles strongly impact soil microbial function by affecting archaeal nitrifiers

    Science.gov (United States)

    Simonin, Marie; Richaume, Agnès; Guyonnet, Julien P.; Dubost, Audrey; Martins, Jean M. F.; Pommier, Thomas

    2016-01-01

    Soils are facing new environmental stressors, such as titanium dioxide nanoparticles (TiO2-NPs). While these emerging pollutants are increasingly released into most ecosystems, including agricultural fields, their potential impacts on soil and its function remain to be investigated. Here we report the response of the microbial community of an agricultural soil exposed over 90 days to TiO2-NPs (1 and 500 mg kg−1 dry soil). To assess their impact on soil function, we focused on the nitrogen cycle and measured nitrification and denitrification enzymatic activities and by quantifying specific representative genes (amoA for ammonia-oxidizers, nirK and nirS for denitrifiers). Additionally, diversity shifts were examined in bacteria, archaea, and the ammonia-oxidizing clades of each domain. With strong negative impacts on nitrification enzyme activities and the abundances of ammonia-oxidizing microorganism, TiO2-NPs triggered cascading negative effects on denitrification enzyme activity and a deep modification of the bacterial community structure after just 90 days of exposure to even the lowest, realistic concentration of NPs. These results appeal further research to assess how these emerging pollutants modify the soil health and broader ecosystem function. PMID:27659196

  7. Silver Nanoparticles Affect Functional Bioenergetic Traits in the Invasive Red Sea Mussel Brachidontes pharaonis

    Science.gov (United States)

    Saggese, Ilenia; Sarà, Gianluca

    2016-01-01

    We investigated the functional trait responses to 5 nm metallic silver nanoparticle (AgNPs) exposure in the Lessepsian-entry bivalve B. pharaonis. Respiration rate (oxygen consumption), heartbeat rate, and absorption efficiency were evaluated across an 8-day exposure period in mesocosmal conditions. Basal reference values from not-exposed specimens were statistically compared with those obtained from animals treated with three sublethal nanoparticle concentrations (2 μg L−1, 20 μg L−1, and 40 μg L−1). Our data showed statistically significant effects on the average respiration rate of B. pharaonis. Moreover, complex nonlinear dynamics were observed as a function of the concentration level and time. Heartbeat rates largely increased with no acclimation in animals exposed to the two highest levels with similar temporal dynamics. Eventually, a decreasing trend for absorption efficiency might indicate energetic constraints. In general, these data support the possible impact of engineered nanomaterials in marine environments and support the relevance of functional trait assessment in present and future ecotoxicological studies.

  8. Titanium dioxide nanoparticles strongly impact soil microbial function by affecting archaeal nitrifiers

    Science.gov (United States)

    Simonin, Marie; Richaume, Agnès; Guyonnet, Julien P.; Dubost, Audrey; Martins, Jean M. F.; Pommier, Thomas

    2016-09-01

    Soils are facing new environmental stressors, such as titanium dioxide nanoparticles (TiO2-NPs). While these emerging pollutants are increasingly released into most ecosystems, including agricultural fields, their potential impacts on soil and its function remain to be investigated. Here we report the response of the microbial community of an agricultural soil exposed over 90 days to TiO2-NPs (1 and 500 mg kg‑1 dry soil). To assess their impact on soil function, we focused on the nitrogen cycle and measured nitrification and denitrification enzymatic activities and by quantifying specific representative genes (amoA for ammonia-oxidizers, nirK and nirS for denitrifiers). Additionally, diversity shifts were examined in bacteria, archaea, and the ammonia-oxidizing clades of each domain. With strong negative impacts on nitrification enzyme activities and the abundances of ammonia-oxidizing microorganism, TiO2-NPs triggered cascading negative effects on denitrification enzyme activity and a deep modification of the bacterial community structure after just 90 days of exposure to even the lowest, realistic concentration of NPs. These results appeal further research to assess how these emerging pollutants modify the soil health and broader ecosystem function.

  9. 不同外邪对正常及免疫功能低下小鼠脾淋巴细胞增殖能力的影响%Effect of attacks factors on the immunesplenic Lymphocytes proliferation capacity of normal and low immune function mice

    Institute of Scientific and Technical Information of China (English)

    马彦平; 郭彩云; 李俊莲; 李艳彦; 杨琬芳; 李孝波; 王平; 陶功定

    2012-01-01

    Objective: To detect the proliferation capacity of splenic lymphocytes of mice in the cold, cold dampness and hot and humid environment, and discusses the effect of different factors of attacks on the immune functions of mice. Methods: We choose knife bean protein (ConA) induced spleen lymphocyte proliferation, use the MTT method to determine the spleen lymphatic proliferation capacity in mice. Results: ①The mice splenic lymphocytes proliferation capacity of all the attack factors processing groups were significantly lower than the normal group (P<0.01).②All the attack factors processing low immune functions groups compared with low immune function group, the splenic lymphocytes proliferation capacity of wind-cold, cold-dampness low immune function groups reduced significantly (P<0.01); the splenic lymphocytes proliferation capacity of dampness-heat low immune function groups decreasd, but this was not statistically significant. ③The wind-cold low immune function group compared with the wind-cold group, the cold-dampness low immune function group compared with the cold-dampness group, the dampness-heat low immune function group compared with the dampness-heat group, all the mice splenic lymphocytes proliferation capacity significantly reduced (P<0.01). Conclusion: Compared with the normal group, the mice splenic lymphocytes proliferation capacity of all the attack factor processing groups reduced, the mice splenic lymphocytes proliferation capacity of low immune modle groups especially signigicant. The study shows that the three attacks factors of wind-cold, cold-dampness, dampness-heat can make the immune function of mice reduce and cause the happen of the disease easily.%目的:通过检测在风寒、寒湿和湿热环境下小鼠脾淋巴细胞的增殖能力,探讨不同外邪因素对小鼠免疫功能的影响.方法:选择刀豆蛋白(ConA)诱导脾淋巴细胞增殖,采用MTT法测定小鼠脾淋巴细胞增殖能力.结果:①各外邪因素处理

  10. Differential requirement for protein tyrosine kinase Fyn in the functional activation of antigen-specific T lymphocyte clones through the TCR or Thy-1.

    Science.gov (United States)

    Lancki, D W; Qian, D; Fields, P; Gajewski, T; Fitch, F W

    1995-05-01

    The protein tyrosine kinase Fyn has been shown to be involved in signal transduction through the TCR and the glycosyl-phosphatidylinositol-linked surface molecule Thy-1 expressed on T cells. In this study, we examine the requirement for Fyn expression in signaling through the TCR or Thy-1 using a panel of Ag-specific T cell clones derived from fyn-/- mutant mice. These clones do not express normal Fyn protein, as measured by immune-complex kinase reaction using anti-Fyn Ab. Stimulation through the TCR, either by APC bearing relevant Ag or by immobilized anti-CD3 mAb, resulted in comparable levels of proliferation, lymphokine production, and cytolysis by clones from both wild-type and fyn-/- mice. In contrast, stimulation through Thy-1, using soluble (or cross-linked) anti-Thy-1 mAb, was deficient, as measured by these responses. Thus, Fyn expression is selectively required for functional activation through Thy-1 in these T cell clones.

  11. Megakaryocytes and platelets express nicotinic acetylcholine receptors but nicotine does not affect megakaryopoiesis or platelet function.

    Science.gov (United States)

    Schedel, Angelika; Kaiser, Kerstin; Uhlig, Stefanie; Lorenz, Florian; Sarin, Anip; Starigk, Julian; Hassmann, Dennis; Bieback, Karen; Bugert, Peter

    2016-01-01

    In our previous investigations we have shown that platelets and their precursors express nicotinic α7 acetylcholine receptors (nAChRα7) that are involved in platelet function and in vitro differentiation of the megakaryoblastic cell line MEG-01. In this study, we were interested in the expression analysis of additional nAChR and the effects of nicotine in an ex vivo model using megakaryocytic cells differentiated from cord blood derived CD34(+) cells (CBMK) and an in vivo model using blood samples from smokers. CBMK were differentiated with thrombopoietin (TPO) for up to 17 days. Quantitative real-time PCR (QRT-PCR), Western blot analysis and flow cytometry were used to investigate nAChR expression (nAChRα7, nAChRα4, nAChRβ2) and nicotine effects. In blood samples of 15 nonsmokers and 16 smokers platelet parameters (count, mean platelet volume--MPV and platelet distribution width--PDW) were determined as indicators for changes of in vivo megakaryopoiesis. Platelet function was determined by the use of whole blood aggregometry and flow cytometry. The functional role of nAChR was evaluated using specific antagonists in aggregometry. CHRNA7, CHRNA4 and CHRNB2 gene transcripts and the corresponding proteins could be identified in CBMK during all stages of differentiation. Platelets contain nAChRα7 and nAChRβ2 but not nAChRα4. Nicotine had no effect on TPO-induced differentiation of CBMK. There was no significant difference in all platelet parameters of the smokers compared to the nonsmokers. In line with this, cholinergic gene transcripts as well as the encoded proteins were equally expressed in both the study groups. Despite our observation of nAChR expression in megakaryopoiesis and platelets, we were not able to detect effects of nicotine in our ex vivo and in vivo models. Thus, the functional role of the nAChR in these cells remains open.

  12. Urokinase plasminogen activator receptor affects bone homeostasis by regulating osteoblast and osteoclast function

    DEFF Research Database (Denmark)

    Furlan, Federico; Galbiati, Clara; Jørgensen, Niklas R;

    2007-01-01

    reorganization in mature osteoclasts. INTRODUCTION: Urokinase receptor (uPAR) is actively involved in the regulation of important cell functions, such as proliferation, adhesion, and migration. It was previously shown that the major players in bone remodeling, osteoblasts and osteoclasts, express u...... with other osteoblasts markers. On the resorptive side, the number of osteoclasts formed in vitro from uPAR KO monocytes was decreased. Podosome imaging in uPAR KO osteoclasts revealed a defect in actin ring formation. CONCLUSIONS: The defective proliferation and differentiation of bone cells, coincident...

  13. Defects in the COG complex and COG-related trafficking regulators affect neuronal Golgi function.

    Directory of Open Access Journals (Sweden)

    Leslie K Climer

    2015-10-01

    Full Text Available The Conserved Oligomeric Golgi (COG complex is an evolutionarily conserved hetero-octameric protein complex that has been proposed to organize vesicle tethering at the Golgi apparatus. Defects in seven of the eight COG subunits are linked to Congenital Disorders of Glycosylation (CDG-type II, a family of rare diseases involving misregulation of protein glycosylation, alterations in Golgi structure, variations in retrograde trafficking through the Golgi and system-wide clinical pathologies. A troublesome aspect of these diseases are the neurological pathologies such as low IQ, microcephaly and cerebellar atrophy. The essential function of the COG complex is dependent upon interactions with other components of trafficking machinery, such as Rab-GTPases and SNAREs. COG-interacting Rabs and SNAREs have been implicated in neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease. Defects in Golgi maintenance disrupts trafficking and processing of essential proteins, frequently associated with and contributing to compromised neuron function and human disease. Despite the recent advances in molecular neuroscience, the subcellular bases for most neurodegenerative diseases are poorly understood. This article gives an overview of the potential contributions of the COG complex and its Rab and SNARE partners in the pathogenesis of different neurodegenerative disorders.

  14. Starch, functional properties, and microstructural characteristics in chickpea and lentil as affected by thermal processing.

    Science.gov (United States)

    Aguilera, Yolanda; Esteban, Rosa M; Benítez, Vanesa; Mollá, Esperanza; Martín-Cabrejas, María A

    2009-11-25

    Changes in starch, functional, and microstructural characteristics that occurred in chickpea and lentil under soaking, cooking, and industrial dehydration processing were evaluated. Available starch in raw legumes represented 57-64%, and resistant starch (RS) is a significant component. As a result of cooking, available starch contents of soaked chickpea and lentil were significantly increased (21 and 12%, respectively) and RS decreased (65 and 49%, respectively) compared to raw flours. A similar trend was exhibited by dehydration, being more relevant in lentil (73% of RS decrease). The minimum nitrogen solubility of raw flours was at pH 3, and a high degree of protein insolubilization (80%) was observed in dehydrated flours. The raw legume flours exhibited low oil-holding capacities, 0.95-1.10 mL/g, and did not show any change by thermal processing, whereas water-holding capacities rose to 4.80-4.90 mL/g of sample. Emulsifying activity and foam capacity exhibited reductions as a result of cooking and industrial dehydration processing. The microstructural observations were consistent with the chemical results. Thus, the obtained cooked and dehydrated legume flours could be considered as functional ingredients for food formulation.

  15. Mexico City air pollution adversely affects olfactory function and intranasal trigeminal sensitivity.

    Science.gov (United States)

    Guarneros, Marco; Hummel, Thomas; Martínez-Gómez, Margaríta; Hudson, Robyn

    2009-11-01

    Surprisingly little is known about the effects of big-city air pollution on olfactory function and even less about its effects on the intranasal trigeminal system, which elicits sensations like burning, stinging, pungent, or fresh and contributes to the overall chemosensory experience. Using the Sniffin' Sticks olfactory test battery and an established test for intranasal trigeminal perception, we compared the olfactory performance and trigeminal sensitivity of residents of Mexico City, a region with high air pollution, with the performance of a control population from the Mexican state of Tlaxcala, a geographically comparable but less polluted region. We compared the ability of 30 young adults from each location to detect a rose-like odor (2-phenyl ethanol), to discriminate between different odorants, and to identify several other common odorants. The control subjects from Tlaxcala detected 2-phenyl ethanol at significantly lower concentrations than the Mexico City subjects, they could discriminate between odorants significantly better, and they performed significantly better in the test of trigeminal sensitivity. We conclude that Mexico City air pollution impairs olfactory function and intranasal trigeminal sensitivity, even in otherwise healthy young adults.

  16. Socio-dramatic affective-relational intervention for adolescents with asperger syndrome & high functioning autism: pilot study.

    Science.gov (United States)

    Lerner, Matthew D; Mikami, Amori Yee; Levine, Karen

    2011-01-01

    This study examined the effectiveness of a novel intervention called 'socio-dramatic affective-relational intervention' (SDARI), intended to improve social skills among adolescents with Asperger syndrome and high functioning autism diagnoses. SDARI adapts dramatic training activities to focus on in vivo practice of areas of social skill deficit among this population. SDARI was administered as a six-week summer program in a community human service agency. Nine SDARI participants and eight age- and diagnosis-group matched adolescents not receiving SDARI were compared on child- and parent-report of social functioning at three week intervals beginning six weeks prior to intervention and ending six weeks post-intervention. Hierarchical Linear Modeling (HLM) was used to estimate growth trends between groups to assess treatment outcomes and post-treatment maintenance. Results indicated significant improvement and post-treatment maintenance among SDARI participants on several measures of child social functioning. Implications for practice and research are discussed.

  17. Land Management Effects on Biogeochemical Functioning of Salt-Affected Paddy Soils

    Institute of Scientific and Technical Information of China (English)

    C.QUANTIN; O.GRUNBERGER; N.SUVANNANG; E.BOURDON

    2008-01-01

    Most lowlands in Northeast Thailand (Isaan region) are cultivated with rice and large areas are affected by salinity,which drastically limits rice production.A field experiment was conducted during the 2003 rainy season to explore the interactions between salinity and land management in two fields representative of two farming practices:an intensively managed plot with organic inputs and efficient water management,and one without organic matter addition.Field measurements,including pH,Eh,electrical conductivity (EC),and soil solution chemistry,were performed at three depths,with a particular focus on Fe dynamics,inside and outside saline patches.High reducing conditions appeared after flooding particularly in plots receiving organic matter and reduction processes leading to oxide reduction and to the release of Fe and,to a lesser extend,Mn to the soil solution.Oxide reduction led to the consumption of H+ and the more the Fe reduction was,the higher the pH was,up to 6.5.Formation of hydroxy-green rust were likely to be at the origin of the pH stabilization.In the absence of organic amendments,high salinity prevented the establishment of the reduction processes and pH value remained around 4.Even under high reduction conditions,the Fe concentrations in the soil solution were below commonly observed toxic values and the amended plot had better rice production yield.

  18. Citrus limon extract: possible inhibitory mechanisms affecting testicular functions and fertility in male mice.

    Science.gov (United States)

    Singh, Nidhi; Singh, Shio Kumar

    2016-01-01

    The effect of oral administration of 50% ethanolic leaf extract of Citrus limon (500 and 1,000 mg/kg body weight/day) for 35 days on fertility and various male reproductive endpoints was evaluated in Parkes strain of mice. Testicular indices such as histology, 3β- and 17β-HSD enzymes activity, immunoblot expression of StAR and P450scc, and germ cell apoptosis by TUNEL and CASP- 3 expression were assessed. Motility, viability, and number of spermatozoa in the cauda epididymidis, level of serum testosterone, fertility indices, and toxicological parameters were also evaluated. Histologically, testes in extract-treated mice showed nonuniform degenerative changes in the seminiferous tubules. Treatment had adverse effects on steroidogenic markers in the testis and induced germ cell apoptosis. Significant reductions were noted in epididymal sperm parameters and serum level of testosterone in Citrus-treated mice compared to controls. Fertility of the extract-treated males was also suppressed, but libido remained unaffected. By 56 days of treatment withdrawal, alterations induced in the above parameters returned to control levels suggesting that Citrus treatment causes reversible suppression of spermatogenesis and fertility in Parkes mice. Suppression of spermatogenesis may result from germ cell apoptosis because of decreased production of testosterone. The present work indicated that Citrus leaves can affect male reproduction.

  19. Performance of Music Elevates Pain Threshold and Positive Affect: Implications for the Evolutionary Function of Music

    Directory of Open Access Journals (Sweden)

    R.I.M. Dunbar

    2012-10-01

    Full Text Available It is well known that music arouses emotional responses. In addition, it has long been thought to play an important role in creating a sense of community, especially in small scale societies. One mechanism by which it might do this is through the endorphin system, and there is evidence to support this claim. Using pain threshold as an assay for CNS endorphin release, we ask whether it is the auditory perception of music that triggers this effect or the active performance of music. We show that singing, dancing and drumming all trigger endorphin release (indexed by an increase in post-activity pain tolerance in contexts where merely listening to music and low energy musical activities do not. We also confirm that music performance results in elevated positive (but not negative affect. We conclude that it is the active performance of music that generates the endorphin high, not the music itself. We discuss the implications of this in the context of community bonding mechanisms that commonly involve dance and music-making.

  20. Zebra pattern in rocks as a function of grain growth affected by second-phase particles

    Directory of Open Access Journals (Sweden)

    Ulrich eKelka

    2015-09-01

    Full Text Available In this communication we present a simple microdynamic model which can explain the beginning of the zebra pattern formation in rocks. The two dimensional model consists of two main processes, mineral replacement along a reaction front, and grain boundary migration affected by impurities. In the numerical model we assume that an initial distribution of second-phase particles is present due to sedimentary layering. The reaction front percolates the model and redistributes second-phase particles by shifting them until the front is saturated and drops the particles again. This produces and enhances initial layering. Grain growth is hindered in layers with high second-phase particle concentrations whereas layers with low concentrations coarsen. Due to the grain growth activity in layers with low second-phase particle concentrations these impurities are collected at grain boundaries and the crystals become very clean. Therefore the white layers in the pattern contain large grains with low concentration of second-phase particles, whereas the dark layers contain small grains with a large second-phase particle concentration.

  1. Performance of music elevates pain threshold and positive affect: implications for the evolutionary function of music.

    Science.gov (United States)

    Dunbar, R I M; Kaskatis, Kostas; MacDonald, Ian; Barra, Vinnie

    2012-10-22

    It is well known that music arouses emotional responses. In addition, it has long been thought to play an important role in creating a sense of community, especially in small scale societies. One mechanism by which it might do this is through the endorphin system, and there is evidence to support this claim. Using pain threshold as an assay for CNS endorphin release, we ask whether it is the auditory perception of music that triggers this effect or the active performance of music. We show that singing, dancing and drumming all trigger endorphin release (indexed by an increase in post-activity pain tolerance) in contexts where merely listening to music and low energy musical activities do not. We also confirm that music performance results in elevated positive (but not negative) affect. We conclude that it is the active performance of music that generates the endorphin high, not the music itself. We discuss the implications of this in the context of community bonding mechanisms that commonly involve dance and music-making.

  2. Stereological quantification of lymphocytes in skin biopsies from atopic dermatitis patients

    DEFF Research Database (Denmark)

    Ellingsen, A R; Sørensen, Flemming Brandt; Larsen, J O;

    2001-01-01

    Atopic dermatitis (AD) is histologically characterized by lymphocytic infiltration of the skin and quantitative assessment is required. This study introduces stereological techniques to quantify the number of lymphocytes in skin biopsies. Four-millimetre punch biopsies were taken from skin...... with active eczema in 8 adults with AD and from clinically normal skin from 4 of the patients. Five persons without allergy or skin disease served as controls. The mean number of lymphocytes in 4-mm skin biopsies was 469,000 and 124,000 in active eczema and in clinically normal skin, respectively. Compared...... with controls, the number of lymphocytes in biopsies increased by a factor of 6.8 in active eczema and a factor of 1.8 in clinically normal skin. If 20% of skin is affected by eczema the total number of lymphocytes located in the affected skin can be estimated to 1.27 x 10(10). A patient with clinically...

  3. Maternal separation affects dopamine transporter function in the Spontaneously Hypertensive Rat: An in vivo electrochemical study

    Directory of Open Access Journals (Sweden)

    Womersley Jacqueline S

    2011-12-01

    Full Text Available Abstract Background Attention-deficit/hyperactivity disorder (ADHD is a developmental disorder characterised by symptoms of inattention, impulsivity and hyperactivity. The spontaneously hypertensive rat (SHR is a well-characterised model of this disorder and has been shown to exhibit dopamine dysregulation, one of the hypothesised causes of ADHD. Since stress experienced in the early stages of life can have long-lasting effects on behaviour, it was considered that early life stress may alter development of the dopaminergic system and thereby contribute to the behavioural characteristics of SHR. It was hypothesized that maternal separation would alter dopamine regulation by the transporter (DAT in ways that distinguish SHR from control rat strains. Methods SHR and control Wistar-Kyoto (WKY rats were subjected to maternal separation for 3 hours per day from postnatal day 2 to 14. Rats were tested for separation-induced anxiety-like behaviour followed by in vivo chronoamperometry to determine whether changes had occurred in striatal clearance of dopamine by DAT. The rate of disappearance of ejected dopamine was used as a measure of DAT function. Results Consistent with a model for ADHD, SHR were more active than WKY in the open field. SHR entered the inner zone more frequently and covered a significantly greater distance than WKY. Maternal separation increased the time that WKY spent in the closed arms and latency to enter the open arms of the elevated plus maze, consistent with other rat strains. Of note is that, maternal separation failed to produce anxiety-like behaviour in SHR. Analysis of the chronoamperometric data revealed that there was no difference in DAT function in the striatum of non-separated SHR and WKY. Maternal separation decreased the rate of dopamine clearance (k-1 in SHR striatum. Consistent with this observation, the dopamine clearance time (T100 was increased in SHR. These results suggest that the chronic mild stress of

  4. Severity of negative symptoms significantly affects cognitive functioning in patients with chronic schizophrenia: the slowing in cognitive processing

    Directory of Open Access Journals (Sweden)

    Flavia S. Galaverna

    2014-09-01

    Full Text Available Background and Objectives: Studies in patients with schizophrenia have shown a decreased overall cognitive performance, and it was found that processing speed and working memory functions are affected. The aim of this study was to describe the general cognitive performance of patients with chronic schizophrenia and analyze its relationship with the severity of psychotic symptoms. Methods: Forty-eight patients diagnosed with DSM IV-TR schizophrenia disorder were examined for symptom improvement, measured by scales SAPS and SANS. Participants also completed the full scale WAIS-III. Results: The results show a generalized cognitive deficit, reflected in the low level of general intelligence, as well as the different index that comprise the scale. The most compromised index was the processing speed. The correlations showed that the overall severity of negative symptoms significantly affects cognitive functioning of chronic patients. The formal thought disorder and alogia significantly correlated with almost all the WAIS-III measures. Conclusions: Multiple studies of specific cognitive domains in schizophrenia have shown that deficits in processing speed are the core element of cognitive impairment in schizophrenia. We support the hypothesis about the slowing in cognitive processing affect both the performance of the basic and more complex cognitive task.

  5. Anti-inflammatory effects of novel barbituric acid derivatives in T lymphocytes.

    Science.gov (United States)

    Xu, Chenjia; Wyman, Arlene R; Alaamery, Manal A; Argueta, Shannon A; Ivey, F Douglas; Meyers, John A; Lerner, Adam; Burdo, Tricia H; Connolly, Timothy; Hoffman, Charles S; Chiles, Thomas C

    2016-09-01

    We have used a high throughput small molecule screen, using a fission yeast-based assay, to identify novel phosphodiesterase 7 (PDE7) inhibitors. One of the most effective hit compounds was BC12, a barbituric acid-based molecule that exhibits unusually potent immunosuppressive and immunomodulatory actions on T lymphocyte function, including inhibition of T cell proliferation and IL-2 cytokine production. BC12 treatment confers a >95% inhibition of IL-2 secretion in phytohaemagglutinin (PHA) plus phorbol-12-myristate-13-acetate (PMA) stimulated Jurkat T cells. The effect of BC12 on IL-2 secretion is not due to decreased cell viability; rather, BC12 blocks up-regulation of IL-2 transcription in activated T cells. BC12 also inhibits IL-2 secretion in human peripheral T lymphocytes stimulated in response to CD3/CD28 co-ligation or the combination of PMA and ionomycin, as well as the proliferation of primary murine T cells stimulated with PMA and ionomycin. A BC12 analog that lacks PDE7 inhibitory activity (BC12-4) displays similar biological activity, suggesting that BC12 does not act via PDE7 inhibition. To investigate the mechanism of inhibition of IL-2 production by BC12, we performed microarray analyses using unstimulated and stimulated Jurkat T cells in the presence or absence of BC12 or BC12-4. Our studies show these compounds affect the transcriptional response to stimulation and act via one or more shared targets to produce both anti-inflammatory and pro-stress effects. These results demonstrate potent immunomodulatory activity for BC12 and BC12-4 in T lymphocytes and suggest a potential clinical use as an immunotherapeutic to treat T lymphocyte-mediated diseases.

  6. Zebrafish: A Model for the Study of Toxicants Affecting Muscle Development and Function

    Science.gov (United States)

    Dubińska-Magiera, Magda; Daczewska, Małgorzata; Lewicka, Anna; Migocka-Patrzałek, Marta; Niedbalska-Tarnowska, Joanna; Jagla, Krzysztof

    2016-01-01

    The rapid progress in medicine, agriculture, and allied sciences has enabled the development of a large amount of potentially useful bioactive compounds, such as drugs and pesticides. However, there is another side of this phenomenon, which includes side effects and environmental pollution. To avoid or minimize the uncontrollable consequences of using the newly developed compounds, researchers seek a quick and effective means of their evaluation. In achieving this goal, the zebrafish (Danio rerio) has proven to be a highly useful tool, mostly because of its fast growth and development, as well as the ability to absorb the molecules diluted in water through its skin and gills. In this review, we focus on the reports concerning the application of zebrafish as a model for assessing the impact of toxicants on skeletal muscles, which share many structural and functional similarities among vertebrates, including zebrafish and humans. PMID:27869769

  7. Zebrafish: A Model for the Study of Toxicants Affecting Muscle Development and Function

    Directory of Open Access Journals (Sweden)

    Magda Dubińska-Magiera

    2016-11-01

    Full Text Available The rapid progress in medicine, agriculture, and allied sciences has enabled the development of a large amount of potentially useful bioactive compounds, such as drugs and pesticides. However, there is another side of this phenomenon, which includes side effects and environmental pollution. To avoid or minimize the uncontrollable consequences of using the newly developed compounds, researchers seek a quick and effective means of their evaluation. In achieving this goal, the zebrafish (Danio rerio has proven to be a highly useful tool, mostly because of its fast growth and development, as well as the ability to absorb the molecules diluted in water through its skin and gills. In this review, we focus on the reports concerning the application of zebrafish as a model for assessing the impact of toxicants on skeletal muscles, which share many structural and functional similarities among vertebrates, including zebrafish and humans.

  8. Urokinase plasminogen activator receptor affects bone homeostasis by regulating osteoblast and osteoclast function

    DEFF Research Database (Denmark)

    Furlan, Federico; Galbiati, Clara; Jørgensen, Niklas R;

    2007-01-01

    reorganization in mature osteoclasts. INTRODUCTION: Urokinase receptor (uPAR) is actively involved in the regulation of important cell functions, such as proliferation, adhesion, and migration. It was previously shown that the major players in bone remodeling, osteoblasts and osteoclasts, express u...... to mechanical tests. UPAR KO calvaria osteoblasts were characterized by proliferation assays, RT-PCR for important proteins secreted during differentiation, and immunoblot for activator protein 1 (AP-1) family members. In vitro osteoclast formation was tested with uPAR KO bone marrow monocytes in the presence...... a proliferative advantage with no difference in apoptosis, higher matrix mineralization, and earlier appearance of alkaline phosphatase (ALP). Surface RANKL expression at different stages of differentiation was not altered. AP-1 components, such as JunB and Fra-1, were upregulated in uPAR KO osteoblasts, along...

  9. Citral exerts its antifungal activity against Penicillium digitatum by affecting the mitochondrial morphology and function.

    Science.gov (United States)

    Zheng, Shiju; Jing, Guoxing; Wang, Xiao; Ouyang, Qiuli; Jia, Lei; Tao, Nengguo

    2015-07-01

    This work investigated the effect of citral on the mitochondrial morphology and function of Penicillium digitatum. Citral at concentrations of 2.0 or 4.0 μL/mL strongly damaged mitochondria of test pathogen by causing the loss of matrix and increase of irregular mitochondria. The deformation extent of the mitochondria of P. digitatum enhanced with increasing concentrations of citral, as evidenced by a decrease in intracellular ATP content and an increase in extracellular ATP content of P. digitatum cells. Oxygen consumption showed that citral resulted in an inhibition in the tricarboxylic acid cycle (TCA) pathway of P. digitatum cells, induced a decrease in activities of citrate synthetase, isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinodehydrogenase and the content of citric acid, while enhancing the activity of malic dehydrogenase in P. digitatum cells. Our present results indicated that citral could damage the mitochondrial membrane permeability and disrupt the TCA pathway of P. digitatum.

  10. Progress in reading and spelling of dyslexic children is not affected by executive functioning.

    Science.gov (United States)

    Walda, Sietske A E; van Weerdenburg, Marjolijn; Wijnants, Maarten L; Bosman, Anna M T

    2014-12-01

    Although poor reading and spelling skills have been associated with weak skills of executive functioning (EF), its role in literacy is not undisputed. Because EF has different theoretical underpinnings, methods of analysis and of assessing, it has led to varying and often contrasting results in its effects in children with dyslexia. The present study has two goals. The first goal is to establish the relationship between a large number of EF tasks and reading and spelling skills in a large number of Dutch dyslexic children (n = 229). More interesting, however, is the second aim. To what extent do EF skills predict progress in reading and spelling in dyslexic children who attended a remediation programme? The results revealed small, but significant relationships between EF and reading and spelling skills, but no relationships between EF and progress in reading and spelling. It is concluded that training EF skills is unlikely to enhance reading and spelling skills.

  11. Morpho-functional characteristics of rat fetal thyroid gland are affected by prenatal dexamethasone exposure.

    Science.gov (United States)

    Manojlović-Stojanoski, Milica N; Filipović, Branko R; Nestorović, Nataša M; Šošić-Jurjević, Branka T; Ristić, Nataša M; Trifunović, Svetlana L; Milošević, Verica Lj

    2014-06-01

    Thyroid hormones (TH) and glucocorticoids strongly contribute to the maturation of fetal tissues in the preparation for extrauterine life. Influence of maternal dexamethasone (Dx) administration on thyroid glands morpho-functional characteristics of near term rat fetuses was investigated applying unbiased stereology. On the 16th day of pregnancy dams received 1.0mg/Dx/kg/b.w., followed by 0.5mg/Dx/kg/b.w. on the 17th and 18th days of gestation. The control females received the same volume of saline. The volume of fetal thyroid was estimated using Cavalieri's principle; the physical/fractionator design was applied for the determination of absolute number of follicular cells in mitosis and immunohistochemically labeled C cells; C cell volume was measured using the planar rotator. The functional activity of thyroid tissue was provided from thyroglobulin (Tg) and thyroperoxidase (TPO) immunohistochemical staining. Applying these design-based modern stereological methods it was shown that Dx treatment of gravid females led to a significant decrease of fetal thyroid gland volume in 19- and 21-day-old fetuses, due to decreased proliferation of follicular cells. The Tg and TPO immunohistochemistry demonstrated that intensive TH production starts and continues during the examined period in control and Dx-exposed fetuses. Under the influence of Dx the absolute number of C cells was lower in both groups of near term fetuses, although unchanged relation between the two populations of endocrine cells, follicular and C cells suggesting that structural relationships within the gland are preserved. In conclusion maternal glucocorticoid administration at the thyroid gland level exerts growth-inhibitory and maturational promoting effects in near term rat fetuses.

  12. Phosphorylation of Staphylococcus aureus Protein-Tyrosine Kinase Affects the Function of Glucokinase and Biofilm Formation

    Science.gov (United States)

    Vasu, Dudipeta; Kumar, Pasupuleti Santhosh; Prasad, Uppu Venkateswara; Swarupa, Vimjam; Yeswanth, Sthanikam; Srikanth, Lokanathan; Sunitha, Manne Mudhu; Choudhary, Abhijith; Krishna Sarma, Potukuchi Venkata Gurunadha

    2017-01-01

    Background: When Staphylococcus aureus is grown in the presence of high concentration of external glucose, this sugar is phosphorylated by glucokinase (glkA) to form glucose-6-phosphate. This product subsequently enters into anabolic phase, which favors biofilm formation. The presence of ROK (repressor protein, open reading frame, sugar kinase) motif, phosphate-1 and -2 sites, and tyrosine kinase sites in glkA of S. aureus indicates that phosphorylation must regulate the glkA activity. The aim of the present study was to identify the effect of phosphorylation on the function of S. aureus glkA and biofilm formation. Methods: Pure glkA and protein-tyrosine kinase (BYK) of S. aureus ATCC 12600 were obtained by fractionating the cytosolic fractions of glkA1 and BYK-1 expressing recombinant clones through nickel metal chelate column. The pure glkA was used as a substrate for BYK, and the phosphorylation of glkA was confirmed by treating with reagent A and resolving in SDS-PAGE, as well as staining with reagent A. The kinetic parameters of glkA and phosphorylated glkA were determined spectrophotometrically, and in silico tools were used for validation. S. aureus was grown in brain heart infusion broth, which was supplemented with glucose, and then biofilm units were calculated. Results: Fourfold elevated glkA activity was observed upon the phosphorylation by BYK. Protein-protein docking analysis revealed that glkA structure docked close to the adenosine triphosphate-binding site of BYK structure corroborating the kinetic results. Further, S. aureus grown in the presence of elevated glucose concentration exhibited an increase in the rate of biofilm formation. Conclusion: The elevated function of glkA is an essential requirement for increased biofilm units in S. aureus, a key pathogenic factor that helps its survival and the progress of infection. PMID:27695030

  13. Functional polymorphisms of interferon-gamma affect pneumonia-induced sepsis.

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    Ding Wang

    Full Text Available OBJECTIVE: Sepsis is an inflammatory syndrome caused by infection, and both its incidence and mortality are high. Because interferon-gamma (IFN-γ plays an important role in inflammation, this work assessed IFN-γ single nucleotide polymorphism (SNPs that may be associated with sepsis. METHODS: A total of 196 patients with pneumonia-induced sepsis and 213 age- and sex-matched healthy volunteers participated in our study from July 2012 to July 2013 in Guangzhou, China. Patient clinical information was collected. Clinical pathology was assessed in subgroups defined based on clinical criteria, APACHE II (acute physiology and chronic health evaluation and SOFA (sepsis-related organ failure assessment scores and discharge rate. Four functional SNPs, -1616T/C (rs2069705, -764G/C (rs2069707, +874A/T (rs2430561 and +3234C/T (rs2069718, were genotyped by Snapshot in both sepsis patients and healthy controls. Pearson's chi-square test or Fisher's exact test were used to analyze the distribution of the SNPs, and the probability values (P values, odds ratios (OR and 95% confidence intervals (CIs were calculated. RESULTS: No mutations in the IFN-γ -764G/C SNP were detected among the participants in our study. The +874A/T and +3234C/T SNPs were in strong linkage disequilibrium (LD (r(2 = 0.894. The -1616 TC+TT, +874 AT+AA genotype and the TAC haplotype were significantly associated with sepsis susceptibility, while the CTT haplotype was associated with protection against sepsis incidence. Genotype of -1616 TT wasn't only protective against severity of sepsis, but also against higher APACHE II and SOFA scores as +874 AA and +3234 CC. The TAC haplotype was was protective against progression to severe sepsis either. CONCLUSION: Our results suggest that functional IFN-γ SNPs and their haplotypes are associated with pneumonia-induced sepsis.

  14. NORMAL VALUES AND FACTORS AFFECTING FUNCTIONAL REACH TEST IN SAUDI ARABIA SCHOOL CHILDREN WITH TYPICAL DEVELOPMENT

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    Hatem A. Emara

    2015-10-01

    Full Text Available Background: The most critical feature of motor development is the ability to balance the body in sitting or standing. Impaired balance limits a child’s ability to recover from unexpected threats to stability. The functional reach test (FRT defines the maximal distance an individual is able to reach forward beyond arm’s length in a standing position without loss of balance, taking a step, or touching the wall. The Purpose of this study was to establish the normal values for FRT in Saudi Arabia school children with typical development and to study the correlation of anthropometric measures with FRT values. Methods: This cross-sectional study was conducted in Almadinah Almonawarah, Kingdom of Saudi Arabia. A total of 280 children without disabilities aged 6 to 12 years were randomly selected. Functional reach was assessed by having subjects extend their arms to 90 degrees and reach as far forward as they could without taking a step. Reach distance was recorded by noting the beginning and final position of the subject's extended arm parallel to a yard stick attached to the wall. Three successive trials of FRT were performed and the mean of the three trials was calculated. Pearson product moment correlation was used to examine the association of FR to age, and anthropometric measures. Results: Normal mean values of FR ranged from 24.2cm to 33.95cm. Age, height and weight significantly correlate with FRT. Conclusion: The FRT is a feasible test to examine the balance of 6-12 year-old children. FRT may be useful for detecting balance impairment, change in balance performance over time.

  15. Hyaluronate degradation affects ventricular function of the early postlooped embryonic rat heart in situ.

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    Baldwin, H S; Lloyd, T R; Solursh, M

    1994-02-01

    Hyaluronic acid is the major glycosaminoglycan of the early cardiac extracellular matrix or "cardiac jelly," yet little is known about its role in the ontogeny of early ventricular performance. To investigate the in situ effect of hyaluronate degradation on ventricular function, whole rat embryos were cultured in rat serum alone (control embryos) or rat serum plus 20 TRU/mL of Streptomyces hyaluronidase (treatment embryos) from gestational day 9.5 (before formation of the heart tube) through initial looping of the heart. Cardiac function was measured before looping (24 hours in culture) and immediately after looping (36 hours in culture) by video motion analysis of the external wall motion of the bulbus cordis and primitive ventricle. Degradation of hyaluronic acid in the treated embryos was confirmed by Alcian blue staining at pH 2.5. Significant increases in heart rate, circumferential shortening fraction, maximum velocity of circumferential contraction, and maximum velocity of circumferential relaxation were observed with looping in both control and treatment embryos. Although there was minimal difference in ventricular performance between control and treatment embryos before looping, there was a significant increase in all parameters of ventricular performance in the hyaluronidase-treated embryos immediately after looping of the heart. Endocardial cushions were absent in hyaluronidase-treated embryos, and an additional group of embryos cultured in the presence of Streptomyces hyaluronidase for 48 to 72 hours failed to develop endocardial cushions. These experiments are the first to (1) document a quantifiable increase in ventricular performance during early cardiac looping and (2) demonstrate that hyaluronate degradation results in abnormal endocardial cushion formation and altered ventricular performance of the postlooped heart.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Lymphocytes and macrophages are infected by Theileria equi, but T cells and B cells are not required to establish infection in vivo.

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    Joshua D Ramsay

    Full Text Available Theileria equi has a biphasic life cycle in horses, with a period of intraleukocyte development followed by patent erythrocytic parasitemia that causes acute and sometimes fatal hemolytic disease. Unlike Theileria spp. that infect cattle (Theileria parva and Theileria annulata, the intraleukocyte stage (schizont of Theileria equi does not cause uncontrolled host cell proliferation or other significant pathology. Nevertheless, schizont-infected leukocytes are of interest because of their potential to alter host cell function and because immune responses directed against this stage could halt infection and prevent disease. Based on cellular morphology, Theileria equi has been reported to infect lymphocytes in vivo and in vitro, but the specific phenotype of schizont-infected cells has yet to be defined. To resolve this knowledge gap in Theileria equi pathogenesis, peripheral blood mononuclear cells were infected in vitro and the phenotype of infected cells determined using flow cytometry and immunofluorescence microscopy. These experiments demonstrated that the host cell range of Theileria equi was broader than initially reported and included B lymphocytes, T lymphocytes and monocyte/macrophages. To determine if B and T lymphocytes were required to establish infection in vivo, horses affected with severe combined immunodeficiency (SCID, which lack functional B and T lymphocytes, were inoculated with Theileria equi sporozoites. SCID horses developed patent erythrocytic parasitemia, indicating that B and T lymphocytes are not necessary to complete the Theileria equi life cycle in vivo. These findings suggest that the factors mediating Theileria equi leukocyte invasion and intracytoplasmic differentiation are common to several leukocyte subsets and are less restricted than for Theileria annulata and Theileria parva. These data will greatly facilitate future investigation into the relationships between Theileria equi leukocyte tropism and pathogenesis

  17. Lymphocytes and macrophages are infected by Theileria equi, but T cells and B cells are not required to establish infection in vivo.

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    Ramsay, Joshua D; Ueti, Massaro W; Johnson, Wendell C; Scoles, Glen A; Knowles, Donald P; Mealey, Robert H

    2013-01-01

    Theileria equi has a biphasic life cycle in horses, with a period of intraleukocyte development followed by patent erythrocytic parasitemia that causes acute and sometimes fatal hemolytic disease. Unlike Theileria spp. that infect cattle (Theileria parva and Theileria annulata), the intraleukocyte stage (schizont) of Theileria equi does not cause uncontrolled host cell proliferation or other significant pathology. Nevertheless, schizont-infected leukocytes are of interest because of their potential to alter host cell function and because immune responses directed against this stage could halt infection and prevent disease. Based on cellular morphology, Theileria equi has been reported to infect lymphocytes in vivo and in vitro, but the specific phenotype of schizont-infected cells has yet to be defined. To resolve this knowledge gap in Theileria equi pathogenesis, peripheral blood mononuclear cells were infected in vitro and the phenotype of infected cells determined using flow cytometry and immunofluorescence microscopy. These experiments demonstrated that the host cell range of Theileria equi was broader than initially reported and included B lymphocytes, T lymphocytes and monocyte/macrophages. To determine if B and T lymphocytes were required to establish infection in vivo, horses affected with severe combined immunodeficiency (SCID), which lack functional B and T lymphocytes, were inoculated with Theileria equi sporozoites. SCID horses developed patent erythrocytic parasitemia, indicating that B and T lymphocytes are not necessary to complete the Theileria equi life cycle in vivo. These findings suggest that the factors mediating Theileria equi leukocyte invasion and intracytoplasmic differentiation are common to several leukocyte subsets and are less restricted than for Theileria annulata and Theileria parva. These data will greatly facilitate future investigation into the relationships between Theileria equi leukocyte tropism and pathogenesis, breed

  18. Expression of an accessory cell phenotype by hairy cells during lymphocyte colony formation in agar culture.

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    Farcet, J P; Gourdin, M F; Testa, U; Andre, C; Jouault, H; Reyes, F

    1983-01-01

    Human T lymphocytes require the cooperation of accessory cells to generate lymphocyte colonies in agar culture under PHA stimulation. Various hairy cell enriched fractions, as well as normal monocytes, have been found to be able to initiate colony formation by normal lymphocytes. Leukemic monocytes from CMML patients were also effective, but not the leukemic lymphocytes from CLL patients. The phenotype expressed by HC in agar colonies was further studied using cell surface and enzymatic markers. We have concluded that HC in agar culture in the presence of both normal T lymphocytes and PHA lose the B phenotype that they express in vivo and function like an accessory cell in contrast to normal or leukemic B lymphocytes.

  19. Does Severe Maternal Morbidity Affect Female Sexual Activity and Function? Evidence from a Brazilian Cohort Study

    Science.gov (United States)

    Andreucci, Carla B.; Cecatti, José G.; Pacagnella, Rodolfo C.; Silveira, Carla; Parpinelli, Mary A.; Ferreira, Elton C.; Angelini, Carina R.; Santos, Juliana P.; Zanardi, Dulce M.; Bussadori, Jamile C.; Cecchino, Gustavo N.; Souza, Renato T.; Sousa, Maria H.; Costa, Maria L.

    2015-01-01

    Objective to assess Female Sexual Function Index (FSFI) scores and delay to resume sexual activity associated with a previous severe maternal morbidity. Method This was a multidimensional retrospective cohort study. Women who gave birth at a Brazilian tertiary maternity between 2008 and 2012 were included, with data extraction from the hospital information system. Those with potentially life-threatening conditions and maternal near miss episodes (severe maternal morbidity) were considered the exposed group. The control group was a random sample of women who had had uncomplicated pregnancy. Female sexual function was evaluated through FSFI questionnaire, and general and reproductive aspects were addressed through specific questions. Statistical analyses were performed using Mann-Whitney and Pearson´s Chi-square for bivariate analyses. Logistic regression was used to identify variables independently associated with lower FSFI scores. Results 638 women were included (315 at exposed and 323 at not exposed groups). The majority of women were under 30 years-old in the control group and between 30 and 46 years-old in the exposed group (p = 0.003). Women who experienced severe maternal morbidity (SMM) had statistically significant differences regarding cesarean section (82.4% versus 47.1% among deliveries without complications, p<0.001), and some previous pathological conditions. FSFI mean scores were similar among groups ranging from 24.39 to 24.42. It took longer for exposed women to resume sexual activity after index pregnancy (mean 84 days after SMM and 65 days for control group, p = 0.01). Multiple analyses showed no significant association of FSFI below cut-off value with any predictor. Conclusion FSFI scores were not different in both groups. However, they were lower than expected. SMM delayed resumption of sexual activity after delivery, beyond postpartum period. However, the proportion of women in both groups having sex at 3 months after delivery was similar

  20. Intermittent hypoxia leads to functional reorganization of mitochondria and affects cellular bioenergetics in marine molluscs.

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    Ivanina, Anna V; Nesmelova, Irina; Leamy, Larry; Sokolov, Eugene P; Sokolova, Inna M

    2016-06-01

    Fluctuations in oxygen (O2) concentrations represent a major challenge to aerobic organisms and can be extremely damaging to their mitochondria. Marine intertidal molluscs are well-adapted to frequent O2 fluctuations, yet it remains unknown how their mitochondrial functions are regulated to sustain energy metabolism and prevent cellular damage during hypoxia and reoxygenation (H/R). We used metabolic control analysis to investigate the mechanisms of mitochondrial responses to H/R stress (18 h at <0.1% O2 followed by 1 h of reoxygenation) using hypoxia-tolerant intertidal clams Mercenaria mercenaria and hypoxia-sensitive subtidal scallops Argopecten irradians as models. We also assessed H/R-induced changes in cellular energy balance, oxidative damage and unfolded protein response to determine the potential links between mitochondrial dysfunction and cellular injury. Mitochondrial responses to H/R in scallops strongly resembled those in other hypoxia-sensitive organisms. Exposure to hypoxia followed by reoxygenation led to a strong decrease in the substrate oxidation (SOX) and phosphorylation (PHOS) capacities as well as partial depolarization of mitochondria of scallops. Elevated mRNA expression of a reactive oxygen species-sensitive enzyme aconitase and Lon protease (responsible for degradation of oxidized mitochondrial proteins) during H/R stress was consistent with elevated levels of oxidative stress in mitochondria of scallops. In hypoxia-tolerant clams, mitochondrial SOX capacity was enhanced during hypoxia and continued rising during the first hour of reoxygenation. In both species, the mitochondrial PHOS capacity was suppressed during hypoxia, likely to prevent ATP wastage by the reverse action of FO,F1-ATPase. The PHOS capacity recovered after 1 h of reoxygenation in clams but not in scallops. Compared with scallops, clams showed a greater suppression of energy-consuming processes (such as protein turnover and ion transport) during hypoxia, indicated

  1. Does Severe Maternal Morbidity Affect Female Sexual Activity and Function? Evidence from a Brazilian Cohort Study.

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    Carla B Andreucci

    Full Text Available to assess Female Sexual Function Index (FSFI scores and delay to resume sexual activity associated with a previous severe maternal morbidity.This was a multidimensional retrospective cohort study. Women who gave birth at a Brazilian tertiary maternity between 2008 and 2012 were included, with data extraction from the hospital information system. Those with potentially life-threatening conditions and maternal near miss episodes (severe maternal morbidity were considered the exposed group. The control group was a random sample of women who had had uncomplicated pregnancy. Female sexual function was evaluated through FSFI questionnaire, and general and reproductive aspects were addressed through specific questions. Statistical analyses were performed using Mann-Whitney and Pearson´s Chi-square for bivariate analyses. Logistic regression was used to identify variables independently associated with lower FSFI scores.638 women were included (315 at exposed and 323 at not exposed groups. The majority of women were under 30 years-old in the control group and between 30 and 46 years-old in the exposed group (p = 0.003. Women who experienced severe maternal morbidity (SMM had statistically significant differences regarding cesarean section (82.4% versus 47.1% among deliveries without complications, p<0.001, and some previous pathological conditions. FSFI mean scores were similar among groups ranging from 24.39 to 24.42. It took longer for exposed women to resume sexual activity after index pregnancy (mean 84 days after SMM and 65 days for control group, p = 0.01. Multiple analyses showed no significant association of FSFI below cut-off value with any predictor.FSFI scores were not different in both groups. However, they were lower than expected. SMM delayed resumption of sexual activity after delivery, beyond postpartum period. However, the proportion of women in both groups having sex at 3 months after delivery was similar. Altered sexual response may

  2. Lipopolysaccharide exposure during the early postnatal period adversely affects the structure and function of the developing rat carotid body.

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    Master, Zankhana R; Porzionato, Andrea; Kesavan, Kalpashri; Mason, Ariel; Chavez-Valdez, Raul; Shirahata, Machiko; Gauda, Estelle B

    2016-09-01

    The carotid body (CB) substantially influences breathing in premature infants by affecting the frequency of apnea and periodic breathing. In adult animals, inflammation alters the structure and chemosensitivity of the CB, yet it is not known if this pertains to neonates. We hypothesized that early postnatal inflammation leads to morphological and functional changes in the developing rat CB, which persists for 1 wk after the initial provoking insult. To test our hypothesis, we exposed rat pups at postnatal day 2 (P2) to lipopolysaccharide (LPS; 100 μg/kg) or saline (SAL) intraperitoneally. At P9-10 (1 wk after treatment), LPS-exposed animals had significantly more spontaneous intermittent hypoxic (IH) events, attenuated ventilatory responses to changes in oxygen tension (measured by whole body plethysmography), and attenuated hypoxic chemosensitivity of the carotid sinus nerve (measured in vitro), compared with SAL-exposed controls. These functional changes were associated with the following: 1) increased inflammatory cytokine mRNA levels; 2) decreased volume of supportive type II cells; and 3) elevated dopamine levels (a major inhibitory neuromodulator) within the CB. These findings suggest that early postnatal inflammation in newborn rats adversely affects the structure and function of the CB and is associated with increased frequency of intermittent desaturations, similar to the phenomenon observed in premature infants. Furthermore, this is the first newborn model of spontaneous intermittent desaturations that may be used to understand the mechanisms contributing to IH events in newborns.

  3. Endogenous subclinical hyperthyroidism affects quality of life and cardiac morphology and function in young and middle-aged patients.

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    Biondi, B; Palmieri, E A; Fazio, S; Cosco, C; Nocera, M; Saccà, L; Filetti, S; Lombardi, G; Perticone, F

    2000-12-01

    To determine the clinical impact of endogenous subclinical hyperthyroidism, specific symptoms and signs of thyroid hormone excess and quality of life were assessed in 23 patients (3 males and 20 females; mean age, 43 +/- 9 yr) and 23 age-, sex-, and lifestyle-matched normal subjects by using the Symptoms Rating Scale and the Short Form 36 Health Survey questionnaires. Because the heart is one of the main target organs of the thyroid hormone, cardiac morphology and function were also investigated by means of standard 12-lead electrocardiogram (ECG), 24-h Holter ECG, and complete Doppler echocardiography. Stable endogenous subclinical hyperthyroidism had been diagnosed in all patients at least 6 months before the study (TSH, 0.15 +/- 0.1 mU/L; free T(3), 6.9 +/- 1.1, pmol/L; free T(4), 17.2 +/- 2.3, pmol/L). Fifteen patients were affected by multinodular goiter, and eight patients by autonomously functioning thyroid nodule. The mean Symptoms Rating Scale score (9. 8 +/- 5.5 vs. 4.3 +/- 2.2, P: affects cardiac morphology and function. Moreover, they suggest that treatment of persistent endogenous subclinical hyperthyroidism should be considered also in young and middle-aged patients to attenuate specific symptoms and signs of thyroid hormone excess, ameliorate the quality of life, and avoid the consequences to the heart of long exposure to a mild excess of thyroid hormone.

  4. Diagnosis of NMOS DRAM functional performance as affected by a picosecond dye laser

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    Kim, Q.; Schwartz, H. R.; Edmonds, L. D.; Zoutendyk, J. A.

    1992-01-01

    A picosec pulsed dye laser beam was at selected wavelengths successfully used to simulate heavy-ion single-event effects (SEEs) in negative channel NMOS DRAMs. A DRAM was used to develop the test technique because bit-mapping capability and previous heavy-ion upset data were available. The present analysis is the first to establish such a correlation between laser and heavy-ion data for devices, such as the NMOS DRAM, where charge collection is dominated by long-range diffusion, which is controlled by carrier density at remote distances from a depletion region. In the latter case, penetration depth is an important parameter and is included in the present analysis. A single-pulse picosecond dye laser beam (1.5 microns diameter) focused onto a single cell component can upset a single memory cell; clusters of memory cell upsets (multiple errors) were observed when the laser energy was increased above the threshold energy. The multiple errors were analyzed as a function of the bias voltage and total energy of a single pulse. A diffusion model to distinguish the multiple upsets from the laser-induced charge agreed well with previously reported heavy ion data.

  5. Loss of Drosophila melanogaster TRPA1 Function Affects "Siesta" Behavior but Not Synchronization to Temperature Cycles.

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    Roessingh, Sanne; Wolfgang, Werner; Stanewsky, Ralf

    2015-12-01

    To maintain synchrony with the environment, circadian clocks use a wide range of cycling sensory cues that provide input to the clock (zeitgebers), including environmental temperature cycles (TCs). There is some knowledge about which clock neuronal groups are important for temperature synchronization, but we currently lack knowledge on the temperature receptors and their signaling pathways that feed temperature information to the (neuronal) clock. Since TRPA1 is a well-known thermosensor that functions in a range of temperature-related behaviors, and it is potentially expressed in clock neurons, we set out to test the putative role of TRPA1 in temperature synchronization of the circadian clock. We found that flies lacking TRPA1 are still able to synchronize their behavioral activity to TCs comparable to wild-type flies, both in 16°C : 25°C and 20°C : 29°C TCs. In addition, we found that flies lacking TRPA1 show higher activity levels during the middle of the warm phase of 20°C : 29°C TCs, and we show that this TRPA1-mediated repression of locomotor activity during the "siesta" is caused by a lack of sleep. Based on these data, we conclude that the TRPA1 channel is not required for temperature synchronization in this broad temperature range but instead is required to repress activity during the warm part of the day.

  6. Lifestyle Engagement Affects Cognitive Status Differences and Trajectories on Executive Functions in Older Adults

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    de Frias, Cindy M.; Dixon, Roger A.

    2014-01-01

    The authors first examined the concurrent moderating role of lifestyle engagement on the relation between cognitive status (cognitively elite, cognitively normal [CN], and cognitively impaired [CI]) and executive functioning (EF) in older adults. Second, the authors examined whether baseline participation in lifestyle activities predicted differential 4.5-year stabilities and transitions in cognitive status. Participants (initial N = 501; 53–90 years) were from the Victoria Longitudinal Study. EF was represented by a 1-factor structure. Lifestyle activities were measured in multiple domains of engagement (e.g., cognitive, physical, and social). Two-wave status stability groups included sustained normal aging, transitional early impairment, and chronic impairment. Hierarchical regressions showed that baseline participation in social activities moderated cognitive status differences in EF. CI adults with high (but not low) social engagement performed equivalently to CN adults on EF. Longitudinally, logistic regressions showed that engagement in physical activities was a significant predictor of stability of cognitive status. CI adults who were more engaged in physical activities were more likely to improve in their cognitive status over time than their more sedentary peers. Participation in cognitive activities was a significant predictor of maintenance in a higher cognitive status group. Given that lifestyle engagement plays a detectable role in healthy, normal, and impaired neuropsychological aging, further research in activity-related associations and interventions is recommended. PMID:24323561

  7. Single Amino Acid Polymorphisms of Pertussis Toxin Subunit S2 (PtxB Affect Protein Function.

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    Scott H Millen

    Full Text Available Whooping cough due to Bordetella pertussis is increasing in incidence, in part due to accumulation of mutations which increase bacterial fitness in highly vaccinated populations. Polymorphisms in the pertussis toxin, ptxA and ptxB genes, and the pertactin, prn genes of clinical isolates of Bordetella pertussis collected in Cincinnati from 1989 through 2005 were examined. While the ptxA and prn genotypes were variable, all 48 strains had the ptxB2 genotype; ptxB1 encodes glycine at amino acid 18 of the S2 subunit of pertussis toxin, while ptxB2 encodes serine. We investigated antigenic and functional differences of PtxB1 and PtxB2. The S2 protein was not very immunogenic. Only a few vaccinated or individuals infected with B. pertussis developed antibody responses to the S2 subunit, and these sera recognized both polymorphic forms equally well. Amino acid 18 of S2 is in a glycan binding domain, and the PtxB forms displayed differences in receptor recognition and toxicity. PtxB1 bound better to the glycoprotein, fetuin, and Jurkat T cells in vitro, but the two forms were equally effective at promoting CHO cell clustering. To investigate in vivo activity of Ptx, one μg of Ptx was administered to DDY mice and blood was collected on 4 days after injection. PtxB2 was more effective at promoting lymphocytosis in mice.

  8. The rate of training response to aerobic exercise affects brain function of rats.

    Science.gov (United States)

    Marton, Orsolya; Koltai, Erika; Takeda, Masaki; Mimura, Tatsuya; Pajk, Melitta; Abraham, Dora; Koch, Lauren Gerard; Britton, Steven L; Higuchi, Mitsuru; Boldogh, Istvan; Radak, Zsolt

    2016-10-01

    There is an increasing volume of data connecting capacity to respond to exercise training with quality of life and aging. In this study, we used a rat model in which animals were selectively bred for low and high gain in running distance to test t whether genetic segregation for trainability is associated with brain function and signaling processes in the hippocampus. Rats selected for low response (LRT) and high response training (HRT) were randomly divided into control or exercise group that trained five times a week for 30 min per day for three months at 70% VO2max. All four groups had similar running distance before training. With training, HRT rats showed significantly greater increases in VO2max and running distance than LRT rats (p brain-derived neurotrophic factor (BDNF), ratio of phospho and total cAMP-response element binding protein (CREB), and apoptotic index, also showed significant differences between LRT and HRT groups. These findings suggest that aerobic training responses are not localized to skeletal muscle, but differently involve signaling processes in the brain of LRT and HRT rats.

  9. How the choice of safety performance function affects the identification of important crash prediction variables.

    Science.gov (United States)

    Wang, Ketong; Simandl, Jenna K; Porter, Michael D; Graettinger, Andrew J; Smith, Randy K

    2016-03-01

    Across the nation, researchers and transportation engineers are developing safety performance functions (SPFs) to predict crash rates and develop crash modification factors to improve traffic safety at roadway segments and intersections. Generalized linear models (GLMs), such as Poisson or negative binomial regression, are most commonly used to develop SPFs with annual average daily traffic as the primary roadway characteristic to predict crashes. However, while more complex to interpret, data mining models such as boosted regression trees have improved upon GLMs crash prediction performance due to their ability to handle more data characteristics, accommodate non-linearities, and include interaction effects between the characteristics. An intersection data inventory of 36 safety relevant parameters for three- and four-legged non-signalized intersections along state routes in Alabama was used to study the importance of intersection characteristics on crash rate and the interaction effects between key characteristics. Four different SPFs were investigated and compared: Poisson regression, negative binomial regression, regularized generalized linear model, and boosted regression trees. The models did not agree on which intersection characteristics were most related to the crash rate. The boosted regression tree model significantly outperformed the other models and identified several intersection characteristics as having strong interaction effects.

  10. Thyroid hormones differentially affect sarcoplasmic reticulum function in rat atria and ventricles.

    Science.gov (United States)

    Kaasik, A; Minajeva, A; Paju, K; Eimre, M; Seppet, E K

    1997-11-01

    The present study was undertaken to compare the effects of hypothyroidism and hyperthyroidism on sarcoplasmic reticulum (SR) Ca(2+)-pump activity, together with assessment of the functional role of SR in providing activator Ca2+ under these altered thyroid states. In response to a shift from hypothyroid to hyperthyroid state, a 10 fold and 2 fold increase in SR Ca(2+)-pump activity in atria and ventricles, respectively, were observed. This was associated with the 8-9 fold increases in atrial contractility (+dT/dt) and relaxation (-dT/dt), but only with a 3-4 fold increase in their ventricular counterparts. Also, the recirculation fraction of activator Ca2+ (RFA) increased to a far greater extent in atria (4 fold) than in papillary muscles, and the relative increment in inhibition of developed tension by ryanodine became 3 times larger in atria than in papillary muscles. A positive force-frequency relationship (FFR) was observed in hypothyroid atria, whereas the hyperthyroid atria, hypothyroid and hyperthyroid papillary muscles showed a negative FFR. These results suggest the greater role of transsarcolemmal (SL) Ca2+ and smaller role of SR Ca2+ in activating contraction in hypothyroid atria compared to other preparations. Thyroid hormones decrease the contribution of SL and increase that of SR in providing activator Ca2+ to the greater extent in atria than in ventricles. This effect of thyroid hormones is based on larger stimulation of SR Ca(2+)-pump in atria compared to ventricles.

  11. Plasticity-Related Gene 1 Affects Mouse Barrel Cortex Function via Strengthening of Glutamatergic Thalamocortical Transmission.

    Science.gov (United States)

    Unichenko, Petr; Kirischuk, Sergei; Yang, Jenq-Wei; Baumgart, Jan; Roskoden, Thomas; Schneider, Patrick; Sommer, Angela; Horta, Guilherme; Radyushkin, Konstantin; Nitsch, Robert; Vogt, Johannes; Luhmann, Heiko J

    2016-07-01

    Plasticity-related gene-1 (PRG-1) is a brain-specific protein that modulates glutamatergic synaptic transmission. Here we investigated the functional role of PRG-1 in adolescent and adult mouse barrel cortex both in vitro and in vivo. Compared with wild-type (WT) animals, PRG-1-deficient (KO) mice showed specific behavioral deficits in tests assessing sensorimotor integration and whisker-based sensory discrimination as shown in the beam balance/walking test and sandpaper tactile discrimination test, respectively. At P25-31, spontaneous network activity in the barrel cortex in vivo was higher in KO mice compared with WT littermates, but not at P16-19. At P16-19, sensory evoked cortical responses in vivo elicited by single whisker stimulation were comparable in KO and WT mice. In contrast, at P25-31 evoked responses were smaller in amplitude and longer in duration in WT animals, whereas KO mice revealed no such developmental changes. In thalamocortical slices from KO mice, spontaneous activity was increased already at P16-19, and glutamatergic thalamocortical inputs to Layer 4 spiny stellate neurons were potentiated. We conclude that genetic ablation of PRG-1 modulates already at P16-19 spontaneous and evoked excitability of the barrel cortex, including enhancement of thalamocortical glutamatergic inputs to Layer 4, which distorts sensory processing in adulthood.

  12. Hydrogen sulfide and reduced-sulfur gases adversely affect neurophysiological functions.

    Science.gov (United States)

    Kilburn, K H; Warshaw, R H

    1995-01-01

    Hydrogen sulfide (H2S) above 50 parts per million (ppm) causes unconsciousness and death. Lower doses of H2S and related gases have been regarded as innocuous, but the effects of prolonged exposure have not been studied. This study was designed to determine whether people exposed to sulfide gases as a result of working at or living downwind from the processing of "sour" crude oil demonstrate persistent neurobehavioral dysfunction. Thirteen former workers and 22 neighbors of a refinery complained of headaches, nausea, vomiting, depression, personality changes, nosebleeds, and breathing difficulties. Their neurobehavioral functions and a profile of mood states (POMS) were compared to 32 controls, matched for age and educational level. The exposed subjects' mean values were statistically significantly abnormal compared to controls for two-choice reaction time, balance (as speed of sway), color discrimination, digit symbol, trail-making A and B, and immediate recall of a story. Their POMS scores were much higher than those of controls. Visual recall was significantly impaired in neighbors, but not in exworkers. It was concluded that neurophysiological abnormalities were associated with exposure to reduced sulfur gases, including H2S from crude oil desulfurization.

  13. Climate-induced die-off affects plant-soil-microbe ecological relationship and functioning.

    Science.gov (United States)

    Lloret, Francisco; Mattana, Stefania; Curiel Yuste, Jorge

    2015-02-01

    This study reports the relationship between the diversity and functioning of fungal and bacterial soil communities with vegetation in Mediterranean woodland that experienced severe die-off after a drought episode. Terminal restriction fragment length polymorfism (TRFLP) was used to describe microbial community structure and diversity five years after the episode in different habitats (Juniperus woodland, shrubland, grassland), when the vegetation had not yet recovered. Vegetation diversity was positively related to TRF bacterial richness under unaffected canopies and was higher in diverse grassland. Fungal TRF richness correlated with vegetation type, being greater in Juniperus woodland. Microbial respiration increased in grassland, whereas microbial biomass, estimated from soil substrate-induced respiration (SIR), decreased with bacterial diversity. Die-off increased bacterial richness and changed bacterial composition, particularly in Juniperus woodland, where herbaceous species increased, while fungal diversity was reduced in Juniperus woodland. Die-off increased microbial respiration rates. The impact on vegetation from extreme weather episodes spread to microbial communities by modifying vegetation composition and litter quantity and quality, particularly as a result of the increase in herbaceous species. Our results suggest that climate-induced die-off triggers significant cascade effects on soil microbial communities, which may in turn further influence ecosystem C dynamics.

  14. Structure and function of subsurface microbial communities affecting radionuclide transport and bioimmobilization

    Energy Technology Data Exchange (ETDEWEB)

    Kostka, Joel E. [Florida State Univ., Tallahassee, FL (United States); Prakash, Om [Florida State Univ., Tallahassee, FL (United States); Green, Stefan J. [Florida State Univ., Tallahassee, FL (United States); Akob, Denise [Florida State Univ., Tallahassee, FL (United States); Jasrotia, Puja [Florida State Univ., Tallahassee, FL (United States); Kerkhof, Lee [Rutgers Univ., New Brunswick, NJ (United States); Chin, Kuk-Jeong [Georgia State Univ., Atlanta, GA (United States); Sheth, Mili [Georgia State Univ., Atlanta, GA (United States); Keller, Martin [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Venkateswaran, Amudhan [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Elkins, James G. [Univ. of Illinois, Urbana-Champaign, IL (United States); Stucki, Joseph W. [Univ. of Illinois, Urbana-Champaign, IL (United States)

    2012-05-01

    Our objectives were to: 1) isolate and characterize novel anaerobic prokaryotes from subsurface environments exposed to high levels of mixed contaminants (U(VI), nitrate, sulfate), 2) elucidate the diversity and distribution of metabolically active metal- and nitrate-reducing prokaryotes in subsurface sediments, and 3) determine the biotic and abiotic mechanisms linking electron transport processes (nitrate, Fe(III), and sulfate reduction) to radionuclide reduction and immobilization. Mechanisms of electron transport and U(VI) transformation were examined under near in situ conditions in sediment microcosms and in field investigations. Field sampling was conducted at the Oak Ridge Field Research Center (ORFRC), in Oak Ridge, Tennessee. The ORFRC subsurface is exposed to mixed contamination predominated by uranium and nitrate. In short, we effectively addressed all 3 stated objectives of the project. In particular, we isolated and characterized a large number of novel anaerobes with a high bioremediation potential that can be used as model organisms, and we are now able to quantify the function of subsurface sedimentary microbial communities in situ using state-of-the-art gene expression methods (molecular proxies).

  15. Microbial diversity affects self-organization of the soil-microbe system with consequences for function.

    Science.gov (United States)

    Crawford, John W; Deacon, Lewis; Grinev, Dmitri; Harris, James A; Ritz, Karl; Singh, Brajesh K; Young, Iain

    2012-06-07

    Soils are complex ecosystems and the pore-scale physical structure regulates key processes that support terrestrial life. These include maintaining an appropriate mixture of air and water in soil, nutrient cycling and carbon sequestration. There is evidence that this structure is not random, although the organizing mechanism is not known. Using X-ray microtomography and controlled microcosms, we provide evidence that organization of pore-scale structure arises spontaneously out of the interaction between microbial activity, particle aggregation and resource flows in soil. A simple computational model shows that these interactions give rise to self-organization involving both physical particles and microbes that gives soil unique material properties. The consequence of self-organization for the functioning of soil is determined using lattice Boltzmann simulation of fluid flow through the observed structures, and predicts that the resultant micro-structural changes can significantly increase hydraulic conductivity. Manipulation of the diversity of the microbial community reveals a link between the measured change in micro-porosity and the ratio of fungal to bacterial biomass. We suggest that this behaviour may play an important role in the way that soil responds to management and climatic change, but that this capacity for self-organization has limits.

  16. Plectin isoform P1b and P1d deficiencies differentially affect mitochondrial morphology and function in skeletal muscle.

    Science.gov (United States)

    Winter, Lilli; Kuznetsov, Andrey V; Grimm, Michael; Zeöld, Anikó; Fischer, Irmgard; Wiche, Gerhard

    2015-08-15

    Plectin, a versatile 500-kDa cytolinker protein, is essential for muscle fiber integrity and function. The most common disease caused by mutations in the human plectin gene, epidermolysis bullosa simplex with muscular dystrophy (EBS-MD), is characterized by severe skin blistering and progressive muscular dystrophy. Besides displaying pathological desmin-positive protein aggregates and degenerative changes in the myofibrillar apparatus, skeletal muscle specimens of EBS-MD patients and plectin-deficient mice are characterized by massive mitochondrial alterations. In this study, we demonstrate that structural and functional alterations of mitochondria are a primary aftermath of plectin deficiency in muscle, contributing to myofiber degeneration. We found that in skeletal muscle of conditional plectin knockout mice (MCK-Cre/cKO), mitochondrial content was reduced, and mitochondria were aggregated in sarcoplasmic and subsarcolemmal regions and were no longer associated with Z-disks. Additionally, decreased mitochondrial citrate synthase activity, respiratory function and altered adenosine diphosphate kinetics were characteristic of plectin-deficient muscles. To analyze a mechanistic link between plectin deficiency and mitochondrial alterations, we comparatively assessed mitochondrial morphology and function in whole muscle and teased muscle fibers of wild-type, MCK-Cre/cKO and plectin isoform-specific knockout mice that were lacking just one isoform (either P1b or P1d) while expressing all others. Monitoring morphological alterations of mitochondria, an isoform P1b-specific phenotype affecting the mitochondrial fusion-fission machinery and manifesting with upregulated mitochondrial fusion-associated protein mitofusin-2 could be identified. Our results show that the depletion of distinct plectin isoforms affects mitochondrial network organization and function in different ways.

  17. Newborn of mothers affected by autoimmune thyroiditis: the importance of thyroid function monitoring in the first months of life

    Directory of Open Access Journals (Sweden)

    Mosca Fabio

    2010-03-01

    Full Text Available Abstract Background evaluation of thyroid function in neonates born from mothers affected by autoimmune thyroiditis in order to define if a precise follow-up is necessary for these children. The influence of maternal thyroid peroxidase antibody (TPOAb and L-thyroxine therapy during pregnancy on neonatal thyroid function was also investigated. Methods 129 neonates were tested for thyroid function by measurement of free thyroxine (FT4 and thyroid stimulating hormone (TSH in 3th day, 15th day and at one month of life. TPOAb were measured in all patients; periodical control of thyroid function were performed until 6 months of life if Ab were positive. Data concerning etiology of maternal hypothyroidism and maternal replacement therapy with L-thyroxine during pregnancy were retrospectively collected. Results 28% neonates showed at least a mild increase of TSH value at the different determinations. In the majority of them, a spontaneous completely normalisation of TSH value was observed within the first month life. L-thyroxine replacement therapy was started in 3 neonates. TPOAb titer and maternal L-thyroxine replacement therapy were not related to alteration of thyroid hormone function in our study population. Conclusions transient mild elevation of serum TSH above the normal reference value for age is frequently observed in the first month of life in infants born from mothers affected by autoimmune thyroiditis. Persistent hyperthyrotropinemia requiring replacement therapy is observed in 2.2% of these neonates. According to our experience, follow-up is recommended in these newborns; the most accurate and not invasive way to carefully monitor these infants after neonatal screening for CH seems to be serum-testing TSH between 2ndand 4th week of life.

  18. Absence of system xc- in mice decreases anxiety and depressive-like behavior without affecting sensorimotor function or spatial vision.

    Science.gov (United States)

    Bentea, Eduard; Demuyser, Thomas; Van Liefferinge, Joeri; Albertini, Giulia; Deneyer, Lauren; Nys, Julie; Merckx, Ellen; Michotte, Yvette; Sato, Hideyo; Arckens, Lutgarde; Massie, Ann; Smolders, Ilse

    2015-06-01

    There is considerable preclinical and clinical evidence indicating that abnormal changes in glutamatergic signaling underlie the development of mood disorders. Astrocytic glutamate dysfunction, in particular, has been recently linked with the pathogenesis and treatment of mood disorders, including anxiety and depression. System xc- is a glial cystine/glutamate antiporter that is responsible for nonvesicular glutamate release in various regions of the brain. Although system xc- is involved in glutamate signal transduction, its possible role in mediating anxiety or depressive-like behaviors is currently unknown. In the present study, we phenotyped adult and aged system xc- deficient mice in a battery of tests for anxiety and depressive-like behavior (open field, light/dark test, elevated plus maze, novelty suppressed feeding, forced swim test, tail suspension test). Concomitantly, we evaluated the sensorimotor function of system xc- deficient mice, using motor and sensorimotor based tests (rotarod, adhesive removal test, nest building test). Finally, due to the presence and potential functional relevance of system xc- in the eye, we investigated the visual acuity of system xc- deficient mice (optomotor test). Our results indicate that loss of system xc- does not affect motor or sensorimotor function, in either adult or aged mice, in any of the paradigms investigated. Similarly, loss of system xc- does not affect basic visual acuity, in either adult or aged mice. On the other hand, in the open field and light/dark tests, and forced swim and tail suspension tests respectively, we could observe significant anxiolytic and antidepressive-like effects in system xc- deficient mice that in certain cases (light/dark, forced swim) were age-dependent. These findings indicate that, under physiological conditions, nonvesicular glutamate release via system xc- mediates aspects of higher brain function related to anxiety and depression, but does not influence sensorimotor function

  19. Regulatory functions of hapten-reactive helper and suppressor T lymphocytes. I. Detection and characterization of hapten-reactive suppressor T-cell activity in mice immunized with hapten-isologous protein conjugate

    Science.gov (United States)

    Yamamoto, H; Hamaoka, T; Yoshizawa, M; Kuroki, M; Kitagawa, M

    1977-01-01

    Helper and suppressor T-cell activities were detected simultaneously in the spleen cells of mice immunized with para-azobenzoate (PAB)-mouse gammaglobulin (MGG). Dinitrophenyl (DNP)-specific B cells were raised by immunization with DNP-keyhole limpet hemocyanin (KLH) and used as the indicator B-cell population. The helper and suppressor T-cell activities were determined after adoptively transferring spleen cells from PAB-MGG- primed donors and DNP-KLH-primed donors into X-irradiated recipients. Stimulation of these recipients with DNP-MGG-PAB detected helper T-cell activity, which was measured in terms of increased anti-DNP antibody responses of DNP-KLH-primed cells over these responses in the presence of unprimed cells. On the other hand, when DNP-KLH-primed cells were stimulated with DNP-KLH-PAB in the presence of PAB-MGG-primed cells, anti-DNP antibody responses were substantially lower than in unprimed normal cells. This suppressor cell population was (a) hapten-reactive, (b) present in B-cell-depleted spleen cells, (c) Thy-1 positive, (d) detectable earlier than the helper T-cell activities after priming (e) more radiosensitive than helper cells, and (f) found in the spleen but not the lymph nodes in contrast to helper T cells. These data indicate that these suppressor T cells are distinct from the helper T cells. PAB-reactive T cells clearly suppressed the antibody response by inhibiting KLH-reactive helper T-cell functions. The hapten-reactive T-lymphocyte system described here should be useful for analyzing and manipulating the immune response and for studying regulatory interactions of helper and suppressor T cells in the induction of antibody responses. PMID:68994

  20. Affect of surgical approaches on functional results of total hip arthroplasty in early postoperative period

    Directory of Open Access Journals (Sweden)

    D. V. Andreyev

    2013-01-01

    Full Text Available Minimally invasive approaches implies a less soft tissue damage and, therefore, more rapid recovery of the patient in the early postoperative period. The present study is a comparison of minimally invasive and standard approaches using biomechanical analysis of standing and walking patients before and after total hip arthroplasty, as well as an analysis of clinical outcomes in the early postoperative period. Fifty patients undergoing primary total hip arthroplasty using a minimally invasive and conventional techniques were divided into three groups. The first group consisted of patients operated on using the MIS AL (modified minimally invasive approach Watson-Jones (n = 17, the second - MDM (minimally invasive approach to the modified Mueller (n = 16 and in the third - with the use of transgluteal conventional approach by Harding (n = 17. The estimation of biomechanical parameters in static and dynamic patients before surgery and at 8-10 days after surgery. Also assessed clinical outcome postoperative visual analogue scale (VAS and Harris scale on day 10, 6 and 12 weeks and 1 year. When comparing the three groups of patients stabilometry best results were observed in groups of minimally invasive approaches MIS AL and MDM. When comparing the three groups significantly better (a moderate increase in the duration of the step, rolling the contralateral limb and a slight increase in the duration of the step the operated limb by increasing the duration of the roll-over were identified in the minimally invasive group MIS AL and MDM. In assessing the scale of Harris in the early postoperative period, higher rates were observed in groups of minimally invasive approaches. A year after the operation functional results become similar in all groups.

  1. Microbial Functional Diversity, Biomass and Activity as Affected by Soil Surface Mulching in a Semiarid Farmland.

    Science.gov (United States)

    Shen, Yufang; Chen, Yingying; Li, Shiqing

    2016-01-01

    Mulching is widely used to increase crop yield in semiarid regions in northwestern China, but little is known about the effect of different mulching systems on the microbial properties of the soil, which play an important role in agroecosystemic functioning and nutrient cycling. Based on a 4-year spring maize (Zea mays L.) field experiment at Changwu Agricultural and Ecological Experimental Station, Shaanxi, we evaluated the responses of soil microbial activity and crop to various management systems. The treatments were NMC (no mulching with inorganic N fertilizer), GMC (gravel mulching with inorganic N fertilizer), FMC (plastic-film mulching with inorganic N fertilizer) and FMO (plastic-film mulching with inorganic N fertilizer and organic manure addition). The results showed that the FMO soil had the highest contents of microbial biomass carbon and nitrogen, dehydrogenase activity, microbial activity and Shannon diversity index. The relative use of carbohydrates and amino acids by microbes was highest in the FMO soil, whereas the relative use of polymers, phenolic compounds and amines was highest in the soil in the NMC soil. Compared with the NMC, an increased but no significant trend of biomass production and nitrogen accumulation was observed under the GMC treatment. The FMC and FMO led a greater increase in biomass production than GMC and NMC. Compare with the NMC treatment, FMC increased grain yield, maize biomass and nitrogen accumulation by 62.2, 62.9 and 86.2%, but no significant difference was found between the FMO and FMC treatments. Some soil biological properties, i.e. microbial biomass carbon, microbial biomass nitrogen, being sensitive to the mulching and organic fertilizer, were significant correlated with yield and nitrogen availability. Film mulching over gravel mulching can serve as an effective measure for crop production and nutrient cycling, and plus organic fertilization additions may thus have improvements in the biological quality of the

  2. Microbial Functional Diversity, Biomass and Activity as Affected by Soil Surface Mulching in a Semiarid Farmland.

    Directory of Open Access Journals (Sweden)

    Yufang Shen

    Full Text Available Mulching is widely used to increase crop yield in semiarid regions in northwestern China, but little is known about the effect of different mulching systems on the microbial properties of the soil, which play an important role in agroecosystemic functioning and nutrient cycling. Based on a 4-year spring maize (Zea mays L. field experiment at Changwu Agricultural and Ecological Experimental Station, Shaanxi, we evaluated the responses of soil microbial activity and crop to various management systems. The treatments were NMC (no mulching with inorganic N fertilizer, GMC (gravel mulching with inorganic N fertilizer, FMC (plastic-film mulching with inorganic N fertilizer and FMO (plastic-film mulching with inorganic N fertilizer and organic manure addition. The results showed that the FMO soil had the highest contents of microbial biomass carbon and nitrogen, dehydrogenase activity, microbial activity and Shannon diversity index. The relative use of carbohydrates and amino acids by microbes was highest in the FMO soil, whereas the relative use of polymers, phenolic compounds and amines was highest in the soil in the NMC soil. Compared with the NMC, an increased but no significant trend of biomass production and nitrogen accumulation was observed under the GMC treatment. The FMC and FMO led a greater increase in biomass production than GMC and NMC. Compare with the NMC treatment, FMC increased grain yield, maize biomass and nitrogen accumulation by 62.2, 62.9 and 86.2%, but no significant difference was found between the FMO and FMC treatments. Some soil biological properties, i.e. microbial biomass carbon, microbial biomass nitrogen, being sensitive to the mulching and organic fertilizer, were significant correlated with yield and nitrogen availability. Film mulching over gravel mulching can serve as an effective measure for crop production and nutrient cycling, and plus organic fertilization additions may thus have improvements in the biological

  3. Interleukins Affect Equine Endometrial Cell Function: Modulatory Action of Ovarian Steroids

    Directory of Open Access Journals (Sweden)

    Anna Z. Szóstek

    2014-01-01

    Full Text Available The aim of the present study was to investigate the interaction between ovarian steroids, interleukins and prostaglandins (PG in equine epithelial and stromal cells in vitro. In Experiment 1, cells were exposed to IL-1α (10 ng/mL, IL-1β (10 ng/mL or IL-6 (10 ng/mL for 24 h and cell proliferation was determined using MTT. In Experiment 2, cells were exposed to progesterone (P4; 10−7 M; 17-β estradiol (E2; 10−9 M or P4+E2 for 24 h and later medium was replaced with a fresh one treated with IL-1α, IL-1β or IL-6 (10 ng/mL, each for 24 h. The oxytocin (OT; 10−7 M was used as a positive control. In Experiment 3, cells were exposed to P4 (10−7 M, E2 (10−9 M or P4+E2 for 24 h and the IL receptor mRNAs transcription was determined using Real-time PCR. Prostaglandins concentration was determined using the direct enzyme immunoassay (EIA method. Our findings reveal a functional linking between ovarian steroids and IL-stimulated PG secretion by equine endometrial cells. This interaction could be one of the mechanisms responsible for endometrial local orchestrating events during the estrous cycle and early pregnancy.

  4. Writing affects the brain network of reading in Chinese: a functional magnetic resonance imaging study.

    Science.gov (United States)

    Cao, Fan; Vu, Marianne; Chan, Derek Ho Lung; Lawrence, Jason M; Harris, Lindsay N; Guan, Qun; Xu, Yi; Perfetti, Charles A

    2013-07-01

    We examined the hypothesis that learning to write Chinese characters influences the brain's reading network for characters. Students from a college Chinese class learned 30 characters in a character-writing condition and 30 characters in a pinyin-writing condition. After learning, functional magnetic resonance imaging collected during passive viewing showed different networks for reading Chinese characters and English words, suggesting accommodation to the demands of the new writing system through short-term learning. Beyond these expected differences, we found specific effects of character writing in greater activation (relative to pinyin writing) in bilateral superior parietal lobules and bilateral lingual gyri in both a lexical decision and an implicit writing task. These findings suggest that character writing establishes a higher quality representation of the visual-spatial structure of the character and its orthography. We found a greater involvement of bilateral sensori-motor cortex (SMC) for character-writing trained characters than pinyin-writing trained characters in the lexical decision task, suggesting that learning by doing invokes greater interaction with sensori-motor information during character recognition. Furthermore, we found a correlation of recognition accuracy with activation in right superior parietal lobule, right lingual gyrus, and left SMC, suggesting that these areas support the facilitative effect character writing has on reading. Finally, consistent with previous behavioral studies, we found character-writing training facilitates connections with semantics by producing greater activation in bilateral middle temporal gyri, whereas pinyin-writing training facilitates connections with phonology by producing greater activation in right inferior frontal gyrus.

  5. Interaction of Berberine derivative with protein POT1 affect telomere function in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Nannan; Chen, Siqi; Ma, Yan; Qiu, Jun; Tan, Jia-Heng; Ou, Tian-Miao; Gu, Lian-Quan; Huang, Zhi-Shu [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, Waihuan East Road 132, Guangzhou 510006 (China); Li, Ding, E-mail: liding@mail.sysu.edu.cn [School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, Waihuan East Road 132, Guangzhou 510006 (China)

    2012-03-16

    Highlights: Black-Right-Pointing-Pointer The protein POT1 plays an important role in telomere protection. Black-Right-Pointing-Pointer Functional POT1 was overexpressed in Escherichia coli for the first time, and purified. Black-Right-Pointing-Pointer Compound Sysu-00692 was found to be the first POT1-binding ligand. Black-Right-Pointing-Pointer Sysu-00692 could interfere with the binding activity of POT1 in vivo. Black-Right-Pointing-Pointer Sysu-00692 had inhibition on telomerase and cell proliferation. -- Abstract: The protein POT1 plays an important role in telomere protection, which is related with telomere elongation and cell immortality. The protein has been recognized as a promising drug target for cancer treatment. In the present study, we cloned, overexpressed in Escherichia coli for the first time, and purified recombinant human POT1. The protein was proved to be active through filter binding assay, FRET and CD experiments. In the initial screening for protein binding ligands using SPR, compound Sysu-00692 was found to bind well with the POT1, which was confirmed with EMSA. Its in vivo activity study showed that compound Sysu-00692 could interfere with the binding between human POT1 and the telomeric DNA through chromatin immunoprecipitation. Besides, the compound showed mild inhibition on telomerase and cell proliferation. As we know, compound Sysu-00692 is the first reported POT1-binding ligand, which could serve as a lead compound for further improvement. This work offered a potentially new approach for drug design for the treatment of cancers.

  6. Disturbance gradient shows logging affects plant functional groups more than fire.

    Science.gov (United States)

    Blair, David P; McBurney, Lachlan M; Blanchard, Wade; Banks, Sam C; Lindenmayer, David B

    2016-10-01

    Understanding the impacts of natural and human disturbances on forest biota is critical for improving forest management. Many studies have examined the separate impacts on fauna and flora of wildfire, conventional logging, and salvage logging, but empirical comparisons across a broad gradient of simultaneous disturbances are lacking. We quantified species richness and frequency of occurrence of vascular plants, and functional group responses, across a gradient of disturbances that occurred concurrently in 2009 in the mountain ash forests of southeastern Australia. Our study encompassed replicated sites in undisturbed forest (~70 yr post fire), forest burned at low severity, forest burned at high severity, unburned forest that was clearcut logged, and forest burned at high severity that was clearcut salvage logged post-fire. All sites were sampled 2 and 3 yr post fire. Mean species richness decreased across the disturbance gradient from 30.1 species/site on low-severity burned sites and 28.9 species/site on high-severity burned sites, to 25.1 species/site on clearcut sites and 21.7 species/site on salvage logged sites. Low-severity burned sites were significantly more species-rich than clearcut sites and salvage logged sites; high-severity burned sites supported greater species richness than salvage logged sites. Specific traits influenced species' sensitivity to disturbance. Resprouting species dominated undisturbed mountain ash forests, but declined significantly across the gradient. Fern and midstory trees decreased significantly in frequency of occurrence across the gradient. Ferns (excluding bracken) decreased from 34% of plants in undisturbed forest to 3% on salvage logged sites. High-severity burned sites supported a greater frequency of occurrence and species richness of midstory trees compared to clearcut and salvage logged sites. Salvage logging supported fewer midstory trees than any other disturbance category, and were distinctly different from

  7. Spondylarthritis in the absence of B lymphocytes.

    Science.gov (United States)

    Baeten, Dominique; Kruithof, Elli; Breban, Maxime; Tak, Paul P

    2008-03-01

    The highly effective treatment of rheumatoid arthritis by B cell depletion and the presence of B cells in the peripheral and axial lesions of patients with spondylarthritis (SpA) raise the question as to whether B lymphocytes could also be an appropriate therapeutic target in the latter disease. We describe 2 male HLA-B27-positive patients who had active SpA despite absence of B cells. One patient developed SpA with sacroiliitis and asymmetric oligoarthritis after having been diagnosed as having severe Bruton agammaglobulinemia. Since extensive investigations excluded an infectious origin of the SpA, this case illustrates that functional B cells and/or gamma globulins are not strictly required for SpA pathogenesis. The second patient had severe axial and peripheral SpA that was treated successfully with etanercept. After discontinuation of etanercept treatment because of non-Hodgkin's B cell lymphoma, both axial and peripheral SpA symptoms relapsed rapidly, and this exacerbation of articular disease activity was not modulated by successful B cell depletion therapy for the lymphoma. Although case reports have obvious limitations, our clinical observations provide evidence that active SpA can occur in the absence of functional mature B cells and thus emphasize the need for systematic studies of the exact role and function of B lymphocytes in this disease.

  8. [Effects of recombinant interleukin-2 on several characteristics of functional activity of lymphocytes from the lymph nodes regional to tumor and mononuclear cells of peripheral blood in cancer patients].

    Science.gov (United States)

    Semenova-Kobzar', R A; Kushko, L Ia; Iakhimovich, L V; Protsyk, V S; Tolstopiatov, B A; Konovalenko, V F; Berezhnaia, N M

    1990-01-01

    The level of endogenous production of IL-2 by lymphocytes of lymph nodes regional to tumour and by mononuclear cells of peripheral blood, proliferative response of these cell to recombinant IL-2, as well as a modifying influence of autologous serum and actively proliferating bioptats of autologous tumours on enumerated parameters have been studied in cancer patients (tumours of the head and neck and locomotor system). Regional IL-2-dependent immunotherapy of malignant tumors with obligatory preliminary testing for individual sensitivity of the tumor bioptat to the influence of the RIL-2 and RIL-2 activated lymphocytes is shown to be promising.

  9. Effect of interleukin-2 and methylprednisolone on in vitro transformation of uremic lymphocytes

    DEFF Research Database (Denmark)

    Langhoff, E; Ladefoged, J; Ødum, Niels

    1986-01-01

    The functional relationship in vitro between mitogen-induced lymphocyte transformation, lymphocyte response to interleukin-2 (IL-2) and steroid, and production of IL-2 was examined in patients with chronic renal failure on hemodialysis (HD) or on continuous ambulatory peritoneal dialysis (CAPD...

  10. Sister chromatid exchange in human lymphocytes induced by propoxur following plant activation by Vicia faba.

    Science.gov (United States)

    Gómez-Arroyo, S; Calderón-Segura, M E; Villalobos-Pietrini, R

    1995-01-01

    Because the carbamate insecticide propoxur induced sister chromatid exchanges (SCE) in Vicia faba but was ineffective in producing SCE in lymphocytes in culture, it was hardly suspected that plant metabolism was involved. Experiments were conducted in which metabolic activation was afforded by Vicia faba roots, and SCE in human lymphocytes in vitro was used to assess cytogenetic damage. Several concentrations of propoxur (250, 500, 1,000, 1,500, and 2,000 ppm) were applied for 4 hr to the roots of Vicia faba. Extracts prepared from these treatments were added to the lymphocyte cultures and a significant increase of SCE frequencies with a concentration-response relationship could be detected. The lymphocyte proliferation kinetics and the proliferation rate index (PRI) were not affected (except in the highest concentration, of 2,000 ppm). This general behavior was in agreement with the presence of an enzymatic system (S10 fraction) in Vicia roots capable of metabolizing or activating the propoxur. With 2,000 ppm, cell necrosis was produced in Vicia; therefore, this extract did not induce SCE in lymphocytes. However, lymphocyte proliferation kinetics were delayed and PRI was significantly decreased. Ethanol, a promutagen activated by this plant, was applied directly to the lymphocyte cultures as a positive control, and the response was negative. On the other hand, the extracts of roots treated with ethanol increased the SCE to more than twice that of the negative control, but the lymphocyte proliferation kinetics and PRI were not affected.

  11. STRUCTURE AND FUNCTION OF SUBSURFACE MICROBIAL COMMUNITIES AFFECTING RADIONUCLIDE TRANSPORT AND BIOIMMOBILIZATION

    Energy Technology Data Exchange (ETDEWEB)

    Joel E. Kostka; Lee Kerkhof; Kuk-Jeong Chin; Martin Keller; Joseph W. Stucki

    2011-06-15

    (comprising 50% to 100% of rRNA detected). (2) We demonstrated for the first time that the function of microbial communities can be quantified in subsurface sediments using messenger RNA assays (molecular proxies) under in situ conditions. (3) Active Geobacteraceae were identified and phylogenetically characterized from the cDNA of messenger RNA extracted from ORFRC subsurface sediment cores. Multiple clone sequences were retrieved from G. uraniireducens, G. daltonii, and G. metallireducens. (4) Results show that Geobacter strain FRC-32 is capable of growth on benzoate, toluene and benzene as the electron donor, thereby providing evidence that this strain is physiologically distinct from other described members of the subsurface Geobacter clade. (5) Fe(III)-reducing bacteria transform structural Fe in clay minerals from their layer edges rather than from their basal surfaces.

  12. Repeated exposure of the developing rat brain to magnetic resonance imaging did not affect neurogenesis, cell death or memory function

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Changlian [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Gao, Jianfeng [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Department of Physiology, Henan Traditional Medical University (China); Li, Qian; Huang, Zhiheng; Zhang, Yu; Li, Hongfu [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatrics, The Third Affiliated Hospital, Zhengzhou University (China); Kuhn, Hans-Georg [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Blomgren, Klas, E-mail: klas.blomgren@neuro.gu.se [Center for Brain Repair and Rehabilitation, University of Gothenburg (Sweden); Department of Pediatric Oncology, The Queen Silvia Children' s Hospital, Gothenburg (Sweden)

    2011-01-07

    Research highlights: {yields} The effect of MRI on the developing brain is a matter of debate. {yields} Repeated exposure to MRI did not affect neurogenesis. {yields} Memory function was not affected by repeated MRI during development. {yields} Neither late gestation nor young postnatal brains were affected by MRI. {yields} Repeated MRI did not cause cell death in the neurogenic region of the hippocampus. -- Abstract: The effect of magnetic fields on the brain is a matter of debate. The objective of this study was to investigate whether repeated exposure to strong magnetic fields, such as during magnetic resonance imaging (MRI), could elicit changes in the developing rat brain. Embryonic day 15 (E15) and postnatal day 14 (P14) rats were exposed to MRI using a 7.05 T MR system. The animals were anesthetized and exposed for 35 min per day for 4 successive days. Control animals were anesthetized but no MRI was performed. Body temperature was maintained at 37 {sup o}C. BrdU was injected after each session (50 mg/kg). One month later, cell proliferation, neurogenesis and astrogenesis in the dentate gyrus were evaluated, revealing no effects of MRI, neither in the E15, nor in the P14 group. DNA damage in the dentate gyrus in the P14 group was evaluated on P18, 1 day after the last session, using TUNEL staining. There was no difference in the number of TUNEL-positive cells after MRI compared with controls, neither in mature neurons, nor in newborn progenitors (BrdU/TUNEL double-labeled cells). Novel object recognition was performed to assess memory function 1 month after MRI. There was no difference in the recognition index observed after MRI compared with the control rats, neither for the E15, nor for the P14 group. In conclusion, repeated exposure to MRI did not appear to affect neurogenesis, cell death or memory function in rats, neither in late gestation (E15-E18) nor in young postnatal (P14-P17) rats.

  13. Development of an auditory emotion recognition function using psychoacoustic parameters based on the International Affective Digitized Sounds.

    Science.gov (United States)

    Choi, Youngimm; Lee, Sungjun; Jung, SungSoo; Choi, In-Mook; Park, Yon-Kyu; Kim, Chobok

    2015-12-01

    The purpose of this study was to develop an auditory emotion recognition function that could determine the emotion caused by sounds coming from the environment in our daily life. For this purpose, sound stimuli from the International Affective Digitized Sounds (IADS-2), a standardized database of sounds intended to evoke emotion, were selected, and four psychoacoustic parameters (i.e., loudness, sharpness, roughness, and fluctuation strength) were extracted from the sounds. Also, by using an emotion adjective scale, 140 college students were tested to measure three basic emotions (happiness, sadness, and negativity). From this discriminant analysis to predict basic emotions from the psychoacoustic parameters of sound, a discriminant function with overall discriminant accuracy of 88.9% was produced from training data. In order to validate the discriminant function, the same four psychoacoustic parameters were extracted from 46 sound stimuli collected from another database and substituted into the discriminant function. The results showed that an overall discriminant accuracy of 63.04% was confirmed. Our findings provide the possibility that daily-life sounds, beyond voice and music, can be used in a human-machine interface.

  14. What is the most important factor affecting the cognitive function of obstructive sleep apnea syndrome patients: a single center study

    Directory of Open Access Journals (Sweden)

    LI Xiang

    2013-05-01

    Full Text Available Objective Patients with obstructive sleep apnea syndrome (OSAS usually complain of daytime hypersomnia and decrease in cognitive function, which affects the quality of their work and life. The reason why the cognitive function of OSAS patients decreased remains controversial. The aim of this study is to evaluate the impairment and the main influencing factors of cognitive function in OSAS. Methods There were totally 50 OSAS patients (OSAS group and 25 volunteers (control group included in our study. All of them were monitored by polysomnography (PSG and tested by Continuous Performance Test (CPT, n-back test and Stroop Color?Word Test (CWT to evaluate their sleep condition and cognitive function. Results No significant difference was found between the two groups in total sleep time and sleep efficiency (P > 0.05, for all. Compared with control group, OSAS group had significant increased time of non-rapid eye movement (NREM sleep stage Ⅰ and stage Ⅱ, significant decreased time of stage Ⅲ (P 0.05, for all, while had significant connection with AI and NREM Ⅲ (P < 0.05, for all. The rate of OSAS patients who underwent nasal continuous positive airway pressure (nCPAP treatment was very low, only 8% (4/50. Conclusion The abnormality of OSAS patients' sleep structure is characterized with sleep fragmentation and decrease of NREM Ⅲ, which may be the main factors of cognitive impairment. Exploration of treatment methods targeted on regulating the effected hormones and receptors is meaningful.

  15. Gender, Race, and Diet Affect Platelet Function Tests in Normal Subjects Contributing to a High Rate of Abnormal Results

    Science.gov (United States)

    Miller, Connie H.; Rice, Anne S.; Garrett, Katherine; Stein, Sidney F.

    2015-01-01

    Summary To assess sources of variability in platelet function tests in normal subjects, 64 healthy young adults were tested on 2–6 occasions at 2 week intervals using 4 methods: platelet aggregation (AGG) in platelet-rich plasma (PRP) in the Bio/Data PAP-4 Aggregometer (BD) and Chrono-Log Lumi-Aggregometer (CL); and AGG in whole blood (WB) in the CL and Multiplate Platelet Function Analyzer (MP), with ATP release (REL) in CL-PRP and CL-WB. Food and medication exposures were recorded prospectively for 2 weeks prior to each blood draw. At least one AGG abnormality was seen in 21% of 81 drug-free specimens with CL-PRP, 15% with CL-WB, 13% with BD-PRP, and 6% with MP-WB, increasing with inclusion of REL to 28% for CL-PRP and 30% for CL-WB. Epinephrine AGG and REL were significantly reduced in males (P<0.0001). Ristocetin AGG and collagen and thrombin REL were significantly reduced in Blacks (P<0.0001). One-third of specimens drawn following flavonoid-rich food exposures had aberrant results, compared to 8.5% of specimens without such exposures (P=0.0035). PRP tests had less intra-individual variation than WB tests. Gender, race, diet, and test system affected results of platelet function testing in healthy subjects, suggesting caution when interpreting the results of platelet function testing in patients. PMID:24617520

  16. Carboxyl- and amino-functionalized polystyrene nanoparticles differentially affect the polarization profile of M1 and M2 macrophage subsets.

    Science.gov (United States)

    Fuchs, Ann-Kathrin; Syrovets, Tatiana; Haas, Karina A; Loos, Cornelia; Musyanovych, Anna; Mailänder, Volker; Landfester, Katharina; Simmet, Thomas

    2016-04-01

    Macrophages are key regulators of innate and adaptive immune responses. Exposure to microenvironmental stimuli determines their polarization into proinflammatory M1 and anti-inflammatory M2 macrophages. M1 exhibit high expression of proinflammatory TNF-α and IL-1β, and M2 promote tissue repair, but likewise support tumor growth and cause immune suppression by expressing IL-10. Thus, the M1/M2 balance critically determines tissue homeostasis. By using carboxyl- (PS-COOH) and amino-functionalized (PS-NH2) polystyrene nanoparticles, the effects of surface decoration on the polarization of human macrophages were investigated. The nanoparticles did not compromise macrophage viability nor did they affect the expression of the M1 markers CD86, NOS2, TNF-α, and IL-1β. By contrast, in M2, both nanoparticles impaired expression of scavenger receptor CD163 and CD200R, and the release of IL-10. PS-NH2 also inhibited phagocytosis of Escherichia coli by both, M1 and M2. PS-COOH did not impair phagocytosis by M2, but increased protein mass in M1 and M2, TGF-β1 release by M1, and ATP levels in M2. Thus, nanoparticles skew the M2 macrophage polarization without affecting M1 markers. Given the critical role of the M1 and M2 polarization for the immunological balance in patients with cancer or chronic inflammation, functionalized nanoparticles might serve as tools for reprogramming the M1/M2 polarization.

  17. Suppressed peripheral blood lymphocyte blastogenesis in pre- and postpartal sheep by chronic heat-stress, and suppressive property of heat-stressed sheep serum on lymphocytes.

    Science.gov (United States)

    Niwano, Y; Becker, B A; Mitra, R; Caldwell, C W; Abdalla, E B; Johnson, H D

    1990-01-01

    Phytohemagglutinin (PHA) and concanavalin A (Con A)-induced blastogenesis of peripheral blood lymphocytes was examined in heat-stressed pre- and postpartal sheep. The peak responses of lymphocytes to PHA and Con A in heat-stressed sheep revealed significant reduction before and after parturition compared with those in the corresponding control animals kept under thermoneutral conditions. Furthermore, the effect of serum from control or heat-stressed sheep on PHA-induced lymphocyte blastogenesis was examined. Supplementation of serum from heat-stressed sheep significantly suppressed the blastogenesis of lymphocytes obtained from healthy sheep, bovine, and human donors. Unlike dexamethasone, heat-stressed sheep serum did not inhibit IL-2 production by PHA-stimulated human peripheral blood lymphocytes. These results indicate that the immunosuppression of heat-stressed sheep is in part mediated by serum factor(s) that can modulate T-cell function in a species nonspecific manner.

  18. Accurately assessing the risk of schizophrenia conferred by rare copy-number variation affecting genes with brain function.

    Science.gov (United States)

    Raychaudhuri, Soumya; Korn, Joshua M; McCarroll, Steven A; Altshuler, David; Sklar, Pamela; Purcell, Shaun; Daly, Mark J

    2010-09-09

    Investigators have linked rare copy number variation (CNVs) to neuropsychiatric diseases, such as schizophrenia. One hypothesis is that CNV events cause disease by affecting genes with specific brain functions. Under these circumstances, we expect that CNV events in cases should impact brain-function genes more frequently than those events in controls. Previous publications have applied "pathway" analyses to genes within neuropsychiatric case CNVs to show enrichment for brain-functions. While such analyses have been suggestive, they often have not rigorously compared the rates of CNVs impacting genes with brain function in cases to controls, and therefore do not address important confounders such as the large size of brain genes and overall differences in rates and sizes of CNVs. To demonstrate the potential impact of confounders, we genotyped rare CNV events in 2,415 unaffected controls with Affymetrix 6.0; we then applied standard pathway analyses using four sets of brain-function genes and observed an apparently highly significant enrichment for each set. The enrichment is simply driven by the large size of brain-function genes. Instead, we propose a case-control statistical test, cnv-enrichment-test, to compare the rate of CNVs impacting specific gene sets in cases versus controls. With simulations, we demonstrate that cnv-enrichment-test is robust to case-control differences in CNV size, CNV rate, and systematic differences in gene size. Finally, we apply cnv-enrichment-test to rare CNV events published by the International Schizophrenia Consortium (ISC). This approach reveals nominal evidence of case-association in neuronal-activity and the learning gene sets, but not the other two examined gene sets. The neuronal-activity genes have been associated in a separate set of schizophrenia cases and controls; however, testing in independent samples is necessary to definitively confirm this association. Our method is implemented in the PLINK software package.

  19. Biochar affects soil organic matter cycling and microbial functions but does not alter microbial community structure in a paddy soil.

    Science.gov (United States)

    Tian, Jing; Wang, Jingyuan; Dippold, Michaela; Gao, Yang; Blagodatskaya, Evgenia; Kuzyakov, Yakov

    2016-06-15

    The application of biochar (BC) in conjunction with mineral fertilizers is one of the most promising management practices recommended to improve soil quality. However, the interactive mechanisms of BC and mineral fertilizer addition affecting microbial communities and functions associated with soil organic matter (SOM) cycling are poorly understood. We investigated the SOM in physical and chemical fractions, microbial community structure (using phospholipid fatty acid analysis, PLFA) and functions (by analyzing enzymes involved in C and N cycling and Biolog) in a 6-year field experiment with BC and NPK amendment. BC application increased total soil C and particulate organic C for 47.4-50.4% and 63.7-74.6%, respectively. The effects of BC on the microbial community and C-cycling enzymes were dependent on fertilization. Addition of BC alone did not change the microbial community compared with the control, but altered the microbial community structure in conjunction with NPK fertilization. SOM fractions accounted for 55% of the variance in the PLFA-related microbial community structure. The particulate organic N explained the largest variation in the microbial community structure. Microbial metabolic activity strongly increased after BC addition, particularly the utilization of amino acids and amines due to an increase in the activity of proteolytic (l-leucine aminopeptidase) enzymes. These results indicate that microorganisms start to mine N from the SOM to compensate for high C:N ratios after BC application, which consequently accelerate cycling of stable N. Concluding, BC in combination with NPK fertilizer application strongly affected microbial community composition and functions, which consequently influenced SOM cycling.

  20. Functional and splicing defect analysis of 23 ACVRL1 mutations in a cohort of patients affected by Hereditary Hemorrhagic Telangiectasia.

    Directory of Open Access Journals (Sweden)

    Ferdos Alaa El Din

    Full Text Available Hereditary Hemorrhagic Telangiectasia syndrome (HHT or Rendu-Osler-Weber (ROW syndrome is an autosomal dominant vascular disorder. Two most common forms of HHT, HHT1 and HHT2, have been linked to mutations in the endoglin (ENG and activin receptor-like kinase 1 (ACVRL1or ALK1 genes respectively. This work was designed to examine the pathogenicity of 23 nucleotide variations in ACVRL1 gene detected in more than 400 patients. Among them, 14 missense mutations and one intronic variant were novels, and 8 missense mutations were previously identified with questionable implication in HHT2. The functionality of missense mutations was analyzed in response to BMP9 (specific ligand of ALK1, the maturation of the protein products and their localization were analyzed by western blot and fluorescence microscopy. The splicing impairment of the intronic and of two missense mutations was examined by minigene assay. Functional analysis showed that 18 out of 22 missense mutations were defective. Splicing analysis revealed that one missense mutation (c.733A>G, p.Ile245Val affects the splicing of the harboring exon 6. Similarly, the intronic mutation outside the consensus splicing sites (c.1048+5G>A in intron 7 was seen pathogenic by splicing study. Both mutations induce a frame shift creating a premature stop codon likely resulting in mRNA degradation by NMD surveillance mechanism. Our results confirm the haploinsufficiency model proposed for HHT2. The affected allele of ACVRL1 induces mRNA degradation or the synthesis of a protein lacking the receptor activity. Furthermore, our data demonstrate that functional and splicing analyses together, represent two robust diagnostic tools to be used by geneticists confronted with novel or conflicted ACVRL1 mutations.

  1. Avermectins differentially affect ethanol intake and receptor function: implications for developing new therapeutics for alcohol use disorders.

    Science.gov (United States)

    Asatryan, Liana; Yardley, Megan M; Khoja, Sheraz; Trudell, James R; Hyunh, Nhat; Louie, Stan G; Petasis, Nicos A; Alkana, Ronald L; Davies, Daryl L

    2014-06-01

    Our laboratory is investigating ivermectin (IVM) and other members of the avermectin family as new pharmaco-therapeutics to prevent and/or treat alcohol use disorders (AUDs). Earlier work found that IVM significantly reduced ethanol intake in mice and that this effect likely reflects IVM's ability to modulate ligand-gated ion channels. We hypothesized that structural modifications that enhance IVM's effects on key receptors and/or increase its brain concentration should improve its anti-alcohol efficacy. We tested this hypothesis by comparing the abilities of IVM and two other avermectins, abamectin (ABM) and selamectin (SEL), to reduce ethanol intake in mice, to alter modulation of GABAARs and P2X4Rs expressed in Xenopus oocytes and to increase their ability to penetrate the brain. IVM and ABM significantly reduced ethanol intake and antagonized the inhibitory effects of ethanol on P2X4R function. In contrast, SEL did not affect either measure, despite achieving higher brain concentrations than IVM and ABM. All three potentiated GABAAR function. These findings suggest that chemical structure and effects on receptor function play key roles in the ability of avermectins to reduce ethanol intake and that these factors are more important than brain penetration alone. The direct relationship between the effect of these avermectins on P2X4R function and ethanol intake suggest that the ability to antagonize ethanol-mediated inhibition of P2X4R function may be a good predictor of the potential of an avermectin to reduce ethanol intake and support the use of avermectins as a platform for developing novel drugs to prevent and/or treat AUDs.

  2. COMT and 5-HT1A-receptor genotypes potentially affect executive functions improvement after cognitive remediation in schizophrenia

    Science.gov (United States)

    Bosia, Marta; Bechi, Margherita; Pirovano, Adele; Buonocore, Mariachiara; Lorenzi, Cristina; Cocchi, Federica; Bramanti, Placido; Smeraldi, Enrico; Cavallaro, Roberto

    2014-01-01

    Cognitive remediation therapy (CRT) has been proved to improve cognitive deficits in schizophrenia and to enhance functional outcomes of classical rehabilitation. However, CRT outcomes are heterogeneous and predictors of response are still unknown. Genetic variability, especially in the dopaminergic system, has been hypothesized to affect CRT. We previously reported that rs4680 of the catechol-O-methyltrasferase (COMT) influences improvements in executive functions in patients treated with CRT, but this result was not confirmed by other studies. Such inconsistent findings may depend, other than on clinical variables, also on other genes involved in cognition. Recent studies proved that serotonin 1A receptor (5-HT1A-R) regulates dopamine in the prefrontal cortex (PFC), and clinical works suggested a 5-HT1A-R role in cognition. We then analysed possible effects of COMT rs4680 and 5-HT1A-R rs6295 on CRT outcomes, taking into account also clinical and demographic factors. Eighty-six clinically stabilized schizophrenia patients treated with three months CRT were assessed with the Wisconsin Card Sorting Test, as a measure of executive functions, at enrolment and after CRT treatment, and underwent COMT and 5-HT1A-R genotyping. We found a significant main effect of COMT genotype and an interaction with 5-HT1A-R on executive function improvement after CRT. The results suggest that these two polymorphisms may have an additive effect on individual capacity to recover from cognitive deficit, probably through their role on PFC dopaminergic transmission modulation, known to be critical for modulating cognitive functions. PMID:25750798

  3. Treatment of chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra; O'Brien, Susan M

    2004-04-01

    Treatment options for patients with chronic lymphocytic leukemia have changed over the past two decades. This article reviews the experience accumulated with the use of alkylating agents alone and in combination; purine analogues alone and in combination and monoclonal antibodies such as rituximab, and alemtuzumab alone and in combination. The results obtained with different treatment strategies are summarized, compared, and reviewed.

  4. Pleiotropic Mutations at the TUP1 Locus That Affect the Expression of Mating-Type-Dependent Functions in SACCHAROMYCES CEREVISIAE.

    Science.gov (United States)

    Lemontt, J F; Fugit, D R; Mackay, V L

    1980-04-01

    The umr7-1 mutation, previously identified in a set of mutants that had been selected for defective UV-induced mutagenesis at CAN1, affects other cellular functions, including many of those regulated by the mating-type locus (MAT) in heterothallic Saccharomyces cerevisiae. The recessive umr7-1 allele, mapping approximately 20 cM distal to thr4 on chromosome III, causes clumpy growth in both a and alpha cells and has no apparent effect on a mating functions. However, alpha umr7 meiotic segregants fail to express several alpha-specific functions (e.g., high-frequency conjugation with a strains, secretion of the hormone alpha-factor and response to the hormone a-factor). In addition, alpha umr7 cells exhibit some a-specific characteristics, such as the barrier phenotype (Bar(+)) that prevents diffusion of alpha-factor and an increased mating frequency with alpha strains. The most striking property of alpha umr7 strains is their altered morphology, in which mitotic cells develop an asymmetric pear shape, like that of normal a cells induced to form "shmoos" by interaction with alpha-factor. Some a/alpha-specific diploid functions are also affected by umr7; instead of polar budding patterns, a/alpha umr7/umr7 diploids have medial budding like a/a, alpha/alpha and haploid strains. Moreover, a/alpha umr7/umr7 diploids have lost the ability to sporulate and are Bar(+) like a or a/a strains. Revertant studies indicate that umr7-1 is a single point mutation. The umr7 mutant fails to complement mutants of both tup1 (selected for deoxythymidine monophosphate utilization) and cyc9 (selected for high iso-2-cytochrome c levels), and all three isolates have similar genetic and phenotypic properties. It is suggested that the product of this gene plays some common central role in the complex regulation of the expression of both MAT-dependent and MAT-independent functions.

  5. Inhibition of human lymphocyte proliferation and cleavage of interleukin-2 by Pseudomonas aeruginosa proteases

    DEFF Research Database (Denmark)

    Theander, T G; Kharazmi, A; Pedersen, B K

    1988-01-01

    This study was undertaken to determine the effect of Pseudomonas aeruginosa alkaline protease (AP) and elastase (ELA) on human lymphocyte function. AP at 50 micrograms/ml and ELA at 12 micrograms/ml caused a 50% inhibition of phytohemagglutinin-induced proliferation. There was no difference......, the inhibition was partly reversed. ELA at 10 micrograms/ml cleaved IL-2, as judged by size chromatography of a reaction mixture containing 125I-labeled IL-2 and the proteases. The ELA-digested IL-2 exhibited a reduced binding capacity to IL-2 receptors on the lymphocytes. Furthermore, treatment...... of phytohemagglutinin-stimulated lymphocytes with AP and ELA resulted in inhibition of binding of intact IL-2 to IL-2 receptors on the stimulated lymphocytes. These results indicated that P. aeruginosa-derived enzymes are able to interfere with human lymphocyte function in vitro and that this effect might be due...

  6. Changes in percentage of lymphocyte subsets after 131I treatment in patients with differentiated thyroid cancer

    Institute of Scientific and Technical Information of China (English)

    LUO Quan-Yong; CHEN Li-Bo; YU Yong-Li; LU Han-Kui; ZHU Rui-Sen

    2005-01-01

    To monitor the extent and the duration of lymphocyte subset changes in patients with thyroid carcinoma undergoing therapeutic 131I administration, the percentage of lymphocyte subsets were serially analyzed before and after 131I treatment. In patients who received 1850 MBq of 131I for ablation of thyroid remnants, only for NK cells and B cells showed a significant reduction. In patients received 3700 MBq of 131I for treatment of local lymph node metastases, NK cells, B cells and CD4+ were found decreased. In patients received 7400 MBq of 131I for treatment of distant metastases, NK cells, B cells and CD4+ and CD8+ were all affected. However, there is no significant reduction compared to the baseline in the percentage of all lymphocyte subsets three months after 131I treatment. The results show that the sensitivity of lymphocytes to 131I internal radiation depends upon lymphocyte phenotype and 131I activity. The immunosuppression effects are temporary and reversible.

  7. Impact of aerobic exercise training on cognitive functions and affect associated to the COMT polymorphism in young adults.

    Science.gov (United States)

    Stroth, Sanna; Reinhardt, Ralf K; Thöne, Jan; Hille, Katrin; Schneider, Matthias; Härtel, Sascha; Weidemann, Wolfgang; Bös, Klaus; Spitzer, Manfred

    2010-10-01

    Physical fitness can serve as a means to enhance cognitive functioning by modulating particular aspects of brain functioning. However, mechanisms underlying this modulating effect remain widely unresolved. To examine the impact and to clarify the mechanisms of physical fitness training in a young and healthy population, it was investigated whether an increase in fitness would result in improvements in executive control processes and positive and negative affect. Moreover, genotype of the Val158Met polymorphism in catechol-O-methyltransferase (COMT) as an index of relative central dopamine bioavailability was determined to elucidate dopamine tuning efficiency and its association with performance in the applied cognitive tasks. Seventy-five individuals participated and underwent an incremental fitness test to assess physical fitness. An exercising group subsequently engaged in a 17 weeks running training consisting of three running sessions at moderate to high, individually adjusted intensities. Associated with increased fitness improved cognitive flexibility and cognitive control were observed, whereas working memory remained unaffected. In runners, Val/Val participants improved cognitive performance to a greater extent compared to individuals carrying a Met allele. From the present results it is concluded that an increase in physical fitness provides a means to improve cognitive functioning via dopaminergic modulation.

  8. Does excessive flatfoot deformity affect function? A comparison between symptomatic and asymptomatic flatfeet using the Oxford Foot Model.

    Science.gov (United States)

    Hösl, Matthias; Böhm, Harald; Multerer, Christel; Döderlein, Leonhard

    2014-01-01

    Treatment of asymptomatic flexible flatfeet is a subject of great controversy. The purpose of this study was to examine foot function during walking in symptomatic (SFF) and asymptomatic (ASFF) flexible flatfeet. Thirty-five paediatric and juvenile patients with idiopathic flexible flatfeet were recruited from an orthopaedic outpatient department (14 SFF and 21 ASFF). Eleven age-matched participants with typically developing feet served as controls (TDF). To study foot function, 3D multi-segment foot kinematics and ankle joint kinetics were captured during barefoot gait analysis. Overall, alterations in foot kinematics in flatfeet were pronounced but differences between SFF and ASFF were not observed. Largest discriminatory effects between flatfeet and TDF were noticed in reduced hindfoot dorsiflexion as well as in increased forefoot supination and abduction. Upon clinical examination, restrictions in passive dorsiflexion in ASFF and SFF were significant. During gait, the hindfoot in flatfeet (both ASFF and SFF) was more everted, but less flexible. In sagittal plane, limited hindfoot dorsiflexion of ASFF and SFF was compensated for by increased forefoot mobility and a hypermobile hallux. Concerning ankle kinetics, SFF lacked positive joint energy for propulsion while ASFF needed to absorb more negative ankle joint energy during loading response. This may risk fatigue and overuse syndrome of anterior shank muscles in ASFF. Hence, despite a lack of symptoms flatfoot deformity in ASFF affected function. Yet, contrary to what was expected, SFF did not show greater deviations in 3D foot kinematics than ASFF. Symptoms may rather depend on tissue wear and subjective pain thresholds.

  9. Renal function affects absorbed dose to the kidneys and haematological toxicity during {sup 177}Lu-DOTATATE treatment

    Energy Technology Data Exchange (ETDEWEB)

    Svensson, Johanna; Berg, Gertrud [Sahlgrenska University Hospital, Department of Oncology, Goeteborg (Sweden); Waengberg, Bo [Sahlgrenska University Hospital, Department of Surgery, Goeteborg (Sweden); Larsson, Maria [University of Gothenburg, Department of Radiation Physics, Institute of Clinical Sciences, The Sahlgrenska Academy, Goeteborg (Sweden); Forssell-Aronsson, Eva; Bernhardt, Peter [University of Gothenburg, Department of Radiation Physics, Institute of Clinical Sciences, The Sahlgrenska Academy, Goeteborg (Sweden); Sahlgrenska University Hospital, Department of Medical Physics and Medical Bioengineering, Goeteborg (Sweden)

    2015-05-01

    Peptide receptor radionuclide therapy (PRRT) has become an important treatment option in the management of advanced neuroendocrine tumours. Long-lasting responses are reported for a majority of treated patients, with good tolerability and a favourable impact on quality of life. The treatment is usually limited by the cumulative absorbed dose to the kidneys, where the radiopharmaceutical is reabsorbed and retained, or by evident haematological toxicity. The aim of this study was to evaluate how renal function affects (1) absorbed dose to the kidneys, and (2) the development of haematological toxicity during PRRT treatment. The study included 51 patients with an advanced neuroendocrine tumour who received {sup 177}Lu-DOTATATE treatment during 2006 - 2011 at Sahlgrenska University Hospital in Gothenburg. An average activity of 7.5 GBq (3.5 - 8.2 GBq) was given at intervals of 6 - 8 weeks on one to five occasions. Patient baseline characteristics according to renal and bone marrow function, tumour burden and medical history including prior treatment were recorded. Renal and bone marrow function were then monitored during treatment. Renal dosimetry was performed according to the conjugate view method, and the residence time for the radiopharmaceutical in the whole body was calculated. A significant correlation between inferior renal function before treatment and higher received renal absorbed dose per administered activity was found (p < 0.01). Patients with inferior renal function also experienced a higher grade of haematological toxicity during treatment (p = 0.01). The residence time of {sup 177}Lu in the whole body (range 0.89 - 3.0 days) was correlated with grade of haematological toxicity (p = 0.04) but not with renal absorbed dose (p = 0.53). Patients with inferior renal function were exposed to higher renal absorbed dose per administered activity and developed a higher grade of haematological toxicity during {sup 177}Lu-DOTATATE treatment. The study confirms the

  10. T、B淋巴细胞功能对流行性牛白血病发生发展的影响%The Relationship Between the Function of T、B Lymphocytes and the Pathogenesis of Enzootic Bovine Leukosis

    Institute of Scientific and Technical Information of China (English)

    王选年; 潘耀谦; 康晓迪; 张改平

    2001-01-01

    本文回顾了T、B淋巴细胞功能与牛白血病发生发展的相关性。阐明了感染BLV牛B细胞淋巴瘤细胞除了来源于B1a(CD5+CD11b+)细胞,也可来源于B1b(CD5- CD11b+)及常规B2(CD5 -CD11b-)细胞。探讨了T细胞功能对牛白血病的发生发展的影响,指出IL-1 2表达下降和IL -10表达增加可能导致了B细胞淋巴肉瘤的形成,Ⅰ型和Ⅱ型细胞因子的不平衡引起了BLV的发展。同时讨论了B-T细胞的相互作用在BLV感染时疾病阶段性发展过程中的作用。%This review focuses on the relationship between the function of T、B lymp hocytes and the pathogenesis of Enzootic Bovine Leukosis. In BLV infection anima l, the phenotypes of B-cells lymphoma can be derived from B1a(CD5+CD11 b+), B1b(C D5-CD11b+) and conventional B2(CD5-CD11b-)cells. Co mbined with previous findi ngs the data suggests that the decrease of IL-12 and the increase of IL-10 res ult in the formation of B-cell lymphosarcoma, and the imbalance of phenotype Ⅰ and Ⅱ cytokines causes the progression of Bovine Leukemia. M eanwhile, the interaction of B and T cells could contribute to the polyclonal ac tivation and proliferation of B lymphocytes in BLV infectea animals.

  11. Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia

    Science.gov (United States)

    2016-07-18

    B-Cell Prolymphocytic Leukemia; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

  12. p53 Regulates the neuronal intrinsic and extrinsic responses affecting the recovery of motor function following spinal cord injury.

    Science.gov (United States)

    Floriddia, Elisa M; Rathore, Khizr I; Tedeschi, Andrea; Quadrato, Giorgia; Wuttke, Anja; Lueckmann, Jan-Matthis; Kigerl, Kristina A; Popovich, Phillip G; Di Giovanni, Simone

    2012-10-01

    Following spinal trauma, the limited physiological axonal sprouting that contributes to partial recovery of function is dependent upon the intrinsic properties of neurons as well as the inhibitory glial environment. The transcription factor p53 is involved in DNA repair, cell cycle, cell survival, and axonal outgrowth, suggesting p53 as key modifier of axonal and glial responses influencing functional recovery following spinal injury. Indeed, in a spinal cord dorsal hemisection injury model, we observed a significant impairment in locomotor recovery in p53(-/-) versus wild-type mice. p53(-/-) spinal cords showed an increased number of activated microglia/macrophages and a larger scar at the lesion site. Loss- and gain-of-function experiments suggested p53 as a direct regulator of microglia/macrophages proliferation. At the axonal level, p53(-/-) mice showed a more pronounced dieback of the corticospinal tract (CST) and a decreased sprouting capacity of both CST and spinal serotoninergic fibers. In vivo expression of p53 in the sensorimotor cortex rescued and enhanced the sprouting potential of the CST in p53(-/-) mice, while, similarly, p53 expression in p53(-/-) cultured cortical neurons rescued a defect in neurite outgrowth, suggesting a direct role for p53 in regulating the intrinsic sprouting ability of CNS neurons. In conclusion, we show that p53 plays an important regulatory role at both extrinsic and intrinsic levels affecting the recovery of motor function following spinal cord injury. Therefore, we propose p53 as a novel potential multilevel therapeutic target for spinal cord injury.

  13. Detection of genetic association and functional polymorphisms of UGDH affecting milk production trait in Chinese Holstein cattle

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    Xu Qing

    2012-11-01

    Full Text Available Abstract Background We previously localized a quantitative trait locus (QTL on bovine chromosome 6 affecting milk production traits to a 1.5-Mb region between BMS483 and MNB-209 via genome scanning followed by fine mapping. Results Totally 15 genes were mapped within such linkage region through bioinformatic analysis of the cattle-human comparative map and bovine genome assembly. Of them, the UDP-glucose dehydrogenase (UGDH was suggested as a potential positional candidate gene for milk production traits based on its corresponding physiological and biochemical functions and genetic effects. By sequencing all the coding exons and the untranslated regions in UGDH with pooled DNA of 8 sires represented the separated families detected in our previous studies, a total of ten SNPs were identified and genotyped in 1417 Holstein cows of 8 separation families. Individual SNP-based association analysis revealed 4 significant associations of SNP Ex1-1, SNP Int3-1, SNP Int5-1, and SNP Ex12-3 with milk yield (P protein percentage (F=4.15; P=0.0418 and fat percentage (F=5.18~7.25; P=0.0072~0.0231. Finally, by using an in vitro expression assay, we demonstrated that the A allele of SNP Ex1-1 and T allele of SNP Ex11-1of UGDH significantly decreases the expression of UGDH by 68.0% at the RNA, and 50.1% at the protein level, suggesting that SNP Ex1-1 and Ex11-1 represent two functional polymorphisms affecting expression of UGDH and may partly contributed to the observed association of the gene with milk production traits in our samples. Conclusions Taken together, our findings strongly indicate that UGDH gene could be involved in genetic variation underlying the QTL for milk production traits.

  14. The use of contrast media in deceased kidney donors does not affect initial graft function or graft survival.

    Science.gov (United States)

    Vigneau, C; Fulgencio, J-P; Godier, A; Chalem, Y; El Metaoua, S; Rondeau, E; Tuppin, P; Bonnet, F

    2006-09-01

    Patients receiving cadaveric kidney transplants often experience delayed graft function. As iodinated contrast media injection (ICMI), necessary for cerebral angiography, which is often used to diagnose brain death, can be nephrotoxic, we compared renal function recovery (RFR) and 1-year and long-term graft survival according to the method used to diagnose brain death. Data from 9921 cadaveric kidneys, transplanted between 1 January 1998 and 31 December 2003, were retrieved from the French National Registry for organ donation. We defined RFR as the number of days for the recipient to reach a plasma creatinine less than 250 mumol/l, and/or a 24-h urine output greater than 1000 ml. RFR and 1-year and long-term graft survival were compared between four different donor groups (according to ICMI and diabetes mellitus). A total of 41.5% of deceased donors received ICMI before organ procurement and 1.95% of them were diabetic. History of ICMI or diabetes in the donor did not influence RFR or 1-year graft survival. Long-term graft survival was decreased in the group of patients transplanted with a diabetic graft as compared to patients transplanted with a non-diabetic graft (P=0.001). History of ICMI in the donor did not affect long-term graft survival in the non-diabetic donor group (P=0.2); however, in the diabetic group, ICMI tended to decrease long-term graft survival (P=0.056). ICMI did not affect RFR or graft survival in non-diabetic deceased donors. However, its use in diabetic deceased donors requires further study.

  15. Loci controlling lymphocyte production of interferon c after alloantigen stimulation in vitro and their co-localization with genes controlling lymphocyte infiltration of tumors and tumor susceptibility.

    Science.gov (United States)

    Lipoldová, Marie; Havelková, Helena; Badalova, Jana; Vojtísková, Jarmila; Quan, Lei; Krulova, Magdaléna; Sohrabi, Yahya; Stassen, Alphons P; Demant, Peter

    2010-02-01

    Low infiltration of lymphocytes into cancers is associated with poor prognosis, but the reasons why some patients exhibit a low and others a high infiltration of tumors are unknown. Previously we mapped four loci (Lynf1–Lynf4) controlling lymphocyte infiltration of mouse lung tumors. These loci do not encode any of the molecules that are involved in traffic of lymphocytes. Here we report a genetic relationship between these loci and the control of production of IFNγ in allogeneic mixed lymphocyte cultures (MLC). We found that IFNγ production by lymphocytes of O20/A mice is lower than by lymphocytes of OcB-9/Dem mice (both H2pz) stimulated in MLC by irradiated splenocytes of C57BL/10SnPh (H2b) or BALB/ cHeA (H2d) mice, or by ConA. IFNγ production in MLCs of individual (O20 9 OcB-9)F2mice stimulated by irradiated C57BL/10 splenocytes and genotyped for microsatellite markers revealed four IFNγ-controlling loci (Cypr4-Cypr7), each of which is closely linked with one of the four Lynf loci and with a cluster of susceptibility genes for different tumors. This suggests that inherited differences in certain lymphocyte responses may modify their propensity to infiltrate tumors and their capacity to affect tumor growth.

  16. Assessment of left ventricular regional function in affected and carrier dogs with duchenne muscular dystrophy using speckle tracking echocardiography

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    Yugeta Naoko

    2011-05-01

    Full Text Available Abstract Background Two-dimensional speckle tracking echocardiography (STE is a relatively new method to detect regional myocardial dysfunction. To assess left ventricular (LV regional myocardial dysfunction using STE in Duchenne muscular dystrophy model dogs (CXMDJ without overt clinical signs of heart failure. Methods Six affected dogs, 8 carrier dogs with CXMDJ, and 8 control dogs were used. Conventional echocardiography, systolic and diastolic function by Doppler echocardiography, tissue Doppler imaging (TDI, and strain indices using STE, were assessed and compared among the 3 groups. Results Significant differences were seen in body weight, transmitral E wave and E' wave derived from TDI among the 3 groups. Although no significant difference was observed in any global strain indices, in segmental analysis, the peak radial strain rate during early diastole in posterior segment at chordae the tendineae level showed significant differences among the 3 groups. Conclusions The myocardial strain rate by STE served to detect the impaired cardiac diastolic function in CXMDJ without any obvious LV dilation or clinical signs. The radial strain rate may be a useful parameter to detect early myocardial impairment in CXMDJ.

  17. A Gain-of-Function Mutation in OsIAA11 Affects Lateral Root Development in Rice

    Institute of Scientific and Technical Information of China (English)

    Zhen-Xing Zhu; Yu Liu; Shao-Jun Liu; Chuan-Zao Mao; Yun-Rong Wu; Ping Wu

    2012-01-01

    Lateral roots are important to plants for the uptake of nutrients and water.Several members of the Aux/IAA family have been shown to play crucial roles in lateral root development.Here,a member of the rice Aux/IAA family genes,OsIAA11 (LOC_Os03g43400),was isolated from a rice mutant defective in lateral root development.The gain-of-function mutation in OsIAA 11 strictly blocks the initiation of lateral root primordia,but it does not affect crown root development.The expression of OsIAA11 is defined in root tips,lateral root caps,steles,and lateral root primordia.The auxin reporter DR5-GUS (β-glucuronidase) was expressed at lower levels in the mutant than in wild-type,indicating that OsIAA11 is involved in auxin signaling in root caps.The transcript abundance of both OsPIN1b and OsPIN10a was diminished in root tips of the Osiaa11 mutant.Taken together,the results indicate that the gain-of-function mutation in OsIAA11 caused the inhibition of lateral root development in rice.

  18. Negative emotions affect postoperative scores for evaluating functional knee recovery and quality of life after total knee replacement

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    A. Qi

    2016-01-01

    Full Text Available This study aimed to determine whether psychological factors affect health-related quality of life (HRQL and recovery of knee function in total knee replacement (TKR patients. A total of 119 TKR patients (male: 38; female: 81 completed the Beck Anxiety Inventory (BAI, Beck Depression Inventory (BDI, State Trait Anxiety Inventory (STAI, Eysenck Personality Questionnaire-revised (EPQR-S, Knee Society Score (KSS, and HRQL (SF-36. At 1 and 6 months after surgery, anxiety, depression, and KSS scores in TKR patients were significantly better compared with those preoperatively (P<0.05. SF-36 scores at the sixth month after surgery were significantly improved compared with preoperative scores (P<0.001. Preoperative Physical Component Summary Scale (PCS and Mental Component Summary Scale (MCS scores were negatively associated with extraversion (E score (B=-0.986 and -0.967, respectively, both P<0.05. Postoperative PCS and State Anxiety Inventory (SAI scores were negatively associated with neuroticism (N score; B=-0.137 and -0.991, respectively, both P<0.05. Postoperative MCS, SAI, Trait Anxiety Inventory (TAI, and BAI scores were also negatively associated with the N score (B=-0.367, -0.107, -0.281, and -0.851, respectively, all P<0.05. The KSS function score at the sixth month after surgery was negatively associated with TAI and N scores (B=-0.315 and -0.532, respectively, both P<0.05, but positively associated with the E score (B=0.215, P<0.05. The postoperative KSS joint score was positively associated with postoperative PCS (B=0.356, P<0.05. In conclusion, for TKR patients, the scores used for evaluating recovery of knee function and HRQL after 6 months are inversely associated with the presence of negative emotions.

  19. [Changes in ingestive behavior during growth affects the functional maturation of temporomandibular joint nociceptive neurons of rats].

    Science.gov (United States)

    Hiranuma, Maya

    2013-03-01

    Temporomandibular joint (TMJ) loading during development promotes its growth and maintains normal structure/function. Continuous change in diet consistency is related to development and maturation of the peripheral nervous system, including the nociceptive system. However, the functional modulation of TMJ-nociceptive neurons under different ingestive behavior is unclear. We fed growing rats a liquid diet to investigate the effects of low TMJ loading on the response properties of neurons in the trigeminal spinal tract subnucleus caudalis (Sp5C). Forty 2-week-old male rats were used. They were fed chow pellets (n = 20, C group) or a liquid diet (n = 20, LD group) soon after weaning. Firing activities of single sensory units in response to TMJ pressure stimuli were recorded at 4, 5, 7 and 9 weeks. In TMJ-nociceptive neurons, the firing threshold (FT) in the LD group was significantly lower than that in the C group at each recording age. The FT in the C group remained unchanged throughout the recording period, whereas that in the LD group was the highest at 4 weeks, and gradually decreased. On the other hand, the initial firing frequency (IFF) was significantly higher in the LD group than in the C group at each recording age. The IFF in the C group remained unchanged throughout the experimental period, whereas that in the LD group was at its lowest at 4 weeks, and gradually increased. Based on these findings, ingestive behavior that results from continuous changes in the physical consistency of the diet during growth may affect the functional maturation of TMJ-nociceptive neurons.

  20. [B lymphocyte ontogeny].

    Science.gov (United States)

    Balandrán, Juan Carlos; Pelayo, Rosana

    2016-01-01

    The B cell development from hematopoietic stem cells is a continuous and highly regulated process where multiple differentiation potentials are gradually lost while acquiring lineage specialized functions. At 50 years of the B cell discovery, the current knowledge of its early differentiation largely derive from the isolation and characterization of bone marrow early progenitor cells initiating the lymphoid program, and from the definition of transcriptional activity patterns that control cell fate decisions. Of particular relevance has been the intercommunication between B cell precursors and key components of the hematopoietic microenvironment, both for generation of novel models integrating all regulatory elements of this complex process, and for the understanding of this branch of the adaptive immune system in disease settings. This review provides an overview of the complex process of lymphoid differentiation: from the hierarchical organization and biological characteristics of primitive cells involved in its earliest stages, to the principles governing its interdependence with the hematopoietic microenvironment.

  1. Novel INHAT repressor (NIR) is required for early lymphocyte development.

    Science.gov (United States)

    Ma, Chi A; Pusso, Antonia; Wu, Liming; Zhao, Yongge; Hoffmann, Victoria; Notarangelo, Luigi D; Fowlkes, B J; Jain, Ashish

    2014-09-23

    Novel inhibitor of histone acetyltransferase repressor (NIR) is a transcriptional corepressor with inhibitor of histone acetyltransferase activity and is a potent suppressor of p53. Although NIR deficiency in mice leads to early embryonic lethality, lymphoid-restricted deletion resulted in the absence of double-positive CD4(+)CD8(+) thymocytes, whereas bone-marrow-derived B cells were arrested at the B220(+)CD19(-) pro-B-cell stage. V(D)J recombination was preserved in NIR-deficient DN3 double-negative thymocytes, suggesting that NIR does not affect p53 function in response to physiologic DNA breaks. Nevertheless, the combined deficiency of NIR and p53 provided rescue of DN3L double-negative thymocytes and their further differentiation to double- and single-positive thymocytes, whereas B cells in the marrow further developed to the B220(+)CD19(+) pro-B-cell stage. Our results show that NIR cooperate with p53 to impose checkpoint for the generation of mature B and T lymphocytes.

  2. Stereotyped B-cell receptors in one-third of chronic lymphocytic leukemia

    DEFF Research Database (Denmark)

    Agathangelidis, Andreas; Darzentas, Nikos; Hadzidimitriou, Anastasia

    2012-01-01

    Mounting evidence indicates that grouping of chronic lymphocytic leukemia (CLL) into distinct subsets with stereotyped BCRs is functionally and prognostically relevant. However, several issues need revisiting, including the criteria for identification of BCR stereotypy and its actual frequency as...

  3. Extension of mental preparation positively affects motor imagery as compared to motor execution: a functional near-infrared spectroscopy study.

    Science.gov (United States)

    Holper, Lisa; Scholkmann, Felix; Shalóm, Diego E; Wolf, Martin

    2012-05-01

    Motor imagery (MI) is widely used to study cognitive action control. Although, the neural simulation theory assumes that MI and motor execution (ME) share many common features, the extent of similarity and whether it spreads into the preparation phase is still under investigation. Here we asked, whether an extension of physiological mental preparation has a comparable effect on MI and ME. Data were recorded using wireless functional near-infrared spectroscopy (fNIRS) in a two-stage task design where subjects were cued with or without preparatory stimuli to either execute or imagine complex sequential thumb-finger tasks. The main finding is that the extended mental preparation has a significant positive effect on oxy-hemoglobin (∆[O(2)Hb]) in response to MI, which is proportionally larger as that found in response to ME. Furthermore, fNIRS was capable to discriminate within each task whether it was preceded by preparatory stimuli or not. Transition from mental preparation to actual performance (ME or MI) was reflected by a dip of the fNIRS signal presumably related to underlying cortical processes changing between preparation and task performance. Statistically significant main effects of 'Preparation' and 'Task' showed that ∆[O(2)Hb] during preparation was preparation-specific, i.e., positively affected by the presence of preparatory stimuli, whereas during task performance ∆[O(2)Hb] was both preparation- and task-specific, i.e., additionally affected by the task mode. These results are particularly appealing from a practical point of view for making use of MI in neuroscientific applications. Especially neurorehabilitation and neural interfaces may benefit from utilizing positive interactions between mental preparation and MI performance.

  4. The sucrose transporter SlSUT2 from tomato interacts with brassinosteroid functioning and affects arbuscular mycorrhiza formation.

    Science.gov (United States)

    Bitterlich, Michael; Krügel, Undine; Boldt-Burisch, Katja; Franken, Philipp; Kühn, Christina

    2014-06-01

    Mycorrhizal plants benefit from the fungal partners by getting better access to soil nutrients. In exchange, the plant supplies carbohydrates to the fungus. The additional carbohydrate demand in mycorrhizal plants was shown to be balanced partially by higher CO2 assimilation and increased C metabolism in shoots and roots. In order to test the role of sucrose transport for fungal development in arbuscular mycorrhizal (AM) tomato, transgenic plants with down-regulated expression of three sucrose transporter genes were analysed. Plants that carried an antisense construct of SlSUT2 (SlSUT2as) repeatedly exhibited increased mycorrhizal colonization and the positive effect of plants to mycorrhiza was abolished. Grafting experiments between transgenic and wild-type rootstocks and scions indicated that mainly the root-specific function of SlSUT2 has an impact on colonization of tomato roots with the AM fungus. Localization of SISUT2 to the periarbuscular membrane indicates a role in back transport of sucrose from the periarbuscular matrix into the plant cell thereby affecting hyphal development. Screening of an expression library for SlSUT2-interacting proteins revealed interactions with candidates involved in brassinosteroid (BR) signaling or biosynthesis. Interaction of these candidates with SlSUT2 was confirmed by bimolecular fluorescence complementation. Tomato mutants defective in BR biosynthesis were analysed with respect to mycorrhizal symbiosis and showed indeed decreased mycorrhization. This finding suggests that BRs affect mycorrhizal infection and colonization. If the inhibitory effect of SlSUT2 on mycorrhizal growth involves components of BR synthesis and of the BR signaling pathway is discussed.

  5. Long intergenic noncoding RNAs: novel drivers of human lymphocyte differentiation

    Directory of Open Access Journals (Sweden)

    Ilaria ePanzeri

    2015-04-01

    Full Text Available Upon recognition of a foreign antigen, CD4+ naïve T lymphocytes proliferate and differentiate into subsets with distinct functions. This process is fundamental for the proper immune system function, as CD4+ T cells orchestrate both the innate and adaptive immune response. Traditionally, this differentiation event has been regarded as the acquisition of an irreversible cell fate so that memory and effector CD4+ T subsets were considered terminally differentiated cells or lineages. Consequently, these lineages are conventionally defined thanks to their prototypical set of cytokines and transcription factors. However, recent findings suggest that CD4+ T lymphocytes possess a remarkable phenotypic plasticity, as they can often redirect their functional program depending on the milieu they encounter. Therefore new questions are now compelling such as which are the molecular determinants underlying plasticity and stability and how the balance between these two opposite forces drives the cell fate. As already mentioned, in some cases the mere expression of cytokines and master regulators could not fully explain lymphocytes plasticity. We should consider other layers of regulation, including epigenetic factors such as the modulation of chromatin state or the transcription of noncoding RNAs, whose high cell-specificity give a hint on their involvement in cell fate determination. In this review, we will focus on the recent advances in understanding CD4+ T lymphocytes subsets specification from an epigenetic point of view. In particular, we will emphasize the emerging importance of noncoding RNAs as key players in these differentiation events. We will also present here new data from our laboratory highlighting the contribution of long noncoding RNAs in driving human CD4+ T lymphocytes differentiation.

  6. IL-10 conditioning of human skin affects the distribution of migratory dendritic cell subsets and functional T cell differentiation.

    Science.gov (United States)

    Lindenberg, Jelle J; Oosterhoff, Dinja; Sombroek, Claudia C; Lougheed, Sinéad M; Hooijberg, Erik; Stam, Anita G M; Santegoets, Saskia J A M; Tijssen, Henk J; Buter, Jan; Pinedo, Herbert M; van den Eertwegh, Alfons J M; Scheper, Rik J; Koenen, Hans J P M; van de Ven, Rieneke; de Gruijl, Tanja D

    2013-01-01

    In cancer patients pervasive systemic suppression of Dendritic Cell (DC) differentiation and maturation can hinder vaccination efficacy. In this study we have extensively characterized migratory DC subsets from human skin and studied how their migration and T cell-stimulatory abilities were affected by conditioning of the dermal microenvironment through cancer-related suppressive cytokines. To assess effects in the context of a complex tissue structure, we made use of a near-physiological skin explant model. By 4-color flow cytometry, we identified migrated Langerhans Cells (LC) and five dermis-derived DC populations in differential states of maturation. From a panel of known tumor-associated suppressive cytokines, IL-10 showed a unique ability to induce predominant migration of an immature CD14(+)CD141(+)DC-SIGN(+) DC subset with low levels of co-stimulatory molecules, up-regulated expression of the co-inhibitory molecule PD-L1 and the M2-associated macrophage marker CD163. A similarly immature subset composition was observed for DC migrating from explants taken from skin overlying breast tumors. Whereas predominant migration of mature CD1a(+) subsets was associated with release of IL-12p70, efficient Th cell expansion with a Th1 profile, and expansion of functional MART-1-specific CD8(+) T cells, migration of immature CD14(+) DDC was accompanied by increased release of IL-10, poor expansion of CD4(+) and CD8(+) T cells, and skewing of Th responses to favor coordinated FoxP3 and IL-10 expression and regulatory T cell differentiation and outgrowth. Thus, high levels of IL-10 impact the composition of skin-emigrated DC subsets and appear to favor migration of M2-like immature DC with functional qualities conducive to T cell tolerance.

  7. Intranasal Oxytocin Affects Amygdala Functional Connectivity after Trauma Script-Driven Imagery in Distressed Recently Trauma-Exposed Individuals.

    Science.gov (United States)

    Frijling, Jessie L; van Zuiden, Mirjam; Koch, Saskia B J; Nawijn, Laura; Veltman, Dick J; Olff, Miranda

    2016-04-01

    Approximately 10% of trauma-exposed individuals go on to develop post-traumatic stress disorder (PTSD). Neural emotion regulation may be etiologically involved in PTSD development. Oxytocin administration early post-trauma may be a promising avenue for PTSD prevention, as intranasal oxytocin has previously been found to affect emotion regulation networks in healthy individuals and psychiatric patients. In a randomized double-blind placebo-controlled between-subjects functional magnetic resonance (fMRI) study, we assessed the effects of a single intranasal oxytocin administration (40 IU) on seed-based amygdala resting-state FC with emotion regulation areas (ventromedial prefrontal cortex (vmPFC), ventrolateral prefrontal cortex (vlPFC)), and salience processing areas (insula, dorsal anterior cingulate cortex (dACC)) in 37 individuals within 11 days post trauma. Two resting-state scans were acquired; one after neutral- and one after trauma-script-driven imagery. We found that oxytocin administration reduced amygdala-left vlPFC FC after trauma script-driven imagery, compared with neutral script-driven imagery, whereas in PL-treated participants enhanced amygdala-left vlPFC FC was observed following trauma script-driven imagery. Irrespective of script condition, oxytocin increased amygdala-insula FC and decreased amygdala-vmPFC FC. These neural effects were accompanied by lower levels of sleepiness and higher flashback intensity in the oxytocin group after the trauma script. Together, our findings show that oxytocin administration may impede emotion regulation network functioning in response to trauma reminders in recently trauma-exposed individuals. Therefore, caution may be warranted in administering oxytocin to prevent PTSD in distressed, recently trauma-exposed individuals.

  8. IL-10 conditioning of human skin affects the distribution of migratory dendritic cell subsets and functional T cell differentiation.

    Directory of Open Access Journals (Sweden)

    Jelle J Lindenberg

    Full Text Available In cancer patients pervasive systemic suppression of Dendritic Cell (DC differentiation and maturation can hinder vaccination efficacy. In this study we have extensively characterized migratory DC subsets from human skin and studied how their migration and T cell-stimulatory abilities were affected by conditioning of the dermal microenvironment through cancer-related suppressive cytokines. To assess effects in the context of a complex tissue structure, we made use of a near-physiological skin explant model. By 4-color flow cytometry, we identified migrated Langerhans Cells (LC and five dermis-derived DC populations in differential states of maturation. From a panel of known tumor-associated suppressive cytokines, IL-10 showed a unique ability to induce predominant migration of an immature CD14(+CD141(+DC-SIGN(+ DC subset with low levels of co-stimulatory molecules, up-regulated expression of the co-inhibitory molecule PD-L1 and the M2-associated macrophage marker CD163. A similarly immature subset composition was observed for DC migrating from explants taken from skin overlying breast tumors. Whereas predominant migration of mature CD1a(+ subsets was associated with release of IL-12p70, efficient Th cell expansion with a Th1 profile, and expansion of functional MART-1-specific CD8(+ T cells, migration of immature CD14(+ DDC was accompanied by increased release of IL-10, poor expansion of CD4(+ and CD8(+ T cells, and skewing of Th responses to favor coordinated FoxP3 and IL-10 expression and regulatory T cell differentiation and outgrowth. Thus, high levels of IL-10 impact the composition of skin-emigrated DC subsets and appear to favor migration of M2-like immature DC with functional qualities conducive to T cell tolerance.

  9. Human, donkey and cow milk differently affects energy efficiency and inflammatory state by modulating mitochondrial function and gut microbiota.

    Science.gov (United States)

    Trinchese, Giovanna; Cavaliere, Gina; Canani, Roberto Berni; Matamoros, Sebastien; Bergamo, Paolo; De Filippo, Chiara; Aceto, Serena; Gaita, Marcello; Cerino, Pellegrino; Negri, Rossella; Greco, Luigi; Cani, Patrice D; Mollica, Maria Pina

    2015-11-01

    Different nutritional components are able, by modulating mitochondrial function and gut microbiota composition, to influence body composition, metabolic homeostasis and inflammatory state. In this study, we aimed to evaluate the effects produced by the supplementation of different milks on energy balance, inflammatory state, oxidative stress and antioxidant/detoxifying enzyme activities and to investigate the role of the mitochondrial efficiency and the gut microbiota in the regulation of metabolic functions in an animal model. We compared the intake of human milk, gold standard for infant nutrition, with equicaloric supplementation of donkey milk, the best substitute for newborns due to its nutritional properties, and cow milk, the primary marketed product. The results showed a hypolipidemic effect produced by donkey and human milk intake in parallel with enhanced mitochondrial activity/proton leakage. Reduced mitochondrial energy efficiency and proinflammatory signals (tumor necrosis factor α, interleukin-1 and lipopolysaccharide levels) were associated with a significant increase of antioxidants (total thiols) and detoxifying enzyme activities (glutathione-S-transferase, NADH quinone oxidoreductase) in donkey- and human milk-treated animals. The beneficial effects were attributable, at least in part, to the activation of the nuclear factor erythroid-2-related factor-2 pathway. Moreover, the metabolic benefits induced by human and donkey milk may be related to the modulation of gut microbiota. In fact, milk treatments uniquely affected the proportions of bacterial phyla and genera, and we hypothesized that the increased concentration of fecal butyrate in human and donkey milk-treated rats was related to the improved lipid and glucose metabolism and detoxifying activities.

  10. Loss of LORELEI function in the pistil delays initiation but does not affect embryo development in Arabidopsis thaliana

    Science.gov (United States)

    Tsukamoto, Tatsuya

    2010-01-01

    Double fertilization, uniquely observed in plants, requires successful sperm cell delivery by the pollen tube to the female gametophyte, followed by migration, recognition and fusion of the two sperm cells with two female gametic cells. The female gametophyte not only regulates these steps but also controls the subsequent initiation of seed development. Previously, we reported that loss of LORELEI, which encodes a putative glycosylphosphatidylinositol (GPI)-anchored protein, in the female reproductive tissues causes a delay in initiation of seed development. From these studies, however, it was unclear if embryos derived from fertilization of lre-5 gametophytes continued to lag behind wild-type during seed development. Additionally, it was not determined if the delay in initiation of seed development had any lingering effects during seed germination. Finally, it was not known if loss of LORELEI function affects seedling development given that LORELEI is expressed in eight-day-old seedlings. Here, we showed that despite a delay in initiation, lre-5/lre-5 embryos recover, becoming equivalent to the developing wild-type embryos beginning at 72 hours after pollination. Additionally, lre-5/lre-5 seed germination, and seedling and root development are indistinguishable from wild-type indicating that loss of LORELEI is tolerated, at least under standard growth conditions, in vegetative tissues. PMID:21051955

  11. Loss of LORELEI function in the pistil delays initiation but does not affect embryo development in Arabidopsis thaliana.

    Science.gov (United States)

    Tsukamoto, Tatsuya; Palanivelu, Ravishankar

    2010-11-01

    Double fertilization, uniquely observed in plants, requires successful sperm cell delivery by the pollen tube to the female gametophyte, followed by migration, recognition and fusion of the two sperm cells with two female gametic cells. The female gametophyte not only regulates these steps but also controls the subsequent initiation of seed development. Previously, we reported that loss of LORELEI, which encodes a putative glycosylphosphatidylinositol (GPI)-anchored protein, in the female reproductive tissues causes a delay in initiation of seed development. From these studies, however, it was unclear if embryos derived from fertilization of lre-5 gametophytes continued to lag behind wild type during seed development. Additionally, it was not determined if the delay in initiation of seed development had any lingering effects during seed germination. Finally, it was not known if loss of LORELEI function affects seedling development given that LORELEI is expressed in eight-day-old seedlings. Here, we showed that despite a delay in initiation, lre-5/lre-5 embryos recover, becoming equivalent to the developing wild-type embryos beginning at 72 hours after pollination. Additionally, lre-5/lre-5 seed germination, and seedling and root development are indistinguishable from wild type indicating that loss of LORELEI is tolerated, at least under standard growth conditions, in vegetative tissues.

  12. Molecular Mechanisms of Lymphocyte-Mediated Cytotoxicity

    Institute of Scientific and Technical Information of China (English)

    Zusen Fan; Qixiang Zhang

    2005-01-01

    Granule-mediated cytotoxicity is the major mechanism for lymphocytes to kill viruses, intracellular bacteria and tumors. The cytotoxic granules move to the immunological synapse by exocytosis after recognition of a killer cell.The contents of the granules are delivered into target cells with the help of perforin by endocytosis. A group of serine protease granzymes cleave their critical substrates to initiate DNA damage and cell death. The most abundant granzymes are granzyme A and B. They induce cell death through alternate and nonoverlapping pathways. The substrates and functions of the majority of the orphan granzymes have not yet been identified. It is possible that the diversity of granzymes provides fail-safe mechanisms for killing viruses and tumor cells.

  13. Specific proliferative response of human lymphocytes to purified soluble antigens from Plasmodium falciparum in vitro cultures and to antigens from malaria patients' sera

    DEFF Research Database (Denmark)

    Bygbjerg, I C; Jepsen, S; Theander, T G;

    1985-01-01

    . The responses were strongest with lymphocytes from individuals infected with falciparum and ovale malaria; vivax malaria infections induced a lower level of response and lymphocytes of unsensitized individuals were little affected. Lymphocytes from unsensitized individuals did not respond to the affinity...

  14. Apolipoprotein E4 (1–272 fragment is associated with mitochondrial proteins and affects mitochondrial function in neuronal cells

    Directory of Open Access Journals (Sweden)

    Michikawa Makoto

    2009-08-01

    Full Text Available Abstract Background Apolipoprotein E allele ε4 (apoE4 is a strong risk factor for developing Alzheimer's disease (AD. Secreted apoE has a critical function in redistributing lipids among central nervous system cells to maintain normal lipid homeostasis. In addition, previous reports have shown that apoE4 is cleaved by a protease in neurons to generate apoE4(1–272 fragment, which is associated with neurofibrillary tanglelike structures and mitochondria, causing mitochondrial dysfunction. However, it still remains unclear how the apoE fragment associates with mitochondria and induces mitochondrial dysfunction. Results To clarify the molecular mechanism, we carried out experiments to identify intracellular apoE-binding molecules and their functions in modulating mitochondria function. Here, we found that apoE4 binds to ubiquinol cytochrome c reductase core protein 2 (UQCRC2 and cytochrome C1, both of which are components of mitochondrial respiratory complex III, and cytochrome c oxidase subunit 4 isoform 1 (COX IV 1, which is a component of complex IV, in Neuro-2a cells. Interestingly, these proteins associated with apoE4(1–272 more strongly than intact apoE4(1–299. Further analysis showed that in Neuro-2a cells expressing apoE4(1–272, the enzymatic activities of mitochondrial respiratory complexes III and IV were significantly lower than those in Neuro-2a cells expressing apoE4(1–299. Conclusion ApoE4(1–272 fragment expressed in Neuro2a cells is associated with mitochondrial proteins, UQCRC2 and cytochrome C1, which are component of respiratory complex III, and with COX IV 1, which is a member of complex IV. Overexpression of apoE4(1–272 fragment impairs activities of complex III and IV. These results suggest that the C-terminal-truncated fragment of apoE4 binds to mitochondrial complexes and affects their activities, and thereby leading to neurodegeneration.

  15. Human liver sinusoidal endothelial cells promote intracellular crawling of lymphocytes during recruitment: A new step in migration.

    Science.gov (United States)

    Patten, Daniel A; Wilson, Garrick K; Bailey, Dalan; Shaw, Robert K; Jalkanen, Sirpa; Salmi, Marko; Rot, Antal; Weston, Chris J; Adams, David H; Shetty, Shishir

    2017-01-01

    The recruitment of lymphocytes via the hepatic sinusoidal channels and positioning within liver tissue is a critical event in the development and persistence of chronic inflammatory liver diseases. The hepatic sinusoid is a unique vascular bed lined by hepatic sinusoidal endothelial cells (HSECs), a functionally and phenotypically distinct subpopulation of endothelial cells. Using flow-based adhesion assays to study the migration of lymphocytes across primary human HSECs, we found that lymphocytes enter into HSECs, confirmed by electron microscopy demonstrating clear intracellular localization of lymphocytes in vitro and by studies in human liver tissues. Stimulation by interferon-γ increased intracellular localization of lymphocytes within HSECs. Furthermore, using confocal imaging and time-lapse recordings, we demonstrated "intracellular crawling" of lymphocytes entering into one endothelial cell from another. This required the expression of intracellular adhesion molecule-1 and stabilin-1 and was facilitated by the junctional complexes between HSECs.

  16. Dimerization of DOCK2 is essential for DOCK2-mediated Rac activation and lymphocyte migration.

    Directory of Open Access Journals (Sweden)

    Masao Terasawa

    Full Text Available The migratory properties of lymphocytes depend on DOCK2, an atypical Rac activator predominantly expressed in hematopoietic cells. Although DOCK2 does not contain the Dbl homology domain typically found in guanine nucleotide exchange factors (GEFs, DOCK2 mediates the GTP-GDP exchange reaction for Rac via its DOCK homology region (DHR-2 (also known as CZH2 or Docker domain. DOCK2 DHR-2 domain is composed of three lobes, and Rac binding site and catalytic center are generated entirely from lobes B and C. On the other hand, lobe A has been implicated in dimer formation, yet its physiological significance remains unknown. Here, we report that lobe A-mediated DOCK2 dimerization is crucial for Rac activation and lymphocyte migration. We found that unlike wild-type DOCK2, DOCK2 mutant lacking lobe A failed to restore motility and polarity when expressed in thymoma cells and primary T cells lacking endogenous expression of DOCK2. Similar results were obtained with the DOCK2 point mutant having a defect in dimerization. Deletion of lobe A from the DHR-2 domain did not affect Rac GEF activity in vitro. However, fluorescence resonance energy transfer analyses revealed that lobe A is required for DOCK2 to activate Rac effectively during cell migration. Our results thus indicate that DOCK2 dimerization is functionally important under the physiological condition where only limited amounts of DOCK2 and Rac are localized to the plasma membrane.

  17. The identification of lymphocyte-like cells and lymphoid-related genes in amphioxus indicates the twilight for the emergence of adaptive immune system.

    Directory of Open Access Journals (Sweden)

    Gonghua Huang

    Full Text Available To seek evidence of a primitive adaptive immune system (AIS before vertebrate, we examined whether lymphocytes or lymphocyte-like cells and the related molecules participating in the lymphocyte function existed in amphioxus. Anatomical analysis by electron microscopy revealed the presence of lymphocyte-like cells in gills, and these cells underwent morphological changes in response to microbial pathogens that are reminiscent of those of mammalian lymphocytes executing immune response to microbial challenge. In addition, a systematic comparative analysis of our cDNA database of amphioxus identified a large number of genes whose vertebrate counterparts are involved in lymphocyte function. Among these genes, several genes were found to be expressed in the vicinity of the lymphocyte-like cells by in situ hybridization and up-regulated after exposure to microbial pathogens. Our findings in the amphioxus indicate the twilight for the emergence of AIS before the invertebrate-vertebrate transition during evolution.

  18. Sustained Dysfunction of Antiviral CD8+ T Lymphocytes after Infection with Hepatitis C Virus

    Science.gov (United States)

    Gruener, Norbert H.; Lechner, Franziska; Jung, Maria-Christina; Diepolder, Helmut; Gerlach, Tilman; Lauer, Georg; Walker, Bruce; Sullivan, John; Phillips, Rodney; Pape, Gerd R.; Klenerman, Paul

    2001-01-01

    Hepatitis C virus (HCV) sets up persistent infection in the majority of those exposed. It is likely that, as with other persistent viral infections, the efficacy of T-lymphocyte responses influences long-term outcome. However, little is known about the functional capacity of HCV-specific T-lymphocyte responses induced after acute infection. We investigated this by using major histocompatibility complex class I-peptide tetrameric complexes (tetramers), which allow direct detection of specific CD8+ T lymphocytes ex vivo, independently of function. Here we show that, early after infection, virus-specific CD8+ T lymphocytes detected with a panel of four such tetramers are abnormal in terms of their synthesis of antiviral cytokines and lytic activity. Furthermore, this phenotype is commonly maintained long term, since large sustained populations of HCV-specific CD8+ T lymphocytes were identified, which consistently had very poor antiviral cytokine responses as measured in vitro. Overall, HCV-specific CD8+ T lymphocytes show reduced synthesis of tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) after stimulation with either mitogens or peptides, compared to responses to Epstein-Barr virus and/or cytomegalovirus. This behavior of antiviral CD8+ T lymphocytes induced after HCV infection may contribute to viral persistence through failure to effectively suppress viral replication. PMID:11356962

  19. Lymphocyte subpopulations in Sheehan's syndrome.

    Science.gov (United States)

    Atmaca, Hulusi; Araslı, Mehmet; Yazıcı, Zihni Acar; Armutçu, Ferah; Tekin, Ishak Özel

    2013-06-01

    The role of autoimmunity in the development of Sheehan's syndrome is obscure. There are a limited number of studies investigating the immunological alterations accompanying Sheehan's Syndrome. Our objective was to evaluate lymphocyte subsets in these patients. We conducted a cross-sectional clinical study. Cytofluorometry was used for the immunophenotyping of peripheral blood leukocytes from patients with Sheehan's syndrome followed up in the endocrine clinic during 2005-2009. Fifteen consecutive patients (mean age 61.6 ± 11.3, range 34-75 years) and 25 healthy controls (mean age 56.7 ± 10.6, range 34-80 years) were included. There was no statistically significant difference between the groups in terms of mean age. The percentages of CD19(+), CD16(+)/56(+), CD8(+)28(-), γδTCR(+), CD8(+); the total lymphocyte counts; and the ratio of CD8(+)28(-)/CD8(+)28(+) were similar (p > 0.05) between patients and controls. Whereas the leucocyte counts (p = 0.003), the percentage of CD3 (+) DR (+) (p Sheehan's syndrome compared to healthy controls. There was a positive correlation between the duration of illness and the percentage of CD3(+)DR(+) (r = 0.53, p = 0.03) expression. Some peripheral lymphocyte cell subsets show marked variation in patients with Sheehan's syndrome in comparison to matched healthy subjects, which may have implications for altered immune regulation in these patients. High CD3 (+) DR (+) expression that correlates with the duration of illness in Sheehan's patients is suggestive of an ongoing inflammation accompanying the slow progression of pituitary dysfunction in Sheehan's syndrome. It is not clear if these cellular alterations contribute to the cause or consequence of pituitary deficiency in Sheehan's syndrome.

  20. Autoimmune hepatitis in association with lymphocytic colitis.

    LENUS (Irish Health Repository)

    Cronin, Edmond M

    2012-02-03

    Autoimmune hepatitis is a rare, chronic inflammatory disorder which has been associated with a number of other auto-immune conditions. However, there are no reports in the medical literature of an association with microscopic (lymphocytic) colitis. We report the case of a 53-year-old woman with several autoimmune conditions, including lymphocytic colitis, who presented with an acute hepatitis. On the basis of the clinical features, serology, and histopathology, we diagnosed autoimmune hepatitis. To our knowledge, this is the first report of autoimmune hepatitis in association with lymphocytic colitis, and lends support to the theory of an autoimmune etiology for lymphocytic colitis.

  1. Adipose tissue lymphocytes: types and roles.

    Science.gov (United States)

    Caspar-Bauguil, S; Cousin, B; Bour, S; Casteilla, L; Castiella, L; Penicaud, L; Carpéné, C

    2009-12-01

    Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, gammadeltaT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except B lymphocytes, are modified in obesity. Several of these modifications in the relative proportions of the lymphocyte classes depend on the degree of obesity, or on leptin concentration, or even fat depot anatomical location. Recent studies suggest that alterations of lymphocyte number and composition precede the macrophage increase and the enhanced inflammatory state of WAT found in obesity. Lymphocytes express receptors to adipokines while several proinflammatory chemokines are produced in WAT, rendering intricate crosstalk between fat and immune cells. However, the evidences and controversies available so far are in favour of an involvement of lymphocytes in the control of the number of other cells in WAT, either adipocytes or immune cells and of their secretory and metabolic activities. Therefore, immunotherapy deserves to be considered as a promising approach to treat the endocrino-metabolic disorders associated to excessive fat mass development.

  2. Telomerase contributes to fludarabine resistance in primary human leukemic lymphocytes.

    Science.gov (United States)

    Shawi, May; Chu, Tsz Wai; Martinez-Marignac, Veronica; Yu, Y; Gryaznov, Sergei M; Johnston, James B; Lees-Miller, Susan P; Assouline, Sarit E; Autexier, Chantal; Aloyz, Raquel

    2013-01-01

    We report that Imetelstat, a telomerase inhibitor that binds to the RNA component of telomerase (hTR), can sensitize primary CLL lymphocytes to fludarabine in vitro. This effect was observed in lymphocytes from clinically resistant cases and with cytogenetic abnormalities associated with bad prognosis. Imetelstat mediated-sensitization to fludarabine was not associated with telomerase activity, but with the basal expression of Ku80. Since both Imetelstat and Ku80 bind hTR, we assessed 1) if Ku80 and Imetelstat alter each other's binding to hTR in vitro and 2) the effect of an oligonucleotide complementary to the Ku binding site in hTR (Ku oligo) on the survival of primary CLL lymphocytes exposed to fludarabine. We show that Imetelstat interferes with the binding of Ku70/80 (Ku) to hTR and that the Ku oligo can sensitize CLL lymphocytes to FLU. Our results suggest that Ku binding to hTR may contribute to fludarabine resistance in CLL lmphocytes. This is the first report highlighting the potentially broad effectiveness of Imetelstat in CLL, and the potential biological and clinical implications of a functional interaction between Ku and hTR in primary human cancer cells.

  3. Telomerase contributes to fludarabine resistance in primary human leukemic lymphocytes.

    Directory of Open Access Journals (Sweden)

    May Shawi

    Full Text Available We report that Imetelstat, a telomerase inhibitor that binds to the RNA component of telomerase (hTR, can sensitize primary CLL lymphocytes to fludarabine in vitro. This effect was observed in lymphocytes from clinically resistant cases and with cytogenetic abnormalities associated with bad prognosis. Imetelstat mediated-sensitization to fludarabine was not associated with telomerase activity, but with the basal expression of Ku80. Since both Imetelstat and Ku80 bind hTR, we assessed 1 if Ku80 and Imetelstat alter each other's binding to hTR in vitro and 2 the effect of an oligonucleotide complementary to the Ku binding site in hTR (Ku oligo on the survival of primary CLL lymphocytes exposed to fludarabine. We show that Imetelstat interferes with the binding of Ku70/80 (Ku to hTR and that the Ku oligo can sensitize CLL lymphocytes to FLU. Our results suggest that Ku binding to hTR may contribute to fludarabine resistance in CLL lmphocytes. This is the first report highlighting the potentially broad effectiveness of Imetelstat in CLL, and the potential biological and clinical implications of a functional interaction between Ku and hTR in primary human cancer cells.

  4. Impairment of diastolic function in adult patients affected by osteogenesis imperfecta clinically asymptomatic for cardiac disease: casuality or causality?

    Science.gov (United States)

    Migliaccio, Silvia; Barbaro, Giuseppe; Fornari, Rachele; Di Lorenzo, Gabriella; Celli, Mauro; Lubrano, Carla; Falcone, Stefania; Fabbrini, Elisa; Greco, Emanuela; Zambrano, Anna; Brama, Marina; Prossomariti, Giancarlo; Marzano, Sara; Marini, Mario; Conti, Francesco; D'Eufemia, Patrizia; Spera, Giovanni

    2009-01-09

    Osteogenesis imperfecta (OI) is a rare inherited connective disorder causing increased bone fragility and low bone mass. OI includes severe bone fragility, impaired dentinogenesis, with less common alterations in the joints, blood vessels, heart valves, skin. Interestingly, description of left ventricular rupture, aortic dissection and heart valves incompetence has been previously described. Death may occur in OI patients for cardiac disease in asyntomatic subjects. Aim of our study has been to evaluate the presence of potential subclinical cardiac disorders and to characterize cardiac functional parameters by echocardiography in adults with OI in absence of cardiac symptoms. Forty patients (21 females and 19 males) affected by type I, III, IV OI and 40 control subjects (20 females and 20 males) were evaluated in the study. Patients and controls underwent clinical examination, screening for endocrine and metabolic disorders, 12-lead electrocardiogram and echocardiogram. In particular, all subjects were evaluated by two-dimensional echocardiography with continuous- and pulse-wave Doppler. Patients and controls belonged to NYHA class I and no significant electrocardiographic alteration was documented in both groups. Thirty-eight patients (95%) showed valvular regurgitation compared to one control subject (2.5%; Prelaxation time (IRT) was increased by 47% (95% CI: 26% to 53%; Pmetabolic alterations. These diastolic echocardiographic parameters might worsen over time, especially if other cardiovascular risk factors (e.g., smoking, hypertension, metabolic and endocrine alterations) are not carefully checked, monitored and treated. In the context of a multidisciplinary evaluation of OI patients, our data suggest that a careful cardiological evaluation of these patients is indicated beside skeletal evaluation and therapeutical skeletal options.

  5. Sodium benzoate, a food preservative, affects the functional and activation status of splenocytes at non cytotoxic dose.

    Science.gov (United States)

    Yadav, Ashish; Kumar, Arvind; Das, Mukul; Tripathi, Anurag

    2016-02-01

    Sodium benzoate (SB) is a widely used food preservative due to its bacteriostatic and fungistatic properties. The acceptable daily intake of SB is 5 mg/kg-bw, however, it has been found to be used in the food commodities at relatively high levels (2119 mg/kg). Earlier studies on SB have shown its immunosuppressive properties, but comprehensive immunotoxicity data is lacking. Our studies have shown that SB was non cytotoxic in splenocytes up to 1000 μg/ml for 72 h, however at 2500 μg/ml it was found to be cytotoxic. Thus, 1000 μg/ml dose of SB was chosen for the subsequent experiments. SB significantly suppresses the proliferation of Con A and LPS stimulated splenocytes at 72 h, while allogenic response of T cells was significantly decreased after 96 h. SB did not affect the relative expression of CD3e or CD4 molecules following 72 h exposure, however, it downregulated the relative expression of CD8 co-receptor. Further, exposure of splenocytes to SB for 72 h led to reduced expression of CD28 and CD95, which play a vital role in T cell activation. SB also suppresses the relative expression of CD19, CD40 and CD95 receptors on B cells after 72 h. In addition to the functional responses, SB lowered the expression of IL4, IL6, IFNγ and IL17 cytokines in Con A stimulated splenocytes; and IL6, IFNγ and TNFα in LPS stimulated splenocytes following 48 h of exposure. Taken together, the present study is suggestive of the immunomodulatory potential of SB.

  6. Decellularized aortic conduits: could their cryopreservation affect post-implantation outcomes? A morpho-functional study on porcine homografts.

    Science.gov (United States)

    Gallo, Michele; Bonetti, Antonella; Poser, Helen; Naso, Filippo; Bottio, Tomaso; Bianco, Roberto; Paolin, Adolfo; Franci, Paolo; Busetto, Roberto; Frigo, Anna Chiara; Buratto, Edward; Spina, Michele; Marchini, Maurizio; Ortolani, Fulvia; Iop, Laura; Gerosa, Gino

    2016-11-01

    Decellularized porcine aortic valve conduits (AVCs) implanted in a Vietnamese Pig (VP) experimental animal model were matched against decellularized and then cryopreserved AVCs to assess the effect of cryopreservation on graft hemodynamic performance and propensity to in vivo repopulation by host's cells. VPs (n = 12) underwent right ventricular outflow tract substitution using AVC allografts and were studied for 15-month follow-up. VPs were randomized into two groups, receiving AVCs treated with decellularization alone (D; n = 6) or decellularization/cryopreservation (DC; n = 6), respectively. Serial echocardiography was carried out to follow up hemodynamic function. All explanted AVCs were processed for light and electron microscopy. No signs of dilatation, progressive stenosis, regurgitation, and macroscopic calcification were echocardiographically observed in both D and DC groups. Explanted D grafts exhibited near-normal features, whereas the presence of calcification, inflammatory infiltrates, and disarray of elastic lamellae occurred in some DC grafts. In the unaltered regions of AVCs from both groups, almost complete re-endothelialization was observed for both valve cusps and aorta walls. In addition, side-by-side repopulation by recipient's fibroblasts, myofibroblasts, and smooth muscle cells was paralleled by ongoing tissue remodeling, as revealed by the ultrastructural identification of typical canals of collagen fibrillogenesis and elastogenesis-related features. Incipient neo-vascularization and re-innervation of medial and adventitial tunicae of grafted aortic walls were also detected for both D and DC groups. Cryopreservation did not affect post-implantation AVC hemodynamic behavior and was topically propensive to cell repopulation and tissue renewal, although graft deterioration including calcification was present in several areas. Thus, these preliminary data provide essential information on feasibility of decellularization and

  7. Lymphocyte respiration in children with Trisomy 21

    Directory of Open Access Journals (Sweden)

    Aburawi Elhadi H

    2012-12-01

    Full Text Available Abstract Background This study measured lymphocyte mitochondrial O2 consumption (cellular respiration in children with trisomy 21. Methods Peripheral blood mononuclear cells were isolated from whole blood of trisomy 21 and control children and these cells were immediately used to measure cellular respiration rate. [O2] was determined as a function of time from the phosphorescence decay rates (1/τ of Pd (II-meso-tetra-(4-sulfonatophenyl-tetrabenzoporphyrin. In sealed vials containing lymphocytes and glucose as a respiratory substrate, [O2] declined linearly with time, confirming the zero-order kinetics of O2 conversion to H2O by cytochrome oxidase. The rate of respiration (k, in μM O2 min-1, thus, was the negative of the slope of [O2] vs. time. Cyanide inhibited O2 consumption, confirming that oxidation occurred in the mitochondrial respiratory chain. Results For control children (age = 8.8 ± 5.6 years, n = 26, the mean (± SD value of kc (in μM O2 per min per 107 cells was 1.36 ± 0.79 (coefficient of variation, Cv = 58%; median = 1.17; range = 0.60 to 3.12; -2SD = 0.61. For children with trisomy 21 (age = 7.2 ± 4.6 years, n = 26, the values of kc were 0.82 ± 0.62 (Cv = 76%; median = 0.60; range = 0.20 to 2.80, pp6.1 mU/L. Fourteen of 26 (54% children with trisomy 21 had kc values of 0.20 to 0.60 (i.e., kc positively correlated with body-mass index (BMI, R >0.302, serum creatinine (R >0.507, blood urea nitrogen (BUN, R >0.535 and albumin (R >0.446. Conclusions Children with trisomy 21 in this study have reduced lymphocyte bioenergetics. The clinical importance of this finding requires further studies.

  8. Transcriptomic Characterization of SF3B1 Mutation Reveals Its Pleiotropic Effects in Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Wang, Lili; Brooks, Angela N; Fan, Jean; Wan, Youzhong; Gambe, Rutendo; Li, Shuqiang; Hergert, Sarah; Yin, Shanye; Freeman, Samuel S; Levin, Joshua Z; Fan, Lin; Seiler, Michael; Buonamici, Silvia; Smith, Peter G; Chau, Kevin F; Cibulskis, Carrie L; Zhang, Wandi; Rassenti, Laura Z; Ghia, Emanuela M; Kipps, Thomas J; Fernandes, Stacey; Bloch, Donald B; Kotliar, Dylan; Landau, Dan A; Shukla, Sachet A; Aster, Jon C; Reed, Robin; DeLuca, David S; Brown, Jennifer R; Neuberg, Donna; Getz, Gad; Livak, Kenneth J; Meyerson, Matthew M; Kharchenko, Peter V; Wu, Catherine J

    2016-11-14

    Mutations in SF3B1, which encodes a spliceosome component, are associated with poor outcome in chronic lymphocytic leukemia (CLL), but how these contribute to CLL progression remains poorly understood. We undertook a transcriptomic characterization of primary human CLL cells to identify transcripts and pathways affected by SF3B1 mutation. Splicing alterations, identified in the analysis of bulk cells, were confirmed in single SF3B1-mutated CLL cells and also found in cell lines ectopically expressing mutant SF3B1. SF3B1 mutation was found to dysregulate multiple cellular functions including DNA damage response, telomere maintenance, and Notch signaling (mediated through KLF8 upregulation, increased TERC and TERT expression, or altered splicing of DVL2 transcript, respectively). SF3B1 mutation leads to diverse changes in CLL-related pathways.

  9. Changes of lymphocyte kinetics in the normal rat, induced by the lymphocyte mobilizing agent polymethacrylic acid

    NARCIS (Netherlands)

    Ormai, S.; Hagenbeek, A.; Palkovits, M.; Bekkum, D.W. van

    1973-01-01

    The changes in lymphocyte kinetics induced by the lymphocyte mobilizing agent polymethacrylic acid (PMAA) were studied in the normal rat. Quantitative data are presented concerning the degree of lymphocyte mobilization in the spleen and in various lymph nodes at different times after PMAA administra

  10. Genotoxicity study in lymphocytes of offset printing workers.

    Science.gov (United States)

    Aksoy, Hüseyin; Yilmaz, Serkan; Celik, Mustafa; Yüzbaşioglu, Deniz; Unal, Fatma

    2006-01-01

    The potential cytogenetic damage in offset printing workers was evaluated using sister chromatid exchanges (SCEs), chromosome aberrations (CAs) and micronuclei (MN) as biomarkers in peripheral lymphocytes of 26 volunteers (14 workers, 12 controls). The CA, SCE and MN frequency of offset printing workers was significantly higher than in their controls. The replication index (RI) was not affected while the mitotic index (MI) was affected most in the workers. It can be concluded from this study that chronic occupational exposure to printing dyes and thinner may lead to a slightly increased risk of genetic damage among offset printing workers.

  11. Is kidney function affecting the management of myocardial infarction? A retrospective cohort study in patients with normal kidney function, chronic kidney disease stage III–V, and ESRD

    Directory of Open Access Journals (Sweden)

    Saad M

    2016-01-01

    between treatment modalities and comorbidities, and to account for possible confounding factors. Three hundred and thirty-four patients (mean age 67.2±13.9 years were included. In terms of management, medical treatment was not different among the three groups. However, cardiac catheterization was performed less in ESRD when compared with no CKD and CKD stage III–V (45.6% vs 74% and 93.9% (P<0.001. CABG was performed in comparable proportions in the three groups and CABG was not associated with the degree of CKD (P=0.078 in binary logistics regression. Cardiac catheterization on the other hand carried the strongest association among all studied variables (P<0.001. This association was maintained after adjusting for other comorbidities. The length of stay for the three cohorts (non-CKD, CKD stage III–V, and ESRD on hemodialysis was 16, 17, and 15 days, respectively and was not statistically different. Many observations have reported discrimination of care for patients with CKD considered suboptimal candidates for aggressive management of their cardiac disease. In our study, medical therapy was achieved at high percentage and was comparable among groups of different kidney function. However, kidney disease seems to affect the management of patients with acute MI; percutaneous coronary angiography is not uniformly performed in patients with CKD and ESRD when compared with patients with normal kidney function. Keywords: myocardial infarction, chronic kidney disease, end-stage renal disease

  12. Comparison of T-lymphocyte Subsets and Phenotypes between HIV-positive Subjects and HIV-negative Subjects

    Institute of Scientific and Technical Information of China (English)

    陈小平; 陈观今; 肖斌权; 施文钧; 徐惠芳; 高凯

    2001-01-01

    With the advance of research on HIV/AIDS, CD8 T-lymphocyte is believed to be independently an important immune factor of controlling HIV infection not only in its number but also in its func-tion. Multiple studies on phenotypic markers or surface antigens of lymphocytes show that level of expression of CD25 decrease while that of HLA-DR increased on lymphocytes in HIV-infected individuals compared with that in HIV-negative subjects and that levels of expression of these molecules represent a part of function of lymphocytes. But function testing of CD4 cell and CD8 cell is complicated in technique and time spending. In addition, some studies indicate that apoptosis of CD4 cells play an important role in HIV/AIDS pathogenesis. So it is clinically important to compare the lymphocyte subsets and phenotypes in HIV-positive subjects with those in HIV-negative individuals.

  13. Comparison of T-lymphocyte Subsets and Phenotypes between HIV-positive Subjects and HIV-negative Subjects

    Institute of Scientific and Technical Information of China (English)

    陈小平; 陈观今; 肖斌权; 施文钧; 徐惠芳; 高凯

    2001-01-01

    @@ With the advance of research on HIV/AIDS, CD8 T-lymphocyte is believed to be independently an important immune factor of controlling HIV infection not only in its number but also in its function. Multiple studies on phenotypic markers or surface antigens of lymphocytes show that level of expression of CD25 decrease while that of HIA-DR increased on lymphocytes in HIV-infected individuals compared with that in HIV-negative subjects and that levels of expression of these molecules represent a part of function of lymphocytes. But function testing of CD4 cell and CD8 cell is complicated in technique and time spending. In addition, some studies indicate that apoptosis of CD4 cells play an important role in HIV/AIDS pathogenesis. So it is clinically important to compare the lymphocyte subsets and phenotypes in HIV-positive subjects with those in HIV-negative individuals.

  14. Supplementation of Eurycoma longifolia Jack Extract for 6 Weeks Does Not Affect Urinary Testosterone: Epitestosterone Ratio, Liver and Renal Functions in Male Recreational Athletes

    Directory of Open Access Journals (Sweden)

    Chee Keong Chen

    2014-01-01

    Conclusions: Supplementation of ElJ i.e. Physta ® at a dosage of 400 mg/day for 6 weeks did not affect the urinary T:E ratio and hence will not breach any doping policies of the International Olympic Committee for administration of exogenous testosterone or its precursor. In addition, the supplementation of ElJ at this dosage and duration was safe as it did adversely affect the liver and renal functions.

  15. Multidrug resistance-1 in T lymphocytes and natural killer cells of adults with idiopathic thrombocytopenic purpura: effect of prednisone treatment.

    Science.gov (United States)

    López-Karpovitch, Xavier; Graue, Gerardo; Crespo-Solís, Erick; Piedras, Josefa

    2008-07-01

    High P-glycoprotein-mediated multidrug resistance-1 (P-gp/MDR1) activity in lymphocytes from idiopathic thrombocytopenic purpura (ITP) patients may affect disease outcome. ITP treatment includes glucocorticoids that are substrates of P-gp; hence, P-gp functional activity and antigenic expression were assessed by flow cytometry in T and natural killer (NK) cells from ITP patients before and after prednisone therapy. Herein, patients' T and NK cells did not show increased MDR1 functional activity, whereas P-gp antigenic expression was significantly enhanced in both therapy-free and prednisone-treated patients. Prednisone treatment did not significantly modify the function and expression of MDR1 in T and NK cells of ITP patients.

  16. Lymphocyte Glucose and Glutamine Metabolism as Targets of the Anti-Inflammatory and Immunomodulatory Effects of Exercise

    Directory of Open Access Journals (Sweden)

    Frederick Wasinski

    2014-01-01

    Full Text Available Glucose and glutamine are important energetic and biosynthetic nutrients for T and B lymphocytes. These cells consume both nutrients at high rates in a function-dependent manner. In other words, the pathways that control lymphocyte function and survival directly control the glucose and glutamine metabolic pathways. Therefore, lymphocytes in different functional states reprogram their glucose and glutamine metabolism to balance their requirement for ATP and macromolecule production. The tight association between metabolism and function in these cells was suggested to introduce the possibility of several pathologies resulting from the inability of lymphocytes to meet their nutrient demands under a given condition. In fact, disruptions in lymphocyte metabolism and function have been observed in different inflammatory, metabolic, and autoimmune pathologies. Regular physical exercise and physical activity offer protection against several chronic pathologies, and this benefit has been associated with the anti-inflammatory and immunomodulatory effects of exercise/physical activity. Chronic exercise induces changes in lymphocyte functionality and substrate metabolism. In the present review, we discuss whether the beneficial effects of exercise on lymphocyte function in health and disease are associated with modulation of the glucose and glutamine metabolic pathways.

  17. Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio are Predictors of Heart Failure

    Directory of Open Access Journals (Sweden)

    Erdal Durmus

    2015-01-01

    Full Text Available AbstractBackground:Neutrophil-to-lymphocyte ratio (NLR and platelet-to-lymphocyte ratio (PLR are inflammatory markers used as prognostic factors in various diseases. The aims of this study were to compare the PLR and the NLR of heart failure (HF patients with those of age-sex matched controls, to evaluate the predictive value of those markers in detecting HF, and to demonstrate the effect of NLR and PLR on mortality in HF patients during follow-up.Methods:This study included 56 HF patients and 40 controls without HF. All subjects underwent transthoracic echocardiography to evaluate cardiac functions. The NLR and the PLR were calculated as the ratio of neutrophil count to lymphocyte count and as the ratio of platelet count to lymphocyte count, respectively. All HF patients were followed after their discharge from the hospital to evaluate mortality, cerebrovascular events, and re-hospitalization.Results:The NLR and the PLR of HF patients were significantly higher compared to those of the controls (p < 0.01. There was an inverse correlation between the NLR and the left ventricular ejection fraction of the study population (r: -0.409, p < 0.001. The best cut-off value of NLR to predict HF was 3.0, with 86.3% sensitivity and 77.5% specificity, and the best cut-off value of PLR to predict HF was 137.3, with 70% sensitivity and 60% specificity. Only NLR was an independent predictor of mortality in HF patients. A cut-off value of 5.1 for NLR can predict death in HF patients with 75% sensitivity and 62% specificity during a 12.8-month follow-up period on average.Conclusion:NLR and PLR were higher in HF patients than in age-sex matched controls. However, NLR and PLR were not sufficient to establish a diagnosis of HF. NLR can be used to predict mortality during the follow-up of HF patients.

  18. Utility of DF-1 for Radioprotection in Lymphocytes

    Science.gov (United States)

    Reynolds, Julia; Casey, Rachael; Wu, Honglu; Huff, Janice; Emami, Kamal; Moore, Valerie; Jeevarajan, Antony

    2007-01-01

    The development of degenerative changes in the vasculature, such as atherosclerosis, is a known consequence of exposure to ionizing radiation, and is thus a concern for astronaut health following long duration space flight. Cellular damage caused by radiation is due to free radical generation and DNA damage. The goal of this project was to assess the ability of a C60-derivative, DF-1, to mitigate cellular damage resulting from radiation exposure in primary human lymphocytes. DF-1 is a water-soluble C60 fullerene encapsulated in dendrimeric functional groups that is proposed to exhibit antioxidant properties. Human lymphocytes are radiosensitive and travel throughout the body potentially causing bystander effects in any tissues they contact. These cells were subjected to varying doses of gamma radiation in the presence or absence of DF-1. Cells were collected at 48 hours post-irradiation for chromosomal aberration studies and at 72 hours post-irradiation for micronuclei studies. These studies showed that the irradiated cells contained more chromosomal aberrations and micronuclei than the control cells. Addition of the DF-1 reduced the amount of observed DNA damage in the irradiated cells. Growth curves were measured for the lymphocytes exposed to 0 and 4 Gray gamma irradiations, and we observed less growth in the cells irradiated at 4 Gy. 2,7-dichlorofluorescein diacetate was used to detect reactive oxygen species production, and increased production of ROS was observed in the irradiated lymphocytes. Human lymphocytes were subjected to varying doses of gamma or photon radiation in the presence and absence of DF-1 and a known radioprotectant, amifostine. After irradiation, the production of reactive oxygen species, growth curves and cell viability were measured. These cells were also collected to quantify chromosomal aberrations and micronuclei formation. We predict that irradiated cells will show the most damage and that DF-1 will provide protective effects similar

  19. Growing B Lymphocytes in a Three-Dimensional Culture System

    Science.gov (United States)

    Wu, J. H. David; Bottaro, Andrea

    2010-01-01

    A three-dimensional (3D) culture system for growing long-lived B lymphocytes has been invented. The capabilities afforded by the system can be expected to expand the range of options for immunological research and related activities, including testing of immunogenicity of vaccine candidates in vitro, generation of human monoclonal antibodies, and immunotherapy. Mature lymphocytes, which are the effectors of adaptive immune responses in vertebrates, are extremely susceptible to apoptotic death, and depend on continuous reception of survival-inducing stimulation (in the forms of cytokines, cell-to-cell contacts, and antigen receptor signaling) from the microenvironment. For this reason, efforts to develop systems for long-term culture of functional, non-transformed and non-activated mature lymphocytes have been unsuccessful until now. The bone-marrow microenvironment supports the growth and differentiation of many hematopoietic lineages, in addition to B-lymphocytes. Primary bone-marrow cell cultures designed to promote the development of specific cell types in vitro are highly desirable experimental systems, amenable to manipulation under controlled conditions. However, the dynamic and complex network of stromal cells and insoluble matrix proteins is disrupted in prior plat